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Cervical cancer in Africa, Latin America and the Caribbean, and Asia: Regional inequalities and changing trends: Cervical cancer in Africa, Latin America and the Caribbean, and Asia
International Journal of Cancer
Abstract
The vast majority (86% or 453,000 cases) of the global burden of cervical cancer occurs in Africa, Latin America and the Caribbean, and Asia, where one in nine new cancer cases are of the cervix. Although the disease has become rare in high-resource settings (e.g. in North America, parts of Europe, Japan) that have historically invested in effective screening programmes, the patterns and trends are variable elsewhere. While favourable incidence trends have been recorded in many populations in Asia and Latin America and the Caribbean in the past decades, rising rates have been observed in sub-Saharan African countries, where high quality incidence series are available. The challenge for countries heavily affected by the disease in these regions is to ensure resource-dependent programmes of screening and vaccination are implemented to transform the situation, so that accelerated declines in cervical cancer are not the preserve of high-income countries, but become the norm in all populations worldwide. This article is protected by copyright. All rights reserved.
... Cervical cancer is the fourth most common cancer among women worldwide with an estimated 604,127 new cases and 341,831 deaths reported in 2020 [1], up from 528,000 new cases and 266,000 deaths reported in 2012 [2]. The bulk of the global burden rests with Africa, Latin America, the Caribbean and Asia where approximately 90% of deaths occur [3]. With an estimated population of 372.2 million women aged 15 years and older who are at risk of developing cervical cancer in Africa, 119, 284 women are diagnosed with cervical cancer while 81,687 die from the disease every year [4]. ...
... With an estimated population of 372.2 million women aged 15 years and older who are at risk of developing cervical cancer in Africa, 119, 284 women are diagnosed with cervical cancer while 81,687 die from the disease every year [4]. Compared to other regions in the world, Africa has higher cervical cancer incidence and mortality rates [1,3,5]. Cervical cancer screening can reduce the incidence of the disease by 70-80% if targeted appropriately [6,7]. ...
... Screening barriers unique to these countries were therefore not explored. Evidence suggests that cervical cancer is uncommon in Northern Africa [3] which could be the reason for lack of research in that area. Nevertheless, findings of this review exclude an important segment of the study population which could be having unique barriers to cervical cancer screening. ...
Introduction
Africa has one of the highest burdens of cervical cancer in the world. The unacceptably high incidence and mortality rates could be reduced through implementing a comprehensive approach to its prevention and control that includes screening, which however, is low in most low-and-middle-income countries. Hence, this systematic review aims at exploring factors that prevent women from utilising cervical cancer screening services in the region.
Methods
A mixed method systematic review was conducted. A search was performed on PubMed (Medline), EMBASE, CINAHL (EBSCOHOST) and Scopus databases for articles published until May 2019 without time, language or study design limits. Two reviewers critically appraised the included studies independently using the standard quality assessment criteria for evaluating primary research papers. Results of the quantitative and mixed methods studies were transformed into qualitative data and synthesised using thematic analysis.
Results
From a potential 2 365 studies, 24 from 11 countries met the eligibility criteria and were selected; eight qualitative, 13 quantitative, and three that used the mixed-method approach. The primary barriers were identified as poor access to screening services, lack of awareness and knowledge on cervical cancer and screening, and socio-cultural influences. Service providers perceived lack of skills, screening equipment and supplies, and staff shortages as the major barriers to the provision of screening services.
Conclusion
Barriers to cervical cancer screening in Africa are multifaceted and require a holistic approach that will address them concurrently at the health system, individual, interpersonal, community and structural levels. Political will complimented by stakeholder involvement is required in the development and implementation of strategies that will ensure acceptability, availability, accessibility, and affordability of screening to minimise barriers in accessing the service.
... The present increasing burden of disease is one reason for this extended timeline. LMICs account for more than 80 % of incidences of cervical cancer , where the death rate from cervical cancer, age-standardized, is at least six times greater than in high-income nations (Vaccarella, Laversanne, Ferlay, & Bray, 2017). ...
... Out of the 118 million women vaccinated against HPV by 2016, only1.4 million (1 %) lived in low-and middle-income countries (LMICs) (Bruni et al., 2016). This difference shows that not many people can easily get help to prevent or treat cervical cancer because there are not enough tools, technical knowledge, and resources available (Vaccarella et al., 2017). This study aims to evaluate how well developing countries are doing in responding to the WHO's call to eradicate cervical cancer by focusing on (1) prevalence of cervical cancer incidence and mortality rates within developing countries, and (2) impact and implementation of HPV vaccination programs, and (3) consideration of proposals in the developing countries to eradicate cervical cancer. ...
The heart shattering impact afflicted by the notorious cervical cancer is rising rapidly as it emerges as the second most prevalent cancer among women in the developing countries. There was an anticipated 604,127 observed reports and 341,831 fatalities reported worldwide in 2020. The mortality rate was 7.2 deaths per 100,000 women-years, while the age-standardized incidence rate was 13.3 cases per 100,000 women annually. In less developed countries, the accountability was around 87–90% of mortality and roughly 84% of newly diagnosed cases. Resource limitations, inadequate public awareness, and late-stage diagnosis aggravate the complications of cancer mitigation in these regions, compared to the higher income nations. While primary and secondary interventions come off as an enticing solution, international collaborations and the integration of technology also emerge as promising avenues for enhancing cancer care accessibility. This study aims to assess the progress of developing countries in meeting the World Health Organization’s mandate to eliminate cervical cancer by scrutinizing the prevalence of cervical cancer incidence and mortality rates, evaluating the impact and execution of HPV vaccination initiatives, and analyzing proposals for cervical cancer eradication within these nations, our objective is to accelerate advancements towards the ultimate goal of eradicating cervical cancer.
... Literature has shown HPV as the epicenter of CC. This virus was detected in 99.7% of all premalignant to invasive cancers of the cervix of the uterus [10,19,11,20,21]. It is also found in perineal, oral, pharyngeal, and oesophageal lesions [22]. ...
... Chlamydia trachomatis is a sexually transmitted disease that can cause inflammation of the genital tract. In general, this infection is asymptomatic [20]. However, its DNA has been found in about 40% of invasive cervical cancers [31]. ...
Background: Cervical cancer (CC) is a public health problem worldwide as well as in Cameroon. 85% of new cases occur in
... По состоянию на май 2020 г. страны с низким уровнем дохода (СНУД) внедрили национальные программы вакцинирования против ВПЧ с <30% охватом, в то время как внедрение аналогичных программ в высокодоходных странах обеспечило охват >80% [20]. Только 44% женщин в странах с низким и средним доходом когда-либо проходили скрининг на РШМ (с наименьшей вовлеченностью среди женщин в странах Африки к югу от Сахары и Латинской Америке) [7,21,22] при охвате >60% в странах с высоким уровнем дохода. В этой связи в низкодоходных регионах крайне важно обеспечение реализации ресурсозависимых программ скрининга и вакцинации для изменения ситуации [22,23]. ...
... AJHMS │ 2/III/2023 мнение о том, что длительность эффективности вакцины является важным параметром определения стоимостной эффективности ВПЧ-вакцинации [17,107]. Однако, уже получены данные о 42% снижении числа эксцизий ШМ в группе вакцинированных женщин по сравнению с таковым в группе плацебо через 4 года наблюдения [21]. ...
В данной работе предпринято обобщённое изложение данных об эпидемиологических аспектах рака шейки матки (РШМ), современных подходах к методологии скрининга РШМ, а также результатах анализа клинико-экономической эффективности различных скрининговых стратегий, имеющихся в доступной англо-, армяно- и русскоязычной литературе. Проанализировано 118 источников, около 95% которых опубликовано за последние 10 лет. Отбор производился по принципу соответствия субъектов проводимых исследований современным представлениям об указанных аспектах РШМ. Изученные данные включали отчёты и рекомендации Всемирной организации здравоохранения (ВОЗ), органов здравоохранения отдельных стран (в частности, Республики Армения, РА) результаты клинических и экономических исследований отдельных авторов, а также систематические обзоры литературы – результаты изучения эффективности отдельных скрининговых методов и их комбинаций. Особого внимания заслуживают данные, опубликованные ВОЗ и специальными целевыми группами профилактических служб США, а также авторами многоцентровых исследований европейских стран, посвящённые сравнительному анализу клинико-экономической эффективности различных скрининговых стратегий в странах с различными уровнями дохода. Как известно, арсенал методов скрининга РШМ, ранее представленный, в основном, цитологическим исследованием и его модификациями, в последние годы пополнился различными инновационными методами, что способствует повышению клинико-экономической эффективности включающих их скрининговых стратегий. Постепенно вымещающий цитологическое исследование (в силу сравнительно низкой чувствительности последнего) тест на вирус папилломы человека (ВПЧ) также не считается абсолютно приемлемым (зависит от ряда обстоятельств) в силу его высокой себестоимости. При исследовании результатов проведения кольпоскопии в неоднородных (с точки зрения доступности здравоохранения, экономической эффективности и т.д.) регионах было показано, что включение кольпоскопии в скрининговую программу способствует надлежащей стандартизации протокола для эффективной сортировки ВПЧ-позитивных женщин. Вместе с тем, обучение и опыт кольпоскопистов, количество собранных биопсий и конкретная локация сбора эндоцервикальных образцов (TZ2 или TZ3) и биоптатов эктоцервикса являются факторами, существенно влияющими на клинико-экономическую эффективность скрининговых программ. Опубликованные в последние годы данные по использованию искусственного интеллекта для квалификации результатов кольпоскопии однозначно свидетельствуют о диагностической ценности данной опции как фактора, способствующего повышению клинико-экономической эффективности скрининга РШМ. Сопоставление вышеуказанных данных с результатами анализа проведённого в 2015-2021 гг. скрининга в Армении позволяет сделать вывод о необходимости разработки и внедрения оптимального для РА клинико-экономически эффективного алгоритма скрининговой диагностики и лечения предраковых состояний шейки матки и выявления РШМ на ранних курабельных стадиях его развития. Внедрение инновационных технологий в стратегию скрининговой диагностики РШМ станет, на наш взгляд, одной из важнейших вех на пути повышения эффективности менеджмента данного контингента больных.
... HPV types are commonly divided into high (carcinogenic) or low-risk (non-carcinogenic) types [30]. Hence, twelve alpha mucosal HPV types (HPV 16,18,31,33,35,39,45,51,52,56,58,and 59), referred to as high-risk HPV types (HR-HPV), were classified as carcinogenic to humans. Eight other alpha HPV types (HPV 26,53,66,67,68,70,73,and 82) were classified as probably or possibly carcinogenic [31]. ...
... CC can be controlled through primary (HPV vaccination), secondary (cervical screening and treatment of precancerous lesions) and tertiary (early diagnosis and treatment of cancer) prevention which should be combined to reduce morbidity and mortality [33]. In LMICs, primary prevention is even more critical than in other regions of the world because of the scarcity of services and infrastructures capable to properly manage advanced forms of the disease [34,35]. However, the implementation of preventive measures and populationbased screening programmes in LMICs in general, and in SSA in particular, has been shown to be challenging due to financial, logistic, and socio-cultural factors [36]. ...
Background:
Women's health in resource-limited settings can benefit from the integrated management of high-burden diseases, such as female genital schistosomiasis (FGS) and human papilloma virus (HPV)-related cervical cancer. In schistosomiasis-endemic countries such as Madagascar, data on FGS and HPV prevalence are lacking as well as preventive measures for both conditions. This study aims to estimate the prevalence of FGS and HPV in rural Madagascar, and to examine associated risk factors to identify opportunities for improving women's health.
Methods:
After initial community outreach activities, interested women aged 18-49 years were recruited consecutively in 2021 at three primary health care centers in the district of Marovoay. FGS was detected by colposcopy. Colposcopy images were double-blind reviewed by two independent specialists. A Luminex bead-based assay was performed on cervical vaginal lavage specimens for HPV typing. Crude (CPR) and adjusted prevalence ratios (APR) of associations between selected factors and FGS and HPV positivity were estimated using univariable and multivariable binary Poisson regression with 95% confidence intervals (CIs).
Results:
Among 500 women enrolled, 302 had complete information on FGS and HPV diagnosis, and were thus eligible for analysis. Within the sample, 189 (62.6%, 95% CI: 56.9-68.1) cases of FGS were detected. A total of 129 women (42.7%, 95% CI: 37.1-48.5) tested positive for HPV. In total, 80 women (26.5%, 95% CI: 21.6-31.8]) tested positive for both conditions. No association was observed between FGS and HPV positivity, while previous pregnancy (APR = 0.65, 95% CI: 0.43-0.78) and older age (APR = 0.59, 95% CI: 0.42-0.81) are showing a negative association with HPV infection compared to no previous pregnancy and younger age groups.
Conclusions:
The results of the study show that FGS and HPV are highly prevalent in rural Madagascar. The concurrent prevalence of these two conditions requires urgent adaptations of public health strategies to improve women's health, such as integrated services at primary level of care.
... Quality control at all steps of the process is essential to ensure effectiveness. In the literature, there is solid evidence that cervical cancer incidence is related to the region's level of development or to the health system's ability to diagnose and treat precursor lesions [2,18,19]. Higher the development of a country or region, earlier the stage at diagnosis [4,14,20,21]. In our study, the proportion of cases in women aged 50 years and over ranged from 54.0 to 60.2% (p = 0.117). ...
... Low and middle-income countries present most cervical cancer cases and many health inequalities [1,19]. At the sub-analysis of the 'inequality' component, no difference was observed in the proportion of cases in any variable used. ...
Background
Barriers to accessing health care result in advanced cervical cancer. In Sao Paulo, Brazil, the Index of Social Responsibility (ISR) synthesizes the situation of each town concerning wealth, education, and longevity. This study aimed to evaluate in 645 municipalities the relation of the ISR with stage, age, and morphology in cervical cancer diagnosis.
Methods
An ecological study that used data from Sao Paulo, Brazil, from 2010 to 2017. The ISR was identified through government platforms and data on cancer through the Hospital Cancer Registry. The subjects were the 9,095 women aged 30 years or older. The ISR summarizes municipalities into five levels: dynamic (ISR5), unequal (ISR4), equitable (ISR3), in transition (ISR2), and vulnerable (ISR1). It was used the chi² tests and logistic regression.
Results
The proportion of stage 1 increased significantly with ISR level, ranging from 24.9% in ISR1 to 30.0% in ISR5 (p = 0.040). To every increase in ISR level, the chance of a woman being diagnosed in stage I was at least 30% higher. Woman living where ISR2 had a 1.4 times higher chance of being diagnosed in stage 1 than those living in ISR1 (OR 1.40, 95% CI 1.07–1.84). Squamous tumors frequency decreased when ISR level increased (p = 0.117). A higher proportion of women under 50 years were observed when they lived in wealthier cities (ISR4 and ISR5) (42.2% vs. 44.6%, p = 0.016).
Conclusion
The ISR was a good health indicator for understanding and predicting the social determinants in cervical cancer diagnosis. The proportion of stage I increased significantly in more favorable social conditions.
... Cervical carcinoma is the most prevalent cancer diagnosed in 23 countries and the primary cause of mortality in 36 nations [1,2]. Furthermore, 85 percent of cervical cancers were encountered in the late stages. ...
... The (W) world age standardized incidence rate is shown in descending order, and the highest national age-standardized incidence and mortality rates are overlaid. In such areas, it is critical to ensure that resourceintensive vaccination and screening programs are carried out to improve the situation [2]. The human-based smear analysis is difficult, laborious, time consuming, costly, and prone to errors since each smear slide consists of approximately 3 million cells with varying overlapping and orientation, necessitating the development of a computerized system capable of analyzing the Pap smear effectively and efficiently [4]. ...
Medical image analysis and classification is an important application of computer vision wherein disease prediction based on an input image is provided to assist healthcare professionals. There are many deep learning architectures that accept the different medical image modalities and provide the decisions about the diagnosis of various cancers, including breast cancer, cervical cancer, etc. The Pap-smear test is the commonly used diagnostic procedure for early identification of cervical cancer, but it has a high rate of false-positive results due to human error. Therefore, computer-aided diagnostic systems based on deep learning need to be further researched to classify the pap-smear images accurately. A fuzzy min–max neural network is a neuro fuzzy architecture that has many advantages, such as training with a minimum number of passes, handling overlapping class classification, supporting online training and adaptation, etc. This paper has proposed a novel hybrid technique that combines the deep learning architectures with machine learning classifiers and fuzzy min–max neural network for feature extraction and Pap-smear image classification, respectively. The deep learning pretrained models used are Alexnet, ResNet-18, ResNet-50, and GoogleNet. Benchmark datasets used for the experimentation are Herlev and Sipakmed. The highest classification accuracy of 95.33% is obtained using Resnet-50 fine-tuned architecture followed by Alexnet on Sipakmed dataset. In addition to the improved accuracies, the proposed model has utilized the advantages of fuzzy min–max neural network classifiers mentioned in the literature.
... Research has revealed that cervical cancer h link to human papillomavirus (HPV). Smoking, HPV, early sexual activity, and ge modifications lead to cervical cancer [97,98]. Undoubtedly, treatment options are av ble, but their outcomes are still uncertain, and there is a need to find other therap alternatives [99][100][101]. ...
... Research has revealed that cervical cancer has a link to human papillomavirus (HPV). Smoking, HPV, early sexual activity, and genetic modifications lead to cervical cancer [97,98]. Undoubtedly, treatment options are available, but their outcomes are still uncertain, and there is a need to find other therapeutic alternatives [99][100][101]. ...
Polydatin or 3-O-β-d-resveratrol-glucopyranoside (PD), a stilbenoid component of Polygonum cuspicadum (Polygonaceae), has a variety of biological roles. In traditional Chinese medicine, P. cuspicadum extracts are used for the treatment of infections, inflammation, and cardiovascular disorders. Polydatin possesses a broad range of biological activities including antioxidant, anti-inflammatory, anticancer, and hepatoprotective, neuroprotective, and immunostimulatory effects. Currently, a major proportion of the population is victimized with cervical lung cancer, ovarian cancer and breast cancer. PD has been recognized as a potent anticancer agent. PD could effectively inhibit the migration and proliferation of ovarian cancer cells, as well as the expression of the PI3K protein. The malignancy of lung cancer cells was reduced after PD treatments via targeting caspase 3, arresting cancer cells at the S phase and inhibiting NLRP3 inflammasome by downregulation of the NF-κB pathway. This ceases cell cycle, inhibits VEGF, and counteracts ROS in breast cancer. It also prevents cervical cancer by regulating epithelial-to-mesenchymal transition (EMT), apoptosis, and the C-Myc gene. The objective of this review is thus to unveil the polydatin anticancer potential for the treatment of various tumors, as well as to examine the mechanisms of action of this compound.
... The GLOBOCAN 2020 report Table 2 Joinpoint analysis of the trends in cancer-specific incidence rates for the combined cancers, female Model selection: weighted Bayesian information Criterion (BIC)/parametric method suggested that improvements in the prevention, screening and diagnosis of this carcinoma might be responsible for these observed declines [2]. However, beyond this conjecture, the declines could be due to lower birth rates and parity, improved hygiene conditions, education and socioeconomic status across the island's female population over time [30]. ...
Background
Globally, estimates of cancer cases and deaths have increased since 2018, particularly in Latin America and Caribbean countries. In Antigua and Barbuda, understanding the burden of common cancers such as female breast, cervical, colorectal and prostate cancers is critical. This study aimed to assess the incidence, trends, and patterns of these four cancers from 2017 to 2021.
Methods
Using a retrospective observational study design, information on these cancers was abstracted from medical records at four key study sites in Antigua and Barbuda. Estimates of age-specific and age-standardized incidence were determined using direct standardization. The KeyFitz method was used to derive standard errors and confidence intervals. Derived estimates were employed to analyze trends and Joinpoint regression modeling was used to determine annual percentage change.
Results
Between 2017 and 2021, 391 cases of female breast (41.7%), cervical (10.2%), colorectal (20.2%) and prostate (27.9%) cancers were diagnosed. Overall mean age at presentation was 61.5 (± 12.9) years, ranging from 24 to 94 years, age-standardized incidence rate 65.2 (95% CI: 58.7–71.6) per 100,000 population. Age-standardized incidence rate for female breast cancer was 49.9 (95% CI: 42.2–57.8), annual percentage change in incidence a low of -0.2%. Prostate cancer had the second highest age-standardized incidence rate at 41.6 (95% CI: 33.8–49.4), annual percentage change showed a gradual but steady increase at 21.7%. Per cancer types, variations in age-standardized incidence rates were noted across age-groups, year-of-presentation, and parishes. Collectively, there was an 8.1% (95% CI: -14.9–37.6) annual percentage change increase in age-standardized incidence rates between 2017 and 2021. Incident cases, age-standardized incidence rates, and trends per cancer type are expected to gradually increase during 2022–2030 (average annual percentage increase is 3.4%).
Conclusions
This study is a first step in providing reasonable evidence on the incidence, trends, and patterns of four common cancers in Antigua and Barbuda. Female breast and prostate cancers were the dominant cancer types in terms of incidence, age-standardized incidence and predicted increasing incidence trends. Variableness in cancer-specific age-standardized rates across parishes and years of presentation were observed. Besides research, this study has importance for instituting cancer prevention and control measures, including surveillance and healthy lifestyles initiatives.
... Still, each year estimated 604.000 women are diagnosed with cervical cancer, over 85% occurs in low-and-middle-income countries (LMICs) [6]. The unequal distribution of cervical cancer burden between high-income countries (HICs) and LMICs is caused by multiple factors including the relatively high prevalence of human papillomavirus (HPV) infections and HIV infections in LMICs, the lack of well-organized prevention programs and the lack of accessible cancer care facilities [5,[7][8][9][10]. ...
Objective
Treatment of cervical cancer patients in Uganda is hampered by late diagnosis due to the unavailability of timely screening and limited availability of advanced cancer care. This study evaluated the clinical presentation and management of cervical cancer patients presenting at the Uganda Cancer Institute (UCI) in Kampala, the tertiary oncology facility in Uganda with access to radiotherapy and reflected on daily clinical practice to identify priority areas for improving cervical cancer care in Uganda.
Patients and methods
We retrospectively analyzed medical records of all cervical cancer patients presenting to UCI between January 2017 and March 2018 for sociodemographic characteristics and clinical variables with descriptive statistics. The clinical management of patients with early and advanced stage disease who initiated treatment at UCI was evaluated using the national targets formulated in the Uganda strategic plan for cervical cancer prevention and control.
Results
Medical records of 583 patients were included, representing less than 10% of the annual estimated incidence in Uganda. The majority (86%) of patients presented with advanced stage of disease. More than half of patients never initiated (31%) or interrupted (30%) treatment. The national treatment targets for surgery (10%) and palliative care (25%) were achieved for eligible patients at UCI, however, the target for chemoradiotherapy (65%) was not met.
Conclusion
Daily clinical practice differed from the ambitions formulated in the national treatment targets on cervical cancer control. While most women presented in advanced stage requiring chemoradiotherapy, the target was not met due to limited availability of radiotherapy. Although targets for surgery and palliative care were achieved at UCI facility level, they mask the unmet need of the majority of cervical cancer patients who never initiated or completed treatment. This demands for further expansion of oncological surgical capacity, chemotherapy and radiotherapy and warrants to focus on accessible prevention programs.
... A single cervical cancer screening in a woman's lifetime significantly reduces the risk of developing cervical cancer (a risk ratio of 0.65 when comparing single lifetime screening to no screening cohorts) 3 However, in low and middle-income areas, access to preventative measures is limited, delaying diagnosis of dysplastic lesions and cervical cancer until advanced stages. 4,5 Access to treatment and limited treatment modalities also result in higher mortality rates. 6 Further, in resource-limited countries increasing HIV prevalence and decreased funding for antiretroviral therapy, potentiates the pathogenesis of HPV. 7 Increased access to vaccines, genomic testing, and artificial intelligence technologies have the potential to vastly improve both primary and secondary prevention of cervical cancer. ...
Purpose
Cervical cancer remains a significant health concern, particularly in developing countries, where it is a leading cause of cancer-related deaths among women. Innovative technologies have emerged to improve the efficiency, cost-effectiveness, and sensitivity of cervical cancer screening and treatment methods. This study aims to explore the various approaches for the detection and treatment of human papillomavirus (HPV), cervical dysplasia (CD), and cervical cancer, highlighting new technologies and updated screening strategies in developing areas.
Patients and Methods
A comprehensive literature search was conducted using PubMed to identify relevant publications on the subject of cervical cancer screening and HPV detection.
Results
HPV infection and cervical cancer continue to pose significant global health challenges. Emerging technologies such as rapid, low-cost HPV testing combined with high-resolution digital colposcopy and artificial intelligence interpretation hold promise for efficient and sensitive screening. Advancements in HPV vaccine distribution, high-risk HPV screening, DNA methylation assays, dual-stain cytology, lab-on-chip assays, and deep learning technologies offer new avenues for improved detection and risk stratification.Research and innovations in detection and treatment methods are crucial for reducing the burden of these diseases worldwide.
Conclusion
Screening for HPV and CD plays a pivotal role in reducing the risk of cervical cancer-related mortality. The development of novel technologies, along with efforts to enhance global health equity and integrate cervical cancer prevention with HIV screening and treatment programs, represent critical steps toward achieving comprehensive cervical cancer screening on a global scale.
... The global population's aging and growth will also increase the absolute number of cases [35]. Ensuring the implementation of resource-dependent screening and vaccination programs is crucial in these places to improve the situation [36]. ...
Cervical cancer remains a leading cause of cancer-related mortality in women in low and middle-income countries despite efforts to improve prevention and standard-of-care interventions. Sub-Saharan Africa (SSA) leads the numbers for global cervical cancer incidence and mortality, with the majority of the incidence diagnosed in the late stage of the malignancy. Although the global cervical cancer death rate has been on the decline for the last two decades owing to advancements in screening and treatment options, the mortality rate in SSA has not declined very much. Chemotherapy has been the treatment of choice for cervical cancer in SSA without meeting the expected survival outcomes in these patients, with the majority having advanced diseases at diagnosis. Immune checkpoint inhibitors have recently shown clinical promise in improving the survival of patients with advanced cervical cancer and have been integrated into the treatment guidelines in most high-income countries, which have helped further reduce the mortality rate of cervical cancer. However, many SSA countries are yet to fully benefit from using immune checkpoint inhibitors in cervical cancer. In this review, we discuss the challenges hindering the effective use of immune checkpoint inhibitors for advanced cervical cancer in Africa and possible solutions.
... Asia acumula la vasta mayoría de casos (285 000) y muertes (144 000 En Latinoamérica, el CaCU tiene un enorme peso para los sistemas de salud de la región, en países como Honduras, Nicaragua, El Salvador, Bolivia, Paraguay y Ecuador, donde representa la principal causa de muerte por cáncer. Aunque, en los últimos veinte años se observa en la región, una reducción en la mortalidad femenina por dicha causa, esta tendencia no está proporcionalmente distribuida, mientras que en algunos países hubo una reducción, en otros la tasa de mortalidad, por el contrario, ha aumentado (6,77,78). ...
Se estudió la infección por Virus del Papiloma Humano (VPH), genotipos circulantes y variantes intratípicas en 320 mujeres con lesiones citológicas y cáncer cervicouterino (CaCU), residentes en la región Litoral del Ecuador; y su relación con variables virales, clínico-epidemiológicas y sociodemográficas entre 2012 y 2015. Se realizó la detección del VPH con iniciadores universales MY09/MY11, genotipado mediante el sistema comercial Anyplex™II HPV28 y filogenia de variantes virales. Resultó una frecuencia de infección del 94% (300/320), predominio de tipos oncogénicos y 92% (276/330) de coinfecciones. Los VPH58, 70, 53, 35 y 16 fueron más frecuentes. De las secuencias de VPH16, el 69% (29/42) se agrupó con el linaje A y el resto con el D. Las 15 secuencias del VPH58 correspondieron al linaje A. El VPH16, en infecciones simples o en coinfecciones se asoció a lesiones de alto grado y CaCU. Las mujeres con nivel educacional básico, solteras, obreras, con inicio precoz de las relaciones sexuales tuvieron mayor probabilidad de infección viral (p<0,05). Aunque el VPH58 fue el más prevalente, no se asoció al CaCU, a menos que estuviera coinfectando con VPH16. La elevada frecuencia de VPH58 y de variantes más oncogénicas de VPH16 indica la necesidad de intensificar el programa de detección precoz del CaCU y fortalecer el programa de vacunación.
... Although CC screening programs are widely implemented, they have not been satisfactorily effective in LMIC because of a lack of pathologists and medical equipment to perform cytology for cancer screening. Therefore, 90% of CC-related deaths worldwide are in LMIC 26,30,31 . Blood sampling is commonly performed in clinical practice and is considered to be a convenient and non-invasive method. ...
Despite widespread cervical cancer (CC) screening programs, low participation has led to high morbidity and mortality rates, especially in developing countries. Because early-stage CC often has no symptoms, a non-invasive and convenient diagnostic method is needed to improve disease detection. In this study, we developed a new approach for differentiating both CC and cervical intraepithelial neoplasia (CIN)2/3, a precancerous lesion, from healthy individuals by exploring CC fatty acid metabolic reprogramming. Analysis of public datasets suggested that various fatty acid metabolizing enzymes were expressed at higher levels in CC tissues than in normal tissues. Correspondingly, 11 free fatty acids (FFAs) showed significantly different serum levels in CC patient samples compared with healthy donor samples. Nine of these 11 FFAs also displayed significant alterations in CIN2/3 patients. We then generated diagnostic models using combinations of these FFAs, with the optimal model including stearic and dihomo-γ-linolenic acids. Receiver operating characteristic curve analyses suggested that this diagnostic model could detect CC and CIN2/3 more accurately than using serum squamous cell carcinoma antigen level. In addition, the diagnostic model using FFAs was able to detect patients regardless of clinical stage or histological type. Overall, the serum FFA diagnostic model developed in this study could be a powerful new tool for the non-invasive early detection of CC and CIN2/3.
... [19] In already developed countries, the mortality rate associated with cervical cancer decreases significantly since many cases are detected early. [20] Cervical cancer incidence decreases in countries with well-established cervical cancer screening programs, with screening accounting for a significant percentage of the drop. [7] In the screening measures, sometimes in the form of basic tests, such as the Pap Smear test, are used during this period. ...
Despite being one of the most preventable and curable types of cancer, cervical cancer still causes death among Filipino women yearly. The pandemic created new obstacles for women to overcome, but some of the obstacles that existed before COVID-19 may now be worsened and will seriously affect women's self-care management, limiting their access to the necessary procedures needed for the screening of cervical cancer. This study aimed to determine the relationship of at-risk Filipino women’s health beliefs towards their intention to have Pap Smear test and the mediating role of fear of COVID-19. A causal predictive approach was conducted and 572 female Filipino currently residing in the Philippines participated in the study. Data were gathered utilizing the Health Belief Model Scale for Cervical Cancer and the Pap Smear Test and the Fear of COVID-19 Scale with the Intention to Screen assessed by a structured question. With p-values of < .05 which is considered statistically significant in this study, the outcome of the mediation analysis shows that the mediated effect of fear of COVID-19 is not particularly (partial mediation) significant. There is still a significant direct association between health beliefs particularly on the benefits of Pap Smear test and health motivation and barriers to Pap Smear test with the intention to screen even without the presence of fear. In conclusion, the fear of COVID-19 plays a minor effect in the association between Filipino women's health beliefs and their intention to attend Pap smear testing.
... At present, cervical cancer ranks fourth in cancer incidence and mortality among women globally (18). In 2020 alone, an estimated 604,000 new cases and 342,000 deaths were reported, with over 80% of these cases occurring in low-and-middle-income countries (18,19). In Latin America and the Caribbean (LAC), most of the countries have implemented cervical screening and HPV vaccination programs, and trends in cervical cancer incidence and mortality have decreased over the past 20 years (20,21). ...
Cervical cancer, primarily caused by human papillomavirus (HPV) infection, poses a significant global health challenge. Due to higher levels of poverty and health inequities, Indigenous women worldwide are more vulnerable to cervical cancer than their non-Indigenous counterparts. However, despite constituting nearly 10% of the population in Latin America and the Caribbean (LAC), the true extent of the burden of cervical cancer among Indigenous people in this region remains largely unknown. This article reviews the available information on cervical cancer incidence and mortality, as well as HPV infection prevalence, among Indigenous women in LAC. The limited existing data suggest that Indigenous women in this region face a heightened risk of cervical cancer incidence and mortality compared to non-Indigenous women. Nevertheless, a substantial knowledge gap persists that must be addressed to comprehensively assess the burden of cervical cancer among Indigenous populations, especially through enhancing cancer surveillance across LAC countries. Numerous structural, social and cultural barriers hindering Indigenous women’s access to HPV vaccination and cervical cancer screening worldwide have been identified and are reviewed in this article. The discussion highlights the critical role of culturally sensitive education, community engagement, and empowerment strategies in overcoming those barriers. Drawing insights from the success of targeted strategies in certain high-income countries, the present article advocates for research, policies and healthcare interventions tailored to the unique context of LAC countries.
... In May 2018, WHO demanded that cervical cancer be eradicated globally. More than seventy countries and worldwide academic groups complied [9]. Since the introduction of preventative programs, the incidence and death of cervical cancer have both declined [10,11]. ...
Cervical cancer emerges as a prominent health issue, demanding attention on a global level for women's well-being, which frequently calls for more specialized and efficient treatment alternatives. Traditional therapies may have limited tumour targeting and adverse side effects. Recent breakthroughs have induced a transformative shift in the strategies employed against cervical cancer. biocompatible herbal nanoparticles and metallic particles made of gold, silver, and iron have become promising friends in the effort to fight against this serious disease and understand the possibility of these nanoparticles for targeted medication administration. this review article delves into the latest advancements in cervical cancer research. The safety and fabrication of these nanomaterials and their remarkable efficacy against cervical tumour spots are addressed. This review study, in short, provides an extensive introduction to the fascinating field of metallic and herbal nanoparticles in cervical cancer treatment. The information that has been examined points to a bright future in which women with cervical cancer may experience fewer side effects, more effective therapy, and an improved quality of life. This review holds promise and has the potential to fundamentally reshape the future of cervical cancer treatment by addressing urgent issues and unmet needs in the field.
... Due to few resources and understaffed hospitals, cervical cancer has a high incidence and fatality rate in low -and middle-income nations. 36 By expediting the radiation treatment planning process, RapidPlan might also alleviate understaffing problems. Similar to previously cited studies, one optimization derived from RapidPlan is already likely to produce acceptable clinical treatment plan while reducing the waiting time to start the treatment for such type of cancer. ...
Treatment with radiation therapy can be relatively inexpensive and highly effective, reducing the overall cost of healthcare,
as well as saving lives of cancer patients. To face the posed challenges of laborious tasks and understaff in radiotherapy, the
use of knowledge-based models (artificial Intelligence) to reduce the treatment planning times up to 95% might be a promising
solution. One such tool, called RapidPlan (Varian Medical Systems, Palo Alto-CA), could be acquired with an investment
of a small fraction of the treatment planning system cost. RapidPlan’s support during treatment planning results in a
considerable increase in plan quality while reducing plan variability and elaboration time. The goal of this dissertation was
to estimate the break-even point from where the time saved during treatment time would pay the initial investment on
RapidPlan. Published data demonstrates that RapidPlan can largely benefit radiation therapy institutions by streamlining the
treatment planning process and the break-even point started to be achieved after treating 112 to 2668 patients, depending on
the cancer types treated for each group. Therefore, it may be possible to realize a return on investment within a reasonable
time frame, while benefiting from gains in efficiency, and possibly mitigating understaffing and lack of experience in treatment
planning.
... INTRODUCTION countries because of inadequate screening [3]. Although preventive vaccines against human papilloma virus (HPV) can decrease the incidence and mortality of CC [4], these are neither effective for infected patients [5] nor affordable for patients in developing countries [6]. Therefore, drug-based treatments are becoming the most common method to cure HPV-infected patients in developing countries [7][8][9]. ...
Background
A traditional Chinese medicine formula, Youdujing (YDJ) ointment, is widely used for treatment of human papilloma virus‐related diseases, such as cervical cancer. However, the underlying mechanisms by which active compounds of YDJ alleviates cervical cancer are still unclear.
Methods
We applied a comprehensive network pharmacology approach to explore the key mechanisms of YDJ by integrating potential target identification, network analysis, and enrichment analysis into classical molecular docking procedures. First, we used network and enrichment analyses to identify potential therapeutic targets. Second, we performed molecular docking to investigate the potential active compounds of YDJ. Finally, we carried out a network‐based analysis to unravel potentially effective drug combinations.
Results
Network analysis yielded four potential therapeutic targets: ESR1, NFKB1, TNF, and AKT1. Molecular docking highlighted that these proteins may interact with four potential active compounds of YDJ: E4, Y2, Y20, and Y21. Finally, we found that Y2 or Y21 can act alone or together with E4 to trigger apoptotic cascades via the mitochondrial apoptotic pathway and estrogen receptors.
Conclusion
Our study not only explained why YDJ is effective for cervical cancer treatment, but also lays a strong foundation for future clinical studies based on this traditional medicine.
... 43 In such high-risk countries and regions, the challenge is to ensure that resource-dependent programs of screening and vaccination are implemented to transform the situation. 69 HPV vaccination programs potentially can reduce the long-term future burden of cervical cancer, and the WHO currently recommends as best buys (effective and cost-effective interventions) vaccinations against HPV (2 doses) of girls aged 9 to 13 years. High-quality screening programs are also important to prevent cervical cancer among unvaccinated older women. ...
... Although high-income countries are on track to eliminate cervical cancer in the coming decades, the incidence of cervical cancer kept rising or remained in regions such as some sub-Saharan African, eastern European and western Asian countries. 3,5,6 Therefore, understanding the regional patterns in cervical cancer burden attributable to HIV infection from 1990 to 2019 is crucial to reduce the geographical disparities in the burden of cervical cancer. ...
Previous studies reported human immunodeficiency virus (HIV) could enhance human papillomavirus (HPV)-induced cervical cancer. Therefore, the burden of cervical cancer associated with HIV across different regions and time periods need to be assessed. We aim to investigate the global burden of cervical cancer associated with HIV infection. Age standardized rates (ASRs) of cervical cancer disability-adjusted life-years (DALYs) in females (≥15 years old) were calculated by standardization, according the age-specific DALYs numbers extracted from GBD data set 2019. Population attributable fractions was calculated by combining the published risk ratio, with the HIV prevalence (≥15 years old) from Joint United Nations Programme on HIV and AIDS (UNAIDS), and transferred to estimate the HIV-associated cervical cancer burden. Expected annual percentage changes (EAPCs) was calculated to describe the temporal trend of ASR from 1990 to 2019. Pearson correlation analysis were conducted to assess the correlation between the ASR or EAPCs and the socio-demographic index. The worldwide DALYs ASR caused by HIV-associated cervical cancer rose from 3.78 (95% confidence interval [CI]: 2.19-5.56) in 1990 to 9.50 (95% CI: 5.66-13.79) in 2019 per 100k population. In 2019, the region with the greatest burden was Eastern and Southern Africa, with the highest DALYs of 273 900 (95% CI: 149 100-476 400) and ASR of 254.44 per 100k population (95% CI: 168.86-329.28). Notably, the Eastern Europe and Central Asia regions had the highest EAPC (14.07%) of HIV-associated DALYs ASR. Women in Eastern and Southern Africa experience the greatest burden of HIV-associated cervical cancer, while the Eastern Europe and Central Asia regions had witnessed the largest increase over the last 30 years. Prioritize the promotion of HPV vaccination and cervical cancer screening for women living with HIV were crucial in these regions.
... Cervical cancer is one of the most common female malignant tumors, and the global incidence ranks second among female malignant tumors (Xiao et al., 2013). According to statistics, 85% of patients are from developing countries (Vaccarella et al., 2017). In 2018, cervical cancer incidence in China accounted for 18.59% of global incidence and 15.43% of mortality (Bray et al., 2018;Arbyn et al., 2020). ...
Objective: The aim of this study was to explore the correlation and difference of influencing factors by analyzing the psychological status of patients with cervical precancerous lesions and cancer in Han and Ethnic minorities. So as to provide evidence for more targeted psychological intervention for categories types of patients. Methods: The Chinese version of Kessler 10 scale was used to investigate 200 Han Chinese patients with cervical lesions and 100 ethnic minority patients with cervical lesions in Yunnan Cancer Center. Statistical analysis was performed using t-test, analysis of variance, and multivariable linear regression. Results: There was no significant difference in the distribution of demographic characteristics between the two groups (P > 0.05).The results of univariate analysis showed that the impression of K10 score was statistically significant among the following factors: educational level, awareness of HPV vaccine, disease screening status, employee medical insurance, economic burden of disease, cancerous or not, pathological type, treatment modalities, marital status, and family genetic history of tumor (P
... Cervical cancer is the fourth most common cancer in women, and~95% of all cervical cancer cases are HPV-associated [66]. Over the years, the incidence of HPV-associated cervical cancer death has been declining due to cervical cancer screening in the United States and European Union, but not in the developing countries in Asia, Africa, Latin Amer-ica, and the Caribbean [67]. HPV is the causative agent of several other cancers, such as vulvar, vaginal, anal, penile, and oropharyngeal [68,69]. ...
Human papillomavirus (HPV) is a group of alpha papillomaviruses that cause various illnesses, including cancer. There are more than 160 types of HPV, with many being “high-risk” types that have been clinically linked to cervical and other types of cancer. “Low-risk” types of HPV cause less severe conditions, such as genital warts. Over the past few decades, numerous studies have shed light on how HPV induces carcinogenesis. The HPV genome is a circular double-stranded DNA molecule that is approximately 8 kilobases in size. Replication of this genome is strictly regulated and requires two virus-encoded proteins, E1 and E2. E1 is a DNA helicase that is necessary for replisome assembly and replication of the HPV genome. On the other hand, E2 is responsible for initiating DNA replication and regulating the transcription of HPV-encoded genes, most importantly the E6 and E7 oncogenes. This article explores the genetic characteristics of high-risk HPV types, the roles of HPV-encoded proteins in HPV DNA replication, the regulation of transcription of E6 and E7 oncogenes, and the development of oncogenesis.
... Cervical cancer (CC) is the third most commonly diagnosed cancer and the fourth leading cause of cancer death in females worldwide (1). More than 90% of patients with CC show positive human papillomavirus (HPV) infection especially in developed countries (2,3). The highest prevalence rate of HPV is in Africa, the Caribbean Islands, and South America, while the lowest rate is observed in Australia, New Zealand, and Western Asia (4). ...
Background
Cervical cancer (CC) is the third most commonly diagnosed cancer and the fourth leading cause of cancer death in females worldwide, associated with the incidence of human papillomavirus (HPV) infection. The CC incidence is low in Iran, ranking 11th among cancers. This study aimed to estimate the survival rate of CC and the reasons for its low survival rate based on the data retrieved from the Iranian National Cancer Registry System.
Methods
In this retrospective cohort study, data for patients diagnosed with CC from 2008 to 2014 were collected and analyzed. The Kaplan-Meier method was used for survival analysis based on epidemiological and clinical factors.
Results
A total of 5,304 women were diagnosed from March 10, 2008 to March 9, 2014 and 2,423 patients were followed. The mean age of the cases was 51.91 years, and 65.91% were alive. The 5- and 10-year survival rates were 58% and 50%, respectively, with no difference between younger cases with SCC or AC but better survival rates for older patients with SCC.
Conclusions
As a preventable disease, CC is related to biological factors and geographical and sociodemographic indices. Geographical, cultural, and religious behaviors affect the CC incidence and survival. In Iran, the 5-year survival rate ranges from 34% to 70% among different geographic regions. Hence, effective screening based on cultural and sociodemographic issues is recommended.
... In the Latin American and Caribbean region and Asia, the incidence of cervical cancer is relatively high. Favorable trends in incidence have been observed in several countries; however, but preventive actions are inefficient and probably this decrease is related to other factors such as decreased fertility and birth rate, hygiene conditions, or improved socioeconomic status 30 . In Brazil, Chile, and Colombia, positive outlook for cervical cancer is related to better structured screening programs and relatively higher coverage rates than other Latin American countries 31 , although the impact of these programs is limited by inequalities in access to diagnostic and treatment services and suboptimal coverage and follow-up rates 32 . ...
Objective:
To analyze the trends of cervical cancer mortality in Brazilian Southeastern states, and to compare them to Brazil and other regions between 1980 and 2020.
Methods:
Time series study based on data from the Sistema de Informações de Mortalidade (Brazilian Mortality Information System). Death data were corrected by proportional redistribution of deaths from ill-defined causes and cervical cancer of unspecified portion. Age-standardized and age-specific rates were calculated by screening target (25-39 years; 40-64 years) and non-target (65 years or older) age groups. Annual percentage changes (APC) were estimated by linear regression model with breakpoints. The coverage of Pap Smear exam in the Unified Health System (SUS) was evaluated between 2009 and 2020 according to age group and locality.
Results:
There were increases in corrected mortality rates both in 1980 and in 2020 in all regions, with most evident increments at the beginning of the series. There was a decrease in mortality nationwide between 1980-2020; however, the state of São Paulo showed a discrete upward trend in 2014-2020 (APC=1.237; 95%CI 0.046-2.443). Noteworthy is the trend increment in the 25-39 year-old group in all study localities, being sharper in the Southeast region in 2013-2020 (APC=5.072; 95%CI 3.971-6.185). Screening coverage rates were highest in São Paulo and lowest in Rio de Janeiro, with a consistent decline from 2012 onwards at all ages.
Conclusions:
São Paulo is the first Brazilian state to show a reversal trend in mortality from cervical cancer. The changes in mortality patterns identified in this study point to the need for reorganization of the current screening program, which should be improved to ensure high coverage, quality, and adequate follow-up of all women with altered test results.
... In recent years, thanks to the strengthening of screening programmers, through the Pap Test, the Human Papilloma Virus (HPV) DNA test and the HPV vaccination, there has been a significant decrease in incidence and an increase in survival rates for CC: [4][5][6][7][8][9]. ...
Introduction: The aim of this study is to analyze the available scientific evidence regarding the quality of life (QoL) and sexual function (SF) in patients affected by cervical cancer (CC) after surgical and adjuvant treatments. Materials and Methods: Preliminary research was conducted via electronic database (MEDLINE, PubMed and Cochrane Library) with the use of a combination of the following keywords: SF, QoL, and CC. The principal findings considered in the present review were the study design, the number of patients included in each study, the information about the malignancy (histology and stage of disease), the questionnaires administered, and the principal findings concerning SF and QoL. Results: All studies were published between 2003–2022. The studies selected consisted of one randomized control study, seven observational studies (three prospective series), and nine case control studies. The scores used were focused on SF, QOL, fatigue, and psychological aspects. All studies reported a decreased SF and QOL. The most developed questionnaires were the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30), the Female Sexual Function Index (FSFI), the Hospital Anxiety and Depression scale (HADS), and the Female Sexual Distress Scale (FSDS). Discussion: All studies reported a decreased SF and QOL. In addition to the perception of body image, several factors coexist in influencing the outcomes such as the physical, hormonal, psychological. Conclusions: Sexual dysfunction after CC treatment has a multifactorial aetiology which negatively affects the quality of life. For these reasons, it is important to follow and support patients with a multidisciplinary team (doctors, nurses, psychologists, dieticians) before and after therapy. This type of tailored therapeutic approach should become a standard. Women should be informed about possible vaginal changes and menopausal symptoms after surgery and on the positive effects of psychological therapy.
... Incidence and mortality data place uterine cervical neoplasia as one of the leading female cancers on the globe. The least developed countries have the highest burden, with 80% of all cancers worldwide [2][3][4]. ...
Background
The prevalence of Human Papillomavirus (HPV) infection in the general population is widely known, however, there are still few studies related to this infection in minority groups, Thus, the objective is to analyze the frequency of human papillomavirus and associated factors in quilombola and gypsy women.
Methods
Cross-sectional research with 145 quilombola and gypsy women from Caxias, Maranhão. Two Pap smear collections were performed and a questionnaire with 46 questions was applied between January, 2020 and March, 2021. Descriptive analysis and Odds Ratio with 95% confidence interval were performed. The research was approved by the ethics committee.
Results
There were 09 cases of atypia. The frequency of human papillomavirus was 41.37%, with a higher risk in quilombolas 55 (91.70%). Multiple infections were prevalent (53%) with high-risk genotypes 21 (35%). Types 16 and 18 together accounted for 42.85% of cases.
Conclusions
The frequency of human papillomavirus infection was higher than those recorded in the Northeast and Brazil, and therefore type 16 predominated. Due to limitations, the virus lineages and sublineages were not evaluated. Quilombola women had a higher rate of infection than gypsies.
... Although cervical cancer screening and prevention measures help to reduce cases of the disease in developed countries, in developing regions this cancer remains one of the main causes of death for women [9,43,44], and considering the limitations of the current treatments available, many studies are focusing on the discovery of new therapeutic approaches that can increase the specificity and efficacy of anticancer agents to reduce adverse effects [45]. Studies have demonstrated the different therapeutic properties of DBAs and their derivatives [18][19][20][21][22][23][24]46], however, there are no reports yet of the cellular mechanism associated with anticancer activity and the biological function of the synthetic DBA A3K2A3 in cervical cancer. ...
Cervical cancer is a health problem among women worldwide. Considering the limitations of prevention and antineoplastic chemotherapy against cervical cancer, research is needed to discover new, more effective, and safe antitumor agents. In the present study, we investigated the in vitro cytotoxicity of a new synthetic dibenzylideneacetone derived from 1,5-diaryl-3-oxo-1,4-pentadienyl (A3K2A3) against cervical cancer cells immortalized by HPV 16 (SiHa), and 18 (HeLa) by MTT assay. Furthermore, we performed spectrofluorimetry, flow cytometry, and Western blot analyzes to explore the inhibitory mechanism of A3K2A3 in cervical cancer cells. A3K2A3 showed cytotoxic activity against both cell lines. Mitochondrial depolarization and reduction in intracellular ATP levels were observed, which may be dependent on the redox imbalance between increased ROS and reduced levels of the antioxidant defense. In addition, damage to the cell membrane and DNA, and effective blocking of cell division in the G2/M phase were detected, which possibly led to the induction of apoptosis. This result was further confirmed by the upregulation of apoptosis-related proteins Bax, cytochrome C, and caspases 9 and 3. Our results provided the first evidence that A3K2A3 contributes to the suppression of cervical cancer in vitro, showing promise as a possible alternative for the treatment of this cancer.
... In contrast, the incidence rate has increased in some sub-Saharan African countries. In these nations, the rate of incidence have either increased or remained mostly at high levels in various eastern European and west-Asian countries (Arbyn et al., 2011;Vaccarella et al., 2017;Arbyn et al., 2020). ...
Recent times have seen a strong surge in therapeutically targeting the hedgehog (HH)/GLI signaling pathway in cervical cancer. HH signaling pathway is reported to be a crucial modulator of carcinogenesis in cervical cancer and is also associated with recurrence and development of chemoresistance. Moreover, our previous reports have established that carvacrol (CAR) inhibited the proliferation of prostate cancer cells via inhibiting the Notch signaling pathway and thus, it was rational to explore its antiproliferative effects in cervical cancer cell lines. Herein, the present study aimed to investigate the anticancer and apoptotic potential of CAR on C33A cervical cancer cells and further explore the underlying mechanisms. We found that CAR significantly suppressed the growth of C33A cells, induced cell cycle arrest, and enhanced programmed cell death along with augmentation in the level of ROS, dissipated mitochondrial membrane potential, activation of caspase cascade, and eventually inhibited the HH signaling cascade. In addition, CAR treatment increased the expression of pro-apoptotic proteins (Bax, Bad, Fas-L, TRAIL, FADDR, cytochrome c) and concomitantly reduced the expression of anti-apoptotic proteins (Bcl-2 and Bcl-xL) in C33A cells. CAR mediates the activation of caspase-9 and -3 (intrinsic pathway) and caspase-8 (extrinsic pathway) accompanied by the cleavage of PARP in cervical cancer cells. Thus, CAR induced apoptosis by both the intrinsic and extrinsic apoptotic pathways. CAR efficiently inhibited the growth of cervical cancer cells via arresting the cell cycle at G0/G1 phase and modulated the gene expression of related proteins (p21, p27, cyclin D1 and CDK4). Moreover, CAR inhibited the HH/GLI signaling pathway by down regulating the expression of SMO, PTCH and GLI1 proteins in cervical carcinoma cells. With evidence of the above results, our data revealed that CAR treatment suppressed the growth of HPV⁻C33A cervical cancer cells and further elucidated the mechanistic insights into the functioning of CAR.
... In 2019, this burden was mainly concentrated in lowand middle-SDI countries in southern Africa, South America, and Asia. This is consistent with the global distribution of the overall burden of cervical cancer; 86% of the global burden of cervical cancer is in Africa, Latin America and the Caribbean, and Asia [29]. Therefore, it is necessary to pay special attention to the fact that although the female smoking rate is relatively low in low-and middle-income countries and regions, the burden of cervical cancer cannot be ignored. ...
Background
Cervical cancer is the fourth most common cause of cancer death in women worldwide. Smoking is one of the risk factors for cervical cancer. Understanding the global distribution of the disease burden of cervical cancer attributable to smoking and related changes is of clear significance for the prevention and control of cervical cancer in key populations and for tobacco control. As far as we know, research on the burden of cervical cancer attributable to smoking is lacking.
Objective
We estimated the disease burden and mortality of cervical cancer attributable to smoking and related trends over time at the global, regional, and national levels.
Methods
Data were obtained from the Global Burden of Disease study website. Age-standardized rates were used to facilitate comparisons of mortality and disability-adjusted life years (DALYs) at different levels. The estimated annual percentage change (EAPC) was used to assess trends in the age-standardized mortality rate (ASMR) and the age-standardized DALY rate (ASDR). A Pearson correlation analysis was used to evaluate correlations between the sociodemographic index and the age-standardized rates.
Results
In 2019, there were 30,136.65 (95% uncertainty interval [UI]: 14,945.09-49,639.87) cervical cancer–related deaths and 893,735.25 (95% UI 469,201.51-1,440,050.85) cervical cancer–related DALYs attributable to smoking. From 1990 to 2019, the global burden of cervical cancer attributable to smoking showed a decreasing trend around the world; the EAPCs for ASMR and ASDR were –2.11 (95% CI –2.16 to –2.06) and –2.22 (95% CI –2.26 to –2.18), respectively. In terms of age characteristics, in 2019, an upward trend was observed for age in the mortality of cervical cancer attributable to smoking. Analysis of the trend in DALYs with age revealed an initially increasing and then decreasing trend. From 1990 to 2019, the burden of disease in different age groups showed a downward trend. Among 204 countries, 180 countries showed downward trends, 10 countries showed upward trends, and the burden was stable in 14 countries. The Pearson correlation analysis revealed a significant negative correlation between sociodemographic index and the age-standardized rates of cervical cancer attributable to smoking (ρ=–0.228, P<.001 for ASMR and ρ=–0.223, P<.001 for ASDR).
Conclusions
An increase over time in the absolute number of cervical cancer deaths and DALYs attributable to smoking and a decrease over time in the ASMR and ASDR for cervical cancer attributable to smoking were observed in the overall population, and differences in these variables were also observed between countries and regions. More attention should be paid to cervical cancer prevention and screening in women who smoke, especially in low- and middle-income countries.
... As reported in the Global Cancer Incidence Report 2020, CC is the fourth most common type of cancer in women, with the fourth highest rate of new cases and fatalities (Sung et al., 2021). In most developing countries, CC is still the top cause of cancer-related death in women (Vaccarella et al., 2017). Although substantial progress has been achieved in the early detection and treatment of CC, there are still many patients with advanced and recurrent disease for whom surgery and radiotherapy or chemotherapy are not suitable, and who have poor prognosis, suggesting that current methods for risk stratification and predicting prognosis based on clinicopathological characteristics of patients may be inadequate (Seol et al., 2014). ...
Background: Given the high incidence and high mortality of cervical cancer (CC) among women in developing countries, identifying reliable biomarkers for the prediction of prognosis and therapeutic response is crucial. We constructed a prognostic signature of cuproptosis-related long non-coding RNAs (lncRNAs) as a reference for individualized clinical treatment.
Methods: A total of seven cuproptosis-related lncRNAs closely related to the prognosis of patients with CC were identified and used to construct a prognostic signature via least absolute shrinkage and selection operator regression analysis in the training set. The predictive performance of the signature was evaluated by Kaplan–Meier (K-M) analysis, receiver operating characteristic (ROC) analysis, and univariate and multivariate Cox analyses. Functional enrichment analysis and single-sample gene set enrichment analysis were conducted to explore the potential mechanisms of the prognostic signature, and a lncRNA–microRNA–mRNA network was created to investigate the underlying regulatory relationships between lncRNAs and cuproptosis in CC. The associations between the prognostic signature and response to immunotherapy and targeted therapy were also assessed. Finally, the prognostic value of the signature was validated using the CC tissues with clinical information in my own center.
Results: A prognostic signature was developed based on seven cuproptosis-related lncRNAs, including five protective factors (AL441992.1, LINC01305, AL354833.2, CNNM3-DT, and SCAT2) and two risk factors (AL354733.3 and AC009902.2). The ROC curves confirmed the superior predictive performance of the signature compared with conventional clinicopathological characteristics in CC. The ion transport-related molecular function and various immune-related biological processes differed significantly between the two risk groups according to functional enrichment analysis. Furthermore, we discovered that individuals in the high-risk group were more likely to respond to immunotherapy and targeted therapies including trametinib and cetuximab than those in the low-risk group. Finally, CC tissues with clinical data from my own center further verify the robustness of the seven-lncRNA risk signature.
Conclusion: We generated a cuproptosis-related lncRNA risk signature that could be used to predict prognosis of CC patients. Moreover, the signature could be used to predict response to immunotherapy and chemotherapy and thus could assist clinicians in making personalized treatment plans for CC patients.
... Cervical cancer is a significant global health problem, as it is the fourth most frequent cancer among women. It remains the leading cause of cancer death in women, particularly in less-resourced countries [1]. Treatment of cervical cancer depends mainly on the stage of the disease. ...
Background:
Bone recurrence occurs in 0.75%-8% of cervical cancer patients after primary treatment. Only a few previous studies have reported on survival times associated with prognostic factors for bone recurrent cervical cancer. This study aimed to evaluate the oncological outcomes and their predictors among cervical cancer patients with bone recurrence.
Methods:
The medical records of cervical cancer patients with bone recurrence who received primary treatment at Songklanagarind Hospital from January 2002 to December 2017 were retrospectively reviewed. Prognostic factors were identified using a Cox regression model.
Results:
The study included 6,354 cervical cancer patients, of whom 98 (1.54%) had bone recurrence at a median time of 25 months after the primary treatment (range 4.9-136 months). The most frequent site of bone recurrence was the spine (81.00%); the two most common visceral coexisting recurrence sites were the lungs and the liver. The median recurrence-free interval (RFI) was 21 months. Of the patients with recurrence, 75 (76.50%) were treated with combined radiation therapy and chemotherapy. The one-year overall survival (OS) after recurrence was 22.70%. On multivariate analysis, age under 60 years at the time of recurrence diagnosis (hazard ratio [HR] = 2.48, 95% CI = 1.47-4.18, p=0.001) and an RFI less than 21 months (HR = 1.63, 95% CI = 1.04-2.55, p=0.03) were independent prognostic factors for OS after recurrence.
Conclusion:
Bone recurrence in cervical cancer patients is rare and is associated with poor survival. Our study found that age and RFI were significant prognostic factors for OS in cervical cancer patients with bone recurrence.
... C ervical cancer is identified as the fourth most common cancer among women in the world, especially in developing countries. [1,2] More than 80% of deaths due to cervical cancer occur in the low-and middle-income countries, [3] which made the World Health Organization call for the global control of cervical cancer in May 2018 to eradicate the disease in the world [4] since this cancer is potentially one of the most preventable cancers. [5] The standard approaches for early detection of cervical cancer are screening women through cytology (Pap smear) and performing an Human Papilloma Virus (HPV) test (cotesting). ...
Background:
Performing appropriate and regular screening can effectively reduce cervical cancer and mortality rate, however, the available evidence suggests that women's participation in cervical cancer screening remains low in middle- and low-income countries, and that it is necessary to identify appropriate intervention methods to change behavior. The present study was designed to determine the effect of decision-aid-based counseling on cervical cancer screening behavior among women.
Materials and methods:
This trial study was conducted on 154 women with no history of Pap smear during the past 3 years and refers to Tabriz health care centers. The participants were assigned to the intervention (decision aid based counseling) and control (routine health education) groups through randomized block design with block sizes of 4 and 6 and a 1:1 allocation ratio. The data were collected using the sociodemographic and fertility characteristics, stages of change checklist, and shared decision-making (SDM) and decisional conflict (DC) questionnaire before and 6 months after the intervention by interview and then, analyzed by SPSS24 software. The independent t-test, ANCOVA tests were used.
Results:
A significant difference was observed between the two groups in terms of changing the stages of cervical cancer screening behavior 6 months after the intervention. As after the intervention, the frequency of individuals entered the preparation or action stage was more than the control group (P = 0.001). The mean score of SDM in the intervention group was significantly higher than the control group after intervention ([45.49 ± 1.18] vs. [27.56 ± 1.18] [Mean Difference (MD): 17.92; 95% confidence interval [CI]: 14.59-21.25; P < 0.001]). The mean score of DC in the intervention group was significantly lower than the control group after intervention ([29.16 ± 1.09] vs. [34.14 ± 1.09] [MD: -4.97; 95% CI: 1.09-8.04; P < 0.002]).
Conclusions:
This study revealed that evidence-based information communicated between clients and clinicians has very important role in clients' health-related behavior. It is recommended, health care providers apply decision-aid-based counseling for promoting the cervical cancer screening behavior among women.
... It was the second most common cancer in 2000 with 468,000 new cases and 233,000 deaths 2 ; in 2008, it ranked third with 530,000 cases and 275,000 deaths 3 ; while in 2018, over 570,000 cases and 311,000 deaths occurred globally 4 . Based on current statistics, most regions of the world have experienced a decline in the incidence of cervical cancer 5 . Conversely, it is still a leading cause of cancer-related death among women in Western Africa, with an approximate estimate of 84% cases and 88% deaths4. ...
Background:
Cervical cancer is the second most frequent cancer and cause of cancer-related deaths among women in Nigeria. The Visual inspection with acetic acid and cryotherapy "see and treat" screening approach is a feasible and effective method that can be implemented in low resource settings like Nigeria; however, screening utilization is still low.
Objective:
This systematic review aims at offering a comprehensive synthesis of studies that assessed the barriers preventing women from utilizing cervical cancer screening services in Nigeria.
Methods:
Electronic data search was performed on PubMed, Cochrane Library, EMbase, Directory of Open Access Journals, Google Scholar, and ScienceDirect, and quality assessment was conducted for the included studies. Data were extracted independently by two authors and thematically analysed for barriers to cervical cancer screening utilization.
Results:
Fifteen studies, consisting of 9,995 women aged 15 and above published between 2007 and 2020, were included. Frequently reported barriers to cervical screening include lack of knowledge of cervical cancer and screening, health service factors, screening is unnecessary, fear of outcome and procedure, and financial constraints.
Conclusion:
Lack of adequate information about cervical cancer is a significant hindrance to screening; this factor is strongly associated with the numerous misconceptions and negative perceptions. The study highlights the need for further assessment of the sociodemographic determinants of cervical cancer screening uptake in Nigeria. Preventive strategies should be targeted at improving the dissemination of valid information, reducing the knowledge gap among women, and addressing the financial and health service factors.
Cervical cancer is the third most common cancer and the fourth leading cause of death in women worldwide. The incidence has declined considerably in developed countries through organized screening programs, which link the Pap smear to molecular biology examinations, thus achieving good diagnostic accuracy. The effectiveness of these programs can be proven by the reduction in the mortality rate caused by cervical cancer. In the least developed countries, molecular biology is not available, which, coupled with few resources and unstructured laboratories, has contributed to the decrease in quality of cervical cancer screening. The aim of this study was to evaluate the 100% rapid review (100%-RR) as an effective tool for internal quality control (IQC) in gynecological cytopathology services in the state of Rio Grande do Norte- Brazil. A total of 8,677 swabs were analyzed; the negative results were submitted to 100%-RR. Divergent cases were discussed in a consensus meeting to reach a conclusion on the final diagnosis. The data were entered into SAS statistical software, and the agreement of the 100%-RR results with the final diagnosis was tested with the weighted kappa statistic. Of the 8,155 smears characterized as negative, 255 (3.13%) were abnormal smears, and 552 (6.77%) unsatisfactory smears were deemed negative. Regarding the results on the 8,155 smears subjected to 100%-RR when compared with the final diagnosis, there was agreement in 7,063 (86.60%) of them, and there were 1,092 (13.40%) discordant results (65.6%, unsatisfactory; 5.47%, atypical squamous cells of undetermined significance [ASC-US]). The κ index had an agreement of 0.867, with κ = 0.734 (p < 0.0001). Compared with the final diagnosis, the sensitivity of 100%-RR was 99.91% and its specificity was 99.4% for severe abnormalities. The sensitivity for high-grade squamous intraepithelial lesions was 88.2%, with a specificity of 100.00%. For abnormalities considered borderline, such as ASC-US, the sensitivity was 94.50% and the specificity was 99.5%. The 100%-RR was considered efficient when used as an IQC method.
Key Words: Quality control, Sensitivity, Diagnostic, Accuracy, Cytology
Background
Cervical cancer is one of the four most prevalent cancers in women, posing a serious threat to women's health worldwide. In view of this, we aimed to investigate epidemiologic changes in the global burden of cervical cancer attributed to unsafe sex and smoking, respectively, and the relationship with social demographic index (SDI).
Methods
The data were obtained from the Global Burden of Disease 2019. Quantile regression and restricted cubic spline were employed to explore the relationship between age-standardized mortality rate (ASMR) or age-standardized Disability-Adjusted Life Years rate (ASDR) of cervical cancer and SDI under different risk factors. Additionally, we used the Nordpred model to predict the ASMR trends in five countries with different SDIs from 2020 to 2034.
Results
The global disease burden of cervical cancer was gradually decreasing. People aged 55–59 years and 95 + years had the highest age- specific incidence and mortality, respectively. The burden attributed to smoking showed an upward and then downward trend with increasing SDI, peaking at the SDI of 0.6, whereas the burden attributable to unsafe sex decreased as the SDI increased. The ASMR of cervical cancer around the world attributed to smoking and unsafe sex is projected to decrease to 0.58 and 6.39 per 100,000 by 2034, respectively. It is also predicted that the ASMR of cervical cancer attributed to smoking in China, and that attributed to unsafe sex in India and Argentina will increase in the future.
Conclusion
Unsafe sex is the main risk factor for cervical cancer, followed by smoking. People aged 55–59 years and over 95 years are the key protection groups for cervical cancer. Low SDI and middle-low SDI areas are the key prevention and control areas for cervical cancer. The projection suggests that China needs to strengthen rational control of smoking, and India and Argentina need to improve scientific prevention of unsafe sex.
Background
Uganda has a high burden of cervical cancer and its current coverage of screening based on visual inspection with acetic acid (VIA) is low. High-risk HPV (hrHPV) testing is recommended by the World Health Organization as part of the global elimination strategy for cervical cancer. In this context, country-specific health economic evaluations can inform national-level decisions regarding implementation. We evaluated the recommended hrHPV screen-and-treat strategy to determine the minimum required levels of coverage and treatment adherence, as well as the maximum price level per test, for the strategy to be cost-effective in Uganda.
Methods
We conducted a headroom analysis to estimate potential room for spending on implementing the hrHPV screen-and-treat strategy at different levels of coverage and treatment adherence (from 10% to 100%) at each screening round, and at different price levels of the hrHPV test. We compared the strategy with the existing VIA-based screen-and-treat policy in Uganda. We calculated headroom as the product of number of life years gained by the strategy and the willingness-to-pay threshold, minus the incremental costs incurred by the strategy. Positive headroom was interpreted as an indication of cost-effectiveness.
Results
Compared with VIA-based screening with low 5% coverage, the hrHPV screen-and-treat strategy required at least 30% coverage and adherence for positive mean headroom, and compared with 30% VIA-based screening coverage, the minimum levels were 60%. At 60% coverage and adherence, the maximum acceptable price per hrHPV test was found to be between 15 and 30 international dollars.
Conclusions
The hrHPV-based screen-and-treat strategy could be cost-effective in Uganda if the screening coverage and treatment adherence are at least 30% in each screening round, and if the price per test is set below 30 international dollars. The minimum required levels of screening coverage and adherence to treatment provide potential starting points for decision-makers in planning the rollout of hrHPV testing. The headroom estimates can guide the planning costs of screening infrastructure and campaigns to achieve the required coverage and treatment adherence in Uganda.
Emerging countries are currently facing an increasing burden of cancer while they do not have adequate prevention, monitoring and research capabilities to tackle the disease. Cancer outcomes are influenced by several factors, including different cancer patterns, national cancer screening guidelines, current stage of disease and access to quality care and treatments. Discrepancies in cancer care between emerging and developed countries requires actions to achieve global health equity. The process of pioneering a sister relationship in oncology field can thwart the global burden of cancer. The objective of such cooperation programs should include research and training programs, evidence-based oncology practice and quality cancer. Building global connections will therefore be the novel approach to addressing the global burden of cancer.
In this paper, an empirical model with the critical number of incidences and deaths for female cancers as adjustable parameters has been developed using life expectancy data from GLOBOCAN world estimates on cancer types. The model was developed based on the cumulative risk and exponential correlation techniques such that the significance of the adjustable parameters ascertains the strength of this research in two ways. First, it indicates indicates the rapid increase in female cancer morbidity with increase in the number of male cancer cases, regardless of incidence or mortality. Second, it suggests that female cancer cases may approach a virtual limiting value as male cancer cases reach extremely high levels. This projection aligns with the global population trends, indicating a proportional increase in cancer cases each year. Additionally, the cumulative risk of cancer incidences of each sex has been modelled separately against the global cumulative risk of cancer incidences of both sexes which revealed regions that have passed their inflection point and those that are yet to reach the inflection point. There was a curvature change, which indicates an inflection point coinciding with the SouthEastern Region and indicating that for the regions beyond the inflection point, the increase of the cumulative risk of cancer incidences of females against that of males is more accentuated compared with the regions before the inflection point. However, when the cumulative risk of cancer mortality of each sex is modelled separately against the global cumulative risk of cancer mortality of both sexes shows a non-linear dependence and the increase is more accentuated for males than for females. This finding indicates that cumulative risk is influenced by factors beyond the male-female population ratio. This study advances cancer studies as it provides a nuanced understanding of gender-specific cancer trends, crucial for developing targeted cancer prevention and treatment strategies. By elucidating the dynamics of cancer incidences and mortalities across different regions and sexes, the findings can inform public health policies and resource allocation to combat cancer more effectively on a global scale.
Background
Unsafe sex is recognized as an important risk factor for cervical cancer (CC). Understanding the global disease burden of CC attributable to unsafe sex can assist policymakers in allocating healthcare resources.
Methods
Data were obtained from the 2019 global burden of disease database (GBD). We examined global, regional, and national levels of CC mortality, disability‐adjusted life years (DALYs), and age‐standardized rates (ASRs) caused by unsafe sex. ASRs were evaluated using estimated annual percentage changes (EAPCs).
Results
Attributable to unsafe sex, there were 280,479 CC‐related deaths in 2019 and 8,955,013 CC‐related DALYs. In the period 1990–2019, the global ASRs of CC due to unsafe sex decreased around the world; for age‐standardized mortality rate (ASMR) and age‐standardized DALY rate (ASDR), the EAPCs were −0.93 and −0.95. The highest ASMRs and ASDRs were found in central sub‐Saharan Africa and the lowest in Australasia.
Conclusion
In the past few decades, the ASMR and ASDR of CC caused by unsafe sexual practices have decreased over time, with significant variations observed among different countries and regions. Increased focus is needed on spreading awareness about sexual health and promoting CC prevention and screening, particularly in low‐ and middle‐income nations.
Understanding the recent global pattern and trends in cervical cancer burden could enable us to prevent and control this condition.
First, we reviewed cervical cancer incidence and mortality according to the human development index (HDI) and geographical region. More than 80% of cancer cases and deaths occurred in areas with a lower or middle level of development. In addition, a remarkable geographic contrast in cervical cancer burden was observed. The highest incidence and mortality were observed in Eastern, Southern and Middle Africa, due to a lack of awareness of disease symptoms, limited access to appropriate prevention and medical services, and the concomitant human immunodeficiency virus (HIV) epidemic in this region.
Next, we reviewed sexual behavior, immunodeficiency disorders owing to HIV infection, history of sexually transmitted infection, tobacco smoking, endogenous and exogenous hormonal factors as risk factors associated with acquiring human papillomavirus (HPV) infection, and impaired immune response to HPV infection and progression of cervical intraepithelial neoplasia (CIN). Although HPV is a main etiological factor in cervical carcinogenesis, the noteworthy geographic contrast might also be attributable to exposure to these risk factors and inequalities in access to the healthcare system.
Eliminating cervical cancer requires—in addition to HPV vaccination, screening and treatment—consideration of lifestyle modification, including tobacco control, sexual education, and HIV control.
Cervical cancer is a leading cause of death for women in low-resource settings despite being preventable through human papillomavirus (HPV) vaccination, early detection, and treatment of precancerous lesions. The World Health Organization recommends high-risk HPV (hrHPV) as the preferred cervical cancer screening strategy, which is difficult to implement in low-resource settings due to high costs, reliance on centralized laboratory infrastructure, and long sample-to-answer times. To help meet the need for rapid, low-cost, and decentralized cervical cancer screening, we developed tailed primer isothermal amplification and lateral flow detection assays for HPV16, HPV18, and HPV45 DNA. We translated these assays into a self-contained cartridge to achieve multiplexed detection of three hrHPV genotypes in a disposable cartridge. The developed test achieves clinically relevant limits of detection of 50–500 copies per reaction with extracted genomic DNA from HPV-positive cells. Finally, we performed sample-to-answer testing with direct lysates of HPV-negative and HPV-positive cell lines and demonstrated consistent detection of HPV16, HPV18, and HPV45 with 5000–50,000 cells/mL in < 35 min. With additional optimization to improve cartridge reliability, incorporation of additional hrHPV types, and validation with clinical samples, the assay could serve as a point-of-care HPV DNA test that improves access to cervical cancer screening in low-resource settings.
Objective:
Some studies have reported that the prognosis of total laparoscopic hysterectomy (TLH) for early-stage cervical cancer (CC) is worse than that of open surgery. And this was associated with the use of uterine manipulator or not. Therefore, this study retrospectively analyzes the efficacy and safety of TLH without uterine manipulator combined with pelvic lymphadenectomy for early-stage CC.
Methods:
Fifty-eight patients with CC (stage IB1-IIA1) who received radical hysterectomy from September 2019 to January 2020 were divided into no uterine manipulator (n = 26) and uterine manipulator group (n = 32). Then, clinical characteristics were collected and intraoperative/postoperative related indicators were compared.
Results:
Patients in the no uterine manipulator group had significantly higher operation time and blood loss than in the uterine manipulator group. Notably, there was no significant difference in hemoglobin change, blood transfusion rate, number of pelvic nodules, anal exhaust time, complications and recurrence rate between the two groups. Additionally, patients in the uterine manipulator group were prone to urinary retention (15.6%) and lymphocyst (12.5%), while the no uterine manipulator group exhibited high probability of bladder dysfunction (23.1%) and urinary retention (15.4%). Furthermore, the 1-year disease-free survival rate and the 1-year overall survival rate were not significantly different between the two groups.
Conclusion:
There was no significant difference in the efficacy and safety of TLH with or without uterine manipulator combined with pelvic lymphadenectomy in the treatment of patients with early-stage CC. However, the latter requires consideration of the negative effects of high operation time and blood loss.
Cervical cancer is a health crisis affecting women and their families across the world. It is known that developed countries have comprehensive protocols with recommendations regarding workforce, expertise, and medical resources to address this common cancer among women. In contrast, disparities in addressing cervical cancer remain present in Latin America and Caribbean countries. Here, we reviewed the current strategies of cervical cancer prevention and control in the region.
Background:
Plant-derived homeopathic medicines (HMs) are cheap and commercially available but are mechanistically less explored entities than conventional medicines.
Purpose:
The aim of our study was to evaluate the impact of selected plant-derived HMs derived from Berberis aquifolium (BA), Berberis vulgaris (BV), Mentha piperita (MP), Curcuma longa (CL), Cinchona officinalis (CO), Thuja occidentalis (TO) and Hydrastis canadensis (HC) on cervical cancer (CaCx) cells in vitro.
Methods:
We screened the mother tincture (MT) and 30C potencies of the above-mentioned HMs for anti-proliferative and cytotoxic activity on human papillomavirus (HPV)-negative (C33a) and HPV-positive CaCx cells (SiHa and HeLa) by MTT assay. Total phenolic content (TPC) and the free-radical scavenging activity of each HM was also determined using standard assays. Phytochemicals reportedly available in these HMs were examined for their potential inhibitory action on HPV16 E6 by in silico molecular docking.
Results:
All tested MTs induced a differential dose-dependent cytotoxic response that varied with cell line. For C33a cells, the order of response was TO > CL > BA > BV > HC > MP > CO, whereas for SiHa and HeLa cells the order was HC > MP > TO > CO > BA > BV > CL and CL > BA > CO, respectively. 30C potencies of all HMs showed an inconsistent response. Further, anti-CaCx responses displayed by MTs did not follow the order of an HM's phenolic content or free radical scavenging activity. Analysis revealed anti-oxidant content of BA, BV and HC had the lowest contribution to their anti-CaCx activity. Using in silico modeling of molecular docking between the HPV16 E6 protein crystallographic structures (6SJA and 4XR8) and main phytochemical components of BV, BA, HC, CL and TO, their potential to inhibit the HPV16 E6 protein carcinogenic interactions was identified.
Conclusion:
The study has shown a comparative evaluation of the potential of several plant-derived MTs and HMs to affect CaCx cell line survival in vitro (through cytotoxicity and free radical scavenging) and their theoretical molecular targets in silico for the first time. Data demonstrated that MTs of BA and BV are likely to be the most potent HMs that strongly inhibited CaCx growth and have a strong anti-HPV phytochemical constitution.
Background
Human Papillomavirus (HPV) is the main etiological factor for the development of cervical cancer. HPV 18 is the second most frequent type, accounting for up to 65% of all cases. HPV intratypic variation may influence the potential for progression to invasive cancer. The aim of this study was to evaluate the prevalence of human papillomavirus 18 intratypic variants in cervical cancer samples from women in the state of Maranhão, Brazil.
Methods
The study included 118 women over 18 years of age with a diagnosis of cervical cancer. Tumor fragments were collected and subjected to DNA extraction and Polymerase Chain Reaction (PCR) for HPV detection using the PGMY09/11 and GP+5/6 primers. Positive samples were submitted to automated sequencing for viral genotyping. To determine the HPV 18 lineages, positive samples were submitted to PCR, using specific primers to amplify the LCR and E6 regions of HPV 18 virus.
Results
HPV was present in 88 women (73.3%). Of those, 48 (54%) were HPV 16, the most prevalent, followed by 12 (13.6%) HPV 18. Histologically, squamous cell carcinoma was predominant (79.1%). Among the HPV 18 variants identified, 10 (80%) belonged to lineage A, and sublineages A1, A2, A3, and A4. Two (29%) HPV 18 B variant was also detected, with the sublineages B1 and B2. In this study, the C variant was not found. There was no statistically significant association between the HPV 18 lineages found and sociodemographic and lifestyle variables (p > 0.05).
Conclusions
A higher frequency of HPV 16 and 18 were found in women with cervical cancer in the state of Maranhão, Brazil, with a high prevalence of the lineage A among women with HPV 18.
Background
Tracking progress and providing timely evidence is a fundamental step forward for countries to remain aligned with the targets set by WHO to eliminate cervical cancer as a public health problem (ie, to reduce the incidence of the disease below a threshold of 4 cases per 100 000 women-years). We aimed to assess the extent of global inequalities in cervical cancer incidence and mortality, based on The Global Cancer Observatory (GLOBOCAN) 2020 estimates, including geographical and socioeconomic development, and temporal aspects.
Methods
For this analysis, we used the GLOBOCAN 2020 database to estimate the age-specific and age-standardised incidence and mortality rates of cervical cancer per 100 000 women-years for 185 countries or territories aggregated across the 20 UN-defined world regions, and by four-tier levels of the Human Development Index (HDI). Time trends (1988–2017) in incidence were extracted from the Cancer Incidence in Five Continents (CI5) plus database. Mortality estimates were obtained using the most recent national vital registration data from WHO.
Findings
Globally in 2020, there were an estimated 604 127 cervical cancer cases and 341 831 deaths, with a corresponding age-standardised incidence of 13·3 cases per 100 000 women-years (95% CI 13·3–13·3) and mortality rate of 7·2 deaths per 100 000 women-years (95% CI 7·2–7·3). Cervical cancer incidence ranged from 2·2 (1·9–2·4) in Iraq to 84·6 (74·8–94·3) in Eswatini. Mortality rates ranged from 1·0 (0·8–1·2) in Switzerland to 55·7 (47·7–63·7) in Eswatini. Age-standardised incidence was highest in Malawi (67·9 [95% CI 65·7 –70·1]) and Zambia (65·5 [63·0–67·9]) in Africa, Bolivia (36·6 [35·0–38·2]) and Paraguay (34·1 [32·1–36·1]) in Latin America, Maldives (24·5 [17·0–32·0]) and Indonesia (24·4 [24·2–24·7]) in Asia, and Fiji (29·8 [24·7–35·0]) and Papua New Guinea (29·2 [27·3–31·0]) in Melanesia. A clear socioeconomic gradient exists in cervical cancer, with decreasing rates as HDI increased. Incidence was three times higher in countries with low HDI than countries with very high HDI, whereas mortality rates were six times higher in low HDI countries versus very high HDI countries. In 2020 estimates, a general decline in incidence was observed in most countries of the world with representative trend data, with incidence becoming stable at relatively low levels around 2005 in several high-income countries. By contrast, in the same period incidence increased in some countries in eastern Africa and eastern Europe. We observed different patterns of age-specific incidence between countries with well developed population-based screening and treatment services (eg, Sweden, Australia, and the UK) and countries with insufficient and opportunistic services (eg, Colombia, India, and Uganda).
Interpretation
The burden of cervical cancer remains high in many parts of the world, and in most countries, the incidence and mortality of the disease remain much higher than the threshold set by the WHO initiative on cervical cancer elimination. We identified substantial geographical and socioeconomic inequalities in cervical cancer globally, with a clear gradient of increasing rates for countries with lower levels of human development. Our study provides timely evidence and impetus for future strategies that prioritise and accelerate progress towards the WHO elimination targets and, in so doing, address the marked variations in the global cervical cancer landscape today.
Funding
French Institut National du Cancer, Horizon 2020 Framework Programme for Research and Innovation of the European Commission; and EU4Health Programme.
Objective:
Cervical cancer (CC) is the fourth most frequent cancer worldwide. Cigarette smoking has been shown to influence CC risk in conjunction with human papillomavirus (HPV) infection. The aim of this study is to provide the most accurate and updated estimate of this association and its dose-response relationship.
Methods:
Using an innovative approach for the identification of original publications, we conducted a systematic review and meta-analysis of studies published up to January 2021. Random effects models were used to provide pooled relative risks (RRs) of CC for smoking status. Dose-response relationships were evaluated using one-stage random effects models with linear or restricted cubic splines models.
Results:
We included 109 studies providing a pooled RR of invasive CC and preinvasive lesions, respectively, of 1.70 [95% confidence interval (CI), 1.53-1.88] and 2.11 (95% CI, 1.85-2.39) for current versus never smokers, and, respectively, 1.13 (95% CI, 1.02-1.24) and 1.29 (95% CI, 1.15-1.46) for former versus never smokers. Considering HPV does not alter the positive association or its magnitude. Risks of CC sharply increased with few cigarettes (for 10 cigarettes/day, RR = 1.72; 95% CI, 1.34-2.20 for invasive CC and RR = 2.13; 95% CI, 1.86-2.44 for precancerous lesions). The risk of CC increased with pack-years and smoking duration and decreased linearly with time since quitting, reaching that of never smokers about 15 years after quitting.
Conclusion:
This comprehensive review and meta-analysis confirmed the association of smoking with CC, independently from HPV infection. Such association rose sharply with smoking intensity and decreased after smoking cessation.
Introduction:
cervical cancer continues to be a major cause of morbidity and mortality among women in the developing world. Despite the national cervical cancer screening programme, findings show low levels of knowledge and practices of cervical cancer screening among rural women in South Africa (SA). The purpose of this study was to determine the knowledge, attitudes and practices of cervical cancer screening among rural women in KwaZulu-Natal, SA.
Methods:
an observational cross-sectional study was performed. The study was conducted at three rural clinics. A systematic sampling technique was used to select 283 women, aged 18-65 years. Data were collected using a standardised structured self-administered questionnaire. Data were analysed using descriptive and analytic statistics.
Results:
findings showed a high level of awareness of cervical cancer (93.3%, n=264) and the Pap smear test (95.1%, n=269). Knowledge of cervical cancer-associated factors, symptoms, screening methods and treatment was poor (28.0%, n=79). An overwhelming majority (81.8%, n=231) displayed a positive attitude towards cervical cancer screening. The practice of cervical cancer screening was fairly good (66.8%, n=189). The results showed that socio-demographics were not statistically significantly associated with knowledge of cervical cancer and cervical cancer screening.
Conclusion:
despite the inadequate knowledge of women, attitudes towards cervical cancer and screening were generally positive. Health care practitioners are encouraged to focus not only on creating awareness but also on improving knowledge so as women will not only undergo screening but appreciate the importance of cervical cancer screening.
Human papillomavirus (HPV)-related screening technologies and HPV vaccination offer enormous potential for cancer prevention, notably prevention of cervical cancer. The effectiveness of these approaches is, however, suboptimal owing to limited implementation of screening programmes and restricted indications for HPV vaccination. Trials of HPV vaccination in women aged up to 55 years have shown almost 90% protection from cervical precancer caused by HPV16/18 among HPV16/18-DNA-negative women. We propose extending routine vaccination programmes to women of up to 30 years of age (and to the 45-50-year age groups in some settings), paired with at least one HPV-screening test at age 30 years or older. Expanding the indications for HPV vaccination and much greater use of HPV testing in screening programmes has the potential to accelerate the decline in cervical cancer incidence. Such a combined protocol would represent an attractive approach for many health-care systems, in particular, countries in Central and Eastern Europe, Latin America, Asia, and some more-developed parts of Africa. The role of vaccination in women aged >30 years and the optimal number of HPV-screening tests required in vaccinated women remain important research issues. Cost-effectiveness models will help determine the optimal combination of HPV vaccination and screening in public health programmes, and to estimate the effects of such approaches in different populations.
Background:
Nordic countries' data offer a unique possibility to evaluate the long-term benefit of cervical cancer screening in a context of increasing risk of human papillomavirus infection.
Methods:
Ad hoc-refined age-period-cohort models were applied to the last 50-year incidence data from Denmark, Finland, Norway and Sweden to project expected cervical cancer cases in a no-screening scenario.
Results:
In the absence of screening, projected incidence rates for 2006-2010 in Nordic countries would have been between 3 and 5 times higher than observed rates. Over 60,000 cases or between 41 and 49% of the expected cases of cervical cancer may have been prevented by the introduction of screening in the late 1960s and early 1970s.
Conclusions:
Our study suggests that screening programmes might have prevented a HPV-driven epidemic of cervical cancer in Nordic countries. According to extrapolations from cohort effects, cervical cancer incidence rates in the Nordic countries would have been otherwise comparable to the highest incidence rates currently detected in low-income countries.
A recent report that 93 per cent of invasive cervical cancers worldwide contain human papillomavirus (HPV) may be an underestimate, due to sample inadequacy or integration events affecting the HPV L1 gene, which is the target of the polymerase chain reaction (PCR)‐based test which was used. The formerly HPV‐negative cases from this study have therefore been reanalysed for HPV serum antibodies and HPV DNA. Serology for HPV 16 VLPs, E6, and E7 antibodies was performed on 49 of the 66 cases which were HPV‐negative and a sample of 48 of the 866 cases which were HPV‐positive in the original study. Moreover, 55 of the 66 formerly HPV‐negative biopsies were also reanalysed by a sandwich procedure in which the outer sections in a series of sections are used for histological review, while the inner sections are assayed by three different HPV PCR assays targeting different open reading frames (ORFs). No significant difference was found in serology for HPV 16 proteins between the cases that were originally HPV PCR‐negative and ‐positive. Type‐specific E7 PCR for 14 high‐risk HPV types detected HPV DNA in 38 (69 per cent) of the 55 originally HPV‐negative and amplifiable specimens. The HPV types detected were 16, 18, 31, 33, 39, 45, 52, and 58. Two (4 per cent) additional cases were only HPV DNA‐positive by E1 and/or L1 consensus PCR. Histological analysis of the 55 specimens revealed that 21 were qualitatively inadequate. Only two of the 34 adequate samples were HPV‐negative on all PCR tests, as against 13 of the 21 that were inadequate ( p < 0·001). Combining the data from this and the previous study and excluding inadequate specimens, the worldwide HPV prevalence in cervical carcinomas is 99·7 per cent. The presence of HPV in virtually all cervical cancers implies the highest worldwide attributable fraction so far reported for a specific cause of any major human cancer. The extreme rarity of HPV‐negative cancers reinforces the rationale for HPV testing in addition to, or even instead of, cervical cytology in routine cervical screening. Copyright © 1999 John Wiley & Sons, Ltd.
Background:
Cervical cancer incidence remains high in several Baltic, central, and eastern European (BCEE) countries, mainly as a result of a historical absence of effective screening programmes. As a catalyst for action, we aimed to estimate the number of women who could be spared from cervical cancer across six countries in the region during the next 25 years, if effective screening interventions were introduced.
Methods:
In this population-based study, we applied age-period-cohort models with spline functions within a Bayesian framework to incidence data from six BCEE countries (Estonia, Latvia, Lithuania, Belarus, Bulgaria, and Russia) to develop projections of the future number of new cases of cervical cancer from 2017 to 2040 based on two future scenarios: continued absence of screening (scenario A) versus the introduction of effective screening from 2017 onwards (scenario B). The timespan of available data varied from 16 years in Bulgaria to 40 years in Estonia. Projected rates up to 2040 were obtained in scenario A by extrapolating cohort-specific trends, a marker of changing risk of human papillomavirus (HPV) infection, assuming a continued absence of effective screening in future years. Scenario B added the effect of gradual introduction of screening in each country, under the assumption period effects would be equivalent to the decreasing trend by calendar year seen in Denmark (our comparator country) since the progressive regional introduction of screening from the late 1960s.
Findings:
According to scenario A, projected incidence rates will continue to increase substantially in many BCEE countries. Very high age-standardised rates of cervical cancer are predicted in Lithuania, Latvia, Belarus, and Estonia (up to 88 cases per 100 000). According to scenario B, the beneficial effects of effective screening will increase progressively over time, leading to a 50-60% reduction of the projected incidence rates by around 2040, resulting in the prevention of cervical cancer in 1500 women in Estonia and more than 150 000 women in Russia. The immediate launch of effective screening programmes could prevent almost 180 000 new cervical cancer diagnoses in a 25-year period in the six BCEE countries studied.
Interpretation:
Based on our findings, there is a clear need to begin cervical screening in these six countries as soon as possible to reduce the high and increasing incidence of cervical cancer over the next decades.
Funding:
None.
A recent report that 93 per cent of invasive cervical cancers worldwide contain human papillomavirus (HPV) may be an underestimate, due to sample inadequacy or integration events affecting the HPV L1 gene, which is the target of the polymerase chain reaction (PCR)-based test which was used. The formerly HPV-negative cases from this study have therefore been reanalysed for HPV serum antibodies and HPV DNA. Serology for HPV 16 VLPs, E6, and E7 antibodies was performed on 49 of the 66 cases which were HPV-negative and a sample of 48 of the 866 cases which were HPV-positive in the original study. Moreover, 55 of the 66 formerly HPV-negative biopsies were also reanalysed by a sandwich procedure in which the outer sections in a series of sections are used for histological review, while the inner sections are assayed by three different HPV PCR assays targeting different open reading frames (ORFs). No significant difference was found in serology for HPV 16 proteins between the cases that were originally HPV PCR-negative and -positive. Type-specific E7 PCR for 14 high-risk HPV types detected HPV DNA in 38 (69 per cent) of the 55 originally HPV-negative and amplifiable specimens. The HPV types detected were 16, 18, 31, 33, 39, 45, 52, and 58. Two (4 per cent) additional cases were only HPV DNA-positive by E1 and/or L1 consensus PCR. Histological analysis of the 55 specimens revealed that 21 were qualitatively inadequate. Only two of the 34 adequate samples were HPV-negative on all PCR tests, as against 13 of the 21 that were inadequate ( p< 0·001). Combining the data from this and the previous study and excluding inadequate specimens, the worldwide HPV prevalence in cervical carcinomas is 99·7 per cent. The presence of HPV in virtually all cervical cancers implies the highest worldwide attributable fraction so far reported for a specific cause of any major human cancer. The extreme rarity of HPV-negative cancers reinforces the rationale for HPV testing in addition to, or even instead of, cervical cytology in routine cervical screening. Copyright
Human papillomaviruses (HPVs) cause cancer at multiple anatomic sites in men and women, including cervical, oropharyngeal, anal, vulvar, and vaginal cancers in women and oropharyngeal, anal, and penile cancers in men. In this EUROGIN 2014 roadmap, differences in HPV-related cancer and infection burden by gender and anatomic site are reviewed. The proportion of cancers attributable to HPV varies by anatomic site, with nearly 100% of cervical, 88% of anal, and less than 50% of lower genital tract and oropharyngeal cancers attributable to HPV, depending on world region and prevalence of tobacco use. Often mirroring cancer incidence rates, HPV prevalence and infection natural history varies by gender and anatomic site of infection. Oral HPV infection is rare and significantly differs by gender; yet HPV-related cancer incidence at this site is several-fold higher than at either the anal canal or penile epithelium. HPV seroprevalence is significantly higher among women compared to men, likely explaining the differences in age-specific HPV prevalence and incidence patterns observed by gender. Correspondingly, among heterosexual partners, HPV transmission appears higher from women to men. More research is needed to characterize HPV natural history at each anatomic site where HPV causes cancer in men and women, information that is critical to inform the basic science of HPV natural history and the development of future infection and cancer prevention efforts. © 2014 Wiley Periodicals, Inc.
Background: Noncommunicable diseases, and especially cancers, are recognized as an increasing problem for low and middle income countries. Effective control programs require adequate information on the size, nature, and evolution of the health problem that they pose.
Methods: We present estimates of the incidence and mortality of cancer in Africa in 2012, derived from “GLOBOCAN 2012,” published by the International Agency for Research on Cancer.
Results: There were 847,000 new cancer cases (6% of the world total) and 591,000 deaths (7.2% of the world total) in the 54 countries of Africa in 2012, with about three quarters in the 47 countries of Sub-Saharan Africa. While the cancer profiles often differ markedly between regions, the most common cancers in men were prostate (16.4% of new cancers), liver (10.7%), and Kaposi sarcoma (6.7%); in women, by far the most important are cancers of the breast (27.6% of all cancers) and cervix uteri (20.4%).
Conclusions: There are still deficiencies in surveillance systems, particularly in Sub-Saharan Africa and, specifically, of their most vital component, population-based cancer registries. With the number of annual cancer cases and deaths likely to increase by at least 70% by 2030, there is a pressing need for a coordinated approach to improving the extent and quality of services for cancer control in Africa, and better surveillance systems with which they can be planned and monitored.
Impact: The results are the best data currently available and provide a reasonable appraisal of the cancer situation in Africa. Cancer Epidemiol Biomarkers Prev; 23(6); 953–66. ©2014 AACR.
The Kampala cancer registry is the longest established in Africa. Trends in incidence rates for a 20-year period (1991–2010) for Kyadondo County (Kampala city and a rural hinterland) illustrate the effects of changing lifestyles in urban Africa, and the effects of the epidemic of HIV-AIDS. There has been an overall increase in the risk of cancer during the period in both sexes, with incidence rates of major cancers such as breast and prostate showing particularly marked increases (3.7% and 5.2% annually, respectively). In the 1960s cancer of the oesophagus was the most common cancer of men (and second in women), and incidence in the last 20 years has not declined. Cancer of the cervix, always the most frequent cancer of women, has shown an increase over the period (1.8% per year), although the rates appear to have declined in the last 4 years. HIV prevalence in adults in Uganda fell from a maximum in 1992 to a minimum (about 6%) in 2004, and has risen a little subsequently, while availability of antiretroviral drugs has risen sharply in recent years. Incidence of Kaposi sarcoma in men fell until about 2002, and has been relatively constant since then, while in women there has been a continuing decline since 2000. Other HIV related cancers—non-Hodgkin lymphoma of younger adults, and squamous cell carcinoma of conjunctiva—have shown major increases in incidence, although the former (NHL) has shown a small decline in incidence in the most recent 2 years.
In four randomised trials, human papillomavirus (HPV)-based screening for cervical cancer was compared with cytology-based cervical screening, and precursors of cancer were the endpoint in every trial. However, direct estimates are missing of the relative efficacy of HPV-based versus cytology-based screening for prevention of invasive cancer in women who undergo regular screening, of modifiers (eg, age) of this relative efficacy, and of the duration of protection. We did a follow-up study of the four randomised trials to investigate these outcomes.
METHODS 176 464 women aged 20-64 years were randomly assigned to HPV-based (experimental arm) or cytology-based (control arm) screening in Sweden (Swedescreen), the Netherlands (POBASCAM), England (ARTISTIC), and Italy (NTCC). We followed up these women for a median of 6·5 years (1 214 415 person-years) and identified 107 invasive cervical carcinomas by linkage with screening, pathology, and cancer registries, by masked review of histological specimens, or from reports. Cumulative and study-adjusted rate ratios (experimental vs control) were calculated for incidence of invasive cervical carcinoma.
FINDINGS The rate ratio for invasive cervical carcinoma among all women from recruitment to end of follow-up was 0·60 (95% CI 0·40-0·89), with no heterogeneity between studies (p=0·52). Detection of invasive cervical carcinoma was similar between screening methods during the first 2·5 years of follow-up (0·79, 0·46-1·36) but was significantly lower in the experimental arm thereafter (0·45, 0·25-0·81). In women with a negative screening test at entry, the rate ratio was 0·30 (0·15-0·60). The cumulative incidence of invasive cervical carcinoma in women with negative entry tests was 4·6 per 10(5) (1·1-12·1) and 8·7 per 10(5) (3·3-18·6) at 3·5 and 5·5 years, respectively, in the experimental arm, and 15·4 per 10(5) (7·9-27·0) and 36·0 per 10(5) (23·2-53·5), respectively, in the control arm. Rate ratios did not differ by cancer stage, but were lower for adenocarcinoma (0·31, 0·14-0·69) than for squamous-cell carcinoma (0·78, 0·49-1·25). The rate ratio was lowest in women aged 30-34 years (0·36, 0·14-0·94).
INTERPRETATION HPV-based screening provides 60-70% greater protection against invasive cervical carcinomas compared with cytology. Data of large-scale randomised trials support initiation of HPV-based screening from age 30 years and extension of screening intervals to at least 5 years.
FUNDING European Union, Belgian Foundation Against Cancer, KCE-Centre d'Expertise, IARC, The Netherlands Organisation for Health Research and Development, the Italian Ministry of Health.
In this chapter, we present the available information on the burden of human papillomavirus (HPV)-related cancers (cancers of the cervix, anogenital cancers, and cancers of the oral cavity and pharynx), as well as available data on the prevalence and distribution of HPV types in women with and without cervical cancer, for the countries of the Extended Middle East and North Africa region (EMENA). The EMENA region is characterized by societies that share similar cultures and religions and that are considered to have a more conservative sexual behaviour compared to Western societies. The incidence of cervical cancer is estimated to be relatively low, although it is difficult to assess precisely because systematic and national cancer registries are lacking in many countries of the EMENA region. In these countries, nationwide programs of cervical cancer screening do not exist or are based on a limited opportunistic cytology-based screening, which often lacks quality assurance. The incidence of anogenital cancers other than cervix is very low. The incidence of cancers of the oral cavity and pharynx is relatively high in some countries, particularly in Pakistan. Relatively low levels of HPV prevalence have been observed in the several surveys conducted in the EMENA region, although only few young women were included in these studies. Possible changes in lifestyle and sexual behaviour in younger generations might, however, change this scenario. Thus, improving the information on the burden of HPV-related cancers and on the HPV prevalence in the general population is essential to develop a comprehensive intervention policy for future management of cervical cancer in this area.
Background:
Cervical cancer trends in a given country mainly depend on the existence of effective screening programmes and time changes in disease risk factors, notably exposure to human papillomavirus (HPV). Screening primarily influences variations by period of diagnosis, whereas changes in risk factors chiefly manifest themselves as variations in risk across successive birth cohorts of women.
Methods:
We assessed trends in cervical cancer across 38 countries in five continents, age group 30-74 years, using age-standardised incidence rates (ASRs) and age-period-cohort (APC) models. Non-identifiability in APC models was circumvented by making assumptions based on a consistent relationship between age and cervical cancer incidence (i.e. approximately constant rates after age 45 years).
Findings:
ASRs decreased in several countries, except in most of Eastern European populations, Thailand as well as Uganda, although the direction and magnitude of period and birth cohort effects varied substantially. Strong downward trends in cervical cancer risk by period were found in the highest-income countries, whereas no clear changes by period were found in lower-resourced settings. Successive generations of women born after 1940 or 1950 exhibited either an increase in risk of cervical cancer (in most European countries, Japan, China), no substantial changes (North America and Australia) or a decrease (Ecuador and India).
Interpretation:
In countries where effective screening has been in place for a long time the consequences of underlying increases in cohort-specific risk were largely avoided. In the absence of screening, cohort-led increases or, stable, cervical cancer ASRs were observed. Our study underscores the importance of strengthening screening efforts and augmenting existing cancer control efforts with HPV vaccination, notably in those countries where unfavourable cohort effects are continuing or emerging.
Funding:
Bill and Melinda Gates Foundation (BMGF).
Human papillomavirus (HPV) is the most common sexually transmitted infectious agent; its 14 oncogenic types are causally associated with 5-10% of all cancers. The major structural HPV protein self-assembles into immunogenic virus-like particles. Two licensed HPV vaccines-the bivalent vaccine comprising HPV types 16 and 18, and the quadrivalent vaccine comprising HPV types 6, 11, 16 and 18-have proven to be safe and efficacious against 6-month-persistent cervical infections of HPV16 and HPV18 and associated precancerous lesions, and both have efficacies of 90-100%. Among baseline HPV-negative adolescent females, vaccine efficacies against the immediate precursor of cervical cancer (intraepithelial neoplasia grade 3) irrespective of HPV type are 93.2% and 43.0% for the bivalent and quadrivalent vaccines, respectively. The quadrivalent vaccine is efficacious (>75% vaccine efficacy) against any of the more-severe precursors of vulval, vaginal and anal cancers. A strong increase in vaccine efficacy with increasing severity of the precancerous lesion is explained by accumulation of the most-oncogenic HPV types 16 and 18 in these lesions. Therefore, prophylactic HPV vaccination will exceed the best results from screening for cancer. With the extremely efficacious prophylactic HPV vaccines, the focus of organized intervention (vaccination and screening) programmes should, however, shift from reducing the HPV disease burden to controlling the prevalence of oncogenic HPV (and nononcogenic HPV) types. Eradication of the major oncogenic HPV types should be pursued.
Incidence rates of different cancers have been calculated for the black population of Harare, Zimbabwe for a twenty year period (1991-2010) coinciding with continuing social and lifestyle changes, and the peak, and subsequent wane, of the HIV-AIDS epidemic. The overall risk of cancer increased during the period in both sexes, with rates cervix and prostate cancers showing particularly dramatic increases (3.3% and 6.4% annually, respectively). By 2004, prostate cancer became the most common cancer of men. The incidence of cancer of the oesophagus, formerly the most common cancer of men, has remained relatively constant, while rates of breast and cervix cancers, the most common malignancies of women, have shown significant increases (4.9% and 3.3% annually, respectively) The incidence of Kaposi sarcoma increased to a maximum around 1998-2000 and then declined in all age groups, and in both sexes The incidence of squamous cell cancers of the conjunctiva is relatively high, with temporal trends similar to those of Kaposi sarcoma. Non-Hodgkin lymphoma, the fifth most common cancer of men and fourth of women, showed a steady increase in incidence throughout the period (6.7% - 6.9% annually), although rates in young adults (15-39) have decreased since 2001. Cancer control in Zimbabwe, as elsewhere in sub-Saharan Africa, involves meeting the challenge of emerging cancers associated with westernisation of lifestyles (large bowel, breast and prostate), while the incidence of cancers associated with poverty and infection (liver, cervix, oesophagus) shows little decline, and the residual burden of the AIDS-associated cancers remains a major burden.
More than ever, clinicians need regularly updated reviews given the continuously increasing amount of new information regarding innovative cervical cancer prevention methods. A summary is given from recent meta-analyses and systematic reviews on 3 possible clinical applications of human papillomavirus (HPV) testing: triage of women with equivocal or low-grade cytologic abnormalities; prediction of the therapeutic outcome after treatment of cervical intraepithelial neoplasia (CIN) lesions, and last not but not least, primary screening for cervical cancer and pre-cancer. Consistent evidence is available indicating that HPV-triage with the Hybrid Capture(®) 2 assay (Qiagen Gaithersburg, Inc., MD, USA [previously Digene Corp.] (HC2) is more accurate (higher sensitivity, similar specificity) than repeat cytology to triage women with equivocal Pap smear results. Several other tests show at least similar accuracy but mRNA testing with the APTIMA(®) (Gen-Probe Inc., San Diego, CA, USA) test is similarly sensitive but more specific compared to HC2. In triage of low-grade squamous intraepithelial lesions (LSIL), HC2 is more sensitive but its specificity is substantially lower compared to repeat cytology. The APTIMA(®) test is more specific than HC2 without showing a loss in sensitivity. Identification of DNA of HPV types 16 and/or 18, or RNA from the five most carcinogenic HPV types allow selecting women at highest risk for CIN3+ but the sensitivity and negative predictive value of these markers are lower than full-range high-risk HPV (hrHPV) testing. After conservative treatment of cervical pre-cancer, HPV testing picks up more quickly, with higher sensitivity and not lower specificity, residual or recurrent high-grade CIN than follow-up cytology. Primary screening for hrHPV generally detects more CIN2, CIN3 or cancer compared to cytology at cut-off atypical squamous cells of undetermined significance (ASC-US) or LSIL, but is less specific. Combined HPV and cytology screening provides a further small gain in sensitivity at the expense of a considerable loss in specificity if positive by either test is referred to colposcopy, in comparison with HPV testing only. Randomised trials and follow-up of cohort studies consistently demonstrate a significantly lower cumulative incidence of CIN3+ and even of cancer, in women aged 30years or older, who were at enrollment hrHPV DNA negative compared to those who were cytologically negative. The difference in cumulative risk of CIN3+ or cancer for double negative (cytology & HPV) versus only HPV-negative women is small. HC2, GP5+/6+ PCR (polymerase chain reaction), cobas(®) 4800 PCR (Roche Molecular Systems Inc., Alameda, CA, USA) and Real Time PCR (Abbott Molecular, Des Plaines, IL, USA) can be considered as clinically validated for use in primary screening. The loss in specificity associated with primary HPV-based screening can be compensated by appropriate algorithms involving reflex cytology and/or HPV genotyping for HPV16 or 18. There exists a substantial evidence base to support that HPV testing is advantageous both in triage of women with equivocal abnormal cytology, in surveillance after treatment of CIN lesions and in primary screening of women aged 30years or older. However, the possible advantages offered by HPV-based screening require a well organised program with good compliance with screening and triage policies. This article forms part of a special supplement entitled "Comprehensive Control of HPV Infections and Related Diseases" Vaccine Volume 30, Supplement 5, 2012.
Cancer is set to become a major cause of morbidity and mortality in the coming decades in every region of the world. We aimed to assess the changing patterns of cancer according to varying levels of human development.
We used four levels (low, medium, high, and very high) of the Human Development Index (HDI), a composite indicator of life expectancy, education, and gross domestic product per head, to highlight cancer-specific patterns in 2008 (on the basis of GLOBOCAN estimates) and trends 1988-2002 (on the basis of the series in Cancer Incidence in Five Continents), and to produce future burden scenario for 2030 according to projected demographic changes alone and trends-based changes for selected cancer sites.
In the highest HDI regions in 2008, cancers of the female breast, lung, colorectum, and prostate accounted for half the overall cancer burden, whereas in medium HDI regions, cancers of the oesophagus, stomach, and liver were also common, and together these seven cancers comprised 62% of the total cancer burden in medium to very high HDI areas. In low HDI regions, cervical cancer was more common than both breast cancer and liver cancer. Nine different cancers were the most commonly diagnosed in men across 184 countries, with cancers of the prostate, lung, and liver being the most common. Breast and cervical cancers were the most common in women. In medium HDI and high HDI settings, decreases in cervical and stomach cancer incidence seem to be offset by increases in the incidence of cancers of the female breast, prostate, and colorectum. If the cancer-specific and sex-specific trends estimated in this study continue, we predict an increase in the incidence of all-cancer cases from 12·7 million new cases in 2008 to 22·2 million by 2030.
Our findings suggest that rapid societal and economic transition in many countries means that any reductions in infection-related cancers are offset by an increasing number of new cases that are more associated with reproductive, dietary, and hormonal factors. Targeted interventions can lead to a decrease in the projected increases in cancer burden through effective primary prevention strategies, alongside the implementation of vaccination, early detection, and effective treatment programmes.
None.
Infections with certain viruses, bacteria, and parasites have been identified as strong risk factors for specific cancers. An update of their respective contribution to the global burden of cancer is warranted.
We considered infectious agents classified as carcinogenic to humans by the International Agency for Research on Cancer. We calculated their population attributable fraction worldwide and in eight geographical regions, using statistics on estimated cancer incidence in 2008. When associations were very strong, calculations were based on the prevalence of infection in cancer cases rather than in the general population. Estimates of infection prevalence and relative risk were extracted from published data.
Of the 12·7 million new cancer cases that occurred in 2008, the population attributable fraction (PAF) for infectious agents was 16·1%, meaning that around 2 million new cancer cases were attributable to infections. This fraction was higher in less developed countries (22·9%) than in more developed countries (7·4%), and varied from 3·3% in Australia and New Zealand to 32·7% in sub-Saharan Africa. Helicobacter pylori, hepatitis B and C viruses, and human papillomaviruses were responsible for 1·9 million cases, mainly gastric, liver, and cervix uteri cancers. In women, cervix uteri cancer accounted for about half of the infection-related burden of cancer; in men, liver and gastric cancers accounted for more than 80%. Around 30% of infection-attributable cases occur in people younger than 50 years.
Around 2 million cancer cases each year are caused by infectious agents. Application of existing public health methods for infection prevention, such as vaccination, safer injection practice, or antimicrobial treatments, could have a substantial effect on the future burden of cancer worldwide.
Fondation Innovations en Infectiologie (FINOVI) and the Bill & Melinda Gates Foundation (BMGF).
A recent report that 93 per cent of invasive cervical cancers worldwide contain human papillomavirus (HPV) may be an underestimate, due to sample inadequacy or integration events affecting the HPV L1 gene, which is the target of the polymerase chain reaction (PCR)-based test which was used. The formerly HPV-negative cases from this study have therefore been reanalyzed for HPV serum antibodies and HPV DNA. Serology for HPV 16 VLPs, E6, and E7 antibodies was performed on 49 of the 66 cases which were HPV-negative and a sample of 48 of the 866 cases which were HPV-positive in the original study. Moreover, 55 of the 66 formerly HPV-negative biopsies were also reanalyzed by a sandwich procedure in which the outer sections in a series of sections are used for histological review, while the inner sections are assayed by three different HPV PCR assays targeting different open reading frames (ORFs). No significant difference was found in serology for HPV 16 proteins between the cases that were originally HPV PCR-negative and -positive. Type-specific E7 PCR for 14 high-risk HPV types detected HPV DNA in 38 (69 per cent) of the 55 originally HPV-negative and amplifiable specimens. The HPV types detected were 16, 18, 31, 33, 39, 45, 52, and 58. Two (4 per cent) additional cases were only HPV DNA-positive by E1 and/or L1 consensus PCR. Histological analysis of the 55 specimens revealed that 21 were qualitatively inadequate. Only two of the 34 adequate samples were HPV-negative on all PCR tests, as against 13 of the 21 that were inadequate ( p< 0.001). Combining the data from this and the previous study and excluding inadequate specimens, the worldwide HPV prevalence in cervical carcinomas is 99.7 per cent. The presence of HPV in virtually all cervical cancers implies the highest worldwide attributable fraction so far reported for a specific cause of any major human cancer. The extreme rarity of HPV-negative cancers reinforces the rationale for HPV testing in addition to, or even instead of, cervical cytology in routine cervical screening.
Human papillomavirus is a necessary cause of invasive cervical cancer worldwide
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