ArticleLiterature Review

Worldwide burden of gynecological cancer: The size of the problem

Authors:
  • Liverpool University Hospitals NHS Foundation Trust
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Abstract

The estimation of cancer burden is valuable to set up priorities for disease control. The comprehensive global cancer statistics from the International Agency for Research on Cancer indicate that gynaecological cancers accounted for 19% of the 5.1 million estimated new cancer cases, 2.9 million cancer deaths and 13 million 5-year prevalent cancer cases among women in the world in 2002. Cervical cancer accounted for 493 000 new cases and 273 000 deaths; uterine body cancer for 199 000 new cases and 50 000 deaths; ovarian cancer for 204 000 new cases and 125 000 deaths; cancers of the vagina, vulva and choriocarcinoma together constituted 45 900 cases. More than 80% of the cervical cancer cases occurred in developing countries and two-thirds of corpus uteri cases occurred in the developed world. Political will and advocacy to invest in healthcare infrastructure and human resources to improve service delivery and accessibility are vital to reduce the current burden in low- and medium-resource countries.

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... Each year, about half a million women globally develop cervical cancer, and about 274,000 die from the disease, with approximately 80% of cervical cancer deaths occurring in developing countries [1][2][3]. In Ghana, cervical cancer is the leading cause of cancer-related deaths in women and is most frequent among women aged 15-44 years, with an estimated crude incidence rate of 26.4/100,000/year [4]. ...
... A total of eight out of the 10 women involved in the pretest exercise were interviewed for a response rate of 80% (Table 8). Messages were reported received by all eight respondents, except for messages 3,17,19,27,12,and 30. Messages 17,19,27,and 12 were received by seven of the respondents, while message 3 was received by only six respondents. ...
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Background There has been extensive research across the globe to understand the barriers and facilitators of cervical cancer (CC) screening. However, few studies have focused on how such information has been used to develop text messages for mHealth screening programs, especially in resource-poor countries. This study elicited information on barriers and facilitators, the preferences of women regarding the modalities for delivery of health SMS messages on screening for cervical cancer, and demonstrates how this information was used to create a health screening program among women in the Greater Accra Region of Ghana. Methods Four main activities were carried out, including (1) a total of five focus group discussions, (2) a baseline survey involving 62 female bankers and 68 women from the communities, (3) a stakeholder meeting involving experts in cervical cancer research and clinical care, and (4) pilot testing of the text messages. Focus group discussions and the baseline survey data were collected concurrently between February and May 2017 and the results were used to develop 5 specific communication objectives during the stakeholder engagements held in June 2017. Results In all, 32 text messages were developed and pretested in July 2017(13 addressed knowledge on CC; 6 highlighted the importance of early detection; 5 allayed fear as a barrier to CC screening; 5 encouraged women to have time for their health, and 3 messages contained information on where to go for screening and the cost involved). Although awareness about the disease was high, knowledge of CC screening was low. For two-thirds of respondents (22/33), perceived lack of time, high cost, and fear (of cc, screening procedure, and potential for negative outcome) accounted for the reasons why respondents will not go for screening, while education on CC, especially from health workers and the mass media enabled uptake of CC screening. Conclusion Several factors prevent women from accessing screening services for CC, however, barriers such as low levels of education on CC, lack of time, and fear can be targeted in SMS messaging programs.
... Cervical cancer screening and free HPV vaccination have reduced cervical cancer mortality rates. However, the success of these programs relied heavily on public awareness of cervical cancer prevention [11]. ...
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Background Increasing women’s health literacy is the key to preventing cervical cancer, and various tools have been developed to assess women’s cancer health literacy. However, many of these tools come from other countries and have not been adapted to Chinese requirements. Furthermore, a system for evaluating cervical cancer health literacy among Chinese women has not been developed. Therefore, we sought to establish an evaluation index system for cervical cancer health literacy among Chinese women and to provide an effective evaluation tool for tertiary prevention of cervical cancer in China. Methods We invited 20 recognized experts to participate in two rounds of Delphi expert consultation, and the modified Delphi process with percentage weighting and multiplication was used. A literature review identified 67 potential indicators. Subsequent discussions within our research team led to the retention of 48 indicators following a rigorous screening process. On this basis, two rounds of Delphi expert consultation were conducted to rate and screen the indexes. Percentage weighting and multiplication were used to determine index weights. Results Twenty experts participated in the first-round Delphi consultations (95.23% recovery rate). In the second-round Delphi consultations, 20 questionnaires were returned (100%), and the expert authority coefficient was 0.93 ± 0.02. After both rounds of Delphi consultation, 4 first-level indicators, 9 second-level indicators, and 32 third-level indicators were identified for cervical cancer literacy among Chinese women. On a five-point scale, importance ratings ranged from 3.76 to 4.95 points, with variation coefficients ranging from 0.06 to 0.25, while sensitivity ratings ranged from 3.71 to 4.83 points, with variation coefficients ranging from 0.08 to 0.24. Across both rounds, Kendall’s W coefficients ranged from 0.168 to 0.248. The weights of first-level indicators of basic knowledge and attitudes about cervical cancer, primary prevention of cervical cancer literacy, secondary prevention of cervical cancer literacy, and tertiary prevention of cervical cancer literacy were 0.257, 0.249, 0.251, and 0.243, respectively. Conclusions We have developed the first tertiary prevention-based, comprehensive evaluation index system for cervical cancer literacy among Chinese women, which will provide theoretical support for cervical cancer prevention and health education programs.
... In developing countries, cervical cancer cases have significantly decreased due to screening tests. However, the mortality and morbidity rates for cervical cancer remain high, at approximately 85% and 83%, respectively [2][3][4][5]. Moreover, more than 80% of patients with cervical cancer in less developed countries are diagnosed at an advanced stage [6]. ...
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Background: Cervical cancer is the fourth most common cancer among females worldwide. Identifying peptide patterns discriminating healthy individuals from those with diseases has gained interest in the early detection of cancers. Our study aimed to determine signature peptide patterns for cervical cancer screening. Methods: Our study focused on the serum peptidome analysis of 83 healthy women and 139 patients with cervical cancer. All spectra derived from matrix-assisted laser desorption/ionization time-of-flight mass spectrometry were analyzed using FlexAnalysis 3.0 and ClinProTools 2.2 software. Results: In the mass range of 1000-10,000 Da, the total average spectra were represented as the signature pattern. Principal component analysis showed that all the groups were separately distributed. Furthermore, the peaks at m/z 1466.91, 1898.01, 3159.09, and 4299.40 significantly differed among the investigated groups (Wilcoxon/Kruskal-Wallis test and ANOVA, p < 0.001). Conclusions: Laboratory-based rapid mass spectrometry showed that serum peptidome patterns could serve as diagnostic tools for diagnosing cervical cancer; however, verification through larger cohorts and association with clinical data are required, and the use of externally validated samples, such as patients with other types of cancers, should be investigated to validate the specific peptide patterns.
... The posttest completed within 5 days, that is one day in each school. Lack of hygiene and more than one sexual contact had been the best chance elements stated with the aid of using 3.9 in step with cent (32) and 1.6 in step with cent (13) An experimental study was undertaken with the objectives to assess and evaluate the effectiveness of an informational booklet on prevention of cervical cancer in terms of knowledge and attitude among female college students before and after the administration of informational booklet Paired "t" test was used to find out the significance Of difference in mean pretest and posttest knowledge The finding recommend that the mean posttest knowledge score (25.9) was essentially higher than mean pre-test information score (20.2) at p < 0. 05 questionnaires. In the study the mean pretest knowledge score was 9.17, median knowledge score 10, and standard deviation was 2.18 in the ranged from 5-13, which indicated that the knowledge level of the patients having cervical cancer were assessed by the researcher. ...
... Around 288,000 people die from cervical cancer each year worldwide. 3 In Sub-Saharan Africa, the annual death rate for the disease is 22.5/100,000 women, while the rate of new cases is 34.8/100,000 women. On the other hand, these numbers are 2.5 and 6.6, respectively, 4 in North America. ...
Article
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Cancer of the cervix is the most common genital tract malignancy in the female and is a major public health problem in developing countries. Study of the sociodemographic data, clinical profile and compliance of patients is the first step in planning preventive measures and treatment facilities. The aims of the study were to determine the sociodemographic data and clinical profile, prognostic factors, compliance to concurrent chemo radiation of cervical cancer patients and study their association with other tumor-related factors. Our study is a record-based retrospective study from a single institution. The data of sociodemographic and clinical factors of 175 cervical cancer patients visited and their compliance to treatment were analyzed over a 2-year period. Data were analyzed using descriptive statistics. The mean age at presentation in our study is 54.8 years. The patients presented with bleeding per vagina as the most common presenting complaint i.e. 42.28%.38.88% patients presented with both bleeding per vagina and white discharge per vagina and 18.85% patients presented with white discharge per vagina.21.14% presented with symptoms less than 1 month, 52 patients presented with symptoms 1to 3 months duration. 49.14% presented with symptoms >3months. In our study, 62.85% patients were married at age < 17> 17 years. squamous cell carcinoma is the most common histology in our study accounting for 85.71% followed by adenocarcinoma 11.42% other histoligies accounted for 2.85%.87.42% were grade 2 histologies. Stage IIB is the most common stage of presentation our study 47.4%. 86.28% patient are compliant with planned treatment (external beam radiotherapy +brachy therapy, 4.57% patients defaulted prior to the start of treatment, 3.42% patients defaulted during external beam radiotherapy, 15.71% defaulted for brachytherapy out of 151 patients who completed planned treatment, 80.79% patients received 5-6 cycles of concurrent ciplatin 40mg/m 2.11.92% were lost to follow up at the end of 1 year. Cervical cancer is a debilitating illness seen to affect mainly elderly women. Late presentation is still the norm, as majority of the patients presented with advanced disease at the time of diagnosis and were treated with radical radiotherapy, with or without chemotherapy. Compliance during treatment was good comparable to the other studies. The response and complication rates were comparable with other datasets. Further, the scope of studying socio-demographic factors is not limited to hospital services, and this information can also be utilized while making public health policies and implementation of cervical cancer control programs.
... Ovarian cancer is a well-known lethal gynecological cancer that impacts females worldwide [1]. Most cases of ovarian cancer are typically due to epithelial cells and are divided into five subtypes: high-grade serous, low-grade serous, mucinous, endometrioid, and clear cell carcinoma [2]. Among ovarian epithelial cells, high-grade serous carcinoma is the most common subtype in ovarian cancer patients [3,4]. ...
Article
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In the current study, we identified a mechanism of resveratrol (RES) underlying its anti-cancer properties against human ovarian adenocarcinoma SKOV-3 cells. We investigated its anti-proliferative and apoptosis-inducing effects in combination with cisplatin, using cell viability assay, flow cytometry, immunofluorescence study and Western blot analysis. We discovered that RES suppressed cancer cell proliferation and stimulated apoptosis, especially when combined with cisplatin. This compound also inhibited SKOV-3 cell survival, which may partly be due to its potential to inhibit protein kinase B (AKT) phosphorylation and induce the S-phase cell cycle arrest. RES in combination with cisplatin strongly induced cancer cell apoptosis through activating the caspase-dependent cascade, which was associated with its ability to stimulate nuclear phosphorylation of p38 mitogen-activated protein kinase (MAPK), well recognized to be involved in transducing environmental stress signals. RES-induced p38 phosphorylation was very specific, and the activation status of extracellular signal-regulated kinase 1/2 (ERK1/2) and c-Jun N-terminal kinase (JNK) was not mainly affected. Taken together, our study provides accumulated evidence that RES represses proliferation and promotes apoptosis in SKOV-3 ovarian cancer cells through activating the p38 MAPK pathway. It is interesting that this active compound may be used as an effective agent to sensitize ovarian cancer to apoptosis induced by standard chemotherapies.
... Contaminated water sources become the sources of spread of human diseases, including diarrhea, hepatitis, encephalitis, cryptosporidiosis, leptospirosis, and typhoid fever; it has been linked Globally, the incidence of hepatitis A is predicted to 1.40 million patients, with a fatality rate between 12,800 and 16,100 per annum [9]. ...
Article
In this research, hydrothermally synthesized tungsten trioxide (WO3) nanocomposites doped polyvinylpyrrolidone (PVP) and chitosan (CS) were studied. Various concentrations (3, 6, and 9 wt%) of PVP were doped into a fixed amount of binary system (CS-WO3) nanocomposites. PVP/CS polymers showed attractive attention because of their different structure, functionality, and architecture control as dopant to WO3. The PVP/CS encapsulates the WO3 (ternary composite), which controls crystallite size (band gap reduction), rapidly overcomes the recombination electron-hole pairs issues, and generates the active sites, resulting in improved catalytic and antimicrobial activity. The synthesized nanocomposites revealed significant catalytic efficiency and methylene blue (MB) dye depletion of 99.9 % in the presence of reducing agent (NaBH4) in neutral and acidic media. Antimicrobial effectiveness of produced nanostructures towards Escherichia coli (E. coli) pathogen at low and high concentrations were investigated by Vernier caliper in mm. Furthermore, to their microbicidal action, docking experiments of CS-doped WO3 and PVP/CS-doped WO3 nanostructures for DHFR and FabI of Escherichia coli suggested blockage of aforesaid enzymes as the plausible pathway.
... Nearly all benign and malignant ovarian tumors originate from one of three cell types: epithelial cells, stromal cells, and germ cells. More than 90% of malignant ovarian tumors are epithelial in origin, 5%-6% of tumors constitute sex cord-stromal tumors, and 2%-3% are germ cell tumors [2]. Due to its unknown pathophysiology some of the proposed hypotheses for the development of ovarian cancer are such as "Incessant ovulation theory", Ovulation includes an inflammatory process with leukocyte infiltration and release of inflammatory mediators and reactive oxidants that can cause DNA damage. ...
Article
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Ovarian cancer is the most fatal gynecological disease and arises from epithelial cells, stromal cells, and germ cells. The incidence of ovarian cancer increases with age, with a peak incidence at the age of 50-60 years. Almost 60% of the women who develop ovarian cancer will lead to death. Some of the risk factors for ovarian cancer involve hysterectomy, pelvic inflammatory disease, and polycystic ovarian syndrome. In this review, we discussed various animal models which accurately represent the cellular and molecular changes associated with the initiation and progression of human ovarian cancer and have significant potential to facilitate the development of better methods for the early detection and treatment of ovarian cancer. Also, we reviewed the reliability and limitations of the existing tumor models.
... Vulvar cancer (VC) is the fourth most common genital tumor in women, accounting for 3% of all gynecological cancers worldwide (Sankaranarayanan and Ferlay 2006). Albeit VC is considered a rare tumor entity, its incidence has increased over the recent decade by 20%. ...
Article
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Purpose Vulvar squamous cell carcinoma (VSCC) is a rare malignancy of the female genital tract with increasing incidence rates. Etiologically, HPV-dependent and HPV-independent VSCC are distinguished. Surgical treatment and/or radiotherapy represent the therapeutic mainstay for localized disease. For recurrent or metastatic VSCC, treatment options are limited. Research has identified trophoblast cell surface antigen 2 (TROP-2) to be broadly expressed across different tumor entities. The aim of the present study was to systematically investigate the expression of TROP-2 in VSCC. Methods TROP-2 protein expression was investigated by immunohistochemistry in a cohort comprising n = 103 patients with primary VSCC. A four-tier scoring system (0: no staining, 1 + : low staining, 2 + : moderate staining, 3 + : high staining) was applied for quantification of protein expression. For further analyses, two groups (low TROP-2 expression: 0/1 + ; high TROP-2 expression: 2 + /3 +) were generated. The entire study cohort, as well as HPV-dependent and HPV-independent VSCC were considered separately. Results In the entire VSCC study cohort, TROP-2 expression was present in 97.1% of all cases (n = 100) with 74.8% displaying high TROP-2 expression (2 + /3 +). Only 2.9% of tumors showed absent TROP-2 expression. Of note, all HPV-dependent VSCC (n = 18) demonstrated high TROP-2 expression (2 + /3 +). In the subgroup of HPV-independent VSCC (n = 70), high TROP-2 expression was associated with favorable clinical outcomes based on log rank test and univariate cox analysis. Conclusion TROP-2 protein expression is of prognostic value in HPV-independent VSCC. The broad expression of TROP-2 in VSCC indicates the TROP-2 directed ADC Sacituzumab govitecan as a potential new therapeutic strategy for VSCC patients.
... Ovarian cancer (OC) is one of the most lethal gynecological malignancies among women worldwide, with 81,584 new cases and 54,220 deaths in 2022 [1,2]. Epithelial Ovarian cancer (EOC) is the most predominant pathologic subtype, accounting for over 90% of OC cases, which is most commonly diagnosed among women of post-menopausal age [3]. Although advanced medical techniques and drugs had been applied, the five-year survival rate of EOC is still below 50% [4,5]. ...
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Background Epithelial ovarian cancer (EOC) is one of the most fatal gynecological malignancies among elderly patients. We aim to construct two nomograms to predict the overall survival (OS) and cancer-specific survival (CSS) in elderly EOC patients. Methods Elderly patients with EOC between 2000 and 2019 were selected from the Surveillance, Epidemiology, and End Results (SEER) database. Enrolled patients were randomly divided into the training and validation set at a ratio of 2:1. The OS and CSS were recognized as endpoint times. The independent prognostic factors from the multivariate analysis were used to establish nomograms for predicting the 3-, 5- and 10-year OS and CSS of elderly EOC patients. The improvement of predictive ability and clinical benefits were evaluated by consistency index (C-index), receiver operating characteristic (ROC), calibration curve, decision curve (DCA), net reclassification improvement (NRI), and integrated discrimination improvement (IDI). Finally, the treatment efficacy of surgery and chemotherapy in low-, medium-, and high-risk groups were displayed by Kaplan–Meier curves. Results Five thousand five hundred eighty-eight elderly EOC patients were obtained and randomly assigned to the training set (n = 3724) and validation set (n = 1864). The independent prognostic factors were utilized to construct nomograms for OS and CSS. Dynamic nomograms were also developed. The C-index of the OS nomogram and CSS nomogram were 0.713 and 0.729 in the training cohort. In the validation cohort, the C-index of the OS nomogram and CSS nomogram were 0.751 and 0.702. The calibration curve demonstrated good concordance between the predicted survival rates and actual observations. Moreover, the NRI, IDI, and DCA curves determined the outperformance of the nomogram compared with the AJCC stage system. Besides, local tumor resection had a higher benefit on the prognosis in all patients. Chemotherapy had a better prognosis in the high-risk groups, but not for the medium- risk and low-risk groups. Conclusions We developed and validated nomograms for predicting OS and CSS in elderly EOC patients to help gynecologists to develop an appropriate individualized therapeutic schedule.
... The clinico-pathologic prognostic elements and existence of more young versus more elderly women with epithelial ovarian cancer ought to be analyzed [5]. From 1988 to 2001, information on patients with ovarian cancer from the Reconnaissance, The study of cancer transmission, and Outcome Program were gathered in a study conducted by Mohammed et al.,. ...
Article
The paper is based on a two-step procedure known as "Systematic Literature Network Analysis (SLNA)" (Colicchia & Strozzi, 2012): a systematic literature review (SLR) and a subsequent analysis of the subset of pertinent articles obtained through a bibliographic network analysis (NA): specifically, the citation network analysis, the co-occurrence networks analysis, and the basic statistics. The first qualitative evaluation is primarily based on the researchers' opinions regarding the choice of keywordsand relies on an explanatory approach, whereas the bibliometric evaluation offers more objective insights through quantitative and statistical data (Aliyev et al., 2018). The most influential author names, journal titles, article titles, article keywords, and publication years are only a few examples of the bibliographic data examined by bibliometric approaches. The topic of the study is ovarian cancer among GenY, from reservoir of academic databases like Pubmed and Scopus, the authors have accumulated list of publications relating to keywords which are ovarian cancer, family risk, IVF and smoking which was limited to the area of medical, human, female, ovary, cancer and health .
... Many lifestylerelated risk factors have been identified including childbirth, tubal ligation, oral contraceptives, menopausal hormone treatment, polycystic ovary syndrome, endometriosis, smoking, and pelvic inflammatory disease. Moreover, some common genetic variations have been identified as risk factors (Bankhead et al., 2008;Sankaranarayanan and Ferlay, 2006;Lheureux et al., 2019;Titus-Ernstoff et al., 2001;Cancer, 2015;Cancer, 2008) A combination of multigene risk scores and epidemiological risk factors has been recognized by Genome-Wide Association Studies (GWAS). Nevertheless, additional polymorphisms in important genes are supposed to influence susceptibility to ovarian cancer. ...
Article
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Ovarian cancer is taken as the most typical malignancy among women and the ninth most typical cancer in Iran. Predictive tools are of great importance as ovarian cancer is usually detected in patients at later stages of the disease. In other countries, the TIPARP gene rs2665390 has been reported to be pertinent to ovarian cancer as a risk factor. This study aims to examine if this polymorphism pertains to the risk of ovarian cancer to diagnose suitable biomarkers in the Iranian population. Method: In the present case-control piliot study, peripheral blood samples were gathered from 60 control subjects and 60 patients with ovarian cancer. The gene was determined by Tetra ARMS PCR after DNA extraction. Tetra ARMS PCR is a flexible, rapid, and cost-effective method to detect allele-specific DNA polymorphisms. The data were analyzed by chi-square test. Results: The results indicated that there was a significant association between the T/T and C/C genotypes distribution and C and T allele in ovarian cancer for rs2665390 polymorphism in the two populations. In addition, significant correlations were observed in patients with the (T/T) genotype (p = 0.0048) as frequencies of ovarian cancer decreased. Discussion & Conclusions: Based on the results, rs2665390 polymorphism of TiPARP gene might be pertained to the susceptibility of ovarian cancer in the Iranian pilot population, which can be used as a suitable biomarker for the population and help physicians with their predictions. However, more studies need to be conducted in this area to broaden our horizons on this issue.
... On average, five million new cancer cases are reported per annum. 13 FGT tumours affect a significant number of the female population in Pakistan, and their incidence is increasing at an alarming rate. ...
Article
Objective: To study the frequency and distribution of Female genital tract (FGT) malignancies through data recouped from the tumour registry of Armed Forces Institute of Pathology, Rawalpindi Pakistan. Study Design: Retrospective longitudinal study. Place and Duration of Study: Histopathology Department, Armed Force Institute of Pathology, Rawalpindi Pakistan, from 2009-2018 Methodology: A total of 1586 cases of malignant tumours of FGT were retrieved from the AFIP tumour registry, and data were analyzed in terms of the age of the patients' site of the tumour. It was also compared with regional and international data. Results: Thirty-seven thousand seven hundred ninety-three malignant cases were reported at AFIP from 2009-2018, out of which 1586(4.19%) were of the female genital tract. Ovarian malignancies were most frequent among FGT tumours,637(40.1%), followed by uterine tumours 519(32.6%). Carcinoma of the cervix was found in 237 cases (15%). Vulva and vaginal cases were seen in only 7.7% patients. The FGTs ranked fourth among the top ten commonest tumours in females. Conclusion: The most common malignancy of the female genital tract was ovarian cancer. Endometrial carcinoma was the second most frequent gynaecological malignancy, followed by cervical carcinoma. Ovarian malignancies were in fourth position among the top ten commonest female tumours in the current analysis as well, as in the previous analysis from AFIP.
... Jacob et al., reported that approximately 1,20,000 women develop cervical cancer annually in India [4]. The annual world-wide incidence of cervical cancer is 5,10,000 with an annual mortality of 2,88,000 as per the data of World Health Organization [5]. In India the incidence and mortality rates are 27 and 15 per 1,00,000 women respectively [6].CC is more prevalent in the rural areas of tamilnadu and it is the second most commonly occurring cancer among women [7]. ...
Article
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This is an Open Access Journal / article distributed under the terms of the Creative Commons Attribution License (CC BY-NC-ND 3.0) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. All rights reserved. Cervical cancer is more prevalent among women in India (6-29%) and so the objective of our study is to evaluate the role of various factors like age, geographical location, tobacco and betel nut consumption, age of marriage and number of pregnancies, status of immune system and Chlamydia infection in cervical cancer patients in Tamilnadu. About 400 cervical cancer patients who visited various hospitals in and around Coimbatore within the 6 months (Nov-2015 to April-2016) volunteered for this study. 400 age and location matched volunteers were chosen for the control group. Questionnaire was used to collect data and the data collected from the patient and control group were categorized according to age. The significance were statistically verified using the Pearson Chi-square test and multiple regression analysis. The factors under study were analyzed and compared between the test and control group. High prevalence in found in patients with 50-60yrs of age. About 39% are from Erode district and 28% were from Namakkal district. 42.5% belonging to 50-60yrs were found to have the habit of tobacco and betel nut consumption. Among the various groups, 73% were married at an early age and 75% have more than 3 children. 77% of test group have compromised immune system and 67% have tested positive for Chlamydia infection. Among the cancers in women, cervical cancer is more prevalent. The factors (age, geographical location, tobacco and betel nut consumption, age of marriage and number of pregnancies, status of immune system and Chlamydia infection) studied were found to correlate with the already existing studies in other population. These factors are the ones that can be controlled if proper measures are taken. This can be achieved if proper awareness in provided to the public. When this awareness becomes effective, the prevalence of cervical cancer in Tamilnadu can be brought under control and to an extent can be made extinct. ABSTRACT RESEARCH ARTICLE
... Often diagnosed in an advanced stage, it is the most lethal gynecological cancer, with a 5-year survival rate of 26-42%, depending on the initial stage [2]; however, more than 40% of stage III/IV patients die within the first year and 25% within the first 90 days following diagnosis [3]. Ovarian tumors may arise from epithelial, stromal, or germ cells, where over 90% of malignant ovarian tumors arise from epithelial cells [4]. A heterogeneous disease, epithelial ovarian cancer (EOC) comprises several histological subtypes: high-grade serous ovarian cancer (HGSOC) (70-80%), endometrioid (10%), clear cell (10%), mucinous (3%), and low-grade serous (<5%) [5]. ...
Article
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Ovarian cancer is the most lethal gynecologic malignancy. Platinum-based chemotherapy is the backbone of treatment for ovarian cancer, and although the majority of patients initially have a platinum-sensitive disease, through multiple recurrences, they will acquire resistance. Platinum-resistant recurrent ovarian cancer has a poor prognosis and few treatment options with limited efficacy. Resistance to platinum compounds is a complex process involving multiple mechanisms pertaining not only to the tumoral cell but also to the tumoral microenvironment. In this review, we discuss the molecular mechanism involved in ovarian cancer cells' resistance to platinum-based chemotherapy, focusing on the alteration of drug influx and efflux pathways, DNA repair, the dysregulation of epigenetic modulation, and the involvement of the tumoral microenvironment in the acquisition of the platinum-resistant phenotype. Furthermore, we review promising alternative treatment approaches that may improve these patients' poor prognosis, discussing current strategies, novel combinations, and therapeutic agents.
... Ovarian cancer is a lethal gynecological malignancy and is commonly regarded as a silent killer due to the lack of symptoms in the early stages of the disease [1,2]. Epithelial ovarian cancer (EOC) arises from the malignant transformation of the cells in the epithelial layer of the ovary, accounting for 90% of the OC cases and is considered the most malignant subtype [3][4][5], while stromal and germ cell tumors constitute 6% and 4% of ovarian cancer, respectively [6]. EOC represents the 8th most common cancer among women worldwide [7], accounting for 3.4% of cancer cases [7]. ...
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More than two-thirds of epithelial ovarian cancer (EOC) patients are diagnosed at advanced stages due to the lack of sensitive biomarkers. Currently, exosomes are intensively investigated as non-invasive cancer diagnostic markers. Exosomes are nanovesicles released in the extracellular milieu with the potential to modulate recipient cells' behavior. EOC cells release many altered exosomal cargoes that exhibit clinical relevance to tumor progression. Exosomes represent powerful therapeutic tools (drug carriers or vaccines), posing a promising option in clinical practice for curing EOC in the near future. In this review, we highlight the importance of exosomes in cell–cell communication, epithelial–mesenchymal transition (EMT), and their potential to serve as diagnostic and prognostic factors, particularly in EOC.
... Numerous patients are without access to satisfactory health facilities, appropriate diagnostic examinations, and capitals for defensive, analytical, and therapy facilities [61] . CHOl cell, a tumorigenic cell with an abnormally high level of p53 enzyme [40] , and HeLa cell were carefully chosen for this experiment due to the high prevalence of gynecological malignancies in premenopausal women, particularly PCOS patients [62] . The mechanism of action for compound l is comparable to that of isotretinoin and metformin, which also displayed significant antiproliferative effects on tumorigenic cells with uncharacteristic FoxOl , p53, and FoxO3 functions in polycystic ovarian syn- drome victims [ 33 , 41 , 63 ] . ...
Article
This study is aimed at evaluating the anti-proliferative activity of a novel hydroxyflavone isolated for the first time from Kigelia africana fruit, against cervical cancer (HeLa) and tumorigenic (CHO-1) cells, and understanding the molecular interaction of the compound against p53 protein target. Compound 1 was isolated and characterization was done via application of physical and spectroscopic approaches (1D-NMR, 2D-NMR, and mass spectroscopy) and its effect on CHO-1 and HeLa cell lines was evaluated. Also, the compound was docked to different conformers obtained from the cluster analysis of the molecular dynamics simulation trajectories of the wild and mutant human p53 core domain protein. The resultant complexes were subjected to a 100 ns molecular dynamics simulation (MDs). A novel hydroxyflavone isolated from Kigelia africana fruit ethyl acetate fraction was identified and characterized as 3,6-dihydroxy-2-(3,4-dimethylphenyl)-4H-chromen-4-one. This compound displayed an anti-proliferative effect on CHO 1 cells with IC50 value of 74.0±10.4 µg/mL but had no significant effect on HeLa cell lines. Compound 1 was able to selectively bind more strangely to the mutant p53 core domain than the wild type in a similar binding manner as the reference compound. The MDs analysis reveals that the binding of Compound 1 to the mutant p53 structure stabilized the protein, which is one of the key mechanisms that was proposed for the restoration of wild-type p53 conformation in p53-Y220C cells. The isolated compound might serve as a starting point for the development of novel anti-proliferative treatments for polycystic ovarian syndrome (PCOS) in reproductive women.
... This classification is associated with prognostic factors and therapeutic modalities. [17][18][19][20][21][22][23] Benign tumors affect women between 20 and 50 years old, while malignant lesions predominate in patients older than 50 years. In the present study, the mean age of patients was 50.24±11.12 ...
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Background: In Indian women, ovarian cancer is one of the most commonly diagnosed cancer. We wanted to analyze the demographic profile, staging, and sensitivity and specificity of CA-125 levels in a patient with ovarian cancer in an indian scenario.Methods: A retrospective study was performed and information was collected from 250 patients who visited SGRD Hospital, Vallah, Amritsar from 1 April 2016 to 30 April 2020, with pelvic lesions of probable ovarian origin on demographic profile, the staging of the disease and CA-125 levels. Data was collected, analyzed, and presented in frequency tables and figures.Results: The study comprised of 250 patients. CA-125 was mainly used to investigate a wide range of signs and symptoms and few tests were for follow up or screening of ovarian cancer. In female patients having a CA-125 for very high suspicion of malignancy/ovarian cancer, only 90 (36%) of the abnormal results were caused by ovarian cancer. False-positive results were largely caused by other malignancies. The specificity of CA-125 for ovarian cancer increased with concentrations over 1000 kU/litre. Serous adenocarcinoma was found the most common malignant tumor type of the ovary (53%). In the demographic profile, ovarian cancer was found to be highest in the sikh religious group (75%) and prevalent in the middle socioeconomic status 32% (n=80).Conclusions: These results confirm the high false-positive rate and poor sensitivity and specificity associated with CA-125 and the most common tumor type. The substantial inappropriate usage of CA-125 has led to results that are useless to the clinician, have cost implications, and add to patient anxiety and clinical uncertainty.
... 1 Although it comprises of only four percent of all women's cancer, it has high mortality and morbidity rates in comparison to the cancers of the reproductive system. 2 The overall incidence of a symptomatic ovarian cyst in a premenopausal female being malignant is approximately 1:1000 which increases to 3:1000 at the age of 50. 3 A preoperative estimation of the risk of malignancy is essential in the assessment of an ovarian mass. Eighty different models have been advocated for this purpose. ...
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Aims: To evaluate the role of modified RMI (RMI 5) in pre-operative evaluation of ovarian tumor. Methods: It was a prospective cross sectional study done in Paropakar Maternity and Women’s Hospital from May to August 2018. During the study, 72 women with ovarian tumor were analyzed. RMI5 was calculated using the ultrasound score, Doppler score, menopausal status and CA125. Cut-off of 200 was used for malignancy discrimination. Chi square test was used to calculate the statistical significance which was set at 0.05. Receiver Operator Characteristics curves for RMI and its individual parameters were plotted using SPSS. Results: There were 72 ovarian tumors operated in four months and mean age was36 years with 10 (14%) at post-menopause. The mean value of RMI 5 was 38 for benign tumors, 80 for borderline tumors and 899 for malignant tumors. The area under curve for RMI 5 was 0.993 for cut-off of 200. The diagnostic accuracy of RMI 5 was 94.4 which was similar to that of Doppler score 2 (94.7) while it was much higher than that of the rest of the parameters (CA-125: 72, ultrasound score: 87 and postmenopausal status: 88.9). Conclusions: RMI 5 is better for malignancy prediction of ovarian masses instead of individual parameters like menopausal status, CA125 and ultrasound score.
... Ovarian cancer (OC) is one of the most lethal gynecological malignancies among women worldwide, with 81,584 new cases and 54,220 deaths in 2022 [1, 2]. Epithelial Ovarian cancer (EOC) is the most predominant pathologic subtype, accounting for over 90% of OC cases, which is most commonly diagnosed among women of post-menopausal age [3]. Although advanced medical techniques and drugs had been applied, the ve-year survival rate of EOC is still below 50% [4,5]. ...
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Background Epithelial ovarian cancer (EOC) is one of the most fatal gynecological malignancies among elderly patients. We aim to construct two nomograms to predict the overall survival (OS) and cancer-specific survival (CSS) in elderly EOC patients. Methods Elderly patients with EOC between 2000 and 2019 were selected from the Surveillance, Epidemiology, and End Results (SEER) database. Enrolled patients were randomly divided into the training and validation set at a ratio of 7:3. The OS and CSS were recognized as endpoint times. The independent prognostic factors from the multivariate analysis were used to establish nomograms for predicting the 3-, 5- and 10-year OS and CSS of elderly EOC patients. The improvement of predictive ability and clinical benefits were evaluated by consistency index (C-index), receiver operating characteristic (ROC), calibration curve, decision curve (DCA), net reclassification improvement (NRI), and integrated discrimination improvement (IDI). Finally, the treatment efficacy of surgery and chemotherapy in low-, medium-, and high-risk groups were displayed by Kaplan-Meier curves. Results A total of 5,588 elderly EOC patients were obtained and randomly assigned to the training set (n = 3724) and validation set (n = 1864). The independent prognostic factors were utilized to construct nomograms for OS and CSS. The C-index of the OS nomogram and CSS nomogram were 0.755 and 0.700 in the training cohort. In the validation cohort, the C-index of the OS nomogram and CSS nomogram were 0.746 and 0.696. The calibration curve demonstrated good concordance between the predicted survival rates and actual observations. Moreover, the NRI, IDI, and DCA curves determined the outperformance of the nomogram compared with the AJCC stage system. Besides, surgery had no benefit on the prognosis in the high-risk group. Chemotherapy had a better prognosis in the medium-, and high-risk groups, but not for the low-risk group. Conclusions We developed and validated nomograms for predicting OS and CSS in elderly EOC patients to help gynecologists to develop an appropriate individualized therapeutic schedule.
... Human diseases, such as hepatitis, diarrhea, cryptosporidiosis, encephalitis, leptospirosis, and typhoid fever, are spreading because of contaminated water. Globally, 1.4 million cases of hepatitis A are diagnosed yearly, with a mortality rate of 12,800 to 16,100 [7]. Hazardous contaminants in effluent contain both inorganic and organic toxic metals and dangerous solvents and compounds, all of which must be primarily decayed to attain a sustainable green environment [8]. ...
Article
A chemical co-precipitation route was used to synthesize novel strontium oxide (SrO), SrO-starch composite and various tellurium (Te) concentrations were incorporated in SrO-starch composite. This study aims to enhance the catalytic activities and bactericidal behavior of SrO, SrO-starch composite with different percentage concentrations of Te doping and a fixed amount of starch nanoparticles. XRD affirmed that the dopant contribution was investigated to improve crystallinity. Surface morphological characteristics and elemental composition evaluation were determined using an FE-SEM and EDS exhibit a doping concentration of an element in the synthesized products. The configuration of Sr–O–Sr bonds and molecular vibrations has been indicated by FTIR spectra. In addition, dye degradation of prepared samples was investigated through catalytic activity (CA) in the existence of NaBH4 act as a reduction representative. The Te-doped SrO-starch composite indicates superior catalytic activity and shows a degradation of Methylene blue dye (91.4 %) in an acidic medium. The synthesis nanocatalyst demonstrated impressive antibacterial activity against Staphylococcus aureus (S. aureus) at high and low concentrations exhibiting zones of inhibition 9.30 mm as compared to ciprofloxacin. Furthermore, molecular docking studies of synthesized nanocomposites were performed against selected enzyme targets, i.e., β-lactamaseE.coli and DNA GyraseE.coli.
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Background Vulvar squamous cell carcinoma (VSCC) is an uncommon gynecologic malignancy but with an increasing incidence in recent years. Etiologically, VSCC is classified into two subtypes: HPV-dependent and HPV-independent. Localized VSCC is treated surgically and/or with radiation therapy, but for advanced, metastatic or recurrent disease, therapeutic options are still limited. N6-methyladenosine (m6A) is the most prevalent post-transcriptional messenger RNA (mRNA) modification and involved in many physiological processes. The group of m6A proteins can be further divided into: ‚writers’ (METTL3, METTL4, METTL14, WTAP, KIAA1429), ‚erasers’ (FTO, ALKBH5), and ‚readers’ (HNRNPA2B1, HNRNPC, YTHDC1, YTHDF1-3). Dysregulated m6A modification is implicated in carcinogenesis, progression, metastatic spread, and drug resistance across various cancer entities. Up to date, however, only little is known regarding the role of m6A in VSCC. Methods Here, we comprehensively investigated protein expression levels of a diverse set of m6A writers, readers and erasers by applying immunohistochemical staining in 126 patients with primary VSCC. Results In the entire study cohort, dominated by HPV-independent tumors, m6A protein expression was not associated with clinical outcome. However, we identified enhanced protein expression levels of the ‚writers’ METTL3, METTL14 and the ‚reader’ YTHDC1 as poor prognostic markers in the 23 patients with HPV-dependent VSCC. Conclusion Our study suggests dysregulated m6A modification in HPV-associated VSCC.
... Epithelial ovarian cancer is the most fatal type of gynecological tumor, and the mortality rate of this disease has not shown any significant reduction over the last 30 years. 1,2 Most patients exhibit high respon-siveness to current platinum-based chemotherapies; however, in terms of long-term survival and cure rates, these treatments are unsatisfactory. This is primarily due to the progressive acquisition of treatment resistance and development of the disease into a recurrent form. ...
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Cancer stem-like cells (CSCs) have been suggested to be responsible for chemoresistance and tumor recurrence owing to their self-renewal capacity and differentiation potential. While WEE1 is a strong candidate target for anticancer therapies, its role in ovarian CSCs is yet to be elucidated. Here, we show that WEE1 plays a key role in regulating CSC properties and tumor resistance to carboplatin via a microRNA-dependent mechanism. We found that WEE1 expression is upregulated in ovarian cancer spheroids because of the decreased expression of miR-424 and miR-503, which directly target WEE1. The overexpression of miR-424/503 suppressed CSC activity by inhibiting WEE1 expression, but this effect was reversed upon the restoration of WEE1 expression. Furthermore, we demonstrated that NANOG modulates the miR-424/503-WEE1 axis that regulates the properties of CSCs. We also demonstrated the pharmacological restoration of the NANOG-miR-424/503-WEE1 axis and attenuation of ovarian CSC characteristics in response to atorvastatin treatment. Lastly, miR-424/503-mediated WEE1 inhibition re-sensitized chemoresistant ovarian cancer cells to carboplatin. Additionally, combined treatment with atorvastatin and carboplatin synergistically reduced tumor growth, chemoresistance, and peritoneal seeding in the intraperitoneal mouse models of ovarian cancer. We identified a novel NANOG-miR-424/503-WEE1 pathway for regulating ovarian CSCs, which has potential therapeutic utility in ovarian cancer treatment.
... [1] Epithelial cancer accounts for more than 90% of all cases of ovarian cancer. [2] For the treatment of epithelial ovarian cancer, surgery to reduce tumor burden as much as possible and adjuvant chemotherapy is necessary; [3] even in the very early stage, chemotherapy is beneficial for prognosis. [4] On chemotherapy, many gynecologic oncologists set 3 weeks between 2 administrations to manage the various toxicities; however, they also try not to delay too long. ...
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In epithelial ovarian cancer, first-line adjuvant chemotherapy is necessary, and patients sometimes require protraction; however, there are only a few recent studies to show its influence. In this study, we investigated whether the protraction of the total period of first-line chemotherapy has a negative influence on the survival outcomes. Of the 101 patients we recruited from February 2011 to February 2021, 70 (69.3%) and 31 (30.7%) were classified into the not protracted and protracted groups, respectively. They underwent surgery and adjuvant chemotherapy for epithelial ovarian cancer. Protraction was defined as the overall duration of the first-line chemotherapy being more than 20 days longer than intended. Number of patients who underwent additional treatments such as bevacizumab or poly(adenosine diphosphate ribose) polymerase inhibitors or pembrolizumab was compared between both groups. Kaplan–Meier survival analysis and Cox regression analysis were used for survival outcomes. There was no significant difference for additional treatments. The progression-free survival (PFS) in the total follow-up period in the protracted group was significantly shorter than that in the not protracted group (P = .037); however, the difference in the overall survival between the 2 groups was not significant (P = .223). For the PFS, the hazard ratio of protraction was 1.646 in the univariate analysis (95% confidence interval, 1.020–2.658; P = .041). Excessive protraction of chemotherapy over 20 days or more can result in significantly shorter PFS within 5 years. A better therapeutic strategy is required for patients requiring protracted first-line chemotherapy in advanced epithelial ovarian cancer.
... Early detection and treatment will decrease mortality from this disease. However, no clinically proven and effective screening method currently exists and routine screening for asymptomatic ovarian cancer is not recommended 9 . CA125 blood test is widely used for ovarian cancer screening but the levels can also be elevated in benign conditions such as endometriosis and fibrosis, making it an unreliable diagnostic method 10 . ...
Article
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Raman spectroscopy (RS) is a widely used non-destructive technique for biosensing applications because of its ability to detect unique ‘fingerprint’ spectra of biomolecules from the vibrational bands. To detect these weak fingerprint spectra, a complex detection system consisting of expensive detectors and optical components are needed. As a result, surface enhanced Raman spectroscopy (SERS) method were used to increase the Raman signal multifold beyond 10¹² times. However, complexity of the entire Raman detection system can be greatly reduced if a short wavelength region/unique single spectral band can distinctly identify the investigating analyte, thereby reducing the need of multiple optical components to capture the entire frequency range of Raman spectra. Here we propose the development of a rapid, single peak Raman technique for the detection of epithelial ovarian cancers (EOC)s through haptoglobin (Hp), a prognostic biomarker. Hp concentration in ovarian cyst fluid (OCF) can be detected and quantified using Raman spectroscopy-based in vitro diagnostic assay. The uniqueness of the Raman assay is that, only in the presence of the analyte Hp, the assay reagent undergoes a biochemical reaction that results in product formation. The unique Raman signature of the assay output falls within the wavenumber region 1500–1700 cm⁻¹ and can be detected using our single peak Raman system. The diagnostic performance of our Raman system had 100.0% sensitivity, 85.0% specificity, 100.0% negative predictive value and 84.2% positive predictive value when compared to gold standard paraffin histology in a proof-of-concept study on 36 clinical OCF samples. When compared to blood-based serum cancer antigen 125 (CA125) levels, the Raman system-based assay had higher diagnostic accuracy when compared to CA125, especially in early-stage EOCs.
... Besides spectrum of NAFLD ranges from steatosis i.e. deposition of vesicular fat exceeds more than 5% of liver weight and has high prevalence in developed countries like America (21%-25%), Europe (24%) [77]. Progression of this with hepatocyte ballooning, inflammation, and fibrosis identified as NASH [78,79]. From the extensive studies of gut-liver axis it is undoubtedly proven that healthy gut can leads to a healthy liver. ...
Article
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Liver diseases are responsible for over 2 million deaths each year and the number is rapidly increasing. There is a strong link between edibles, gut microbiota, liver fat and the liver damage. There are very limited therapeutic options for treatment specifically for Alcoholic liver disease (ALD) and Non-Alcoholic liver disease (NAFLD). Recently, identified Edible Exosomes-like nanoparticles (ELNs) are plant derived membrane bound particles, released by microvesicular bodies for cellular communication and regulate immune responses against many pathogens. Many studies have identified their role as hepatoprotective agent as they carry bioactive material as cargoes which are transferred to recipient cells and affect various biological functions in liver. They are also known to carry specific miRNA, which increases the copy number of beneficial bacteria and the production of lactic acid metabolites in gut and hence restrains from liver injury through portal vein. Few in-vitro studies also have been reported about the anti-inflammatory, anti-oxidant and detoxification properties of ELNs which again protects the liver. The properties such as small size, biocompatibility, stability, low toxicity and non-immunogenicity make ELNs as a better therapeutic option. But, till now, studies on the effect of ELNs as therapeutics are still at its infancy yet promising. Here we discuss about the isolation, characterization, their role in maintaining the gut microbiome and liver homeostasis. Also, we give an outline about the latest advances in ELNs modifications, its biological effects, limitations and we propose the future prospective of ELNs as therapeutics.
... In 2018, GLOBOCAN reported nearly 1.16 million newly diagnosed cases and 0.78 million deaths due to cancer in India 2 . Breast cancer is now the leading cause of mortality in Indian women, followed by cervical and ovarian cancer 3,4 . These cancers can be prevented if diagnosed early 5 . ...
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Gynaecological cancers are the major cause of cancer-related deaths in Indian women. The poor prognosis and lack of symptoms in the early stages make early cancer diagnosis difficult. The absence of mandatory screening programmes and the lack of awareness pose to be a real challenge in a developing economy as India. Prompt intervention is required to enhance cancer patient survival statistics and to lessen the social and financial burden. Conventional screening and cytological techniques employed currently have helped to reduce the incidence of cancers considerably. However, these tests offer low sensitivity and specificity and are not widely used for risk assessment, leading to inadequate early-stage cancer diagnosis. The accomplishment of Human Genome Project (HGP) has opened doors to exciting 'omics' platforms. Promising research in genomics and proteomics has revolutionized cancer detection and screening methodologies by providing more insights in the gene expression, protein function and how specific mutation in specific genes corresponds to a particular phenotype. However, these are incompetent to translate the information into clinical applicability. Various factors such as low sensitivity, diurnal variation in protein, poor reproducibility and analytical variables are prime hurdles. Thus the focus has been shifted to metabolomics, which is a much younger platform compared to genomics and proteomics. Metabolomics focuses on endpoint metabolites, which are final products sustained in the response to genetic or environmental changes by a living system. As a result, the metabolome indicates the cell's functional condition, which is directly linked to its phenotype. Metabolic profiling aims to study the changes occurred in metabolic pathways. This metabolite profile is capable of differentiating the healthy individuals from those having cancer. The pathways that a cell takes in turning malignant are exceedingly different, owing to the fact that transformation of healthy cells to abnormal cells is linked with significant metabolic abnormalities. This review is aimed to discuss metabolomics and its potential role in early diagnosis of gynaecological cancers, viz. breast, ovarian and cervical cancer.
... The even rarer germ cell tumors (2%-3%) stem from the egg-producing cells (Figure 3). [15][16][17] Within each of the 3 main histologic categories of ovarian tumors, many subtypes exist and are further classified as benign, malignant, or borderline, that is, with atypical proliferation but low potential for malignancy. SCTs fall under the sex cord-stromal tumors and are classified as pure stromal tumors based on their location of origin within the ovary and their histologic appearance (Figure 4). ...
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Androgen-producing steroid cell ovarian tumors are rare, comprising less than 1% of ovarian neoplasms, and can present with infertility and rapid virilization. Here we discuss the case of a 28-year-old woman who presented with an unusually insidious 2-year history of infertility, hirsutism, and clitoromegaly who was found to have an elevated serum testosterone and a left ovarian mass. She underwent oophorectomy and pathology revealed a steroid cell tumor, not otherwise specified (NOS), with no malignant features. Following surgery, the patient’s hyperandrogenic symptoms resolved with normalization of testosterone within 6 months, and she was able to conceive spontaneously. In reproductive-aged women with progressive hyperandrogenic symptoms, androgen-producing tumors, including those of ovarian origin, should be suspected. Thorough investigation, including plasma hormone levels and tumor histology, can lead to accurate diagnosis and management. Treatment should be guided by histology and surgical staging, with consideration for future fertility desires. Women who have not completed childbearing can undergo unilateral oophorectomy or tumor resection for benign tumors, with close monitoring of sex hormone levels postoperatively.
Article
Objective We compared the performance of high-risk human papillomavirus (HPV) messenger RNA testing of physician- and self-collected specimens for detecting histological grade 2 or higher cervical intraepithelial neoplasia (CIN) among women who visited a colposcopy clinic in Thailand. Methods From January 2022 to April 2022, 500 women participated in this cross-sectional multicenter study; 494 had complete data and valid specimen results. The participants were women who attended any one of the 10 participating institutes’ colposcopy clinics due to abnormal cytology, positive high-risk HPV testing, or for follow-up. Participants used a self-sampling Aptima Multitest Swab specimen collection kit to self-collect vaginal samples before physicians biopsied the cervix during the colposcopic examination. The self- and physician-collected specimens were tested for high-risk HPV messenger RNA using Aptima nucleic acid amplification assays. Cervical tissues were collected during colposcopic-directed biopsy from the most severe lesion or a random biopsy and endocervical curettage specimen if no lesion was detected. Results We detected high-risk HPV messenger RNA in 75.4% of self-collected specimens and 70.6% of physician-collected specimens. The prevalence of histological grade 2 or higher CIN from cervical histology was 25.1% (n=124). For self-collected specimens, the sensitivity and specificity of high-risk HPV messenger RNA for grade 2 or higher CIN were 87.0% (95% CI 79.7% to 92.4%; n=108) and 28.5% (95% CI 24.0% to 33.4%). For physician-collected specimens, the sensitivity and specificity of high-risk HPV messenger RNA for grade 2 or higher CIN were 90.2% (95% CI 83.6% to 94.9%; n=112) and 36.1% (95% CI 31.2% to 41.3%). Conclusions Self-collected specimens for high-risk HPV messenger RNA testing demonstrated good sensitivity and negative predictive value for detecting grade 2 or higher CIN in Thai women attending the participating institutes’ colposcopy clinics. Self-collected samples performed similarly to physician-collected ones.
Article
Introduction: there is a great diversity in the profile of cancers in the world. This study set out to analyze the profile of gynecological cancer in Federal University Teaching Hospital, Owerri, [FUTHO] (former Federal Medical Centre, Owerri, Imo state, Nigeria). Methods: this was a retrospective cross sectional descriptive study of the records of women admitted in the gynecological ward in FUTHO from January 2020 to November 2022. It was analyzed using SPSS version 23.0 and reported in simple percentages for categorical variables and measures of central tendency for quantitative variables. Results: a total of 1,378 gynecological patients were admitted into the Gynaecological ward of the hospital, out of which 242 (17.6%) were cancer cases. The most common cancer over the three years in review, was ovarian, 81 (33.5%), followed by cervical, 66 (27.3%), endometrial, 65 (26.8%), choriocarcinoma, 22 (9.1%), vulvar, 6 (2.5%) and vagina, 2 (0.8%). The most common gynecological cancers in this study is very different from previous reports from Nigeria and other African countries. The pattern looks like that seen in developed countries where endometrial and ovarian cancers top the list. Conclusion: this report shows a possible change in lifestyle and improved access to cervical cancer prevention strategies. It is also assumed that all the facilities who have recorded cervical cancer as the most common cancer can actually have a similar result as ours if a more current review is done.
Chapter
Antitumor immune response requires the presence, activation, and stimulation of all lymphoid components of the immune system. An increasing number of studies on this topic have led to the recognizing that the accumulation of tumor-infiltrating lymphocytes (TILs) in gynecological cancer is prognostic for increased survival through activation of an advanced immune response.Cancer immunoediting, the interaction process between the immune system and tumor, represents a dynamic process, with TILs playing an important role in antitumor response. Cancer development may be constrained or promoted by the immune system in three specific steps: elimination, equilibrium, and escape.Recently, therapies that modulate the immune system have emerged as a new, effective, life-changing approach in several cancers. Combination of immunotherapy and traditional treatments has proved effective in preventing tumor development, thus improving both the prognosis and overall survival of cancer patients. Immunomodulatory therapies have already become standard of care for some cancers. Such an approach can possibly be extended also to gynecological cancers. Despite extensive knowledge in tumor diagnosis and treatment, new strategies are strongly required that while effective at attacking the disease, can also be more tolerable.This chapter is devoted to authors’ analysis of tumor response mechanisms and TILs action in gynecological malignancies, both from a molecular and a clinical perspective.KeywordsCervical cancerEndometrial cancerEpithelial ovarian cancerImmune systemProgrammed cell death-1 (PD-1)Tumor-infiltrating lymphocytes (TILs)
Article
Purpose: To provide perspective on patient-reported outcome measurement (PROM) instruments to adopt in patients diagnosed with gynecological cancers. Methods: A systematic search was conducted to identify PROMs developed for or applied in gynecological cancer populations. PROMs identified in more than one study subsequently underwent assessment according to the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) criteria. Results: Overall, 55 PROMs were identified within the gynecological cancer setting, and 20 were assessed according to COSMIN guidelines. Most PROMs had limited information reported, but a best fit approach was adopted to recommend a number of instruments for use in patients with gynecological cancer. Conclusion: Further study to assess the methodological quality of each PROM utilized in gynecological cancers is warranted to endorse the recommendations of this review.
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Background: The distribution of ovarian tumour characteristics differs between germline BRCA1 and BRCA2 pathogenic variant carriers and non-carriers. In this study, we assessed the utility of ovarian tumour characteristics as predictors of BRCA1 and BRCA2 variant pathogenicity, for application using the American College of Medical Genetics and the Association for Molecular Pathology (ACMG/AMP) variant classification system. Methods: Data for 10,373 ovarian cancer cases, including carriers and non-carriers of BRCA1 or BRCA2 pathogenic variants, were collected from unpublished international cohorts and consortia and published studies. Likelihood ratios (LR) were calculated for the association of ovarian cancer histology and other characteristics, with BRCA1 and BRCA2 variant pathogenicity. Estimates were aligned to ACMG/AMP code strengths (supporting, moderate, strong). Results: No histological subtype provided informative ACMG/AMP evidence in favour of BRCA1 and BRCA2 variant pathogenicity. Evidence against variant pathogenicity was estimated for the mucinous and clear cell histologies (supporting) and borderline cases (moderate). Refined associations are provided according to tumour grade, invasion and age at diagnosis. Conclusions: We provide detailed estimates for predicting BRCA1 and BRCA2 variant pathogenicity based on ovarian tumour characteristics. This evidence can be combined with other variant information under the ACMG/AMP classification system, to improve classification and carrier clinical management.
Article
Background: Neutrophil-to-lymphocyte ratio (NLR) has been described as a predictor of progression-free and overall survival, and in the field of peri-operative care it seems to be a factor that can help discriminate patients at risk of developing post-operative complications. In the present study we sought to determine whether NLR is useful as a biomarker in predictive models that aim to identify patients with gynecologic cancer undergoing surgery at risk of developing post-operative infectious morbidity. Patients and Methods: We designed a prospective cohort study that enrolled 208 patients with gynecologic cancer. Post-operative infectious morbidity was evaluated based on a 30-day follow-up interval from the procedure. Results: Forty-three patients (20.5%) developed post-operative infectious morbidity. Using an optimal cutoff value of 1.7 for the pre-operative NLR we observed that the sensitivity of the biomarker was 76.7% and the specificity 73.3% with a produced area under the curve of 0.760 (95% confidence interval [CI], 0.680-0.839). Univariable logistic regression indicated that NLR is a predictor of post-operative morbidity. Cox regression analysis revealed that NLR was the only factor that was associated with the timing of infectious morbidity (hazard ratio [HR], 1.339; 95% CI, 1.180-1.519; p < 0.001). Using random forest analysis and decision trees we achieved a diagnostic accuracy of the predictive model that exceeded 90%. Conclusions: Neutrophil-to-lymphocyte ratio may be a factor that could potentially help evaluate the risk of post-operative morbidity in patients with gynecologic cancer.
Article
Introduction: Ovarian and breast cancers are highly prevalent in the population of Jammu and Kashmir (J&K). However, case-control association studies on breast and ovarian cancers are lacking in this population. Moreover, no case-control study is available on variant rs10937405 of TP63 in breast and ovarian cancers. Thus, we designed to replicate the cancer susceptible variant rs10937405 of TP63 in ovarian and breast cancers in the population of J&K because the TP63 gene act as a tumor suppressor gene and was previously associated with various cancers. Materials and methods: This case-control association study conducted at the Shri Mata Vaishno Devi University, includes 150 breast, 150 ovarian cancer cases, and 210 healthy controls (age and sex-matched). Variant rs10937405 of the TP63 gene was determined by the TaqMan assay. Hardy-Weinberg equilibrium for the variant was assessed using the Chi-square test. The allele and genotype-specific risks were estimated by odds ratios (ORs) with 95% confidence intervals (CI). Results: In this study, variant rs10937405 of TP63 gene did not show any risk with ovarian and breast cancer with (P-value = 0.70) having OR 0.94, (0.69-1.28 at 95% CI) and (P-value = 0.16) having OR 0.80, (0.59-1.10). Discussion: Our results indicate that the variant rs10937405 of the TP63 gene did not impart any risk of breast and ovarian cancer in the population of J&K. Our results indicate that a larger sample size is needed for further statistical validation. As the study was for a particular variant, it warrants the analysis of other variants of this gene.
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Background Epithelial ovarian cancer (EOC) is one of the leading causes of cancer-related death in women. Approximately 70% of patients with EOC are diagnosed in advanced stage [The International Federation of Gynecology and Obstetrics(FIGO stage III and IV)] with an expected 5-year survival rate of 30%. Numerous studies have shown that survival with neoadjuvant chemotherapy (NACT) followed by interval debulking surgery (IDS) is noninferior to primary debulking surgery followed by chemotherapy. Materials and Methods In this retroprospective observational study, 50 patients with advanced ovarian cancer, diagnosed from January 2012 to January 2015, were included and followed-up till January 2017. Correlation of NACT with patient profile, CA125 levels, clinicopathologic parameters, progression-free survival (PFS), and treatment response was studied. Statistical analysis was performed using log-rank test and Kaplan-Meir survival plots. Results The extent of cytoreduction significantly correlated with PFS. The PFS was maximum in patients who had optimal cytoreduction (19 months) and 10 months in patients with suboptimal cytoreduction with p-value < 0.05. The survival was not significantly correlated with other parameters such as age, stage, preoperative CA125 levels, and ascites. Conclusions The extent of cytoreduction following NACT in this study was associated with statistically significant PFS advantage in patients who were able to undergo optimal cytoreduction, but not significantly correlated to other factors such as age, stage, preoperative CA125 levels, and ascites. NACT followed by interval cytoreduction is an important modality affecting survival in advanced EOC. Further studies and longer follow-up are needed to demonstrate survival advantage over standard treatment.
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The class of viruses which has the potential to cause cancer in animals, including humans, are referred to as oncogenic viruses. Generally, they are a kind of viruses with DNA or RNA genome that cause cancer, of which DNA oncogenic viruses such as HPV, HBV & EBV, contribute to about 20% of human cancers. Epidemiology of these kinds of viruses differs based on their types, like HPV is omnipresent and contributes to 4.5% of new cancer cases worldwide, HBV is more prevalent in Africa (12%) and Southeast Asia (~5%–7%), EBV in all regions, Burkitt’s lymphoma in New Guinea and equatorial Africa, NPC in china & Southeast Asia and contributes to about 0.7% of cancers worldwide, HSV and cytomegalovirus are widespread among people. It is found that globally, developing countries are mostly affected by these types of DNA oncoviruses. In DNA oncoviruses a new transforming gene that encodes functions for viral replication without any normal homologs are introduced into the cell or the expression of pre-existing genes or cellular genes gets altered. The non-permissive cells, which are the type of cells that do not allow the invading viruses to replicate inside them and are henceforth transformed by this type of transforming genes, whereas a permissive cell usually allows the replication of such viral cells, are not transformed unless the viral replicative cell gets blocked by other means. They result in the unrepaired DNA damage which is caused due to the reacting O2 species with triggering of inflammatory cascades and further can lead to alterations in the genome set and epigenetic modifications. Studies say that about 50% of cancers are caused due to infectious agents and these kinds of persistent infections will lead to Reactive Oxygen Species production, which plays a vital role in cell signaling and homeostasis. On further combining with Reactive Nitrogen Species stimulates DNA damage repair proteins. These viruses may contain oncogenes which takes control over the host cell environment and activates tumor inducing environment. Different types of viral proteins are involved in these types of viruses which account for their functions. HPV contains E5, E6 & E7 proteins (which forms a complex with Rb & p53), whereas EBV contains LMP1, EBNA1, etc., Adenoviruses contain E1A (which binds Rb), E1B & E4QRF1 (which binds p53) etc., and polyomavirus contain 3 structural proteins VP1, VP2 & VP3. Since tumor viruses cause over 20% of human cancers, it is important to interpret the association between different tumor viruses with the types of cancer. One of the most promising detection for these types of viral particles is done by electron microscopy. Many kinds of Research are going on about the associations between viral cancers & potential treatments for non-viral and genetic factors. Once the associations between the different types of cancer with the viruses are understood, these viruses can be effectively used as a potential biomarker for cancer cells.
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A paradigm transition in cancer treatment gradually moved from "one drug-one target" toward "multi-target selective drugs design", because different drugs simultaneously inhibit tumor progression differently. The underlying mechanism has encountered significant challenges, such as encapsulating chemotherapies into a nanosized particulate system, adverse side effects, and managing multidrug-resistant. To address these issues, herein we engineered the gold nanoparticles’ surfaces with cross-linked polyethylene glycol that have well-controlled morphology and further encapsulated with commonly known chemo-drugs paclitaxel and bleomycin for nanovectorization of therapeutics to the intended site and there act through the concurrent action of dual targeting mechanisms without creating undesired side effects. The structures of the nanovectorization particulate system were confirmed by various spectroscopic techniques. The efficacy of nanovectorization particulate system and non-targeted free drugs was evaluated using the human cervical adenocarcinoma cell model. Our findings indicate that this nanovectorization particulate system had synergic stimuli-responsive characteristics and unrivaled control of efficient transportation of therapeutics agents. This system meets the high demand for multiple targeting delivery and has substantial benefits across multiple fields of nanomedicine, especially in chemotherapy.
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Purpose: Intracavitary brachytherapy is one of the important methods of gynecological cancer treatment. The effect of attenuation is not considered in the dose calculation method released by the American Association of Physicists in Medicine (AAPM) Task Group No. 43 Report (TG-43). In this study, the effect of high-dose rate (HDR) brachytherapy applicators on dose distribution was measured using Gafchromic films and well-type ionization chamber. Materials and methods: A plan created by the treatment planning system was first executed using a well-type ionization chamber with a water equivalent elasto-gel in place for charge collection. Again, same plan was executed using central tandems of various angulations with different diameters of vaginal cylinders and charge collection was measured. For in vitro dose measurements this plan was also executed on tandem and vaginal cylinder assembly with Gafchromic films fixed on the surface of vaginal cylinder. Results: The results show that the central tandem when used with different vaginal cylinders resulted in increase in effective attenuation of the beam. The central tandem of 300 angulations when used with a 35-mm diameter vaginal cylinder results in maximum attenuation whereas the 0º tandem when used with 20-mm diameter vaginal cylinder results in least attenuation of the beam. Conclusion: Due to the attenuation by various applicators used in brachytherapy for the treatment of gynecological cancers, it can be concluded that the difference between practical dose and the treatment planning system calculated dose should be considered for the correct estimation of the dose to the target and the organs-at-risk.
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Multiple variants of oncogenic human papilloma viruses (HPVs) are the one of the main causes of genital cancers, most specifically cervical cancer, oral cancer, vaginal cancer along with the increasing incidences of head and neck cancers. In spite of the accessibility of numerous prophylactic vaccines against the most prevalent subtypes of oncogenic HPV, HPV-induced carcinomas are still a major public health and economic burden. However, standard therapeutical regimen involving surgery, chemotherapy radiation, and immunotherapy is coming out as an effectual adjuvant option. Here, in this book chapter, we have reviewed available literature on current immunotherapeutic interventions against HPV-associated malignancies as well as various ongoing clinical studies using immune checkpoint inhibitors, therapeutic vaccines, cell-based therapies, and novel immunotherapies which are demonstrating beneficial outcomes and could lead to substantial amelioration in the therapeutic and management of HPV-associated carcinomas.
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Human papillomaviruses (HPVs) are an important group of ubiquitous DNA viruses associated with several types of malignancies that include cervical, vulvar, vaginal, anal, penile, oropharyngeal, and esophageal cancer. HPV predominantly results in cervical cancer (70%) and oropharyngeal cancers (25%). Most of the HPV-associated malignancies are caused by high-risk HPVs, notably HPV-16 and HPV-18, while low-risk HPVs are involved in the formation of condylomas. Primarily, HPV infection occurs through sexual contact; however, evidence of HPV infections through nonsexual contact is also available. HPV genome integrates into the host cell genome and overexpresses key oncoproteins encoded by HPV genomes that play a crucial role in carcinogenesis. Oncoproteins are responsible for genomic instability, uncontrolled cell proliferation, disturbance in the cell cycle, and malignant transformation in HPV-infected cells. This chapter will primarily focus on the epidemiology and pathology of different types of cancer associated with HPV infection along with a brief elaboration on HPV-encoded oncoproteins vital for cancer development.
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Epithelial ovarian cancer (EOC) is the most lethal gynaecological cancer among women worldwide, with the 5-year survival rate ranging between 30 and 40%. Due to the asymptomatic nature of the condition, it is more likely to be diagnosed at an advanced stage, requiring an aggressive therapeutic approach. Cytoreductive surgery (CRS) along with systemic chemotherapy with paclitaxel and carboplatin has been the mainstay of the treatment in the frontline management of EOC. In recent years, neo-adjuvant chemotherapy, followed by interval CRS has become an important strategy for the management of advanced EOC. Due to the high rate of recurrence, the oncology community has begun to shift its focus to molecular-targeted agents and maintenance therapy in the frontline settings. The rationale for maintenance therapy is to delay the progression or relapse of the disease, as long as possible after first-line treatment, irrespective of the amount of residual disease. Tumours with homologous recombination deficiency (HRD) including BReast CAncer gene ( BRCA) mutations are found to be sensitive to polyadenosine diphosphate-ribose polymerase (PARP) inhibitors and understanding of HRD status has become important in the frontline setting. PARP inhibitors are reported to provide a significant improvement in progression-free survival and have an acceptable safety profile. PARP inhibitors have also been found to act regardless of BRCA status. Recently, PARP inhibitors as maintenance therapy in the frontline settings showed encouraging results in EOC; however, the results from further trials and survival data from ongoing trials are awaited for understanding the role of this pathway in treatment of EOC. This review discusses an overview of maintenance strategies in newly diagnosed EOC along with considerations for maintenance therapy in EOC with a focus on PARP inhibitors.
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Background Epithelial ovarian cancer (EOC) is one of the leading causes of cancer-related death in women. Approximately 70% of patients with EOC are diagnosed in advanced stage [The International Federation of Gynecology and Obstetrics(FIGO stage III and IV)] with an expected 5-year survival rate of 30%. Numerous studies have shown that survival with neoadjuvant chemotherapy (NACT) followed by interval debulking surgery (IDS) is noninferior to primary debulking surgery followed by chemotherapy. Materials and Methods In this retroprospective observational study, 50 patients with advanced ovarian cancer, diagnosed from January 2012 to January 2015, were included and followed-up till January 2017. Correlation of NACT with patient profile, CA125 levels, clinicopathologic parameters, progression-free survival (PFS), and treatment response was studied. Statistical analysis was performed using log-rank test and Kaplan-Meir survival plots. Results The extent of cytoreduction significantly correlated with PFS. The PFS was maximum in patients who had optimal cytoreduction (19 months) and 10 months in patients with suboptimal cytoreduction with p-value < 0.05. The survival was not significantly correlated with other parameters such as age, stage, preoperative CA125 levels, and ascites. Conclusions The extent of cytoreduction following NACT in this study was associated with statistically significant PFS advantage in patients who were able to undergo optimal cytoreduction, but not significantly correlated to other factors such as age, stage, preoperative CA125 levels, and ascites. NACT followed by interval cytoreduction is an important modality affecting survival in advanced EOC. Further studies and longer follow-up are needed to demonstrate survival advantage over standard treatment.
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Background: Ovarian cancer (OC) average lifetime risk is 1 in 70(1.4%).Ovarian cancer is diagnosed in 7300 women every year in UK and 239,000 women world wide.There are variations in incidence with ethnicity, white women have the highest incidence approximately14/100,000 where as Asian women have a lower incidence at 10/100,000. Aim: To find the frequency and different types of ovarian carcinomas in women presenting with pain lower abdomen. Methods: This cross-sectional study was conducted in the Department of Obstetrics and Gynecology, DHQ Hospital Gujranwala from1st May 2020 to 31st October 2020.A total of 282 women presenting with pain lower abdomen were included.All women underwent ultrasonography and ovarian tumors were noted as per operational definition. Patients with ovarian tumor underwent laparotomy, the specimen of tumors were collected with excision biopsies and sent for histopathological analysis. Results: The mean age of cases was 33.808±7.70 years, and the mean duration of complaint was 4.322±1.46 weeks and mean weight was 69.560±13.00 kg. Majority of the patients (82.3%) belonged to 20-40 years age groups. Ovarian Tumor was seen in 65(23%) patients. Among 65 patients with ovarian tumor, 72.3% were benign, 3.1% borderline and 24.6% were malignant. Conclusion: It was concluded that ovarian tumors were common between the 20 and 40 years of age. The frequency of Malignant neoplastic lesions was higher than the benign neoplastic lesions. Keywords: Women, Pain lower abdomen, Ovarian tumors
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Metastatic gynecological malignancies are the primary cause of cancer-related morbidity and mortality among women worldwide. Although constant advances in cancer early diagnosis and treatment have rendered gynecological cancers more manageable before metastasization, overall survival rates remain still low once cancers metastasize. Current standard strategies remain systemic chemotherapy and/or radiotherapy, along with best supportive care end enrollment in clinical trials. In addition, surgery can be considered in highly selected patients. Recently, new generation antitumor agents targeting specific molecules involved in crucial metastatic steps (detachment, migration, invasion, and adhesion) have been investigated with the aim to improve the paradigm of care and the survival rates. However, our knowledge of the exact biochemical mechanisms and pathways involved in the metastatic process is still lacking. Further research is required to find new effective multimodal strategies to prevent and treat metastases in gynecological cancers.
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Background and Objectives: Cervical cancer is the most common cancer in females and a leading cause of cancer death in developing countries. The objectives are (1) to assess knowledge regarding cervical cancer and its risk factors among female adolescents and (2) to analyze human papilloma virus (HPV) vaccine status and reasons for vaccine hesitancy. Materials and Methods: This is a cross-sectional interventional study in a women’s engineering college in Pune city, Maharashtra, India. About 230 students were administered pre-test. Educational intervention using videos on cervical cancer was done. Post-test was administered to check the change in knowledge. Statistical Analysis Used: SPSS software is used to calculate percentages and to apply the χ2 test. Results: Most participants had poor knowledge about cervical cancer. About 52% and 57% of the students did not know the cause and mode of spread of HPV. Only 15% were aware about vaccine. Unawareness was a major barrier to HPV vaccination. Conclusion: A need to empower females by educating them about cervical cancer was realized. The risk factors for this malignancy are preventable, and educational intervention can go a long way in raising awareness. Keywords: Cervical cancer, health education, human papilloma virus, vaccination
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Implementation of Enhanced Recovery After Surgery (ERAS) protocols in gynecology-oncology has resulted in improved perioperative outcomes. However, ERAS does not include preoperative interventions to address the comorbidities, malnutrition, weight loss/obesity, decreased functional capacity and high degree of anxiety and depression that are present in the gynecology-oncology patients. The amalgamation of these risk factors with the surgical stress response and chemoradiotherapy-related toxicities is associated with worse postoperative functional capacity and impaired quality of life. Not surprisingly, surgical-related decline in physical fitness is one of the most distressing symptoms reported by cancer patients. Restoring pre-treatment physical status and accelerating recovery can be done through prehabilitation. Prehabilitation is a multimodal program combining exercise, nutrition and psychological interventions to strengthen patients physically and mentally before surgery by addressing modifiable risk factors during the preoperative period thereby filling this existing gap. It has shown promising results in the colorectal and thoracic surgery populations. This paper elaborates on risk factors specific to the gynecology-oncology population, highlights selection criteria that should prompt referral to a prehabilitation program and advocates for the implementation of these programs in this population.
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Infection with human papilloma virus (HPV) is the main cause of cervical cancer, but the risk associated with the various HPV types has not been adequately assessed. We pooled data from 11 case-control studies from nine countries involving 1918 women with histologically confirmed squamous-cell cervical cancer and 1928 control women. A common protocol and questionnaire were used. Information on risk factors was obtained by personal interviews, and cervical cells were collected for detection of HPV DNA and typing in a central laboratory by polymerase-chain-reaction-based assays (with MY09/MY11 and GP5+/6+ primers). HPV DNA was detected in 1739 of the 1918 patients with cervical cancer (90.7 percent) and in 259 of the 1928 control women (13.4 percent). With the GP5+/6+ primer, HPV DNA was detected in 96.6 percent of the patients and 15.6 percent of the controls. The most common HPV types in patients, in descending order of frequency, were types 16, 18, 45, 31, 33, 52, 58, and 35. Among control women, types 16, 18, 45, 31, 6, 58, 35, and 33 were the most common. For studies using the GP5+/6+ primer, the pooled odds ratio for cervical cancer associated with the presence of any HPV was 158.2 (95 percent confidence interval, 113.4 to 220.6). The odds ratios were over 45 for the most common and least common HPV types. Fifteen HPV types were classified as high-risk types (16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 68, 73, and 82); 3 were classified as probable high-risk types (26, 53, and 66); and 12 were classified as low-risk types (6, 11, 40, 42, 43, 44, 54, 61, 70, 72, 81, and CP6108). There was good agreement between our epidemiologic classification and the classification based on phylogenetic grouping. In addition to HPV types 16 and 18, types 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 68, 73, and 82 should be considered carcinogenic, or high-risk, types, and types 26, 53, and 66 should be considered probably carcinogenic.
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Vaccination against the most common oncogenic human papillomavirus (HPV) types, HPV-16 and HPV-18, could prevent development of up to 70% of cervical cancers worldwide. We did a randomised, double-blind, controlled trial to assess the efficacy, safety, and immunogenicity of a bivalent HPV-16/18 L1 virus-like particle vaccine for the prevention of incident and persistent infection with these two virus types, associated cervical cytological abnormalities, and precancerous lesions. We randomised 1113 women between 15-25 years of age to receive three doses of either the vaccine formulated with AS04 adjuvant or placebo on a 0 month, 1 month, and 6 month schedule in North America and Brazil. Women were assessed for HPV infection by cervical cytology and self-obtained cervicovaginal samples for up to 27 months, and for vaccine safety and immunogenicity. In the according-to-protocol analyses, vaccine efficacy was 91.6% (95% CI 64.5-98.0) against incident infection and 100% against persistent infection (47.0-100) with HPV-16/18. In the intention-to-treat analyses, vaccine efficacy was 95.1% (63.5-99.3) against persistent cervical infection with HPV-16/18 and 92.9% (70.0-98.3) against cytological abnormalities associated with HPV-16/18 infection. The vaccine was generally safe, well tolerated, and highly immunogenic. The bivalent HPV vaccine was efficacious in prevention of incident and persistent cervical infections with HPV-16 and HPV-18, and associated cytological abnormalities and lesions. Vaccination against such infections could substantially reduce incidence of cervical cancer.
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Cervical cancer is an important public health problem among adult women in developing countries in South and Central America, sub-Saharan Africa, and south and south-east Asia. Frequently repeated cytology screening programmes--either organized or opportunistic--have led to a large decline in cervical cancer incidence and mortality in developed countries. In contrast, cervical cancer remains largely uncontrolled in high-risk developing countries because of ineffective or no screening. This article briefly reviews the experience from existing screening and research initiatives in developing countries. Substantial costs are involved in providing the infrastructure, manpower, consumables, follow-up and surveillance for both organized and opportunistic screening programmes for cervical cancer. Owing to their limited health care resources, developing countries cannot afford the models of frequently repeated screening of women over a wide age range that are used in developed countries. Many low-income developing countries, including most in sub-Saharan Africa, have neither the resources nor the capacity for their health services to organize and sustain any kind of screening programme. Middle-income developing countries, which currently provide inefficient screening, should reorganize their programmes in the light of experiences from other countries and lessons from their past failures. Middle-income countries intending to organize a new screening programme should start first in a limited geographical area, before considering any expansion. It is also more realistic and effective to target the screening on high-risk women once or twice in their lifetime using a highly sensitive test, with an emphasis on high coverage (>80%) of the targeted population. Efforts to organize an effective screening programme in these developing countries will have to find adequate financial resources, develop the infrastructure, train the needed manpower, and elaborate surveillance mechanisms for screening, investigating, treating, and following up the targeted women. The findings from the large body of research on various screening approaches carried out in developing countries and from the available managerial guidelines should be taken into account when reorganizing existing programmes and when considering new screening initiatives.
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In health services planning, in addition to the basic measures of disease occurrence incidence and mortality, other indexes expressing the demand of care are also required to develop strategies for service provision. One of these is prevalence of the disease, which measures the absolute number, and relative proportion in the population, of individuals affected by the disease and that require some form of medical attention. For most cancer sites, cases surviving 5 years from diagnosis experience thereafter the same survival as the general population, so most of the workload is therefore due to medical acts within these first 5 years. This article reports world-wide estimates of 1-, 2-3- and 4-5-year point prevalence in 1990 in the population aged 15 years or over, and hence describes the number of cancer cases diagnosed between 1986 and 1990 who were still alive at the end of 1990. These estimates of prevalence at 1, 2-3 and 4-5 years are applicable to the evaluation of initial treatment, clinical follow-up and point of cure, respectively, for the majority of cancers. We describe the computational procedure and data sources utilised to obtain these figures and compare them with data published by 2 cancer registries. The highest prevalence of cancer is in North America with 1.5% of the population affected and diagnosed in the previous 5 years (about 0.5% of the population in years 4-5 and 2-3 of follow-up and 0.4% within the first year of diagnosis). This corresponds to over 3.2 million individuals. Western Europe and Australia and New Zealand show very similar percentages with 1.2% and 1.1% of the population affected (about 3.9 and 0.2 million cases respectively). Japan and Eastern Europe form the next batch with 1.0% and 0.7%, followed by Latin America and the Caribbean (overall prevalence of 0.4%), and all remaining regions are around 0.2%. Cancer prevalence in developed countries is very similar in men and women, 1.1% of the sex-specific population, while in developing countries the prevalence is some 25% greater in women than men, reflecting a preponderance of cancer sites with poor survival such as liver, oesophagus and stomach in males. The magnitude of disease incidence is the primary determinant of crude prevalence of cases diagnosed within 1 year so that differences by region mainly reflect variation in risk. In the long-term period however different demographic patterns with long-life expectancy in high-income countries determine a higher prevalence in these areas even for relatively uncommon cancer sites such as the cervix.
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It is uncertain whether male circumcision reduces the risks of penile human papillomavirus (HPV) infection in the man and of cervical cancer in his female partner. We pooled data on 1913 couples enrolled in one of seven case-control studies of cervical carcinoma in situ and cervical cancer in five countries. Circumcision status was self-reported, and the accuracy of the data was confirmed by physical examination at three study sites. The presence or absence of penile HPV DNA was assessed by a polymerase-chain-reaction assay in 1520 men and yielded a valid result in the case of 1139 men (74.9 percent). Penile HPV was detected in 166 of the 847 uncircumcised men (19.6 percent) and in 16 of the 292 circumcised men (5.5 percent). After adjustment for age at first intercourse, lifetime number of sexual partners, and other potential confounders, circumcised men were less likely than uncircumcised men to have HPV infection (odds ratio, 0.37; 95 percent confidence interval, 0.16 to 0.85). Monogamous women whose male partners had six or more sexual partners and were circumcised had a lower risk of cervical cancer than women whose partners were uncircumcised (adjusted odds ratio, 0.42; 95 percent confidence interval, 0.23 to 0.79). Results were similar in the subgroup of men in whom circumcision was confirmed by medical examination. Male circumcision is associated with a reduced risk of penile HPV infection and, in the case of men with a history of multiple sexual partners, a reduced risk of cervical cancer in their current female partners.
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Cervical cancer remains the second most common cancer in women worldwide and the most frequent in developing countries. Pre-neoplasic cervical lesions represent an additional burden in countries where screening is widespread. The human papillomavirus (HPV) prevalence and type distribution in normal smears and in cancer specimens are being described and show relatively small international variation. State-of-the-art detection techniques have unequivocally shown that HPV-DNA can be detected in 95% to 100% of adequate specimens of cervical cancer, supporting the claim that HPV is the necessary cause. The odds ratios for cervical cancer related to a cross sectional detection of HPV-DNA range from 50 to several hundred in all studies. The risk for any of 15 high-risk types is not statistically different from the risk reported for HPV16. The estimates of the attributable fraction range from 90% to 98%. Additional work should be done in providing information on incidence of cervical cancer and on HPV infection in areas where the disease is common. Theoretical work including modeling of the incidence could be of potential use in the evaluation of the existing and novel preventive strategies. Research is currently being conducted on the mechanisms of HPV carcinogenesis. These include the determinants of the systemic and cellular immune response to the viral infection, the interaction between the host and the virus and the relevance of the different strains and variants of the HPV viral types. Technology developments in this area suitable for epidemiological studies are needed.
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The impact of a single round of screening of visual inspection with acetic acid (VIA) on cervical cancer incidence and mortality was investigated in a cluster randomized trial in south India. Women 30-59 years of age in 113 clusters in Dindigul District were randomized to VIA screening (57 clusters, 48,225 women) by nurses and to a control group (56 clusters, 30,167 women). 30,577 eligible women were screened between May 2000 and April 2003; 2,939 (9.6%) screen-positive women were investigated with colposcopy by nurses and 2,777 (9.1%) women had biopsy. CIN 1 was diagnosed in 1,778 women, CIN 2-3 lesions were found in 222, and there were 69 screen detected invasive cervical cancers. The detection rates of lesions per 1,000 screened women were 58.2 for CIN 1, 7.3 for CIN 2-3, and 2.3 for invasive cancer. The detection rate of high-grade lesions in our study was 2-3-fold higher than those observed in repeatedly screened populations in developed countries. 71% of women with CIN 1 and 80% of those with CIN 2-3 lesions accepted cryotherapy provided by nurses and surgical treatment by mid-level clinicians. Overall, 97 and 34 incident cervical cancer cases were observed in the intervention and control arms, respectively. The intervention arm accrued 124,144 person years and the control arm accrued 90,172 during the study period. The age standardized cervical cancer incidence rates were 92.4/100,000 person-years in the intervention and 43.1/100,000 in the control arms. In the screened arm, 35.0% of cases were in Stage I as opposed to none in the control arm. The preliminary findings from our study indicate that not only is a VIA-based screening programme feasible, safe and acceptable to a population in rural settings, it also results in early detection of cervical neoplasia.
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Human papillomavirus (HPV) vaccines for the prevention of cervical cancer have produced encouraging results in recent clinical trials, and expectations are high that one or more vaccines will be licensed for commercial distribution within the next five years. The availability of an HPV vaccine would raise several implementation issues that must be addressed if the vaccine is to achieve the coverage necessary to significantly reduce the incidence of cervical cancer. The main implementation issues will differ between developing countries, where cervical cancer is often a leading cause of cancer deaths in women, and developed countries, where cervical cancer screening programmes have already substantially reduced the number of deaths from cervical cancer.
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Epidemiological data on the occurrence of cancer in sub-Saharan Africa are sparse, and population-based cancer survival data are even more difficult to obtain due to various logistic difficulties. The population-based Cancer Registry of Kampala, Uganda, has followed up the vital status of all registered cancer patients with one of the 14 most common forms of cancer, who were diagnosed and registered between 1993 and 1997 in the study area. We report 5-year absolute and relative survival estimates of the Ugandan patients and compare them with those of black American patients diagnosed in the same years and included in the SEER Program of the United States. In general, the prognosis of cancer patients in Uganda was very poor. Differences in survival between the two patient populations were particularly dramatic for those cancer types for which early diagnosis and effective treatment is possible. For example, 5-year relative survival was as low as 8.3% for colorectal cancer and 17.7% for cervical cancer in Uganda, compared with 54.2 and 63.9%, respectively, for black American patients. The collection of good-quality follow-up data was possible in the African environment. The very poor prognosis of Ugandan patients is most likely explained by the lack of access to early diagnosis and treatment options in the country. On the policy level, the results underscore the importance of the consistent application of the national cancer control programme guidelines as outlined by the World Health Organization.
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More than one in 20 female cancers in Europe are of the endometrium. Surveillance of incidence rates is imperative given the rapidly changing profile in the prevalence and distribution of the underlying determinants. This study presents an analysis of observed and age-period-cohort-modeled trends in 13 European countries. There were increasing trends among postmenopausal women in many Northern and Western countries. Denmark and possibly France and Switzerland were exceptions, with decreasing trends in postmenopausal women. In premenopausal and perimenopausal women, declines were observed in Northern and Western Europe, most evidently in Denmark, Sweden, and the United Kingdom, affecting consecutive generations born after 1925. These contrast with the increasing trends regardless of menopausal age in some Southern and Eastern European countries, particularly Slovakia and Slovenia. These observations provide evidence of changes in several established risk factors over time and have implications for possible primary prevention strategies. In postmenopausal women, changes in reproductive behavior and prevalence of overweight and obesity may partially account for the observed increases, as well as hormone replacement therapy use in certain countries. Combined oral contraceptive use may be responsible for the declines observed among women aged <55 years. Whereas there are some prospects for chemoprevention in premenopausal women as oral contraceptive use becomes more widespread in Europe, increases in obesity and decreases in fertility imply that endometrial cancer in postmenopausal women will become a more substantial public health problem in the future.
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Population-based cancer registries from Algeria, China, Costa Rica, Cuba, India, the Philippines, and Thailand are collaborating with the International Agency for Research on Cancer in a study of cancer survival in developing countries. Comparisons with the SEER program results of the National Cancer Institute in the United States, and the EUROCARE study of survival in European countries revealed considerable differences in the survival of patients with certain tumors associated with intensive chemotherapeutic treatment regimes (Hodgkin's disease and testicular tumors), more modest differences in the survival of patients with tumors for which early diagnosis and treatment confer an improved prognosis (carcinomas of the large bowel, breast, and cervix), and only slight differences for tumors associated with poor prognosis (carcinomas of the stomach, pancreas, and lung). With limited resources to meet the challenge of the increasing incidence of cancer expected in the next few decades, health authorities in developing countries should be aware of the importance of investing in a range of cancer control activities, including primary prevention and early detection programs as well as treatment. Cancer 1996; 78:2461-4.
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Time trends in the incidence of cervical adenocarcinoma and adenosquamous cell carcinomas during the period 1973–1991 were examined using data provided by 60 population-based cancer registries from 32 defined populations in 25 countries. Three components of the incidence trend were studied: age, calendar period of diagnosis and birth cohort. Cumulative incidence rates per 1,000 for 2 groups with age ranges 25–49 and 50–74 years were calculated from the model that best described the incidence data. There was a significant increase in the cumulative incidence of cervical adenocarcinomas in women born in the mid-1930s and in successive cohorts thereafter in some populations in the United States (whites and Hispanic women), Australia, New Zealand (non-Maori), England, Scotland, Denmark, Slovenia, Slovakia and Japan (Osaka) and among Chinese women in Singapore, with a general decline in the incidence in women born in earlier periods. In Sweden and Slovenia there is a suggestion of an increasing trend in both age groups. A decrease in incidence in both age groups was apparent in Finland, France and Italy. There were no changes in incidence in 24 registries covering other European, Asian and black populations in the United States. Part of the increase may be attributable to an increasing prevalence of human papillomavirus infection, and part to improvements in screening. Int. J. Cancer 75:536–545, 1998.© 1998 Wiley-Liss, Inc.
Article
Objective: The aim of this study was to compare the age-adjusted incidence and survival for invasive adenocarcinoma and squamous cell carcinoma of the uterine cervix using population-based data. Methods: The SEER database was used to identify all cases of cervical cancer registered between 1973 and 1996. Stage was defined as localized, regional, or distant. Age-adjusted incidence rates were analyzed statistically using the Jonchkeere-Terpstra exact test for trends. Relative and observed survival rates, respectively, were compared using z tests and log-rank tests. Results: The age-adjusted incidence rates per 100,000 for all invasive cervical cancers decreased by 36.9% over 24 years [12.35 (1973-1977) vs 7.79 (1993-1996)]. Similarly, the age-adjusted incidence rates for squamous cell carcinoma declined by 41.9% [9.45 (1973-1977) vs 5.49 (1993-1996)]. In contrast, the age-adjusted incidence rates for adenocarcinoma increased by 29.1% [1.34 (1973-1977) vs 1.73 (1993-1996)]. The proportion of adenocarcinoma increased 107.4% relative to all cervical cancer, 95.2% relative to squamous cell carcinoma, and 49.3% relative to the population of women at risk [10. 8% vs 22.4% (P < 0.001), 12.4% vs 24.0% (P < 0.001), and 1.40 vs 2. 09 per 100,000 women (P < 0.001), respectively]. Observed survival rates for adenocarcinoma vs squamous cell carcinoma were poorer for regional (P = 0.04), but not localized or distant disease. Conclusions: Over the past 24 years, the incidence of all cervical cancer and squamous cell carcinoma has continued to decline. However, the proportion of adenocarcinoma relative to squamous cell carcinoma and to all cervical cancers has doubled, and the rate of adenocarcinoma per population at risk has also increased. These results suggest that current screening practices in the United States are insufficient to detect a significant proportion of adenocarcinoma precursor lesions.
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It has been accepted generally that the cancer registry has more of a 'back room' than a 'front line' role in cancer control, its particular responsibilities lying in description of cancer patterns, care, and outcome, in monitoring these variables in relation to control activities, and in providing a research database--often, for others to utilize. While readily justifiable, this prevailing concept of the cancer registry's role may not be sustainable in times of economic restraint. A survey of members of the International Association of Cancer Registries showed that most registries fit the accepted mold. Some, however, extend beyond it, particularly in the direct conduct of epidemiologic research and in the implementation of control programs, particularly screening. Sixteen percent appeared only to be collecting incidence statistics and may be at risk of economic rationalization. It would be consonant with their basic role and skills, and promote more rational cancer control, if cancer registries were to take on an expanded role, including direct participation in epidemiologic research, evaluation of interventions against cancer at the population level, situation analysis and cancer control planning, and implementation of aspects of cancer control--particularly coordination of screening--and monitoring the performance of cancer control programs. This expanded role could become the responsibility of specialized cancer control units of which cancer registration would be the central function.
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The American Cancer Society's Department of Epidemiology and Statistics reports its 29th annual compilation of cancer incidence, survival and mortality data for the United States and around the world.
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BACKGROUND. Ovarian cancer is the fifth most common cause of cancer-related death in American women. The median age at diagnosis is about 62 years; incidence rises rapidly after age 60. Pelvic examination has been the primary method for detection of ovarian carcinoma. It is insensitive for the detection of early disease, however: most women present with disease beyond the pelvis (Stages III and IV) and are not curable with existing techniques. Two new technologies may be useful as screening tools for earlier detection of ovarian cancer. CA 125 is an antigenic determinant expressed on an ovarian cancer cell line. Transvaginal ultrasound (TVUS) images the ovaries from within the vagina and can be performed by a technician in about 10 minutes. In small preoperative studies of women with ovarian masses, serum CA 125 levels have been elevated (typically above 35 U/ml) in over two-thirds of cases and in up to 50% of Stage I cases. The test is not absolutely specific: elevations have been reported with pregnancy, endometriosis, menstruation, benign ovarian tumors, and with cancers of the breast, colon, pancreas, lung, stomach, and liver. Nevertheless, the specificity of CA 125 in postmenopausal women has been reported at about 95% or more. TVUS provides higher resolving power for ovarian abnormalities than transabdominal ultrasound or physical examination; however, experience with it is limited. CA 125 and TVUS may be complementary. CONCLUSIONS. For these reasons, the National Cancer Institute is planning a randomized trial of all three tests versus routine medical care in women of ages 60-74 years. This is part of a larger trial to determine the efficacy of screening for lung, colorectal, and ovarian cancers in women, and for lung, colorectal, and prostatic cancers in men. Seventy-four thousand women will be randomized in the study.
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Huge differences in incidence rates of invasive cervical cancer occur among populations. These differences reflect the influences of both etiological environmental factors and removal of precursor lesions detected upon screening. The purposes of this article are (i) to describe similarities and differences in the shapes and magnitudes of age-specific incidence rates of invasive cervical cancer before screening had an effect, (ii) to provide baseline data for further global study of screening effects, and (iii) to provide baseline incidence data for the design of optimal screening programs. To eliminate the impact of screening effects, we have selected age-specific incidence rates from times when and from populations in which screening was insignificant. The selected rates were suitably scaled and compared regarding age at onset of increase in incidence, age at peak incidence, and rate of subsequent decline. Despite a 16-fold difference in incidence rates, all curves had the same basic structure, with an increase to a peak followed by a decline or a plateau. Although all populations but one had an onset around age 25, 7 European countries showed an earlier peak age (mean = 46 vs. 59) and a more rapid decline after the peak than most other populations. The common basic shape of the age-specific incidence curve, overall, suggests a relatively similar development of invasive cervical cancer in different populations. These results illustrate the underlying similarities in the markedly different age-specific incidence rates of invasive cervical cancer. They also provide a basis for studying screening effects and for optimizing screening programs in specific geographic areas.
Article
The value of screening for ovarian cancer is uncertain. We did a pilot randomised trial to assess multimodal screening with sequential CA 125 antigen and ultrasonography. Postmenopausal women aged 45 years or older were randomised to a control group (n=10,977) or screened group (n=10,958). Women randomised to screening were offered three annual screens that involved measurement of serum CA 125, pelvic ultrasonography if CA 125 was 30 U/mL or more, and referral for gynaecological opinion if ovarian volume was 8.8 mL or more on ultrasonography. All women were followed up to see whether they developed invasive epithelial cancers of the ovary or fallopian tube (index cancers). Of 468 women in the screened group with a raised CA 125, 29 were referred for a gynaecological opinion; screening detected an index cancer in six and 23 had false-positive screening results. The positive predictive value was 20.7%. During 7-year follow-up, ten further women with index cancers were identified in the screened group and 20 in the control group. Median survival of women with index cancers in the screened group was 72.9 months and in the control group was 41.8 months (p=0.0112). The number of deaths from an index cancer did not differ significantly between the control and screened groups (18 of 10,977 vs nine of 10,958, relative risk 2.0 [95% CI 0.78-5.13]). These results show that a multimodal approach to ovarian cancer screening in a randomised trial is feasible and justify a larger randomised trial to see whether screening affects mortality.
Article
Africa is the least developed continent as regards radiation oncology resources. The documented ASR of cancer is of the order of 1 to 2 per 1000. With improving health care this is becoming more significant. This review was undertaken to help develop priorities for the region. Radiation Oncology departments in Africa were identified and a survey of their equipment performed. These were compared to the reported situation in 1991. Population tables for the year 2000 were compared to available megavoltage machines. Of 56 countries in Africa, only 22 are confidently known to have megavoltage therapy concentrated in the southern and northern extremes of the continent. The 155 megavoltage machines operating represents over 100% increase over the past 8 years. The population served by each megavoltage machine ranges from 0.6 million to 70 million per machine. Overall, only 50% of the population have some access to Radiation Oncology services. Progress has been made in initiating radiation oncology in Ghana, Ethiopia and Namibia. There has been some increase in machines in Algeria, Egypt, Libya, Morocco and Tunisia. However, a large backlog exists for basic radiation services.
Article
The Singapore Cancer Registry has provided comprehensive population-based incidence data since 1968. This paper describes the population-based survival analysis of the registry data. All invasive primary cancers diagnosed from January 1, 1968 to December 31, 1992 were passively followed up until December 31, 1997. Only 5.8% were lost to follow-up. Cumulative and observed survival rates were calculated using Hakulinen's method. Overall 5-year relative survival rates have increased dramatically over the 25-year period in both genders. Significant increases are seen with nasopharynx, stomach and colo-rectum cancers, non-Hodgkin's lymphoma, leukemias and cancers of the testis, cervix, ovaries and breast. When compared with the Surveillance, Epidemiology and End Results (SEER) rates in the United States, the 5-year relative survival rates in Singapore are generally lower. However, the rate of change between the two countries is fairly similar. On the average, the rates are 10 to 15 years behind the SEER rates and 5 to 10 years behind Finland, Switzerland and Japan, but they are close to the UK rates. The age-standardized 5-year survival rate for Singapore is higher for most sites compared with other developing countries like Qidong (China), Madras (India), Bombay (India) and Chiang Mai (Thailand). The 25-year trend in cancer survival in Singapore showed two extreme groups: those showing no change and those showing significant improvements. Reducing the incidence of cancers belonging to the first group remains the only viable mode of cancer control. For cancers in the second group, improvement in survival is due to a combination of successful early detection measures and effective treatment services in Singapore.
Article
Resources for radiation therapy in Asian and Pacific countries were analyzed to obtain a better understanding of the status of radiation oncological practice in the region. The data were obtained mainly through surveys on the availability of major equipment and personnel which were conducted through an International Atomic Energy Agency regional project. The study included 17 countries in South Asia, South East Asia, East Asia and Australasia. Data were related to national populations and economic and a general health care indices. Large differences in equipment and personnel among countries were demonstrated. The availability of both teletherapy and brachytherapy was related to the economic status of the countries. The shortage of teletherapy machines was evident in more countries than that of brachytherapy. Many departments were found to treat patients without simulators or treatment planning systems. The number of radiation oncologists standardized by cancer incidence of a country did not correlate well with economic status. There were significant deficiencies in the availability of all components of radiation therapy in the analyzed countries. The deficiencies were linked predominantly to the economic status of the country. Cognisance should be taken of the specific shortfalls in each country to ensure that expansion or any assistance offered appropriately match its needs and can be fully utilized. The information on the resources currently available for radiation oncological practice in the region presented in this paper provides a valuable basis for planning of development aid programs on radiation therapy.
Article
Approximately 20 percent of adults become infected with human papillomavirus type 16 (HPV-16). Although most infections are benign, some progress to anogenital cancer. A vaccine that reduces the incidence of HPV-16 infection may provide important public health benefits. In this double-blind study, we randomly assigned 2392 young women (defined as females 16 to 23 years of age) to receive three doses of placebo or HPV-16 virus-like-particle vaccine (40 microg per dose), given at day 0, month 2, and month 6. Genital samples to test for HPV-16 DNA were obtained at enrollment, one month after the third vaccination, and every six months thereafter. Women were referred for colposcopy according to a protocol. Biopsy tissue was evaluated for cervical intraepithelial neoplasia and analyzed for HPV-16 DNA with use of the polymerase chain reaction. The primary end point was persistent HPV-16 infection, defined as the detection of HPV-16 DNA in samples obtained at two or more visits. The primary analysis was limited to women who were negative for HPV-16 DNA and HPV-16 antibodies at enrollment and HPV-16 DNA at month 7. The women were followed for a median of 17.4 months after completing the vaccination regimen. The incidence of persistent HPV-16 infection was 3.8 per 100 woman-years at risk in the placebo group and 0 per 100 woman-years at risk in the vaccine group (100 percent efficacy; 95 percent confidence interval, 90 to 100; P<0.001). All nine cases of HPV-16-related cervical intraepithelial neoplasia occurred among the placebo recipients. Administration of this HPV-16 vaccine reduced the incidence of both HPV-16 infection and HPV-16-related cervical intraepithelial neoplasia. Immunizing HPV-16-negative women may eventually reduce the incidence of cervical cancer.
Article
Each year, the American Cancer Society estimates the number of new cancer cases and deaths expected in the United States in the current year, and compiles the most recent data on cancer incidence, mortality, and survival by using incidence data from the National Cancer Institute (NCI) and mortality data from the National Center for Health Statistics (NCHS). Incidence and death rates are age adjusted to the 2000 US standard population. In the year 2003, we estimate that 1,334,100 new cases of cancer will be diagnosed, and 556,500 people will die from cancer in the United States. Age-adjusted cancer death rates declined in both males and females in the 1990s, though the magnitude of decline is substantially higher in males than in females. In contrast, incidence rates continued to increase in females while stabilizing in males. African-American males showed the largest decline for mortality. However, African Americans still carry the highest burden of cancer with diagnosis of cancer at a later stage and poorer survival within each stage compared with Whites. In spite of the continued decline in cancer death rates in the most recent time period, the total number of recorded cancer deaths in the United States continues to increase slightly due to the aging and expanding population.
Article
Despite its history of success in cancer screening, Pap cytology has important limitations, particularly its high false-negative rate, which carries important public health implications. Since the mid-1990s, there has been substantial interest in the use of human papillomavirus (HPV) DNA testing in cervical cancer screening under the premise that the testing of cervical cells for the causative agent of cervical cancer could have acceptable screening performance, while being more reproducible in clinical practice than Pap cytology. There have been several studies assessing the utility of HPV testing compared with the Pap test as a screening tool. These studies varied widely in lesion-outcome definition and in methodology. No studies were based on cervical cancer incidence or mortality. No randomized controlled trials have yet been published; all of the studies were based on concomitant testing for HPV and cytology or additional tests. HPV testing has greater sensitivity (average, 27%) but somewhat lower specificity (average, 8%) than Pap cytology for detecting high-grade lesions. Screening of women aged 30 years or older tends to improve test specificity, but it also does so for cytology. The combination of cytology and HPV attained high-negative predictive values, which suggests that their joint use could allow screening intervals to be safely increased, thus lowering costs. Although evidence is yet to come from long-term studies and from randomized controlled trials with high-grade lesions and invasive cancer as outcomes, HPV testing is clearly one of the most promising new technologies and has the potential to improve cervical cancer-screening effectiveness in many settings.
Article
Gestational trophoblastic diseases (GTD) consist of a group of neoplastic disorders arising from placental trophoblastic tissue after normal or abnormal fertilisation. The WHO classification of GTD includes hydatidiform mole, invasive mole, choriocarcinoma, placental site trophoblastic tumour, and miscellaneous and unclassified trophoblastic lesions. GTD have a varying potential for local invasion and metastases and they generally respond to chemotherapy. Broad variations in the distribution of GTD exist worldwide, with higher frequencies in some parts of Asia, the Middle East and Africa, but the extent to which they can be attributed to methodological difficulties in obtaining accurate rates is unclear. Maternal age and a history of GTD have been established as strong risk factors for hydatidiform mole and choriocarcinoma. We review published data on the worldwide distribution of GTD, original data from cancer- registry-based statistics on choriocarcinoma, and major aetiological hypotheses, including parental age, AB0 blood groups, history of GTD, reproductive factors, oral contraceptive use, and other environmental factors.
Article
This paper provides the first comprehensive population based cancer survival estimates from the African continent. Five-year absolute and relative survival estimates are presented for black and white Zimbabwean patients diagnosed with cancer in Harare, Zimbabwe between the years 1993 and 1997. The survival of black Zimbabwean cancer patients are among the lowest ever reported from population based cancer registries. For most cancer sites, white Zimbabwean patients have much higher survival than black Zimbabweans, except for lung and colorectal cancer, for which the estimates are similarly poor. Race specific comparisons to cancer patients in the United States show that Zimbabwean patients have much lower survival than American cancer patients and that the gap between black Zimbabwean patients and black American patients is broader than between white Zimbabwean and white American patients. Access to and the ability to pay for medical care may be a very important barrier to better survival for the majority of black Zimbabwean patients and the most important cause for the very low cancer survival in this population.
Article
Estimates of the worldwide incidence, mortality and prevalence of 26 cancers in the year 2002 are now available in the GLOBOCAN series of the International Agency for Research on Cancer. The results are presented here in summary form, including the geographic variation between 20 large "areas" of the world. Overall, there were 10.9 million new cases, 6.7 million deaths, and 24.6 million persons alive with cancer (within three years of diagnosis). The most commonly diagnosed cancers are lung (1.35 million), breast (1.15 million), and colorectal (1 million); the most common causes of cancer death are lung cancer (1.18 million deaths), stomach cancer (700,000 deaths), and liver cancer (598,000 deaths). The most prevalent cancer in the world is breast cancer (4.4 million survivors up to 5 years following diagnosis). There are striking variations in the risk of different cancers by geographic area. Most of the international variation is due to exposure to known or suspected risk factors related to lifestyle or environment, and provides a clear challenge to prevention.
Article
The impact of screening by visual inspection with acetic acid (VIA), cytology or HPV testing on cervical cancer incidence and mortality is investigated in a cluster randomized controlled trial in India. We report findings after the screening phase, when 52 clusters, with a total of 142,701 women aged 30-59 years in Osmanabad District, India, were randomized into 4 arms for a single round of screening by trained midwives with either VIA, cytology or HPV testing as well as a control group. All laboratory tests were done locally. Test-positive women underwent investigations (colposcopy/biopsy) and treatment in the base hospital. Data on participation, test positivity, positive predictive value and detection rates of cervical neoplasia were analyzed using cluster design methodology. Of the eligible women, 72-74% were screened. Test positivity rates were 14.0% for VIA, 7.0% for cytology and 10.3% for HPV. The detection rate of high-grade lesions was similar in all intervention arms (0.7% for VIA, 1.0% for cytology and 0.9% for HPV testing) (p = 0.06, Mann-Whitney test). While the detection rate for VIA dropped to 0.5% with declining test positivity during the course of the study, it remained constant for cytology and HPV testing. Over 85% of women with high-grade lesions received treatment. Our results show that a high level of participation and good-quality cytology can be achieved in low-resource settings. VIA is a useful alternative but requires careful monitoring. Detection rates obtained by HPV testing were similar to cytology, despite higher investments.
Article
The objective of cervical cancer screening is to reduce cervical cancer incidence and mortality by detecting and treating precancerous lesions. Conventional cytology is the most widely used cervical cancer screening test. Although cytology has been effective in reducing the incidence of and mortality from cervical cancer in developed countries in both opportunistic and--more dramatically--organized national programs, it has been less successful and largely ineffective in reducing disease burden in low-resource settings where it has been implemented. Liquid-based cytology, testing for infection with oncogenic types of human papillomaviruses, visual inspection with 3-5% acetic acid, magnified visual inspection with acetic acid, and visual inspection with Lugol's iodine have been evaluated as alternative tests. Their test characteristics, and the applications and limitations in screening, are discussed with an emphasis on the work of the Alliance for Cervical Cancer Prevention over the past 5 years.