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Baseman JG, Koutsky LA.. The epidemiology of human papillomavirus infections. J Clin Virol 32: S16-S24
Abstract
Infection with oncogenic human papillomavirus (HPV) types is a necessary cause of cervical cancer, the second most frequently occurring cancer in women worldwide. Rates of acquisition of HPV are high, particularly among sexually active young adults. Reported estimates of incident HPV infection among initially negative women have reached as high as 60% over a 5-year follow-up period. In this article, we review the epidemiology of HPV infection. In addition to estimates of disease frequency, we highlight risk factors for HPV infection, including the number of lifetime sex partners, which is the most salient risk factor. We discuss significant issues surrounding the natural history of HPV infection, including viral persistence versus clearance, immune response, development of lesions and development of cancer. Finally, we discuss strategies for preventing HPV infection.
... Kırktan fazla HPV tipi insanlarda anogenital bölge infeksiyonlarına neden olmaktadır ve infeksiyon etkeni olan HPV tipi serviks kanseri gelişmesinde iyi tanımlanmış bir risk faktörüdür [22] . Servikal kanser ve HPV arasındaki ilişkiyi araştıran, birden çok ülkede yapılmış 11 olgu-kontrol çalışmasına ait verilerin bir havuzda toplanarak değerlendirildiği bir çalışmada, servikal kanser gelişmesinde 15 HPV tipi yüksek riskli, üç tip olası yüksek riskli, 12 tip düşük riskli ve üç tip de risk düzeyi belli olmayanlar şeklinde sınıflandırılmıştır (Tablo 1) [23,24] . HPV-16 en yaygın yüksek riskli HPV tipidir ve servikal kanser olgularının yaklaşık yarısında (%50'sinde) bulunur. ...
... Servikal prekanser ve invaziv kanser gelişimi için bir onkojenik HPV tipi ile infeksiyonun gerekli bir ne-den olduğu gösterilmiş olsa da, bu yeterli bir neden değildir. Genel popülasyonda HPV'nin yüksek insidans ve yaygınlığıyla beraber yüksek viral klerens oranı bu görüşü desteklemektedir [24] . Belirli HPV tipi ile infekte olduktan 6-12 ay sonra kadınların çoğunda aynı HPV tipinin varlığına dair bir bulgu gösterilememektedir [24] . ...
... Genel popülasyonda HPV'nin yüksek insidans ve yaygınlığıyla beraber yüksek viral klerens oranı bu görüşü desteklemektedir [24] . Belirli HPV tipi ile infekte olduktan 6-12 ay sonra kadınların çoğunda aynı HPV tipinin varlığına dair bir bulgu gösterilememektedir [24] . Üniversite öğrencileri üzerinde yapılan prospektif bir çalışmada, kadınların yaklaşık %70'inde HPV infeksiyonunu takip eden 12 ay içinde tespit edilebilir düzeylerde HPV-DNA saptanamamış, 18 aydan sonra ise infeksiyonların %80'in üzerinde temizlendiği gösterilmiştir [31] . ...
... The human papillomavirus virus (HPV) is responsible for the most frequent sexually transmitted infection in the world (Koutsky, 1997;Baseman and Koutsky, 2005) [13,14]. The HPV vaccine is therefore offered to adolescents before sexual debut and to midadulthood persons at increased risk of HPV infection. ...
... The human papillomavirus virus (HPV) is responsible for the most frequent sexually transmitted infection in the world (Koutsky, 1997;Baseman and Koutsky, 2005) [13,14]. The HPV vaccine is therefore offered to adolescents before sexual debut and to midadulthood persons at increased risk of HPV infection. ...
The calculation of the return on investment (ROI) allows the estimation of the opportunity cost of a series of interventions and can therefore help to make allocative choices. The objective of this study is to estimate the ROI of three vaccinations (HPV for adolescents, HZ for adults, and influenza for the elderly) in the Italian context, considering the impact of increasing vaccination coverage based on target objectives of the National Immunization Plan (PNPV) 2017–2019 and accounting for different eligibility criteria of each vaccination. Three separate static cohort models were constructed, including the eligible population for these vaccinations on the basis of the PNPV 2017–2019 and following this population until death (lifetime horizon) or until vaccination waning. Each model compares the level of investment at current vaccine coverage rates (current VCRs scenario) with that of optimal NIP target VCRs with a non-vaccination scenario. The ROI for HPV vaccination was the highest among the programs compared and was always above 1 (range: 1.4–3.58), while lower values were estimated for influenza vaccination in the elderly (range 0.48–0.53) and for vaccination against HZ (range: 0.09–0.27). Our analysis showed that a significant proportion of savings generated by vaccination programs occurred outside the NHS perspective and might often not be estimated with other forms of economic evaluation.
... HPV infection is very common in humans, with reported infections from birth in infants to elderly individuals over 80 years of age. During a woman's lifetime, the chance of HPV infection in the genital tract is greater than 75% [6] and can be 40% or greater in young women in particular [7]. Most HPV infections are transient [8][9][10][11] and typically subside within a few months to 2 years post-infection. ...
Objective
To study the outcome of human papillomavirus (HPV) infection in women with cervical pathology results of non-cervical intraepithelial neoplasia (CIN) or cervical cancer and positive high-risk HPV test, as well as analyze the associated risk factors affecting the outcome of infection.
Methods
To investigate the outcome of high-risk (HR)-HPV infection in the female genital tract and analyze the associated risk factors affecting their outcome, a total of 196 women with positive HR-HPV test results and non-CIN or cervical cancer cervical pathology results were selected for follow-up at the Cervical Disease Clinic of the Obstetrics and Gynecology Hospital, Zhejiang University School of Medicine from January 2017 to March 2020. The follow-up interval was every 6 months, and both cervical cytology (TCT) and HR-HPV testing were performed at each follow-up visit. If the cervical cytology results were normal upon recheck and the HR-HPV test was negative, the woman was considered to be cleared of the HPV infection and was entered into the routine cervical screening population. When the repeat HR-HPV test remained positive after 6 months, the woman was defined as having a persistent HR-HPV infection. If HR-HPV persisted but the TCT results were normal, follow-up was continued. If HR-HPV persisted and the TCT results were abnormal, a colposcopy-guided biopsy was performed immediately. In this situation, if the histological results were still non-CIN or cervical cancer, the follow-up was continued. If the histological results confirmed the development of CIN or invasive cancer, then enter another study follow-up to further track its development and outcome, and the woman commenced the treatment process. The HPV infection clearance time was analyzed by the Kaplan-Meier method, and the comparison of the HPV clearance rate and infection clearance time between each of the different groups was performed using aχ ² test or Fisher’s exact test, as appropriate. After the univariate analysis, several significant factors were included in the Cox model and independent risk factors were analyzed.
Results
A total of 163 women were enrolled in this study. The median age was 40.0 years (22–67 years) and the median follow-up time was 11.5 months (6–31 months). The spontaneous clearance rate of HR-HPV infection was 51.5%, and the median time to viral clearance was 14.5 months. Age and the initial viral load were high risk factors affecting the spontaneous clearance of HR-HPV infection. The factors significantly associated with HPV clearance rate and time to HPV clearance consisted of menopause and full-term delivery ( P < 0.05).
Conclusions
In women with normal or low-grade lesions on the cell smear, the spontaneous clearance rate of HR-HPV infection was 51.5% and the time to clearance was 14.5 months. Age and the initial viral load were independent associated factors affecting the spontaneous clearance of HR-HPV infection in the female genital tract. These findings suggest that non-young women or those with high viral loads have a higher rate of persistent HR-HPV infection. Thus, intensive screening should be recommended.
... 21 Considering that the global prevalence of HPV in women varies from 2 to 44%, the overall prevalence rate of 31.8% indicates the high prevalence of HPV in Mashhad compared to the national and global HPV prevalence. 22,23 A worldwide meta-analysis study showed that the HPV prevalence in women with normal cervical cytology was 10.4%. Accordingly, the highest prevalence of HPV was found in Africa (22.1%), followed by Central America and Mexico (20.4%) and North America (11.3%), and to a lesser extent in Europe (8.1%) and Asia (8.0%). ...
Background: Cervical cancer is the fourth most common cancer in women, and human papillomavirus (HPV) is the leading cause of cervical cancer. Cervical cancer screening and HPV vaccination are important in the incidence of cervical cancer. Methods: This study was performed on Liquid Base Cytology (LBC) samples of 1214 women in Mashhad who were referred for cervical cancer screening in 2015-2020. Samples were examined by Single-Step PCR and Reverse Line Blot for HPV genotyping. Results: 386 women (31.8%) were HPV PCR positive. HPV genotyping of 277 samples showed that HPV 31 (3%), 16 (2.5%), 51 (2.2%), 18 (2%), and 66 (1.8%) were the most prevalent high-risk HPV (hrHPV) genotypes. Among low-risk HPV (lrHPV) genotypes, HPV 6 (9.2%), 53 (4.7%), and 42 (2.8%) were the most common genotypes. The range of multiple infections varied between two to eight genotypes and the prevalence of multiple HPV infections (12.4%) was higher than single infections (10.4%). For women with single HPV infections, HPV 31 and 66 were equally the most common hrHPV genotypes, followed by HPV 16 and 39. In women with multiple HPV infections, HPV 31 was the most common hrHPV genotype, followed by HPV 51 and 16. For both the single and multiple HPV infections, HPV 6 was the most common lrHPV genotype, followed by HPV 53 and 42. Conclusion: In conclusion, due to the high prevalence of HPV single and multiple infections, the need for governmentally supported HPV vaccination and through cervical cancer screening should be emphasized to prevent cervical cancer.
... For the first objective, we used two different outcomes: (1) incident type-specific HPV detection, defined as the first detection of homologous HPV DNA at follow-up among HPV DNA-negative individuals at baseline (as defined by included studies), and (2) persistent HPV positivity, defined as the detection of homologous HPV DNA at two or more consecutive follow-up visits within a 6-or 12-month interval among HPV DNA-negative individuals at baseline. For both outcomes, we focused on HPV-16 and HPV-18 in our main meta-analyses, since these HPV types were the most commonly reported [35]. We presented results on other HPV types for the first outcome in Additional file 1 for completion. ...
Background: Understanding the role of naturally acquired (i.e., infection-induced) human papillomavirus (HPV) antibodies against reinfection is important given the high incidence of this sexually transmitted infection. However, the protective effect of naturally acquired antibodies in terms of the level of protection, duration, and differential effect by sex remains incompletely understood. We conducted a systematic review and a meta-analysis to (1) strengthen the evidence on the association between HPV antibodies acquired through past infection and subsequent type-specific HPV detection, (2) investigate the potential influence of type-specific HPV antibody levels, and (3) assess differential effects by HIV status.
Methods: We searched Embase and Medline databases to identify studies which prospectively assessed the risk of type-specific HPV detection by baseline homologous HPV serostatus among unvaccinated individuals. Random-effect models were used to pool the measures of association of naturally acquired HPV antibodies against subsequent incident detection and persistent HPV positivity. Sources of heterogeneity for each type were assessed through subgroup analyses stratified by sex, anatomical site of infection, male sexual orientation, age group, and length of follow-up period. Evidence of a dose-response relationship of the association between levels of baseline HPV antibodies and type-specific HPV detection was assessed. Finally, we pooled estimates from publications reporting associations between HPV serostatus and type-specific HPV detection by baseline HIV status.
Results: We identified 26 publications (16 independent studies, with 62,363 participants) reporting associations between baseline HPV serostatus and incident HPV detection, mainly for HPV-16 and HPV-18, the most detected HPV type. We found evidence of protective effects of baseline HPV seropositivity and subsequent detection of HPV DNA (0.70, 95% CI 0.61-0.80, N E = 11) and persistent HPV positivity (0.65, 95% CI 0.42-1.01, N E = 5) mainly for HPV-16 among females, but not among males, nor for HPV-18. Estimates from 8 studies suggested a negative dose-response relationship between HPV antibody level and subsequent detection among females. Finally, we did not observe any differential effect by baseline HIV status due to the limited number of studies available.
Conclusion: We did not find evidence that naturally acquired HPV antibodies protect against subsequent HPV positivity in males and provide only modest protection among females for HPV-16. One potential limitation to the interpretation of these findings is potential misclassification biases due to different causes.
... Destes, 18-20 são considerados de alto risco oncogênico e cerca de 12-15, de baixo risco40,42 . Os HPV 16, CP6108 como de baixo risco43 . Os HPV 16 e 18 são responsáveis por 70% dos casos de câncer do colo de útero e 80-90% dos casos de cânceres HPV induzidos em outras áreas. ...
... Parece que o fator de risco mais importante para a infecção pelo HPV seja o elevado número de parceiros sexuais 36 . As mulheres com 4 ou mais parceiros em um período de 6 meses apresentam risco quatro vezes maior de adquirir o HPV oncogênico 37 . ...
... Human papillomaviruses (HPVs) are the most common sexually transmitted viruses [3] and are divided into two groups, high-risk (HR)-HPV and low-risk (LR)-HPV, HR-HPV including HPV16, 18,31,33,35,39,45,51,52,56,58,59,68, 73 and HPV82 [4]. Seventy-five percent of women are infected with HPV in their lifetime; 90% of these infections resolve spontaneously [5]. ...
Purpose
To investigate the distribution of the incidence and genotypes of human papillomavirus (HPV) among women with cervical cancer (CC) and precancerous cervical lesions in Yueyang City, China, to develop prevention and control strategies for CC.
Methods
A total of 3674 patients with cervical lesions and cervical cancer who attended 7 hospitals in Yueyang City between September 2019 and September 2022 were included. They included 1910 cervical intraepithelial neoplasia (CIN) I, 718 CIN II, 576 CIN II and 470 CC, respectively. The HPV genotyping of the above patients was detected by Real time-PCR in the laboratory department of each hospital.
Results
The total HPV prevalence was 74.69% (95% CI 73.28–76.09%) in 3674 patients. The incidence of high- and low-risk HPV was 73.46% and 7.21%, respectively. The prevalence of HPV in CIN I, CIN II, CIN III, and invasive CC (ICC) groups was 66.65% (1273/1910, 95% CI 64.53–68.77%), 80.78% (580/718, 95% CI 77.89–83.67%), 83.88% (483/576, 95% CI 80.84–86.87%), and 86.81% (408/470, 95% CI 83.74–89.88%), respectively. The top three HPV subtypes in ICC are HPV16, HPV52, and HPV58. The prevalence of HPV 16 increased with increasing disease severity, with this genotype being present in 12.57%, 20.89%, 36.98%, and 50.85% of CIN I, CIN II, CIN III, and ICC cases, respectively (p < 0.001). Single HPV infection was predominant in cervical lesions, with a prevalence of 48.50% (95% CI 46.89–50.12%). The HPV prevalence varied by age, being highest among women with ICC, CIN I, CIN II and CIN III aged ≥ 60 years, 50–59 years, 40–49 years, and 40–49 years, respectively.
Conclusion
The prevalence of HPV in patients with cervical lesions in Yueyang City was very high, with HPV 16, 52, 58, 53, and 51 being the five most common HPV genotypes in patients with cervical lesions.
... An abnormal cervical cancer screening result (cervical dysplasia or high-risk human papillomavirus (HPV) infection) raises a person's risk of developing cervical cancer and often initiates a cascade of surveillance testing and potentially invasive treatments (Perkins et al., 2020). A minority of patients with an abnormal screen will go on to develop cancer (Baseman and Koutsky, 2005), but many more experience stigma, shame, anxiety, and fear associated with an abnormal result (McBride et al., 2020). ...
Female Veterans report cervical cancer risk factors at higher rates than non-Veterans. Using data from the National Health Interview Survey (NHIS), we tested whether Veterans with a recent cervical cancer screening test were more likely than non-Veterans to have received an abnormal result. NHIS is a population-based cross-sectional household survey with a stratified, multistage sampling design. We pooled screening data from 2010, 2015, and 2018, and restricted the sample to female participants without a hysterectomy who had a cervical cancer screening test in the prior 3 years. The primary outcome was self-reported abnormal result on a Pap and/or HPV test in the prior 3 years. Our main predictor was Veteran status. We used survey-weighted multivariable logistic regression to estimate odds of an abnormal screening result in the prior 3 years as a function of Veteran status, controlling first for age and survey year, then adding sociodemographic and health factors in subsequent models. The sample included 380 Veterans and 25,102 non-Veterans (weighted total population 104.9 million). Overall, 19.0% of Veterans and 13.7% of non-Veterans reported an abnormal cervical cancer screening test result in the prior 3 years (unadjusted p = 0.03). In the adjusted regression model, the previously observed association between Veteran status and abnormal screening result was explained by differences in sociodemographic and health factors between Veterans and non-Veterans (aOR 1.21, 95%CI 0.78–1.87). Nearly 1 in 5 Veterans with a recent cervical cancer screening test received an abnormal result. Clinicians should address modifiable risk factors and provide evidence-based follow-up for abnormal results.
... Human papillomaviruses (HPVs) are the most common sexually transmitted viruses [3] and are divided into two groups, high-risk (HR)-HPV and low-risk (LR)-HPV, HR-HPV including HPV16 18 31 33 35 39 45 51 52 56 58 59 68 73 and HPV82 [4]. Seventy-ve percent of women are infected with HPV in their lifetime; 90% of these infections resolve spontaneously [5]. ...
PURPOSE
To investigate the distribution of the incidence and genotypes of human papillomavirus (HPV) among women with cervical cancer (CC) and precancerous cervical lesions in Yueyang City, China, to develop prevention and control strategies for CC.
METHODS
3674 patients with cervical lesions diagnosed by pathology as a gold standard at 7 hospitals in Yueyang City between September 2019 and September 2022 were selected. They included 1910, 718, 576, and 470 cases of cervical intraepithelial neoplasia (CIN) I, CIN II, CIN III, and CC, respectively. A cross-sectional study combining HPV test results from these cases.
RESULTS
The total HPV prevalence was 74.69% (95%CI: 73.28–76.09%) in 3674 patients. The incidence of high- and low-risk HPV was 73.46% and 7.21%, respectively. The prevalence of HPV in CIN I, CIN II, CIN III, and invasive CC (ICC) groups was 66.65% (1273/1910, 95%CI: 64.53–68.77%), 80.78% (580/718, 95%CI: 77.89–83.67%), 83.88% (483/576, 95%CI: 80.84–86.87%), and 86.81% (408/470, 95%CI: 83.74–89.88%), respectively. The top three HPV subtypes in ICC are HPV16, HPV52, and HPV58. The prevalence of HPV 16 increased with increasing disease severity, with this genotype being present in 12.57%, 20.89%, 36.98%, and 50.85% of CIN I, CIN II, CIN III, and ICC cases, respectively (p < 0.001). Single HPV infection was predominant in cervical lesions, with a prevalence of 48.50% (95%CI: 46.89–50.12%). The HPV prevalence varied by age, being highest among women with ICC, CIN I, CIN II and CIN III aged ≥ 60 years, 50 to 59 years, 40 to 49 years, and 40 to 49 years, respectively.
CONCLUSION
The prevalence of HPV in patients with cervical lesions in Yueyang City was very high, with HPV 16, 52, 58, 53, and 51 being the five most common HPV genotypes in patients with cervical lesions. These results serve as data for supporting future vaccination and screening programs.
... A byproduct of this highly effective cancer prevention program is that, in previously published estimates, between $1 and 2 billion USD in healthcare expenditures was attributed to the follow-up management of women with screen positive tests (Chesson et al. 2012), and nearly a quarter of a million U.S. women were diagnosed with low-grade cervical intraepithelial neoplasia (LGCIN) (Henk et al. 2010). Vaccine uptake and changes to screening guidelines (HPV co-testing and increasing screening intervals for some women) have undoubtedly impacted these estimates in more recent years; however, one thing remains clear: low-grade dysplasia resolves without treatment for most women and progresses to high-grade dysplasia in fewer than one in ten women (Baseman and Koutsky 2005). While treatment intervention is compulsory for HGCIN, the clinical management algorithm for LGCIN remains complex and relies heavily on management-by-observation approaches with repeat screening tests at short-term intervals. ...
Purpose
Only a fraction of low-grade cervical intraepithelial neoplasia (CIN) progresses to high-grade CIN; however, the biological processes that differentiate progressive CIN from CIN that resolves naturally are poorly understood. MicroRNAs (miRNAs) are important epigenetic regulators of gene expression and thus, miRNA expression profiling can reveal the dysregulated biology underlying disease processes. The purpose of this case–control study was to reveal miRNA expression patterns and predict the underlying biological pathways that are associated with clinical outcomes of low-grade CIN.
Methods
Women with low-grade CIN diagnosis and definitive clinical outcomes (n = 51) were identified retrospectively using electronic clinical records. Comprehensive miRNA expression profiling was performed on the low-grade CIN diagnostic cervical biopsies retrieved from pathology archives. Differential miRNA expression was analyzed by comparing women with CIN that progressed to women with CIN that resolved naturally.
Results
Differential expression of 29 miRNAs was observed in low-grade CIN that progressed to high-grade compared to low-grade CIN that resolved. Of these, 24 were significantly downregulated in progressive CIN, including miR-638, miR-3196, miR-4488, and miR-4508, while 5 miRNAs, including miR-1206a, were significantly upregulated. Computational gene ontology analysis based on the discovered miRNAs and their putative mRNA targets revealed biological processes associated with oncogenic phenotypes.
Conclusion
Distinct miRNA expression profiles are associated with clinical outcomes of low-grade CIN. The functional effects of the differentially expressed miRNAs may be biological determinants of CIN progression or resolution.
... Regarding the practice of oral sex, 56.67% of the patients admitted to practicing it. A high number of lifetime sexual partners is one of the main risk factors for HPV acquisition according to Baseman & al. [42]. They also found that having four or more lifetime oral sex partners increased the risk of cancers of the oropharynx and base of the tongue was associated with having two sexual partners, compared with one. ...
... Human papillomaviruses (HPV) are the most common sexually transmitted viral infections worldwide [1]. Highrisk HPV types -predominantly 16 and 18 are involved in almost 100% of cervical cancer [2]. ...
Background
The incidence of anal cancer, largely associated with anal human papillomavirus (HPV) infection, is increasing among men who have sex with men (MSM), and transgender women living with or without HIV. Screening for anal cancer to detect anal precancerous lesions in high-risk groups is an important opportunity for prevention but still lacking in many low-and-middle-income countries. The aim of this study was to explore the readiness of Pakistan’s healthcare system to integrate anal cancer and HPV screening into a national HIV program, as perceived by policymakers, health managers, and healthcare providers.
Design
This qualitative study using key-informant interviews with participants influence in policy making, implementation and advocacy from public and private sector were conducted between March 2021 to August 2021 in Karachi Pakistan.
Methods
Key informants were purposely selected from different domains of the healthcare system responsible for the target group of interest, MSM and transgender-women in general and people living with HIV in particular. A total of 18 key informants, at different levels of seniority were recruited from governmental and non-governmental organizations, high-level infectious disease healthcare managers, and United Nations Program representatives. Qualitative content analysis was used to identify the manifest and latent themes, based on socioecological framework.
Results
The results were grouped into five major themes; (1) The policy context and priorities, (2) Health systems factors, (3) Community environment, (4) Healthcare setting & providers and (5) Individual-level obstacles. The policy actors expressed their concerns about their limited voice in country’s health and health related priority setting. Informants reported a lack of political will and suggested that government should bring a change in the paradigm of healthcare service delivery from reactive to proactive approach. Although, participants unanimously favored integration of HPV preventive services into existing HIV program, they also identified several service delivery barriers including trained workforce shortage, limited capacity of information technology, lack of supplies needed for screening, lack of financing, and lack of services that could meet key-populations needs. Participants also predicted other implementation challenges such as stigma, social victimization, and systemic discrimination against at-risk groups at healthcare facilities.
Conclusion
Although policy makers and health providers in Pakistan saw a clear need to scale-up and integrate anal cancer screening for key populations, the feasibility of this is dependent on political will, financing, anti-stigma and discrimination interventions and health system efficiency.
... Chronic infection with certain types of human papillomavirus (HPV) is the main cause of cervical cancer and cervical intraepithelial neoplasia (CIN). More than 100 different HPV types have been described, and they can be further subdivided into low-risk and high-risk types according to their oncogenic potential [2]. There are 13 high-risk HPV (HR-HPV) types, including HPV types 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, and 68 [3-5]. ...
... The human papilloma virus (HPV) is a nonenveloped DNA virus which mainly spreads by direct contact, sexual and perinatal routes as well as through contaminated fomites [1]. HPV reportedly is a very common sexually transmitted infection (STI), with at least one HPV type commonly detected in roughly 50-80% of females who are sexually active at some point in their lives [2,3]. Women aged 20-24 years reportedly have the highest HPV prevalence rates globally, and infection with this virus typically occurs within 5-10 years of the very first sexual encounter [4,5]. ...
Aims: This study was initiated to assess the knowledge of human papillomavirus (HPV) infection and vaccination, attitudes towards HPV vaccines, as well as risky sexual practices of young university students towards HPV infection. Study Design: This was a cross-sectional descriptive study that included university-going young adults of both sexes, aged 18 to 25 years. Place and Duration of Study: The study was conducted in four randomly selected state universities, located in different geographic regions of Cameroon. The study took place between April and July 2022. Methodology: The survey instrument was a self-administered anonymous questionnaire. Participants were randomly given questionnaires to be completed. Data was imported into SPSS version 23 software for analyses. Participants were categorised into one of two groups - poor level of knowledge and good level of knowledge, depending on the number of correct answers to 7 questions about knowledge of HPV infection and vaccination. Chi-square test and logistic regression were used to examine differences in parameters. Results: 1263 questionnaires were returned. Most participants (78.9%) were undergraduates aged 20 - 21 years (32.7%). Overall, just 87/1263 (6.9%) of participants had a good knowledge of HPV infection and vaccination, most of whom were females (56.7%). Educational level (OR 3.11, 95% CI (1.24 – 7.85), P = .02), field of study (OR 0.42, 95% CI (0.17 – 1.04), P = .04) and plans to become vaccinated (OR 0.33, 95% CI (0.14 – 0.76), P = .009) were predictors of good knowledge of HPV. Attitudes towards HPV vaccination were overall positive. 71.9% participants were sexually active, most of whom only used condoms sometimes (47.2%). Conclusion: These findings underscore the need for educational programs and public health policies targeted to this age bracket, to increase students’ awareness of the risks associated with HPV infection as this can potentially increase the vaccination rate in the country.
... Human papilloma virus (HPV) has been recognized as one of the most common sexually transmitted virus infections in men and women, including both oncogenic and nononcogenic viruses [1,2]. HPV infections are associated with benign diseases, such as genital warts and malignancies such as cervical, oropharynx and penile cancers [3,4]. ...
Background: Several reports highlighted the role of nutraceutical compounds in the prevention and management of HPV-related genital lesions both in men and women, with interesting results. Here, we reviewed the effect of ellagic acid and Annona muricata for managing HPV-related genital lesions. Methods: Relevant databases were searched by using methods recommended by the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. The primary endpoint was the clinical cure, defined as the clinical and/or laboratory and/or histopatologically demonstrated absence of HPV-related lesions at the end of the treatment. Results: We enclosed two retrospective studies, two prospective studies and one randomized controlled trial. In men, ellagic acid and Annona muricata complex improves seminal parameters and HPV-DNA clearance. In women, it has a chemopreventive action in cervical cancer and increases the HPV viral clearance. No clinically significant adverse effects have been reported. Conclusions: In conclusion, the combination of ellagic acid and Annona muricata shows interesting and promising results in terms of HPV viral clearance and HPV related genital lesions. However, more data are necessary to confirm these results.
... Literature data support the hypothesis that 80% of HR-HPV infections spontaneously clear within 18 months thanks to the host's immune system [37][38][39][40]. The persistent infection (around 10%) develops an LSIL/CIN1 lesion, and its progression to HSIL/CIN2+ is sustained by a failure in the immune system. ...
Background:
Low-grade cervical lesions have a high percentage of clearance in young women, even if 71-82% of low-grade intraepithelial lesion/atypical squamous cells of undetermined significance (LSIL/ASCUS) reported a High-Risk Human Papillomavirus (HR-HPV) infection, which correlates with an increased risk of Cervical Intraepithelial Neoplasia (CIN)2+. The immunogenic effect of the anti-HPV vaccine appears to be significant. The aim of the study is to evaluate the effect, two years after the diagnosis, of the anti-HPV preventive vaccination on patients with low-grade cervical lesions.
Methods:
We collected clinical, colposcopic, histological, and virological data from patients aged 21-45 years who attended the colposcopy service of the department of Obsetrics and Gynecology of IRCCS Foundation Policlinico San Matteo, Pavia, Italy. In the 2005-2019 period and had a low-grade pap-smear.
Results:
We enrolled 422 women consecutively, divided into two groups (vaccinated and not vaccinated) for the retrospective analysis. The rate of persistence and progression of CIN were higher in the not-vaccinated group (p = 0.019). The relative risk (RR) to develop CIN2+ during follow-up vs. the the CIN1 persistence was 1.005 (95% Confidence Interval-CI 0.961-1.051) vs. 0.994 (95% CI 0.994-1.018) for age, 3.472 (95% CI 1.066-11.320) vs. 1.266 (95% CI 0.774-2.068) for non-vaccinated, 0.299 (95% CI 0.088-1.018) vs. 0.518 (95% CI 0.242-1.109) for HIV status negative, respectively. Analyzing the time to negativity, the odds ratio (OR) was 1.012 (95% CI 1-1.024) for age and 1.591 (95% CI 1.223-2.069) for vaccination; on the other hand, considering the relationship between the time to negative and the HPV genotypes contained in the 9-valent HPV vaccines, the OR was 1.299 (95% CI 1.026-1.646) for at least one of these at recruitment and 0.631 (95% CI 0.471-0.846) at follow-up. Furthermore, the presence of at least one of the HPV genotypes targeted by the HPV nonavalent vaccine is a key indicator of the risk of progression to CIN2+: OR was 3.443 (95% CI 1.065-11.189) for the presence of at least one HPV genotype at enrollment and 5.011 (95% CI 1.899-13.224) for the presence of at least one HPV genotype at follow-up, respectively.
Conclusions:
We reported in a retrospective study the benefit of anti-HPV vaccination in promoting negativity and increasing low-grade cervical lesions regression.
... 1 Human papillomavirus (HPV), and mainly its highrisk subtypes (hr-HPVs) have been recognized as the main etiologic agent of CxCa. 2 Generally, HPV infection occurs in more than half of sexually active women during their lifetime. 3 Even though most HPV infections are transient, without cytologic abnormality, long-term persistent infection from hr-HPVs (especially HPV-16 and HPV-18) is strongly associated with progression to highgrade cervical intraepithelial lesions (CIN) and CxCa. 4 Nowadays, there are various HPV diagnostic tests available in the market for the detection and typing of hr-HPV DNA and mRNA. 5,6 Hr-HPVs screening is significantly more sensitive than cytology alone at predicting CIN2+. ...
Aim:
To compare the diagnostic parameters of electrical impedance spectroscopy (EIS) via ZedScan, a device that measures spectra to differentiate between normal and abnormal cervical tissues, when used as an adjunct to colposcopies in the diagnosis of HSILs/CIN2+ in Greek women with abnormal referral cytology toward colposcopy alone and HPV mRNA-testing.
Methods:
This study analyzed 86 women, patients of the Colposcopy and Cervical Pathology Clinic of 2nd Obstetrics and Gynecology Department, Aristotle University of Thessaloniki at Hippokration General Hospital, between January 2022 and September 2022. During the visits, women were subjected to cytology, colposcopy alone and then with EIS/ZedScan and histological sampling.
Results:
Common use of colposcopies and EIS/ZedScan allowed detecting an additional 14 cases of CIN2+ (16.2%) that colposcopy alone failed to report. EIS enhanced the sensitivity of colposcopy from 80.65% to 100% equal with that of HPV-mRNA test while retaining a high specificity (94.74%) which is much higher than specificity of HPV mRNA-testing (65.45%). EIS-assisted colposcopy had the highest value combination of positive and negative predictive values (96.15% and 100%) compared to colposcopy alone (100% and 75%) and HPV mRNA-testing (72.46% and 100%).
Conclusions:
Colposcopies performed with EIS/ZedScan demonstrated effectiveness in the diagnosing of CIN2+ leading to a significant increase in the number of CIN2+ that would have been missed if only colposcopy was applied especially in women with LSIL referral cytology. EIS/ZedScan seems to possess the ideal diagnostic threshold for sensitivity, specificity, and predictive values for CIN2+ compared to colposcopy alone and HPV mRNA-testing.
... Human papillomavirus (HPV) is the most common sexually transmitted virus, and more than 200 HPV types have been identified so far [1,2]. Many studies have shown that over half of sexually active women have been infected by one or more genital HPV types at some point in time [3]. Furthermore, HPV infection also appears to be very common in men, though it has not been studied as extensively as infection in women [4]. ...
Purpose
Three licensed human papillomavirus (HPV) vaccines (Cervarix, Gardasil, and Gardasil 9) have been effectively used to prevent infection with oncogenic HPV types; however, many adverse events (AEs) have also been reported following their vaccinations. We assessed AE profiles after receiving the HPV vaccines based on the reported data from Vaccine Adverse Event Reporting System (VAERS).
Methods
The AE data associated with Cervarix, Gardasil, and Gardasil 9 were retrieved from VAERS database respectively. The combinatorial biomedical statistical methods were used to identify the statistically significant AEs. The Gamma-Poisson Shrinker (GPS) model with gender/age stratification was applied to ascertain the serious adverse events (SAEs) related to the three licensed HPV vaccines. The AE profiles were classified and represented by the Ontology of Adverse Events (OAE) for further analysis.
Results
As of July 31, 2020, VAERS recorded 3,112, 31,606, and 6,872 AE case reports for Cervarix, Gardasil, and Gardasil 9, respectively. Our Frequentist statistical methods identified 135 Cervarix-enriched AEs, 55 Gardasil-enriched AEs, and 17 Gardasil 9-enriched AEs. Based on the OAE hierarchical classification, these AEs were clustered in the AEs related to behavioral and neurological conditions, immune system, nervous system, and reproductive system. Combined with GPS modeling, 46 unique statistically significant SAEs were founded to be associated with at least one of the three vaccines.
Conclusions
Our study led to the better understanding of the AEs associated with the licensed HPV vaccines. The hypotheses on the cause and effect relationships between the HPV vaccination and specific AEs deserve further epidemiological investigations as well as clinical trial studies.
... More than 200 HPV genotypes have been identified, and they can be classified into high-risk (HR) and low-risk HPV (LR) genotypes based on their carcinogenicity. It has been demonstrated that persistent infection with HR HPV genotype including HPV16/18/31/33/35/39/45/52/58/ 59 is a major cause of cervical precancerous lesions and cervical cancer [2,3], while LR-HPVgenotypes such as HPV6/11 are associated with condyloma acuminatum or hyperplastic lesions [4]. Approximately 99% cervical cancers were associated with HPV infection worldwide [5], and there are over 130,000 women suffered from cervical cancer per year in China [6]. ...
Background
The evaluation of human papillomavirus (HPV) prevalence rate dynamics and genotype distribution could support the adoption of more targeted prevention and treatment of cervical cancer. We aimed to assess the infection status and genotype characteristics of HPV among gynecological outpatients in Shanghai, China.
Methods
Clinical specimens were collected from patients attending gynaecological department of the Putuo Hospital, Shanghai University of Traditional Chinese Medicine, between January 2015 and December 2019. The cervicovaginal infection of 17 high-risk genotypes and 10 low-risk genotypes were analyzed by Luminex-based multiple assays.
Results
The overall HPV infection rate was 18.81% (95% CI 18.31–19.30%) in Shanghai city, with high-risk, low-risk and mixed high- and low-risk HPV prevalence being 11.65% (95% CI 11.24–12.06%), 4.19% (95% CI 3.94–4.44%) and 2.96% (95% CI 2.74–3.17%), respectively. The five most prevalent high-risk genotypes were HPV-52 (2.95%), HPV-16 (2.34%), HPV-58 (2.07%), HPV-53 (1.67%) and HPV-39 (1.36%). The most common low-risk genotype was HPV-61 (1.52%), followed by HPV-6 (1.29%) and HPV-81 (1.19%). Moreover, the coverage of HPV genotype by nonavalent vaccine was 10.42%, and non-vaccine-covered high-risk genotype was 7.70%. The 15–24 years age group demonstrated the highest HPV prevalence (43.14%), and significant differences were observed among different age groups ( P < 0.001).
Conclusions
This study revealed the HPV prevalence and genotype distribution among women in Shanghai city, which could serve as guidance for HPV vaccination and preventative strategies against cervical cancer in this area.
... Servikal kanserin toplum taramasında klinisyenlere yol gösterecek belirteçlere çalışmamızda ağırlık verilmiştir. Yapılmış farklı çalışmalara baktığımız zaman HPV DNA pozitifliği ile servikal kanser gelişmesi arasındaki ilişki %96-99 oranında ispat edilmiştir (5,7). Servikal lezyonun ortaya çıkması için HPV'nin olması gerektiği fakat bunun tek başına yeterli ve anlamlı olmadığı bilinmektedir (8). ...
Amaç: Servikal kanser dördüncü sıklıkta görülen ve önlenebilir bir kanserdir. Bu nedenle birçok tarama programı geliştirilmiştir. Çalışmamızda anormal servikal sitolojide anormal endoservikal patoloji ve Human Papilloma Virus (HPV) prevalansını ve endoservikal örneklemenin önemini saptamayı amaçlamış bulunmaktayız. Materyal ve Metodlar: Çalışmamız Ocak 2013 ve Nisan 2016 tarihleri arasında Aydın Adnan Menderes Üniversitesi Hastanesinde yapılmıştır. Çalışmamız HPV DNA bakılmış ve endoservikal küretaj ile örneklem yapılmış hastalar üzerinde yapılmıştır. Servikal sitoloji anormalliği olan 215 hasta ile 175 kontrol grubu mevcuttur. Servikal sitoloji Bethesda 2001 sınıflandırma sistemine göre yorumlanmıştır. İstatiksel analiz SPSS 22.0 for Windows programı ile yapılmıştır. Bulgular: Çalışmamızda 390 hasta üzerinde yapılmıştır. 215 (%55) hastada anormal Pap smear, 175 (%45) hastada normal Pap smear saptanmıştır. Olguların ortalama yaşı 45.5±9’dur. Anormal Pap smearli olgularda HPV pozitifliği prevalansı %68.8, endoservikal örneklem patoloji prevalansı %40 olarak saptandı. Kontrol grubunda HPV pozitifliği prevalansı %53.7 idi. Endoservikal örneklem sonucu anormal olan hastaların prevalansı %2.8 idi. Anormal smear sitolojisi ile HPV DNA pozitifliği arasında istatistiksel olarak anlamlı ilişki saptandı (p=0.002). Servikal sitoloji anormalliği ile anormal endoservikal örnekleme patoloji sonuçları arasında istatistiksel olarak anlamlı ilişki saptandı (p˂0.001). Servikal sitoloji anormalliğinin derecesi arttıkça endoservikal örneklem anormallikleri ve HPV DNA pozitifliğinin sıklığında artma olduğu görüldü (p=0.002). Sonuç: HPV pozitifliği servikal sitoloji anormalliği ile ilişkili bulunmuştur. Anormal servikal sitoloji ile anormal endoservikal patoloji arasında anlamlı ilişki bulunmuştur. Servikal sitoloji anormalliğinin derecesi arttıkça endoservikal örneklem anormallikleri ve HPV DNA pozitifliğinin sıklığında artma olduğu saptanmıştır
... In fact, most HPV infections are transient and around 80% are cleared by the immune system after two years since the evidence of the presence of HPV genotypes, before developing a pathogenic and cytopathic effect, especially in women < 30 years old 40 . Our study's population, in both groups, is instead around 35-year-old, and this data may impact negatively on HPV virus natural clearance with low chances to spontaneous negativization 41,42 . To date, immune mechanisms involved in HPV clearance are not completely clear, and many immune factors, further than cell-mediated immune response, could contribute differently in HPV clearance, as aging progresses 43,44 . ...
Objective:
The nonavalent HPV vaccine has demonstrated its efficacy in women and men who already suffer from HPV genital lesions, with little chances to clear the infection. The efficacy of new therapeutic or complementary alternatives as Ellagic acid plus Annona Muricata (Ellagic acid complex) has emerged recently. Our retrospective study compares the evolution of persistent cervical HPV infection in two cohorts of immunocompetent women after the administration of nonavalent vaccine or Ellagic acid complex.
Patients and methods:
At Tor Vergata University Hospital, Rome, forty women in childbearing age, suffering from persistent cervical HPV infection, were enrolled in two study's groups: nonavalent HPV vaccine (20 women) vs. Ellagic acid complex tablets (20 who refused the vaccine). Cytological features, HPV DNA genotypes and mRNA oncogenic genes E6/E7 presence and clearance were analyzed and confronted between the groups.
Results:
Demographics and clinical features of the cohorts were comparable. Evaluation of Pap smear, HPV DNA test and mRNA genes E6/E7, were performed at baseline (T0) and after 6 months (T1) and 12 months (T2) from the last dose of vaccine/tablet. At T1 and T2, Ellagic acid complex group showed a statistical reduction of abnormalities in Pap smears (p = 0.018 and 0.006, respectively), probably due to its direct anti-inflammatory, antioxidative and antiviral activities. At T1, vaccinated group showed a higher rate of HPV clearance (p = 0.001), instead Ellagic acid complex group didn't report significative differences. At T2, respect to T0, both groups showed an increase in percentage of negative HPV DNA detection, although more marked for vaccinated group respect to Ellagic acid complex group (p = 0.039 and 0.062 respectively). Regarding mRNA E6/E7 clearance, at T1 and T2, the group of vaccinated women showed a higher negativization respect to the other group (p= 0.077 and 0.042, respectively).
Conclusions:
Despite the limited sample of women enrolled for the present study, the results confirmed the clinical usefulness of HPV vaccination as adjuvant agent for the immune system of women affected by persistent HPV infection. Moreover, in women who refused to be vaccinated, the administration of a biocompound like Ellagic acid plus Annona Muricata, represented an interesting clinical strategy in terms of increasing chance of HPV viral clearance.
... Entretanto, embora sua infecção seja um fator necessário, muitas vezes apenas a infecção não é suficiente para o desenvolvimento da neoplasia (5). Outros fatores como o tabagismo, número de parceiros, uso prolongado de contraceptivos orais e multiparidade têm sido associados ao câncer cervical por serem determinantes da persistência da infecção por HPV (6). ...
O objetivo do estudo foi analisar a prevalência de Papilomavírus Humano (HPV) e Chlamydia trachomatis em mulheres. Foi realizado um estudo documental como dados de mulheres de captura híbrida para HPV e Chlamydia trachomatis. Os dados foram analisados pelo programa estatístico Epi Info, utilizou-se o Qui-Quadrado e Razão de Chances com intervalos de 95% de confiança (IC 95). Foi considerado de significância estatística o valor p associado menor ou igual a 0,05 (p≤0,05). Trezentas e treze mulheres, 24,6% apresentaram positividade para HPV, 10,9% para Chlamydia e 3,5% para co-infecção. O HPV foi de 85,7% para mulheres com diagnóstico de ASCUS, 80% com LSIL, 100% com ASCH e HSIL, e 21,4% com citologia normal. Para CT, no exame citopatológico, foi de 28,6% para mulheres com diagnóstico de ASCUS, 10% com LSIL e 10,5% com citologia normal. A frequência de co-infecção foi maior em mulheres com idade inferior ou igual a 32 anos. No exame citopatológico, 18,2% tiveram diagnóstico para ASCUS, 9,1% para LSIL e 72,7% para citologia normal. Os dados encontrados sugerem estratégias de esclarecimentos sobre a prevenção e agravos relacionados a essas IST, bem como incentivo do rastreamento e a importância da biologia molecular na detecção dessas duas IST.
... • Multiple Sex partners: The major risk factor for HPV infection is the number of sexual partners. There is a strong association between the acquisition of HPV infection and number of sexual partners [7]. ...
Cervical cancer is the third most common cancer in women
worldwide, more than half a million women are being diagnosed with
cervical cancer, and resulting in 0.3 million deaths worldwide. About
95% cervical cancer are caused by a persistent Human Papillomavirus (HPV) infection. High-risk subtypes of the HPV are responsible
for 99% cervical cancer cases. It is largely preventable, as early detection and treatment of precancerous lesions can avert its progression to tumour. Thus, improving triage, treatment, and follow-up in
infected patients. A combination of HPV vaccination and screening
could almost eradicate cervical cancer and reduce the burden of other tumours and diseases related to HPV.
The aim of this review article is to summarize current understanding along with updated information concerning the afore known
aspects of role of HPV infection in cervical cancer, also including
discussion about its molecular biology, and carcinogenesis. This
review also focuses on the expanding knowledge of the diagnosis
and preventive strategies to maximize reductions in cervical cancer
cases worldwide
... Human papillomaviruses (HPV) are a large family of epitheliotropic DNA tumor viruses [1]. Approximately 80% of sexually active women are infected with at least one HPV subtype at some point in their lifetimes [2]. Continuous infection with a high-risk HPV subtype is the main cause of cervical cancer [3]. ...
Background
Human papillomavirus (HPV) vaccines have been proven effective against cervical cancer. However, HPV vaccination is not included in the Chinese immunization program. This study aimed to assess the cost-effectiveness of incorporating different HPV vaccines into immunization programs at the Chinese national and provincial levels.
Methods
The Papillomavirus Rapid Interface for Modeling and Economics model was used to estimate the possible cost and social and economic benefits of adopting various HPV vaccination immunization strategies in 31 provinces in Mainland China in 2019. Demographic and regional economic data were obtained from the national and provincial Statistical Yearbook. The cost of vaccines was gathered from the centralized procurement information platform of all Chinese provinces. Treatment costs, epidemiological data, and other model parameters were obtained from published literature. The cost of vaccination, treatment costs saved, net costs, cases and deaths averted, life years saved, disability-adjusted life years (DALYs) prevented, and incremental cost-effectiveness ratios were predicted both provincially and nationally. Deterministic sensitivity analyses were used to explore model uncertainty.
Results
The net cost of vaccinating with the domestic bivalent HPV vaccine was the lowest. At the national level, after bivalent or quadrivalent HPV vaccination, the number of cases and deaths averted due to cervical cancer were 12,545 and 5109, respectively, whereas the 9-valent HPV vaccine averted 28,140 cases and 11,459 deaths. HPV vaccines were cost-effective at a national level (maximum cost US$ 18,165 per DALY gained.) compared to the 3 times GDP per capita (US$ 30,837). Bivalent HPV vaccines were cost-effective in all 31 provinces. Imported quadrivalent and 9-valent HPV vaccines were cost-effective in 29 provinces, except Heilongjiang and Gansu. The univariate sensitivity analysis showed that the results were robust when the model parameters were changed, and that the discount rate was the main factor affecting the baseline results.
Conclusions
This study provides evidence that the inclusion of HPV vaccination in the immunization program would be cost-effective at a national level and in most provinces. Provinces with a higher population have more prevented cases, deaths, and DALYs . The economics of HPV vaccination at the provincial level differs from that at the national level, and provinces with an inability to pay should seek help from state subsidies.
Introdução A infecção genital pelo HPV é a mais freqüente infecção sexualmente transmissível (IST) na mulher e no homem 1. Atualmente existem mais de 200 tipos diferentes identificados de HPV, entre os quais mais de 100 estão completamente seqüenciados geneticamente e mais de 120 com seqüenciamento parcial. Cerca de 45 tipos infectam o epitélio do trato anogenital masculino e feminino 2. Destes, cerca de 18 são
Objective:
The aim of this study was to explore the prevalence of low and high-risk HPV genotypes in PAP smear samples of women in northern region of the UAE using HPV direct flow CHIP method.
Methods:
A cross-sectional retrospective study was conducted between September 2021 to April 2022. A total of 104 liquid-based cervical cytology samples were obtained from women aged 20-59 years attending the Gynaecology out-patient department of Thumbay University Hospital and other hospitals of Northern Emirates of UAE, processed for the routine cytological examination to identify and differentiate morphological changes of the PAP smear samples. HPV genotyping was performed using HPV direct flow CHIP method.
Results:
In total, 112 HPV genotypes were detected in 63 women (60.57%) included 18 abnormal cytological and 45 normal epithelial samples. 63 LR and 49 HR HPV genotypes were identified in all the 63 positive samples. Highest rate of infection with multiple LR and HR HPV genotypes were detected in women aged 40-49 years (25.9%) and 20-29 years (23.5%). Infection by HPV6 (13.46%), HPV11 (9.61%), HPV16 (9.61%), HPV62/81 (7.69%) and HPV45 (7.69%) were the most common genotypes. A moderate increase than expected incidence of HPV45 and 62/81 (7.69%) were detected. Co-infection with multiple low and high-risk genotypes is present in 20.2% cases; in that, HPV6 (15.9%) was the most common followed by HPV62/81 (12.7%) and HPV16 (11.11%). The prevalence of HPV18 was found to be 1.6%.
Conclusion:
The genotypes 6, 45, 16, 11, 67, 62/81 were the most common HPV infections in the women between the age group of 21 and 59-years-old. A moderate increase of HPV45, 62/81 and much less prevalence of HPV18 were detected in the study population. 43.27% of the normal epithelia were positive to different low and high-risk HPV genotypes. This finding highlights the importance of molecular genotyping of HPV to emphasize the cervical screening triage.
El cáncer de cuello uterino es causado por la infección persistente del epitelio cervical con los genotipos de alto riesgo del Virus del Papiloma Humano. Para su detección se realizan pruebas moleculares que detectan el gen L1 del VPH. Este gen puede perderse hasta en el 11 % de los casos durante la integración del ADN viral en el genoma del hospedero originando falsos negativos. Por otra parte, el oncogén E7 se expresa durante todas las etapas de progresión de la enfermedad. El objetivo de este trabajo fue estandarizar una PCR en tiempo real del oncogén E7 (E7-qPCR) para genotipificación y cuantificación de 6 VPH-AR. Los resultados muestran que la E7- qPCR amplificó VPH-16, -18, -31, -33, -35 y -45 con una alta sensibilidad con límites de detección desde 102 copias, eficiencias entre 90 y 110 %, valores R2 > 0,97 y análisis de curva de fusión que revelan productos específicos.
Background and Design: The human papillomavirus (HPV) is a non-enveloped DNA virus infecting skin and mucosal surfaces and causes one of the most common sexually transmitted infections worldwide. Thus, physicians must know about HPV infections, associated cancers, and immunization for public health. This study aimed to determine the knowledge of medical faculty students about HPV infections, related cancers, and vaccines and examine related variables.
Materials and Methods: This descriptive study included all students in the first to fifth grades of the faculty of medicine. Data were collected with a two-part questionnaire consisting of 37 questions. Questionnaires were filled voluntarily. Data were analyzed with SPSS version 18.0. Results: The study included 250 medical students, and 52.4% (n=131) were men. While 95.6% (n=239) stated that they were aware of HPV, only 39.2% thought that they had sufficient knowledge. The most important sources of information were lectures and the Internet. Only 3.6% (n=9) of the students had been vaccinated against HPV. The most important reason (58%) for not being vaccinated was not having heard of the HPV vaccine before or not knowing someone who had it, and the other important reason was economics. Nearly 80% of the students thought that HPV vaccines should be included in routine vaccination. While 60% of the students stated that they would get an HPV vaccine if a free vaccine is provided, the lack of sufficient information was cited as the most important reason (45%) against the widespread use. Conclusion: The knowledge of medical school students about HPV infection and vaccines was not very sufficient, and the vaccination rate was low. Our results suggest that HPV-related courses in medical education and reimbursement of vaccines by health authorities require some adjustments in the core education curriculum and national health policies.
Objective:
The clinical outcome of high-risk HPV (hr-HPV) infection varies according to genotype(s). Patients may harbor either one (s-HPV) or multiple HPV (m-HPV) genotypes. Recently, the relationship between m-HPV infections and high-grade dysplasia has been questioned, and controversial results have been obtained; therefore, its clinical significance has not been elucidated. This study aimed to evaluate which group is associated with higher grade dysplasia by analyzing colposcopic punch biopsies.
Material and methods:
A total of 690 patients who were scheduled for a diagnostic excisional procedure between April 2016 and January 2019 due to the detection of high-grade dysplasia (CIN 2/3) in colposcopy were included. Patients who were not scheduled for colposcopic examination or cervical punch biopsy, or who were scheduled for an excisional procedure due to smear-biopsy incompatibility or persistent low-grade dysplasia were excluded. Patients with a negative HPV test and an unknown HPV genotype were also excluded. SPSS was used for analysis.
Results:
Among the patients scheduled for excision (n= 404), 74.5% had a s-HPV and 25.5% had a m-HPV infection. The number of CIN 1, 2, and 3 per patient in the m-HPV group was significantly higher than the s-HPV group (P= 0.017). When this analysis was made over the number of CIN 2,3 per patient in the s-HPV and m-HPV groups, it was calculated as 1.29 (389/301) and 1.36 (140/103), respectively and no difference was found (p=0.491).
Conclusion:
Patients in the multiple HPV group, who underwent more colposcopic cervical biopsies, had higher numbers of CIN lesions, regardless of age and cytology results.
Importance:
Human papillomavirus vaccination coverage rates lie below desired thresholds in Switzerland. Because general practitioners are the main contact for the relatively rare health issues of many Swiss young adults, primary care offers an important opportunity to provide catch-up human papillomavirus vaccination.
Objective:
To examine the knowledge, experiences, and attitudes of Swiss university students in the context of receiving human papillomavirus vaccination during primary care visits.
Design, setting, and participants:
This self-administered, cross-sectional, web-based survey study was conducted among students of 3 universities and 1 educational institution for health professions in the Swiss Canton of Zurich. Specific questions about human papillomavirus vaccination experience were directed to respondents who had received at least 1 dose administered by a general practitioner. Responses were collected during 12-week intervals between November 11, 2020, and April 7, 2021, and data were analyzed from August 3 to August 30, 2022.
Main outcomes and measures:
The primary outcome was whether human papillomavirus vaccination had been administered on the patient's or the general practitioner's initiative.
Results:
The responses of 5524 participants (median [IQR] age, 23 [21-25] years; 3878 women [70.2%]) were analyzed. The survey completion rate was 90.9% (5524 of 6076 students who consented to participate). A total of 2029 respondents (1792 women [46.2%] and 237 men [14.6%]) reported having received at least 1 human papillomavirus vaccination dose, of whom 740 (36.5%) had received at least 1 dose administered by a general practitioner. Among these, 190 respondents (25.7%) reported that vaccine administration had occurred on their request rather than on their general practitioner's initiative. Among all respondents, 4778 (86.5%) wanted to obtain more information about human papillomavirus vaccination at a general practitioner's office, and 2569 (55.3%) rated acute consultations in general practice as inappropriate for addressing human papillomavirus vaccination.
Conclusions and relevance:
The findings of this survey study of Swiss university students suggest that primary care shows a high potential for increasing human papillomavirus vaccination coverage rates in Switzerland. However, there was room for improvement in the proactivity of general practitioners, especially with men, and in the attitudes of students toward the appropriateness of acute consultations in general practice for addressing human papillomavirus vaccination.
The current practice of determining histologic grade with a single molecular biomarker can facilitate differential diagnosis but cannot predict the risk of lesion progression. Cancer is caused by complex mechanisms, and no single biomarker can both make accurate diagnoses and predict progression risk. Modelling using multiple biomarkers can be used to derive scores for risk prediction. Mathematical models (MMs) may be capable of making predictions from biomarker data. Therefore, this study aimed to develop MM–based scores for predicting the risk of precancerous cervical lesion progression and identifying precancerous lesions in patients in northern Thailand by evaluating the expression of multiple biomarkers. The MMs (Models 1–5) were developed in the test sample set based on patient age range (five categories) and biomarker levels (cortactin, p16INK4A, and Ki–67 by immunohistochemistry [IHC], and HPV E6/E7 ribonucleic acid (RNA) by in situ hybridization [ISH]). The risk scores for the prediction of cervical lesion progression (“risk biomolecules”) ranged from 2.56–2.60 in the normal and low–grade squamous intraepithelial lesion (LSIL) cases and from 3.54–3.62 in cases where precancerous lesions were predicted to progress. In Model 4, 23/86 (26.7%) normal and LSIL cases had biomolecule levels that suggested a risk of progression, while 5/86 (5.8%) cases were identified as precancerous lesions. Additionally, histologic grading with a single molecular biomarker did not identify 23 cases with risk, preventing close patient monitoring. These results suggest that biomarker level–based risk scores are useful for predicting the risk of cervical lesion progression and identifying precancerous lesion development. This multiple biomarker–based strategy may ultimately have utility for predicting cancer progression in other contexts.
Cancer is a disease, the very name of which induces panic in those diagnosed with it and
their near ones .A major public health problem- it is a scourge on the economy. A big
concern in low- and middle-income countries (LMICs) and everyday this burden is
looming larger while resources to control cancer in LMICs, either from domestic budgets
or international aid, have not increased proportionately. This book is a lucid account on
cervical cancer keeping both general public and health care workers in mind. Most
populations in LMICs lack access to effective cervical cancer prevention, treatment, and
palliation. Attempts to provide an up-to-date review of etiology, epidemiology,
effectiveness, cost-effectiveness, and feasibility of interventions for cervical cancers.
Serious progress in cervical cancer prevention and treatment began about half a century
ago in high-income countries. The knowledge that has fueled progress became available
immediately for LMICs. Newer and better technologies are now available: HPV testing
can replace the more resource- and infrastructure-intensive Pap smear for cervical cancer
screening. Increasing national incomes and broader national health coverage in middle income countries , have already made a range of services available to a wider population.
The pace needs to be accelerated and efforts increased in low-income countries, India
only accounts for one-third of global cancer deaths.
The best approach to lowering the cervical cancer burden is a system that promotes
prevention as well as early detection and treatment. A focus on preventive measures that
include awareness generation of risk factors and screening benefits, mass screening
programmes and free packages of feasible interventions for masses is need of the hour .
Policy makers and those involved in planning need to make concerted efforts to save large
numbers of lives at an affordable cost and same should be prioritized by the public sector
as well NGO's have to be seriously involved . We profoundly thank Department of Biotechnology
Government of India for funding our mass cervical cancer screening programme under its
societal schemes.
In high income countries cervical cancer is no longer as dreaded as it was with the
increasing list of cancer survivors same can happen in LMIC its only a matter of serious
efforts and resolve on part of policy makers.
This book is a humble attempt to try and help in fighting cervical cancer
CharmakeelaArsha (Anal warts) are small growths in and around the anal region caused by the human papillomavirus (HPV). The patient, the age 39- years female, came to O.P.D. of shalyatantra complaining of baddhamalapravruti (hard stools), sarakta malapravruti (bleeding per rectum on and off), Guda pradeshi Mamsankura prachiti (feeling of mass at anal region), sashoola malapravruti (pain during and after defecation) since six months. Clinically diagnosed patient as a case of Charmakeelaarsha (anal warts) with internal piles and sentinel tag. Chedana (Excision) of anal warts and Sentinel tag by Agnikarma (electric cautery) was performed with ligation haemorrhoidectomy under spinal anaesthesia. It is challenging to manage post-operative wound healing with simple ointments. So there is a need to intervene in the ayurvedic ointments and treatment of post-operative wounds to heal them faster with no complications. After the operative procedure, the patient was managed with Ayurvedic protocols like laghu ahara, deepana, panchana, Virecheniya dravya, and Vranaropaka ointment for 15 days. The patient was assessed by Subjective and Objective parameters like the Numerical pain Scale, WHO are bleeding Scale, and VranaPariksha based on signs and Symptoms. The patient showed improvement in signs and Symptoms on the 15th Day. After two months of follow-up, the patient recovered well, and no recurrence or complaint was observed. Hence, such a study is more important for better wound healing and pain management. Instead of taking more extended oral therapies or anaesthetic blocks in post-operative management, the short procedure, like the present study, can save time. This case proved the efficacy of ayurvedic management in Shashtrakruta Charmakeela Arsha.
To identify new genetic risk factors for cervical cancer, we conducted a genome-wide association study in the Han Chinese population. The initial discovery set included 1,364 individuals with cervical cancer (cases) and 3,028 female controls, and we selected a 'stringently matched samples' subset (829 cases and 990 controls) from the discovery set on the basis of principal component analysis; the follow-up stages included two independent sample sets (1,824 cases and 3,808 controls for follow-up 1 and 2,343 cases and 3,388 controls for follow-up 2). We identified strong evidence of associations between cervical cancer and two new loci: 4q12 (rs13117307, Pcombined, stringently matched = 9.69 × 10(-9), per-allele odds ratio (OR)stringently matched = 1.26) and 17q12 (rs8067378, Pcombined, stringently matched = 2.00 × 10(-8), per-allele ORstringently matched = 1.18). We additionally replicated an association between HLA-DPB1 and HLA-DPB2 (HLA-DPB1/2) at 6p21.32 and cervical cancer (rs4282438, Pcombined, stringently matched = 4.52 × 10(-27), per-allele ORstringently matched = 0.75). Our findings provide new insights into the genetic etiology of cervical cancer.
It is estimated that viral infections contribute 15-20% of all human cancers. Several types of human papillomaviruse (HPV) are related to the development of many cancer types and their treatment. About 200 HPV viruses have been identified, and each type of virus is integrated with a certain type of clinical lesions affecting the areas of skin and mucous membranes. Infections associated with HPV are known to cause multiple cancer types such as uterine cancer, cervical, vaginal carcinoma, and other varieties of carcinomas such as genital and oropharyngeal, penile, and short-lived carcinomas. Most of the HPV types are considered as high-risk mutants that can provoke cervical cancer in females in addition to significant contribution to other cancer types such as anogenital cancer and tumor in head and neck regions. Among them, high risk human papilloma viruses (HR-HPV) subtypes 16 and 18 play a major role in the etiology of cervical cancer worldwide. Although, cervical cancer incidence and fatality rates vary greatly depending on geographical area, it is the leading cause of mortality in women around the world. In addition, it is epidemiologically similar to a sexually transmitted disease of low infectivity. In this review article, the association of HPV with different types of cancers have been explained, but the main focus remains on cervical cancer.
Background: Human papillomaviruses (HPVs) are non-enveloped, double-stranded DNA viruses and most women in the world are probably infected with at least one type of the virus during their sexual life. Oncogenic HPVs are predominantly sexually-transmitted pathogens and several high-risk types are associated with nearly all cases of cervical cancer worldwide. In view of paucity of data on the prevalence and distribution of various high risk HPV subtypes, this study was carried out to provide evidence based local data for cervical cancer preventive programs within this region.Methodology: This was a descriptive cross-sectional study involving 145 consenting women living in Ugbegun rural community of Edo central senatorial district, Edo State, Nigeria. Informed consent of each participant was obtained and socio-demographic information collected through interviewer-administered collection tool. Cervical swab sample was collected using the female cervical cell collection kit for HPV DNA testing. HPV DNA was detected by the Hybribio 21 HPV Geno array test kit which uses polymerase chain reaction (PCR) amplification and flow through hybridization assay. Summary statistics were presented as mean, standard deviation, median, frequency and proportions as appropriate using the Statistical Package for the Social Sciences (SPSS) version 22.0. Association of sociodemographic characteristics of the women with HPV prevalence was done using the ‘t’ test, with p value less than 0.5 considered statistical significance.Results: Twenty four of the 145 women tested positive, giving HPV prevalence of 16.6%. Six HPV serotypes were detected; types 16, 18, 35, 45, 52 and 58. HPV types 16 and 18 were most frequent, contributing 54.2%, and coinfection occurred in 29.2%. HPV-positive women had significantly higher mean number of life time sexual partners (p=0.046) and mean parity (p=0.0001) compared to HPV-negative women. The mean age of the women (p=0.710), mean age at menarche (p=0.570) and mean age at coitarche (p=0.940) were not significantly associated with prevalence of HPVConclusion: CThis study showed predominance of oncogenic cervical HPV types 16 and 18 within this sub region of rural Nigeria. Strengthening reproductive and sexual education in both males and females with focus on HPV vaccination, delaying sexual activities and reduction in number of child birth are strategies which could prevent high risk HPV infection and cervical cancer in rural communities. Contexte: Les papillomavirus humains (VPH) sont des virus à ADN double brin sans enveloppe et la plupart des femmes dans le monde sont probablement infectées par au moins un type de virus au cours de leur vie sexuelle. Les VPH oncogènes sont principalement des agents pathogènes sexuellement transmissibles et plusieurs types à haut risque sont associés à presque tous les cas de cancer du col de l'utérus dans le monde. Compte tenu du manque de données sur la prévalence et la distribution de divers sous-types de VPH à haut risque, cette étude a été réalisée pourfournir des données locales fondées sur des preuves pour les programmes de prévention du cancer du col de l'utérus dans cette région.Méthodologie: Il s'agissait d'une étude transversale descriptive impliquant 145 femmes consentantes vivant dans la communauté rurale d'Ugbegun du district sénatorial central d'Edo, dans l'État d'Edo, au Nigeria. Le consentement éclairé de chaque participant a été obtenu et les informations socio-démographiques ont été collectées via un outil de collecte administré par l'intervieweur. Un échantillon d'écouvillon cervical a été prélevé à l'aide du kit de collecte de cellules cervicales féminines pour le test ADN du VPH. L'ADN du VPH a été détecté par le kit de test Hybribio 21 HPV Geno array qui utilise une amplification par réaction en chaîne par polymérase (PCR) et un test d'hybridation en flux continu. Les statistiques sommaires ont été présentées sous forme de moyenne, d'écart-type, de médiane, de fréquence et de proportions, selon le cas, à l'aide de la version 22.0 du package statistique pour les sciences sociales (SPSS). L'association des caractéristiques sociodémographiques des femmes avec la prévalence du VPH a été réalisée à l'aide du test «t», avec une valeur de p inférieure à 0,5 considérée comme une signification statistique.Résultats: Vingt-quatre des 145 femmes ont été testées positives, ce qui donne une prévalence du VPH de 16,6 %. Six sérotypes de VPH ont été détectés ; types 16, 18, 35, 45, 52 et 58. Les types de VPH 16 et 18 étaient les plus fréquents, contribuant à 54,2%, et une co-infection s'est produite dans 29,2%. Les femmes séropositives pour le VPH avaient un nombre moyen de partenaires sexuels (p=0,046) et une parité moyenne (p=0,0001) significativement plus élevés que les femmes séronégatives pour le VPH. L'âge moyen des femmes (p=0,710), l'âge moyen à la ménarche (p=0,570) et l'âge moyen à la coïtarche (p=0,940) n'étaient pas significativement associés à la prévalence du VPH Conclusion: Cette étude a montré la prédominance des types de VPH cervicaux oncogènes 16 et 18 dans cette sousrégion du Nigéria rural. Le renforcement de l'éducation reproductive et sexuelle chez les hommes et les femmes en mettant l'accent sur la vaccination contre le VPH, le report des activités sexuelles et la réduction du nombre de naissances sont des stratégies qui pourraient prévenir les infections à VPH à haut risque et le cancer du col de l'utérus dans les communautés rurales.
Background
HPV16 and 18 are the most common high-risk human papillomavirus (HPV) types causing cervical lesions. Women with HPV16 and/or 18(HPV16/18) infections are the main targets for cervical screening. But the HPV16/18 infection status is complex, and clarifying the risk of different infection patterns for cervical lesions is essential for subsequent management options. Our study aimed to assess the risk of HPV16 or 18 combined with other high-risk(HR) and/or low-risk(LR) HPV types for cervical lesions and their clinical characteristics.
Methods
In this retrospective study, we analyzed the clinical data of 3,217 patients with HPV16/18 infection.We divided HPV16 or HPV18 multiple infections into 8 patterns: HPV16 + HR, HPV16 + LR, HPV16 + HR + LR, HPV18 + HR, HPV18 + LR, HPV18 + HR + LR, HPV16 + 18 and HPV16 + 18 + other-HPV. The analysis of data was performed by Chi-square test and multinational logistic regression. P < 0.05 was considered statistically significant.
Results
Among the HPV16/18 positive population, multiple infections accounted for 41.5% (1336/3217), and multiple infections were mainly associated with LSIL while single infection was more associated with HSIL+. And the risk of cervical lesions varied with different infection patterns. After adjusting co-factors, multiple logistic regression showed that compared with single HPV16 or 18 infection, HPV16 + HR and HPV18 + HR had a higher risk for LSIL(OR = 1.659, 95%=1.278–2.153; OR = 1.744,95%=1.046–2.907) while HPV16 + LR had a lower risk for HSIL+(OR = 0.477, 95%CI = 0.277–0.822).
Conclusion
Single HPV16 or 18 infection is more relevant to HSIL + with respect to multiple infections. Multiple infections may be transient that mainly lead to LSIL. Different infection patterns of multiple infections have different risks for cervical lesions, HPV16 or 18 combined with other HR-HPV are associated with a higher risk of LSIL, but HPV16 combined with LR-HPV decreases the risk of HSIL+. We propose that there is antagonistic relationship between HPV16 and some LR-HPV types.
Objective:
To determine the prevalence of HPV and investigate factors associated with the infection in women in the city of Francisco Beltrão, southwest Paraná, attending the public health system.
Methods:
This cross-sectional study included 324 women, aged between 18 and 65 years, who were attending public health services for routine gynecological consultation. Interviews were conducted to obtain information about socioeconomic, sexual, gynecological, and life habits. After performing the Papanicolaou test, endocervical brush was employed to detect HPV by polymerase chain reaction with the primers MY09-MY11.
Results:
The prevalence of HPV was 6.8%, out of which 58.3% presented with cytopathologic alterations. And the presence of current cervical alterations can increase the chances of having HPV by almost 33 times (ORadj: 32.688; p < 0.001), recent vaginal infection increased the chances of HPV infection by 2.7 times (ORadj: 2.773; p = 0.04). The non-white ethnicity increased HPV infection chances threefold (ORadj: 3.058; p = 0.039).
Conclusion:
The main finding was low prevalence of HPV infection. Factors that may be linked to HPV infection were cervical alterations, recent vaginal infection, and women's ethnicity.
Background: Infection with high-risk human papilloma virus (HPV) has been recognised as a causal factor for development of cervical pre-cancerous and cancerous lesions. So far more than 150 types of HPV are identified. Their distribution varies from country to country, also from region to region. Background knowledge about the distribution of HPV genotypes in invasive cervical cancer is crucial to guide the introduction of prophylactic vaccines. Objective: The study was aimed to assess the distribution of type specific human papilloma Virus DNA among cervical cancer patients. Methods: The study was a cross sectional, observational and single centred one. It was carried out in the department of gynaecological oncology, of Bangabandhu Sheikh Mujib Medical University (BSMMU). Purposive sampling was done according to the availability of patients. Results: HPV type 16 was detected in 35 cases (76.1%) followed by type 18 in 4 (8.7%) cases of cervical carcinoma. HPV 39, 56 and 68 were also detected, each was in 1 case (2.2 %). It was to be also found that 1 co-infection (2.2%) with HPV 33+35. HPV 16 was detected in 79.4 % of squamous cell carcinoma and in 70.0% of adenocarcinomas. HPV 18 was detected in 5.9 % of squamous cell carcinoma and 20.0% of adenocarcinomas. HPV 39 was detected in one case of small cell carcinoma (100.0%). One case of HPV 68 (2.9%) and one coinfection with HPV 33+35 (2.9 %) were found in squamous cell carcinoma. One case of HPV 56 (10.0%) was detected in adenocarcinoma of cervix. HPV DNA was not found in 3 cases of squamous cell carcinoma of cervix. Conclusion: The distribution of HPV infection among Bangladesh women is similar to other regions of Asia. However, type specific patterns are different. The study findings will guide the formulation of HPV vaccination policies in Bangladesh, impact of vaccination programmes, to predict the efficacy of cost effective prophylactic vaccine, introduction of newer generation vaccine and finally prevention of cervical carcinoma in the country. Bangladesh Med Res Counc Bull 2022; 48(1): 48-55
In Algeria in 2015 colorectal cancer represents the 2nd cause of
cancer mortality after lung cancer in men and after breast cancer
in women, according to Bejaïa’s register (2015) it is in first position in
men with a standardized incidence of 24 / 100,000 inhabitants and
second place among women with a standardized incidence of 16 /
100,000 inhabitants. The increasing CRC incidence and mortality
can be reduced by screening and treating adenomas and early can�cers. A pilot CRC screening program using immunochemical fecal
occult blood testing (iFOBT) and colonoscopy for test-positives were
implemented in Bejaïa a north-east district of Algeria, to inform the
acceptability, feasibility and scaling-up of screening in Algeria. This
report describes the implementation, coverage and performance in�dicators of this pilot project. This is a pilot study for colorectal cancer
screening with an immunological test of an average risk population
aged [50-74] over a 20-month period. A target population aged 50-
74 years was informed about and invited to undergo CRC screening
by community different aways. The referent generalist doctors pro�vided fecal sample collection kits and participants brought their
samples to one of the primary health units where nurses performed
iFOBT. iFOBT-positive persons were referred for colonoscopy at the
Bejaïa university hospital, and endoscopic polypectomy/biopsies
were performed according to the colonoscopic findings. Those with
confirmed CRC received appropriate treatment. Of the 10,000 target
population, 26% were screened using iFOBT between January 2016
and November 2017. Participation was higher among women (52 %)
than men (48 %) and lower in 60-74-year-old persons than in 50-54
year-olds. Of those screened, 156 (6.11 %) were found positive; positi�vity was equitably between men and woman. Conclusions : The
successful implementation of the pilot CRC screening with satisfac�tory process measures indicate the feasibility of scaling-up organized
CRC screening through existing health services In Algeria and Mena
Region in order to be able to propose an effective program to our health
system resulting from an evaluation based on a scientific research study
adapted to our society.
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.
Human papillomavirus (HPV) has been associated with cervical intraepithelial neoplasia, but the temporal relation between the infection and the neoplasia remains unclear, as does the relative importance of the specific type of HPV, other sexually transmitted diseases, and other risk factors.
We studied prospectively a cohort of 241 women who presented for evaluation of sexually transmitted disease and had negative cervical cytologic tests. The women were followed every four months with cytologic and colposcopic examinations of the uterine cervix and tests for HPV DNA and other sexually transmitted diseases.
Cervical intraepithelial neoplasia grade 2 or 3 was confirmed by biopsy in 28 women. On the basis of survival analysis, the cumulative incidence of cervical intraepithelial neoplasia at two years was 28 percent among women with a positive test for HPV and 3 percent among those without detectable HPV DNA: The risk was highest among those with HPV type 16 or 18 infection (adjusted relative risk as compared with that in women without HPV infection, 11; 95 percent confidence interval, 4.6 to 26; attributable risk, 52 percent). All 24 cases of cervical intraepithelial neoplasia grade 2 or 3 among HPV-positive women were detected within 24 months after the first positive test for HPV. After adjustment for the presence of HPV infection, the development of cervical intraepithelial neoplasia was also associated with younger age at first intercourse, the presence of serum antibodies to Chlamydia trachomatis, the presence of serum antibodies to cytomegalovirus, and cervical infection with Neisseria gonorrhoeae.
Cervical intraepithelial neoplasia is a common and apparently early manifestation of cervical infection by HPV, particularly types 16 and 18.
Oral contraceptive (OC) use was examined as a risk factor for cytological abnormalities of the cervix among 1964 women receiving Papanicolaou smears at three hospitals in the Washington, D.C., area. A single pathologist classified cytological results from all women as normal (n = 1423), atypia (n = 314), low grade squamous intraepithelial lesion (SIL; n = 208), or high grade SIL (n = 19). Women in each of the three abnormal groups were compared to women with normal cytological diagnoses. A subset of 579 patients, including most of the women with low or high grade SIL and a matched group of controls, was tested for human papillomavirus (HPV) by type-specific Southern blot hybridization to examine the effects of OC use while taking into account the effects of HPV infection. OC use was found to be unrelated to risk of atypia or low grade SIL but was associated with an elevated risk of high grade SIL that increased with longer duration of use (relative risk = 4.6, 95% confidence interval = 1.1-18.1 for greater than or equal to 5 years of use). HPV infection was associated, as expected, with risk of low and high grade SIL but not with atypia. Taking the HPV results into consideration did not alter the OC findings. There was no evidence that OC use synergistically increased the risk of cervical neoplasia among HPV-infected women, although small numbers prevented a reliable evaluation for high grade SIL. OC use did appear to increase the detection of HPV types 16/18, but the etiological importance of this finding is unclear.
From 1950 through 1978, condyloma acuminatum was diagnosed in 746 residents of Rochester, Minn (246 male and 500 female subjects). With the number of cases increasing almost every year until 1975, the mean annual incidence rate reached 106.5 per 100,000 population in the period 1975 through 1978, apparently the highest reported to date. Among age groups, the rate was highest in the 20- through 24-year-old group. Female patients contracted the infection at a higher rate and at a younger age than male patients. Anal condyloma occurred in one third of the male subjects studied and recurrent condyloma in 30% of the male subjects. More female than male patients had lesions at multiple locations.
Human papillomavirus DNA was detected in cervical specimens from 366 sexually active young women with cytomorphologically normal cervices using the polymerase chain reaction. In 93% (25/27) of initially infected women, the same viral type was not detected upon re-examination four menstrual cycles later. These results suggest that the majority of HPV infections in young women are transient.
Thirty-nine patients with condylomas (12 women and 27 men) attending a dermatology clinic were tested for genital human papillomavirus (HPV) DNA and for seroprevalence to HPV type 6 (HPV6) L1 virus-like particles. The L1 consensus PCR system (with primers MY09 and MY11) was used to determine the presence and types of HPV in sample specimens. All 37 (100%) patients with sufficient DNA specimens were positive for HPV DNA, and 35 (94%) had HPV6 DNA detected at the wart site. Three patients (8%) had HPV11 detected at the wart site, and one patient had both HPV6 and -11 detected at the wart site. Thirteen additional HPV types were detected among the patients; the most frequent were HPV54 (8%) and HPV58 (8%). Baculovirus-expressed HPV6 L1 virus-like particles were used in enzyme-linked immunosorbent assays to determine seroprevalence among the patients with warts. Seronegativity was defined by a control group of 21 women who were consistently PCR negative for HPV DNA. Seroprevalence was also determined for reference groups that included cytologically normal women who had detectable DNA from either HPV6 or HPV16 and women with HPV16-associated cervical intraepithelial neoplasia. Among the asymptomatic women with HPV6, only 2 of 9 (22%) were seropositive, compared with 12 of 12 (100%) female patients with warts. A similar trend in increased HPV6 seropositivity with increased grade of disease was found with the HPV16 DNA-positive women, whose seroprevalence increased from 1 in 11 (9%) in cytologically normal women to 6 in 15 (40%) among women with cervical intraepithelial neoplasia 1 or 3. However, only 4 of 25 (16%) male patients were seropositive. No factors examined, such as age, sexual behavior, or a history of warts, were found to definitively account for the gender difference in seroresponse.
Cervicovaginal lavage samples from 124 human immunodeficiency virus type 1 (HIV-1)-seropositive and 126 HIV-1-seronegative
women were collected monthly for 8 months and tested for human papillomavirus (HPV) DNA. The estimated prevalence of HPV was
42.8% in HIV-1-seropositive and 13.4% in -seronegative women (P < .00l). There was no significant difference in HPV DNA detection in HIV-1-seropositive women with CD4 cell counts of <300/mm3 (50% HPV-positive), 300–499/mm3 (36.4% HPV-positive), or ⩾500/mm3 (40.5% HPV-positive). However, HIV-1-seropositive women who were more immunocompromised, as indicated by lower CD4 cell counts,
were more likely to shed HPV persistently. The quantity of HPV DNA detected in cervicovaginal lavage samples was similar in
HIV-1-seropositive and -seronegative women. This study further defined the characteristics of HPV infections in HIV-1-infected
women.
Risk factors for cervicovaginal human papillomavirus (HPV) infection were investigated in 604 college women. HPV was detected
in 168 (27.8%) ofthe subjects by L1 consensus primer polymerase chain reaction, Southern blot hybridization, or both. Significant
independent risk factors for HPV (P < .05) included age (odds ratios [DRs]: 2.6 for 21-23 years old and 1.6 for >23, vs. ⩽0;20), ethnicity (DRs: 3.2 for black,
2.2 for Hispanic, vs. white/other), number of lifetime male vaginal sex partners (DRs: 4.5 for 2, 5.8 for 3 or 4, 10.3 for
⩾5, vs. 1), living with smokers (OR: 1.9), male partner's number of lifetime sex partners (DRs: 2.1 for 2 or 3, 3.1 for 4-10,
2.7 for ⩽11, vs. 1), duration of sexual relationship for > 12 months (OR: 0.6), and male partner currently in college (OR:
0.6). These data demonstrate that the predominant risk factors for genital HPV infection in young women are related not only
to their own sexual behaviors but also to those of their male partners.
To study the temporal relationship between serum antibody response and human papillomavirus type 16 (HPV-16) infection, a
cohort of 325 university women were scheduled for examinations at 4-month intervals. At every examination, interviews were
completed, cells were obtained for polymerase chain reaction–based testing and for Pap screening, and serum was obtained for
testing with a HPV-16 capsid-capture ELISA. Seroreactivity was associated with detection of HPV-16 DNA and with increased
numbers of sex partners. The median time to seroconversion was 8.3 months among women with incident HPV-16 infections. Within
16 months following HPV-16 DNA detection, 93.7% of women with prevalent and 67.1% of women with incident infections seroconverted.
After seroconversion, antibody responses were maintained during follow-up among HPV-16 DNA–positive women. Women who seroconverted
were 5.7 times (95% confidence interval = 2.4–13.4) more likely to have squamous intraepithelial lesions associated with the
detection of HPV-16 DNA than were women who did not seroconvert.
Genital human papillomavirus (HPV) infection is highly prevalent in sexually active young women. However, precise risk factors for HPV infection and its incidence and duration are not well known.
We followed 608 college women at six-month intervals for three years. At each visit, we collected information about lifestyle and sexual behavior and obtained cervicovaginal-lavage samples for the detection of HPV DNA by polymerase chain reaction and Southern blot hybridization. Pap smears were obtained annually.
The cumulative 36-month incidence of HPV infection was 43 percent (95 percent confidence interval, 36 to 49 percent). An increased risk of HPV infection was significantly associated with younger age, Hispanic ethnicity, black race, an increased number of vaginal-sex partners, high frequencies of vaginal sex and alcohol consumption, anal sex, and certain characteristics of partners (regular partners having an increased number of lifetime partners and not being in school). The median duration of new infections was 8 months (95 percent confidence interval, 7 to 10 months). The persistence of HPV for > or =6 months was related to older age, types of HPV associated with cervical cancer, and infection with multiple types of HPV but not with smoking. The risk of an abnormal Pap smear increased with persistent HPV infection, particularly with high-risk types (relative risk, 37.2; 95 percent confidence interval, 14.6 to 94.8).
The incidence of HPV infection in sexually active young college women is high. The short duration of most HPV infections in these women suggests that the associated cervical dysplasia should be managed conservatively.
Imagine this. You are a doctor in Tanzania. Annual health expenditure is $4 (£2.50) per head; malaria, tuberculosis, and maternal death are pressing problems; 150,000 people died from AIDS last year; and 9% of adults are infected with HIV. Life expectancy is 53 years. As an oncologist in the country's only cancer centre, you saw 1650 new cases last year. This probably represents about 10% of the total - your centre is inaccessible to the rest of the population. Around 90% of patients present with late stage, incurable disease. How do you begin to tackle cancer in such a context? This was the stark challenge posed by Twalib Ngoma of the Tanzania Cancer center to a conference on 'Cancer Strategies for the New Millenium.' This report synthesises selected themes from the discussion on how best to combat cancer in the developing world.
Human papillomavirus (HPV) is the main cause of cervical neoplasia. Because few population-based studies have investigated the prevalence of type-specific infection in relation to cervical disease, we studied a high-risk population, estimating the prevalence of HPV infection and the risk associated with various HPV types.
We screened 9175 women in Guanacaste, Costa Rica, to obtain a referent standard final diagnosis, and tested 3024 women for more than 40 types of HPV with a polymerase chain reaction-based system.
Among women with normal cytology, HPV infections peaked first in women younger than 25 years, and they peaked again at age 55 years or older with predominantly non-cancer-associated types of HPV and uncharacterized HPV types. Low-grade squamous intraepithelial lesions (LSILs) (n = 189) decreased consistently with age. The prevalence of high-grade squamous intraepithelial lesions (HSILs) (n = 128) peaked first around age 30 years and again at age 65 years or older. Seventy-three percent of LSILs were HPV positive, with HPV16 being the predominant type (16% of positive subjects). HPV was found in 89% of HSILs and 88% of cancers, with HPV16 being strongly predominant (51% and 53% of positive subjects). Virtually all HSILs and cancers had cancer-associated HPV types, with high odds ratios (ORs) and attributable fractions around 80%. Risk for HPV16 was particularly high (OR for HSILs = 320, 95% confidence interval [CI] = 97-1000; OR for cancer = 710, 95% CI = 110-4500).
We confirm the early decline of HPV infection with age but note increased prevalence after menopause, which could be related to a second peak of HSILs, an observation that warrants further investigation. At least 80% of HPVs involved in cervical carcinogenesis in this population have been characterized. Polyvalent vaccines including the main cancer-associated HPV types may be able to prevent most cases of cervical disease in this region.
Cervical scrapes from 116 British women referred with cervical cancer were tested for the presence of high oncogenic risk human papillomavirus (HPV) genotypes (HPV(hr)). Ninety-four per cent of the scrapes had one or more of these virus types and 66% were HPV16-positive. HPV18 was more frequent in adenocarcinoma. No evidence was found for an increased cancer risk associated with the HPV16 E6 350G variant. The HLA DRB1* and DQB1* alleles in these women and in 155 women with normal cytology and negative for HPV(hr) DNA were compared. DQB1*0301 alone (2P = 0.02) and in combination with DRB1*0401 (2P = 0.02) was found to be associated with cervical cancer. This was more marked in cancers positive for HPV types other than HPV16. In contrast, DRB1*1501 alone and in combination with DQB1*0602 was not significantly elevated in cancers overall, but did show some excess in HPV16-positive cancers (2P = 0.05), associated with HPV16-positive cervical cancers. Taking all cancers together, a marginally significant protective effect was found for DQB1*0501 (2P = 0.03) but no protective effect could be seen for DRB1*1301.
To distinguish risk factors for acquisition of cervical human papillomavirus (HPV) infection from the determinants of neoplasia among infected individuals we have conducted a three-arm case-control study nested within a large population-based cohort of women (the Manchester cohort) screened for HPV at entry using L1 consensus primer PCR. The study includes 181 HPV-positive controls who did not develop high-grade cervical intraepithelial neoplasia (CIN3) during follow-up, 203 HPV-negative controls, and 199 HPV-positive cases with histologically confirmed CIN3. Detailed information on sexual, reproductive and gynaecological history, oral contraceptive use and smoking was obtained at face-to-face interview. There was a striking division between risk factors for infection and those predictive of disease. Comparing the HPV-positive against the HPV-negative controls, the only risk factors for infection were number of sexual partners (OR for six or more = 3.89; 95% Cl = 1.99-7.62), a relatively recent new sexual relationship (OR for a new partner within the previous 2 years = 4.17; 95% Cl = 2.13-8.33), and a history of previous miscarriage (OR = 2.59; 95% Cl = 1.28-5.21). The determinants of CIN3 among infected women were, in contrast, early age at first intercourse (OR for 16 years old or less = 3.23; 95% Cl = 1.33-7.69), a long time since starting a new sexual relationship (OR for 6 years or more = 4.94; 95% Cl = 2.51-9.71), and cigarette smoking, with strong evidence for a dose- response (OR for current smoking habit 20+ per day = 2.57; 95% Cl = 1.49-4.45). Oral contraceptive use was not significantly associated with either HPV infection or CIN3.
HPV infections of the genital tract are one of the most common sexually transmitted viral infections in the United States. Data from STD clinics and private physicians’ offices reveal that genital warts, one manifestation of genital HPV infection, have been diagnosed more frequently in recent years. Using a variety of diagnostic techniques, asymptomatic HPV infection has been identified in men and women and is probably much more common than clinically apparent infection.
To assess long‐term trends in the prevalence of oncogenic human papillomavirus (HPV) infection, we performed a cross‐sectional serosurvey of the seroprevalence of the major oncogenic HPV type, HPV16, among 3,512 pregnant women undergoing population‐based serological screening at the first trimester of pregnancy in the same catchment area in Stockholm, Sweden, during 1969, 1983 or 1989. The overall HPV16 seroprevalence rates were 16% in 1969, 22% in 1983 and 21% in 1989. Seroprevalence was significantly increased, comparing both 1969 vs. 1983 (p = 0.0005) and 1969 vs. 1989 (p = 0.008). By comparison, the previously reported herpes simplex 2 (HSV‐2) seroprevalence in the same women increased from 17% in 1969 to 32% in 1983 and 33% in 1989, whereas the seroprevalence rates of HSV‐1 were the same (69% in 1969, 63% in 1983 and 68% in 1989). Odds ratios for HPV16‐positive women to also be HSV‐2‐positive were 1.8 in 1969 (p < 0.005), 1.1 in 1983 (p = NS) and 1.0 in 1989. Our results suggest that both HSV‐2 and HPV16 became more generally spread in the Swedish population between 1969 and 1983 but that the spread has been stable during the 1980s. Int. J. Cancer 76:341–344, 1998.© 1998 Wiley‐Liss, Inc.
Aims
If human papillomavirus (HPV) testing is to be included within cervical screening programmes, the importance of multiple HPV infections in cervical neoplasia needs to be determined. This study investigated the diversity of multiple HPV types in a routine cervical screening population, and assessed associations with cervical neoplasia.
Methods
Overall HPV prevalence, type specific prevalence, and extent of multiple infection were assessed in residual material from 3444 liquid based cytology samples, using real time GP5+/GP6+ polymerase chain reaction for screening and linear array assay for genotyping. HPV status was studied in relation to age and concurrent cytological evidence of dyskaryosis.
Results
Twenty per cent of samples were HPV positive. HPV type diversity was broad, and multiple HPV infections occurred in half of the HPV positive samples. Younger women were significantly more likely to harbour multiple high risk HPV (HR-HPV) infections. Infections with multiple HR-HPV types were found in 3.4% of samples negative for neoplasia and in 33.3%, 41.8%, and 40.4% of samples with borderline, mild, or high grade dyskaryosis, respectively. Single HR-HPV infections were found in 4.9%, 38.6%, 45.0%, and 51.1% of negative, borderline, mild, or high grade dyskaryosis samples, respectively.
Conclusions
Multiple HR-HPV infections were most prevalent in young women. Multiple HR-HPV infections were not more frequent in high grade than in low grade cervical neoplasia, reflecting common sexual transmission of multiple HR-HPV. Prospective cohort studies linking sequential loss or gain of HPV types with cytological analysis are required to assess the impact of multiple HR-HPV infections on neoplastic progression.
The risk of cervical neoplasia for women with normal Papanicolaou smears was calculated for those whose smears were human papillomavirus (HPV) positive and those whose smears were HPV negative. Data on 347 cases and controls were analyzed in a population-based, nested case-control study. Cases (n = 77) were women who participated in the Utrecht screening program (1976-1984) in the Netherlands and who developed cervical intraepithelial neoplasia 3 or microinvasive or invasive squamous cervical cancer after having a negative smear (1980-1986). Controls (n = 270) were matched on age (±5 years) and follow-up period. DNA was isolated from the Papanicolaou smears and was tested for the presence of HPV DNA by using the ultrasensitive broad-spectrum, general short-fragment polymerase chain reaction. HPV was found in 55 (71%) of the baseline smears of the 77 cases and in 31 (11%) of those of the 270 controls. The age-adjusted odds ratios for developing cervical intraepithelial neoplasia or microinvasive or invasive cervical cancer were 19.2 (95 percent confidence interval (Cl): 10.3, 35.7) for HPV positivity in general, 5.4 (95% CI : 1.5, 19.5) for infection with low-risk HPV genotypes, 24.0 (95% Cl: 12.4, 46.4) for high-risk HPV genotypes, and 104.8 (95% Cl: 29.5, 372.7) for HPV type 16.
Incidence data on human papillomavirus (HPV) infection are limited, and risk factors for transmission are largely unknown. The authors followed 603 female university students in Washington State at 4-month intervals between 1990 and 2000. At each visit, a sexual and health questionnaire was completed and cervical and vulvovaginal samples were collected to detect HPV DNA. At 24 months, the cumulative incidence of first-time infection was 32.3% (95% confidence interval: 28.0, 37.1). Incidences calculated from time of new-partner acquisition were comparable for enrolled virgins and nonvirgins. Smoking, oral contraceptive use, and report of a new male sex partner—in particular, one known for less than 8 months before sex occurred or one reporting other partners—were predictive of incident infection. Always using male condoms with a new partner was not protective. Infection in virgins was rare, but any type of nonpenetrative sexual contact was associated with an increased risk. Detection of oral HPV was rare and was not associated with oral-penile contact. The data show that the incidence of HPV associated with acquisition of a new sex partner is high and that nonpenetrative sexual contact is a plausible route of transmission in virgins. cohort studies; incidence; papillomavirus, human; sexual abstinence; sexual partners; sexually transmitted diseases
To clarify the role of human papillomavirus (HPV) in penile cancer we evaluated the prevalence of HPV DNA in different histological subtypes of penile carcinoma, dysplasia, and condyloma using a novel, sensitive SPF10 HPV polymerase chain reaction assay and a novel genotyping line probe assay, allowing simultaneous identification of 25 different HPV types. Formalin-fixed, paraffin-embedded tissue samples were collected from the United States and Paraguay. HPV DNA was detected in 42% cases of penile carcinoma, 90% cases of dysplasia, and 100% cases of condyloma. There were significant differences in HPV prevalence in different histological cancer subtypes. Although keratinizing squamous cell carcinoma and verrucous carcinoma were positive for HPV DNA in only 34.9 and 33.3% of cases, respectively, HPV DNA was detected in 80% of basaloid and 100% of warty tumor subtypes. There was no significant difference in HPV prevalence between cases from Paraguay and the United States. In conclusion, the overall prevalence of HPV DNA in penile carcinoma (42%) is lower than that in cervical carcinoma (∼100%) and similar to vulvar carcinoma (∼50%). In addition, specific histological subtypes of penile cancer—basaloid and warty—are consistently associated with HPV, however, only a subset of keratinizing and verrucous penile carcinomas is positive for HPV DNA, and thus these two tumor groups seem to develop along different pathogenetic pathways.
High parity has long been suspected of being associated with an increased risk of cervical cancer, but previous analyses of this association have not taken the strong effect of human papillomavirus (HPV) into account. To assess the role of reproductive factors in the progression from HPV infection to cancer, we did a pooled analysis including only HPV-positive women.
We pooled data from eight case-control studies on invasive cervical carcinoma (ICC) and two on in-situ carcinoma (ISC) from four continents. 1465 patients with squamous-cell ICCs, 211 with ISCs, 124 with adenocarcinomas or adenosquamous ICCs, and 255 control women, all positive for HPV DNA by PCR-based assays, were analysed. We calculated pooled odds ratios by means of unconditional multiple logistic regression models, and adjusted them for sexual and non-sexual confounding factors. The 95% CI were estimated by treating the odds ratio as floating absolute risk.
We found a direct association between the number of full-term pregnancies and squamous-cell cancer risk: the odds ratio for seven full-term pregnancies or more was 3.8 (95% CI 2.7-5.5) compared with nulliparous women, and 2.3 (1.6-3.2) compared with women who had one or two full-term pregnancies. There was no significant association between risk of adenocarcinoma or adenosquamous carcinoma and number of full-term pregnancies.
High parity increases the risk of squamous-cell carcinoma of the cervix among HPV-positive women. A general decline in parity might therefore partly explain the reduction in cervical cancer recently seen in most countries.
Use of oral contraceptives could increase risk of cervical cancer; however the effect of human papillomavirus (HPV), the main cause of cervical cancer, is not usually taken into account. We aimed to assess how use of oral contraceptives affected risk of cervical cancer in women who tested positive for HPV DNA.
We pooled data from eight case-control studies of patients with histologically confirmed invasive cervical carcinoma (ICC) and from two studies of patients with carcinoma in situ (ISC). Information about use of oral contraceptives was obtained from personal interviews. Effects were estimated as odds ratios, with logistic-regression models adjusted for possible confounders.
1465 of 1561 (94%) patients with ICC, 211 of 292 (72%) with ISC, and 255 of 1916 (13%) controls were positive for HPV DNA. Compared with never-users, patients who had used oral contraceptives for fewer than 5 years did not have increased risk of cervical cancer (odds ratio 0.73; 95% CI 0.52-1.03). The odds ratio for use of oral contraceptives was 2.82 (95% CI 1.46-5.42) for 5-9 years, and 4.03 (2.09-8.02) for use for 10 years or longer, and these risks did not vary by time since first or last use.
Long-term use of oral contraceptives could be a cofactor that increases risk of cervical carcinoma by up to four-fold in women who are positive for cervical HPV DNA. In the absence of worldwide information about HPV status, extra effort should be made to include long-term users of oral contraceptives in cervical screening programmes.
A recombinant vaccinia virus termed pLC201 VV was designed to coexpress the Li and L2 late genes of human papillomavirus type 16 (HPV16). Synthesis of the Li and L2 proteins occurred in cells infected with pLC201VV, and 40-nm virus-like particles with a density of 1.31 g/ml were produced in the nuclei of cells synthesizing both L1 and L2, but not in cells synthesizing either protein alone. Virus-like particles were partially purified from infected cells by sucrose gradient sedimentation and shown to consist of capsomeres similar to HPV and contain glycosylated L1 viral capsid protein. The production of HPV-like particles using recombinant vaccinia virus should be useful for biochemical studies and could provide a safe source of material for the development of a vaccine.
Thesis (Ph. D.)--University of Washington, 1997 Prospective studies were conducted among women attending a University and women presenting to a STD clinic to evaluate an association between risk of cervical intraepithelial neoplasia grade 2-3 (CIN 2-3) and human papillomavirus type 16 (HPV16) variants. CIN 2-3 was histologically confirmed in 9 of 57 HPV16 positive women attending the University and in 10 of 66 HPV16 positive women presenting to the STD clinic. Among university students, those with HPV16 non-prototype-like (NPL) variants were 6.5 (95% CI, 1.6-27.2) times more likely to develop CIN 2-3 than those with prototype-like (PL) variants. A similar association was observed among women presenting to the STD clinic (RR = 4.5; 95% CI, 0.9-23.8).An association between risk of anal intraepithelial neoplasia grade 3 or carcinoma in situ (AIN3/CIS) and HPV16 variants was examined in a cohort of bisexual or homosexual men. Of 589 men, 37% were positive for HPV16, including 33% with PL variants and 4% with NPL variants. AIN3/CIS was histologically confirmed in 22 cases. Among men with HPV16 infection, those with NPL variants were 4.3 times (95% CI = 1.6-11.6) more likely to develop AIN3/CIS than those with PL variants. Additional adjustments for HIV status and CD4 count or the level of HPV16 DNA did not alter risk estimates substantially. Neither a high level of viral DNA nor a prolonged period of DNA detection was associated with HPV16 NPL variants.To verify whether HPV16 variants change over time, sequence variation of variants was examined in consecutive specimens from individuals. Seventy subjects who were repeatedly HPV16 DNA positive, over 2-8 four-monthly visits, showed an identical polymorphism at every visit. Sequencing many clones from each specimen confirmed that one major variant seemed to predominate over time, whereas minor variants appeared more transient.While the data suggest that HPV16 NPL as compared to PL variants are associated with an increased risk of high grade lesions, the biological mechanism relating to this excess risk remains undetermined. In view of the relatively short time followed, it would not be appropriate to generalize our data beyond the observed time period nor to the risk of invasive cancer.
Carcinoma of the cervix has several well–established epidemiologic risk factors, including multiple sexual partners and early age at first intercourse. Human papillomavirus (HPV) infection appears to have an etiologic role in the development of cervical neoplasia, but evidence linking HPV infection to known risk factors for cervical cancer has been inconsistent. The lack of expected correlations may be due to the inaccuracy of HPV assays previously used. A polymerase chain reaction DNA amplification method for the detection of HPV was used to investigate the determinants of genital HPV infection in a cross-sectional sample of 467 women attending a university health service. In contrast to studies using less accurate detection methods, the risk factors for HPV infection found here were consistent with those for cervical neoplasia. The risk of HPV infection was strongly and independently associated with increasing numbers of sexual partners in a lifetime, use of oral contraceptives, younger age, and black race. Age at first intercourse, smoking, and history of a prior sexually transmitted disease were correlated with, but not independently predictive of, HPV infection. These results demonstrate that the key risk factors for cervical carcinoma are strongly associated with genital HPV infection. This correlation suggests that HPV has an etiologic role in cervical neoplasia and reaffirms the sexual route of HPV transmission. [J Natl Cancer Inst 83: 997–1003, 1991]
By a collaborative effort among British cytopathologists, 101 women were identified who had had unsuspected "positive" cervical smears but who, after at least 2 years, had still escaped biopsy through refusal, default, or failure to trace. Of these, 31 still could not be traced; 10 were traced but could not be further examined (8 because they refused); 7 had clinically diagnosed carcinoma of the cervix; and the remaining 53 had further smears and/or biopsies after a mean interval of 5.2 years. In 19 of the 53 the smear had become negative or biopsy showed no lesion. Regression was confined to women aged under 40 at the time of the initial positive smear. In 20 cases biopsy showed dysplasia or carcinoma-in-situ, in 3 microinvasive carcinoma, and in 3 occult invasive carcinoma. Of the 7 women who presented clinically with carcinoma of the cervix, this caused death in 5.
Infection by certain human papillomavirus types is regarded as the major risk factor in the development of cervical cancer, one of the most common cancers of women worldwide. Analysis of the immunogenic and structural features of papillomavirus virions has been hampered by the inability to efficiently propagate the viruses in cultured cells. For instance, it has not been established whether the major capsid protein L1 alone is sufficient for virus particle assembly. In addition, it is not known whether L1, L2 (the minor capsid protein), or both present the immunodominant epitopes required for induction of high-titer neutralizing antibodies. We have expressed the L1 major capsid proteins of bovine papillomavirus type 1 and human papillomavirus type 16 in insect cells via a baculovirus vector and analyzed their conformation and immunogenicity. The L1 proteins were expressed at high levels and assembled into structures that closely resembled papillomavirus virions. The self-assembled bovine papillomavirus L1, in contrast to L1 extracted from recombinant bacteria or denatured virions, also mimicked intact bovine papillomavirus virions in being able to induce high-titer neutralizing rabbit antisera. These results indicate that L1 protein has the intrinsic capacity to assemble into empty capsid-like structures whose immunogenicity is similar to infectious virions. This type of L1 preparation might be considered as a candidate for a serological test to measure antibodies to conformational virion epitopes and for a vaccine to prevent papillomavirus infection.
Carcinoma of the cervix has several well-established epidemiologic risk factors, including multiple sexual partners and early age at first intercourse. Human papillomavirus (HPV) infection appears to have an etiologic role in the development of cervical neoplasia, but evidence linking HPV infection to known risk factors for cervical cancer has been inconsistent. The lack of expected correlations may be due to the inaccuracy of HPV assays previously used. A polymerase chain reaction DNA amplification method for the detection of HPV was used to investigate the determinants of genital HPV infection in a cross-sectional sample of 467 women attending a university health service. In contrast to studies using less accurate detection methods, the risk factors for HPV infection found here were consistent with those for cervical neoplasia. The risk of HPV infection was strongly and independently associated with increasing numbers of sexual partners in a lifetime, use of oral contraceptives, younger age, and black race. Age at first intercourse, smoking, and history of a prior sexually transmitted disease were correlated with, but not independently predictive of, HPV infection. These results demonstrate that the key risk factors for cervical carcinoma are strongly associated with genital HPV infection. This correlation suggests that HPV has an etiologic role in cervical neoplasia and reaffirms the sexual route of HPV transmission.
In an investigation conducted in student health clinic patients, the polymerase chain reaction was used to detect human papillomavirus (HPV) DNA, thereby allowing measurement of the prevalence of HPV infection and study of the association between HPV infection and risk factors for cervical cancer. Of 159 women eligible to participate, 105 (66%) provided a specimen of cervical cells for HPV typing, and also answered an interviewer-administered questionnaire which sought information on risk factors for cervical cancer. Nucleic acid extracted from cervical cells was screened with primers for HPV types 6, 11, 16, 18, 33 and with an HPV Consensus primer. Overall, the prevalence of HPV infection was 18.1%, while for HPV-6/11 it was 2.9% and for HPV-16/18 it was 10.5%. There were statistically significant increases in risk of HPV infection with a history of ever having smoked cigarettes (overall, and for HPV-16 alone) and with a history of usually having sexual intercourse during menstrual periods (overall, but not for HPV-16), and these associations were independent of the effects of age at first sexual intercourse and number of sexual partners. The latter 2 variables, as well as the total number of occasions of sexual intercourse, a history of anal intercourse, and a history of ever having used oral contraceptives, were not associated with statistically significant alterations in risk of HPV infection.
HPV infections of the genital tract are one of the most common sexually transmitted viral infections in the United States. Data from STD clinics and private physicians' offices reveal that genital warts, one manifestation of genital HPV infection, have been diagnosed more frequently in recent years. Using a variety of diagnostic techniques, asymptomatic HPV infection has been identified in men and women and is probably much more common than clinically apparent infection.
Previous studies of relationships between genital human papillomavirus infection and tentative risk factors have yielded conflicting results, possibly because of inaccuracy of the viral detection methods used and differences in selection criteria.
To determine human papillomavirus prevalence and identify risk factors in a group of young Swedish women.
This was a population-based study involving completion of a structured questionnaire, analysis of cervical scrapings for human papillomavirus and Chlamydia trachomatis, and serologic tests for C. trachomatis and herpes simplex virus antibodies.
The prevalence of human papillomavirus infection was 22% among the sexually active women and 4% among the virgins. A number of factors were associated with human papillomavirus prevalence in univariate analysis, but logistic regression analysis showed that lifetime number of male sexual partners was the only independent risk factor for human papillomavirus infection (adjusted odds ratio, 7.45; 95% CI, 2.79-19.92 for six or more partners vs. one partner).
Human papillomavirus infection is a prevalent sexually transmitted disease among young Swedish women, and the lifetime number of male sexual partners is a major risk factor.
Sequence differences in the noncoding region of the human papillomavirus type 16 (HPV-16) genome were displayed using single-stranded
conformational polymorphism (SSCP) analysis of polymerase chain reaction (PCR)-amplified material. Two variants accounted
for 50%–70% of all HPV-16 variants from 3 cohorts in Seattle. Seventy subjects who were repeatedly HPV-16 DNA-positive over
2–8 4-monthly visits showed an identical SSCP pattern at every visit. Only 10%–20% of the specimens showed evidence of infection
by multiple variants when assessed by SSCP. However, cloning and sequencing of the PCR products revealed a substantially higher
proportion of specimens with > 1 variant. Sequencing many clones from each specimen confirmed that 1 major variant seemed
to predominate over time, whereas minor variants appeared more transient. These results suggest that HPV-16 establishes a
persistent infection in which a single variant predominates: coinfection with additional HPV-16 variants results in a minor
population of HPV-16 genomes.
The prevalence of human papillomavirus (HPV) infection in cervical cell scrapes from a cohort of 276 young women was determined
by a general two-step polymerase chain reaction. HPV infection fluctuated among young women during a 2-year interval. The
total prevalence of HPV infection decreased from 21%to 8.3%. The most prevalent HPV types at enrollment were HPV16 (3.3%)
and HPV-6 (2.9%). At follow-up, the most common type was HPV-16 (2.9%), while no HPV-6 was detected. In 2 women only, the
same HPV type persisted. Regression of HPV infection was found in 80% of the women. A new HPV type-specific infection was
detected in 7.2% of the women and was independently associated with a new sex partner or an abnormal smear since enrollment.
In many cervical cancers, human papillomavirus type 16 (HPV-16) DNA genomes are found to be integrated into the host chromosome. In this study, we demonstrate that integration of HPV-16 DNA leads to increased steady-state levels of mRNAs encoding the viral oncogenes E6 and E7. This increase is shown to result, at least in part, from an increased stability of E6 and E7 mRNAs that arise specifically from those integrated viral genomes disrupted in the 3' untranslated region of the viral early region. Further, we demonstrate that the A+U-rich element within this viral early 3' untranslated region confers instability on a heterologous mRNA. We conclude that integration of HPV-16 DNA, as occurs in cervical cancers, can result in the increased expression of the viral E6 and E7 oncogenes through altered mRNA stability.
