Human papillomavirus type competition and the associations between HPV types and future HPV acquisition in men

Infection with human papillomavirus (HPV) is the primary cause of cervical cancer and other anogenital cancers. Multiple HPV infections have been detected in up to 70% of HPV infected men, yet there are no data on the association between HPV types in men, which may impact the type-specific efficacy of HPV vaccination through HPV type competition and replacement. In a cohort of uncircumcised, human immunodeficiency virus (HIV)-seronegative men aged 17-28 years from Kisumu, Kenya, we assessed the associations between HPV types at baseline (N=2,702) using semi-Bayesian multivariate logistic regression. In a prospective analysis (N=1,064) we used parametric survival models to compare rates of acquisition of HPV infections among men infected and uninfected with vaccine-relevant types HPV-16, 18, 31, 45, 6, and 11 at baseline. Half of all men were HPV positive at baseline, of whom 57% had multiple HPV infections. In the cross-sectional analysis, HPV types 31, 39, 56, 58, and 59 were positively associated with both vaccine types HPV-16 and 18 (two-sided p-value <0.05); no negative associations between individual HPV types were observed. Over 2,462 person-years of follow-up, 2,233 incident HPV infections were detected. Men with HPV-18, 31, 45, or 11, but not HPV-16 or 6, had higher rates of any-HPV and high-risk (HR) HPV acquisition compared to men without each HPV type at baseline. Relative rates of acquisition of individual HR-HPV types varied by baseline HPV type; however, we did not observe a clear pattern of HPV acquisition by degree of phylogenetic relatedness to the baseline infection. Except for HPV-39 acquisition among men with HPV-6 (aHR: 0.1 (0.0, 0.8)), there was no evidence of negative associations between HPV types or reduced HPV acquisition among men with baseline infections that indicate a strong potential for HPV type competition. To better understand the potential for changes in the HPV type distribution following HPV vaccination, future studies that monitor HPV type distributions in pre- and post-vaccinated populations are needed.Doctor of Philosoph

Knowledge, Attitudes, Practices, and Perceived Risk of Cervical Cancer Among Kenyan Women: Brief Report

Eastern Africa has the highest incidence and mortality rates from cervical cancer worldwide. It is important to describe the differences among women and their perceived risk of cervical cancer in order to determine target groups to increase cervical cancer screening

Incidence and progression of cervical lesions in women with HIV: a systematic global review

Global data on cervical lesion incidence and progression in HIV-positive is essential for understanding the natural history of cervical neoplasia and informing screening policy

Worldwide incidence of cervical lesions: a systematic review

We conducted a systematic review summarizing data on incidence of high- and low-grade lesions in women with normal baseline cervical cytology, stratified by age (<30 and ⩾30 years), and baseline human papillomavirus (HPV) infection. Incidence of high- and low-grade lesions in women aged ⩾30 years with a baseline HPV infection increased over follow-up time (5-127 months), although incidence generally remained <10%. Without baseline HPV infection, incidence of high-grade lesions remained low over follow-up time (<5% over 5-122 months). Incidence of high-grade lesions in women aged ⩾30 years with baseline HPV infection appeared similar to that in women aged <30 years. In some women aged <30 years, high-grade lesions can develop relatively shortly after initial HPV infection. We observed an increase in low-grade lesions over time in women aged ⩾30 years with baseline HPV infection, potentially indicative of an HPV infection that is potentially progressing to higher grade lesions

Human papillomavirus and abnormal cervical lesions among HIV-infected women in HIV-discordant couples from Kenya

Objective HIV infection increases the risk of high-grade cervical neoplasia and invasive cervical carcinoma. The study addresses the limited data describing human papillomavirus (HPV) infection and cervical neoplasia among HIV-infected women in HIV-discordant relationships in sub-Saharan Africa, which is needed to inform screening strategies. Methods A cross-sectional study of HIV-infected women with HIV-uninfected partners was conducted to determine the distribution of type-specific HPV infection and cervical cytology. This study was nested in a prospective cohort recruited between September 2007 and December 2009 in Nairobi, Kenya. Cervical cells for HPV DNA testing and conventional cervical cytology were collected. HPV types were detected and genotyped by Roche Linear Array PCR assay. Results Among 283 women, the overall HPV prevalence was 62%, and 132 (47%) had ≥1 high-risk (HR)-HPV genotype. Of 268 women with cervical cytology results, 18 (7%) had high-grade cervical lesions or more severe by cytology, of whom 16 (89%) were HR-HPV-positive compared with 82 (41%) of 199 women with normal cytology (p<0.001). The most common HR-HPV types in women with a high-grade lesion or more severe by cytology were HPV-52 (44%), HPV-31 (22%), HPV-35 (22%), HPV-51 (22%) and HPV-58 (22%). HR-HPV genotypes HPV-16 or HPV-18 were found in 17% of women with high-grade lesions or more severe. HR-HPV screening applied in this population would detect 89% of those with a high-grade lesion or more severe, while 44% of women with normal or low-grade cytology would screen positive. Conclusion HR-HPV prevalence was high in this population of HIV-infected women with an uninfected partner. Choice of screening for all HR genotypes versus a subset of HR genotypes in these HIV-infected women will strongly affect the performance of an HPV screening strategy relative to cytological screening. Regional and subpopulation differences in HR-HPV genotype distributions could affect screening test performance

Planning for resilience in screening operations using discrete event simulation modeling: example of HPV testing in Peru

ABSTRACT: Background: The World Health Organization (WHO) has called for the elimination of cervical cancer. Unfortunately, the implementation of cost-effective prevention and control strategies has faced significant barriers, such as insufficient guidance on best practices for resource and operations planning. Therefore, we demonstrate the value of discrete event simulation (DES) in implementation science research and practice, particularly to support the programmatic and operational planning for sustainable and resilient delivery of healthcare interventions. Our specific example shows how DES models can inform planning for scale-up and resilient operations of a new HPV-based screen and treat program in Iquitos, an Amazonian city of Peru. Methods: Using data from a time and motion study and cervical cancer screening registry from Iquitos, Peru, we developed a DES model to conduct virtual experimentation with “what-if” scenarios that compare different workflow and processing strategies under resource constraints and disruptions to the screening system. Results: Our simulations show how much the screening system’s capacity can be increased at current resource levels, how much variability in service times can be tolerated, and the extent of resilience to disruptions such as curtailed resources. The simulations also identify the resources that would be required to scale up for larger target populations or increased resilience to disruptions, illustrating the key tradeoff between resilience and efficiency. Thus, our results demonstrate how DES models can inform specific resourcing decisions but can also highlight important tradeoffs and suggest general “rules” for resource and operational planning. Conclusions: Multilevel planning and implementation challenges are not unique to sustainable adoption of cervical cancer screening programs but represent common barriers to the successful scale-up of many preventative health interventions worldwide. DES represents a broadly applicable tool to address complex implementation challenges identified at the national, regional, and local levels across settings and health interventions—how to make effective and efficient operational and resourcing decisions to support program adaptation to local constraints and demands so that they are resilient to changing demands and more likely to be maintained with fidelity over time

Epstein-Barr Virus, High-Risk Human Papillomavirus and Abnormal Cervical Cytology in a Prospective Cohort of African Female Sex Workers

Background High-oncogenic-risk human papillomavirus (hrHPV) is necessary, although insufficient, to promote cervical cancer. Like HPV, Epstein-Barr virus (EBV) is a common pathogen with the capacity to promote epithelial neoplasms. We examined the association between cervical EBV, hrHPV, and cytology in female sex workers in Nairobi, Kenya. Methods Women (n = 332) with known cervical cytology and hrHPV mRNA results were evaluated for cervical EBV DNA by conventional polymerase chain reaction. Prevalence ratios (PRs) were calculated to assess the relationships between EBV, hrHPV, and cervical cytology. Prospective analyses used risk ratios and time-to-event analyses to determine the association of EBV with hrHPV clearance and with abnormal cytology outcomes. Results Baseline prevalence of hrHPV and EBV was 29% and 19%, respectively. Higher EBV prevalence was found among women with older age, HIV, hrHPV, abnormal cytology, Mycoplasma genitalium infection, smoking habits, younger age at sexual debut, and less frequent condom use. At baseline, women with EBV had a higher prevalence of hrHPV infection than did EBV-negative women (52% vs. 24%; HIV-adjusted PR [95% confidence interval], 1.8 [1.3-2.6]). Epstein-Barr virus-positive women had a higher prevalence than did EBV-negative women of high-grade precancer (15% vs. 2%) and abnormal cytology (37% vs. 15%), although HIV- and hrHPV-adjusted associations were not significant (high-grade precancer: PR, 2.0 [0.7-5.9]; abnormal cytology: PR, 1.4 [0.9-2.2]). In prospective analyses, a marginal association was observed between baseline EBV detection and delayed hrHPV clearance. Conclusions Our data support a possible role for EBV as a high-risk marker or cofactor for HPV-mediated cervical cancer development

The incidence of human papillomavirus infection following treatment for cervical neoplasia: A systematic review

To systematically review the published literature in order to estimate the incidence and describe the variability of human papillomavirus (HPV) infection in women following treatment for cervical neoplasia

Can the careHPV test performed in mobile units replace cytology for screening in rural and remote areas?

BACKGROUND Human papillomavirus (HPV) DNA testing can be crucial for women who have limited access to traditional screening. The current study compared the results obtained through HPV DNA testing with those obtained through cytology-based screening. METHODS A total of 3068 women aged 18 to 85 years were enrolled in an opportunistic cervical cancer screening program developed by the Barretos Cancer Hospital and performed by a team of health professionals working within a mobile unit from March to December 2012, followed by statistical analyses. For each patient, 2 different cervical samples were collected and preserved in a careHPV assay and SurePath medium, respectively. RESULTS High-risk HPV (hr-HPV) DNA was detected in 10.0% of women, with the majority (86.7%) demonstrating no abnormal Papanicolaou test results. The following cytological samples were found to be hr-HPV positive: 8.2% of the normal samples; 39.4% of the samples with atypical squamous/glandular cells of undetermined significance; 38.5% of the samples with atypical squamous/glandular cells of undetermined significance, cannot exclude high-grade lesion; 55.3% of the samples with low-grade squamous intraepithelial lesions; and 100% of the samples with high-grade squamous intraepithelial lesions. Colposcopy examinations were performed among 33.4% of the women with positive results on at least 1 of the tests (HPV DNA positive and/or cytology with atypical squamous/glandular cells of undetermined significance, cannot exclude high-grade lesion or high-grade squamous intraepithelial lesions), and 59.5% of these women underwent biopsies. Among these samples, 18.2% were confirmed as cervical intraepithelial neoplasia. CONCLUSIONS The careHPV test was demonstrated to be a feasible alternative to primary screening in low-resource settings accessed through the use of mobile units.Adriana T. Lorenzi was supported (via a scholarship) by CNPq process no. 573799/2008-3 and FAPESP process no. 2008/57889-1 through the National HPV Research and Technology Institute of São Paulo, Brazil (INCT-HPV)info:eu-repo/semantics/publishedVersio

PATTERNS OF PERSISTENT GENITAL HUMAN PAPILLOMAVIRUS INFECTION AMONG WOMEN WORLDWIDE: A LITERATURE REVIEW AND META-ANALYSIS

Persistent high-risk human papillomavirus (HR-HPV) infection is the strongest risk factor for high-grade cervical precancer. We performed a systematic review and meta-analysis of HPV persistence patterns worldwide. Medline and ISI Web of Science were searched through January 1, 2010 for articles estimating HPV persistence or duration of detection. Descriptive and meta-regression techniques were used to summarize variability and the influence of study definitions and characteristics on duration and persistence of cervical HPV infections in women. Among 86 studies providing data on over 100,000 women, 73% defined persistence as HPV positivity at a minimum of two time points. Persistence varied notably across studies and was largely mediated by study region and HPV type, with HPV-16, 31, 33 and 52 being most persistent. Weighted median duration of any-HPV detection was 9.8 months. HR-HPV (9.3 months) persisted longer than low-risk HPV (8.4 months), and HPV-16 (12.4 months) persisted longer than HPV-18 (9.8 months). Among populations of HPV positive women with normal cytology, the median duration of any-HPV detection was 11.5 and HR-HPV detection was10.9 months. In conclusion, we estimated that approximately half of HPV infections persist past 6–12 months. Repeat HPV testing at 12 month intervals could identify women at increased risk of high-grade cervical precancer due to persistent HPV infections