The role of human papillomavirus (HPV) viral load in penile HPV infection and clearance among young Kenyan men

Persistent infections with human papillomavirus (HPV) types 16 and 18 are causes of cervical cancer in women and various penile squamous cell carcinomas (SCC) in men. Male circumcision has been found to be protective against penile HPV, but the association between circumcision and HPV viral load remains unclear. Additionally, the role of HPV viral load in HPV persistence and subsequent development of penile SCC is unknown. An HPV-ancillary study, nested within a randomized controlled trial (RCT) of male circumcision, was conducted in Kisumu, Kenya. Eligible participants were HIV seronegative, uncircumcised and aged 18-24. Penile swabs were collected from glans and shaft sites every 6 months for 24 months. GP5+/6+ PCR was used to identify HPV DNA types. HPV viral load was measured with LightCyler real-time PCR and classified as high (>250copies/scrape) or low (≤250copies/scrape). Of 2,299 men with HPV baseline results, 1,159 were randomized to immediate circumcision and 1,140 to the control arm and asked to remain uncircumcised until study end. The acquisition of high viral load infections in the glans was lower in the circumcision than control arm for HPV16 [Hazard Ratio(HR)=0.32(0.20-0.49)] and HPV18 [HR=0.34(0.21-0.54)]. For prevalent high viral load infections in the glans at baseline, risk of persistence to 6 months was lower in the circumcision arm [0.20(0.09-0.34)] than control arm [0.55(0.39-0.68)] for HPV16 and HPV18 [0.17(0.05-0.34) and 0.50(0.25-0.71), respectively]. In uncircumcised men, the hazard of HPV16 clearance at 6 months after first HPV16 detection was found to be lower for high versus low viral load incident infections in the glans [adjusted hazard ratio (aHR) =0.58 (95%confidence interval, 0.36-0.93)]. HPV16 and HPV18 clearance in the shaft was comparable for high and low viral load infections. Male circumcision reduces the acquisition and possibly enhances the clearance of high viral load HPV16 or HPV18 infections in the glans, and thus could potentially reduce HPV transmission to women. The reduced rate of high versus low viral load HPV16 clearance in uncircumcised men could be associated with increased development of penile SCC, and may also explain the increase in HPV16 transmission in men with high viral load to their female partners.Doctor of Philosoph

Acquisition and Persistence of Human Papillomavirus 16 (HPV-16) and HPV-18 Among Men With High-HPV Viral Load Infections in a Circumcision Trial in Kisumu, Kenya

Background. Circumcision and lower human papillomavirus (HPV) viral loads in men are possibly associated with a reduced risk of HPV transmission to women. However, the association between male circumcision and HPV viral load remains unclear

Comparative accuracy of Pap smear and HPV screening in Ubon Ratchathani in Thailand

We evaluate the potential for using high-risk human papillomavirus (hr-HPV) testing-based screening for cervical intraepithelial neoplasia (CIN) in routine health services in Thailand; its accuracy in comparison to that of conventional cytology (CC); and the utility of HPV16/18 positive results and liquid-based cytology (LBC) triage for HPV-positive women in the detection of high-grade CIN. Women aged 30â60 years in Ubon Ratchathani province, Thailand were screened with CC and hr-HPV testing and those abnormal on either tests were referred for colposcopy and/or directed biopsies. The final diagnosis using COBAS was based on histology or colposcopy when histology was not available. Estimation of test accuracy parameters was done using latent class analysis using Bayesian models. Of the 5004 women were enrolled, 20 (0.4%) had abnormal CC and 174 (3.5%) women were HPV-positive. Among 185 women abnormal on CC or HPV-positive, 176 (95.1%) underwent colposcopy, of whom 101 (57.4%) had abnormal colposcopy findings. Ninety-seven women with abnormal and 69 with normal colposcopy had biopsies performed. All 21 women with histological CIN2 or worse had hr-HPV and none were abnormal on CC. The estimated sensitivity, specificity and positive predictive value were respectively 71.8%, 97.0% and 13.0% of HPV testing; 53%, 98.7% and 20.3% for triage of HPV-positive women with LBC; and 70.4%, 98.2% and 16.9% when test positivity was taken as HPV16/18 irrespective of LBC result or positive for hr-HPV non 16/18 types and LBC triage. Our study findings indicate poor performance of cytology screening and demonstrate the potential and utility of using HPV testing in public health services in Thailand as well as the utility of primary HPV testing and LBC triage in screening for cervical neoplasia. Keywords: Cervix cancer, Early detection, HPV screening, Cytology screening, Accurac

CDC Activities for Improving Implementation of Human Papillomavirus Vaccination, Cervical Cancer Screening, and Surveillance Worldwide

Cervical cancer incidence and mortality rates are high, particularly in developing countries. Most cervical cancers can be prevented by human papillomavirus (HPV) vaccination, screening, and timely treatment. The US Centers for Disease Control and Prevention (CDC) provides global technical assistance for implementation and evaluation of HPV vaccination pilot projects and programs and laboratory-related HPV activities to assess HPV vaccines. CDC collaborates with global partners to develop global cervical cancer screening recommendations and manuals, implement screening, create standardized evaluation tools, and provide expertise to monitor outcomes. CDC also trains epidemiologists in cancer prevention through its Field Epidemiology Training Program and is working to improve cancer surveillance by supporting efforts of the World Health Organization in developing cancer registry hubs and assisting countries in estimating costs for developing population-based cancer registries. These activities contribute to the Global Health Security Agenda action packages to improve immunization, surveillance, and the public health workforce globally

Acceptability of two- versus three-dose human papillomavirus vaccination schedule among providers and mothers of adolescent girls: a mixed-methods study in five countries

PURPOSE: The World Health Organization revised its human papillomavirus (HPV) vaccination recommendations to include a two (2-) dose schedule for girls aged ≤ 15 years. We investigated acceptability of 2- versus 3-dose schedule among adolescent vaccination providers and mothers of adolescent girls in five countries. METHODS: Adolescent vaccination providers (N = 151) and mothers of adolescent girls aged 9-14 years (N = 118) were recruited from Argentina, Malaysia, South Africa, South Korea, and Spain. We assessed providers' preference for a 2- versus 3-dose HPV vaccination schedule via quantitative surveys. Mothers' attitudes towards a 2-dose schedule were assessed through focus group discussions. RESULTS: Most adolescent providers preferred a 2- over a 3-dose HPV vaccination schedule (overall: 74%), with preference ranging from 45.2% (South Africa) to 90.0% (South Korea). Lower cost, fewer clinic visits, and higher series completion were commonly cited reasons for 2-dose preference among providers and mothers. Safety and efficacy concerns were commonly cited barriers to accepting a 2-dose HPV vaccination schedule among providers and mothers. Mothers generally accepted the reduced schedule, however requested further information from a trusted source. CONCLUSIONS: Adolescent vaccination providers and mothers preferred the 2-dose over 3-dose HPV vaccination schedule. Acceptability of a 2-dose HPV vaccination could be improved with additional information to providers and mothers on HPV vaccination safety and efficacy.Área de Salud, Economía y Socieda

Higher HPV16 and HPV18 Penile Viral Loads Are Associated With Decreased Human Papillomavirus Clearance in Uncircumcised Kenyan Men

BACKGROUND: Whether higher penile human papillomavirus (HPV) viral load is associated with a lower rate of HPV clearance remains unknown. OBJECTIVES: We examined the association between penile HPV16 and HPV18 viral load and subsequent HPV clearance in uncircumcised Kenyan men. STUDY DESIGN: Participants were human immunodeficiency virus (HIV)-seronegative, sexually active, 18- to 24-year-old men randomized to the control arm of a male circumcision trial in Kisumu, Kenya. Men provided exfoliated penile cells from two anatomical sites (glans/coronal sulcus and shaft) every 6 months for 2 years. GP5+/6+ polymerase chain reaction was used to identify 44 HPV-DNA types. Human papillomavirus viral load testing was conducted using a LightCyler real-time polymerase chain reaction assay; viral load was classified as high (>250 copies/scrape) or low (≤250 copies/scrape), for nonquantifiable values. The Kaplan-Meier method and Cox regression modeling were used to examine the association between HPV viral load and HPV clearance. RESULTS: A total of 1097 men, with 291 HPV16 and 131 HPV18 cumulative infections over 24 months were analyzed. Human papillomavirus clearance at 6 months after first HPV detection was lower for high versus low viral load HPV16 infections in the glans (adjusted hazard ratio [aHR], 0.65; 95% confidence interval [CI], 0.46-0.92)] and shaft (aHR, 0.44; 95% CI, 0.16-0.90), and HPV18 infections in the glans (aHR, 0.05; 95% CI, 0.01-0.17). DISCUSSION: High versus low HPV viral load was associated with a reduced HPV clearance for HPV16 infections in the glans and shaft, and for HPV18 infections in the glans, among young uncircumcised men. Reduced clearance of high viral load HPV16 and HPV18 infections in men may increase HPV transmission to their female partners as well as enhance the development of penile lesions in comparison to men with low viral load HPV infections