Male circumcision and the incidence and clearance of genital human papillomavirus (HPV) infection in men: the HPV Infection in men (HIM) cohort study

Background: Reported associations of male circumcision (MC) with human papillomavirus (HPV) infection in men have been inconsistent. Methods: 4,033 healthy men were examined every six months for a median of 17.5 months. In each study visit, exfoliated cell specimens from the coronal sulcus/glans penis, penile shaft, and scrotum were collected and combined into one sample per person for HPV DNA detection. Samples were tested for 37 HPV types. Cox proportional hazards models were used to evaluate the association between MC and the incidence and clearance of HPV infections and specific genotypes. Results: The overall incidence of new HPV infections did not differ by MC status (for any HPV, adjusted hazard ratio (aHR) 1.08, 95% confidence interval (CI) 0.91-1.27). However, incidence was significantly lower among circumcised versus uncircumcised men for HPV types 58 (p = 0.01), 68 (p < 0.001), 42 (p = 0.01), 61 (p < 0.001), 71 (p < 0.001), 81 (p = 0.04), and IS39 (p = 0.01), and higher for HPV types 39 (p = 0.01) and 51 (p = 0.02). Despite the lack of an overall association in the risk of HPV clearance by MC (for any HPV, aHR 0.95, 95% CI 0.88-1.02), median times to clearance were significantly shorter among circumcised than uncircumcised men for HPV types 33 (p = 0.02) and 64 (p = 0.04), and longer for HPV types 6 (p < 0.001), 16 (p < 0.001), and 51 (p = 0.02). Conclusions: MC is not associated with the incidence and clearance of genital HPV detection, except for certain HPV types. The use of a single combined sample from the penis and scrotum for HPV DNA detection likely limited our ability to identify a true effect of MC at the distal penis

Male circumcision and prevalence of genital human papillomavirus infection in men : a multinational study

Background: Accumulated evidence from epidemiological studies and more recently from randomized controlled trials suggests that male circumcision (MC) may substantially protect against genital HPV infection in men. The purpose of this study was to assess the association between MC and genital HPV infection in men in a large multinational study. Methods: A total of 4072 healthy men ages 18-70 years were enrolled in a study conducted in Brazil, Mexico, and the United States. Enrollment samples combining exfoliated cells from the coronal sulcus, glans penis, shaft, and scrotum were analyzed for the presence and genotyping of HPV DNA by PCR and linear array methods. Prevalence ratios (PR) were used to estimate associations between MC and HPV detection adjusting for potential confounders. Results: MC was not associated with overall prevalence of any HPV, oncogenic HPV types or unclassified HPV types. However, MC was negatively associated with non-oncogenic HPV infections (PR 0.85, 95% confident interval: 0.76-0.95), in particular for HPV types 11, 40, 61, 71, and 81. HPV 16, 51, 62, and 84 were the most frequently identified genotypes regardless of MC status. Conclusions: This study shows no overall association between MC and genital HPV infections in men, except for certain non-oncogenic HPV types for which a weak association was found. However, the lack of association with MC might be due to the lack of anatomic site specific HPV data, for example the glans penis, the area expected to be most likely protected by MC

Association of Chlamydia trachomatis Infection and Herpes Simplex Virus Type 2 Serostatus With Genital Human Papillomavirus Infection in Men: The HPV in Men Study

Background: Studies in women indicate that some sexually transmitted infections promote human papillomavirus (HPV) persistence and carcinogenesis. Little is known about this association in men; therefore, we assessed whether Chlamydia trachomatis (CT) infection and herpes simplex virus type 2 (HSV-2) serostatus are associated with genital HPV prevalence, an early event in HPV-related pathogenesis. Methods: Genital exfoliated cells, first-void urine, and blood from 3971 men recruited in the United States, Mexico, and Brazil were tested for HPV, CT, and HSV-2 antibodies, respectively. Multivariable logistic regression was used to assess the association of CT infection and HSV-2 serostatus with 4 HPV outcomes (any, oncogenic, nononcogenic only, and multiple infections). Results: A total of 64 (1.6%) men were CT positive, and 811 (20.4%) men were HSV-2 seropositive. After adjustment for potential confounders, CT was associated with any HPV (adjusted odds ratio [aOR], 2.19; 95% confidence interval [CI], 1.13-4.24), oncogenic HPV (aOR, 3.10; 95% CI, 1.53-6.28), and multiple HPV (aOR, 3.43; 95% CI, 1.69-6.95) prevalence. Herpes simplex virus type 2 serostatus was associated with any HPV (aOR, 1.25; 95% CI, 1.02-1.52), nononcogenic HPV only (aOR, 1.38; 95% CI, 1.08-1.75), and multiple HPV (aOR, 1.33; 95% CI, 1.06-1.68) prevalence. In analyses stratified by sexual behavior, CT infection was significantly associated with HPV detection among men reporting 2 or more recent sexual partners, whereas HSV-2 serostatus was significantly associated with HPV detection in men reporting 0 to 5 lifetime sexual partners. Conclusion: In this population, CT infection and HSV-2 serostatus were associated with prevalent genital HPV infection. Future prospective studies should investigate whether these infections influence HPV acquisition and/or persistenc

An analysis of HPV infection incidence and clearance by genotype and age in men: The HPV Infection in Men (HIM) Study

Objectives: Genital HPV infection in men causes benign and cancerous lesions, the incidence of which differs by age. The goal of this work was to comprehensively evaluate incidence and clearance of individual HPV genotypes among men by age group. Methods: HIV-negative men ages 18–70 with no history of anogenital cancer were recruited for the HPV Infection in Men (HIM) Study. Participants completed clinical exams and questionnaires every six months for up to ~4 years. Genital specimens underwent HPV genotyping, with associations between age and HPV assessed using Cox analyses. Results: 4085 men were followed for a median of 48.6 months (range: 0.3–94.0). Significantly lower HPV incidence rates were observed among the oldest age group (55–70 years) for grouped high-risk (incidence rate ratio [IRR]=0.71), HPV16 (IRR=0.54), grouped low-risk (IRR=0.74), and HPV6 (IRR=0.57) infections compared to men ages 18–24. However, incidence of the grouped 9-valent HPV vaccine types remained constant across the lifespan. Likelihood of HPV6 and HPV16 clearance remained constant until age 54, then increased significantly for men ages 55–70 (adjusted hazard ratio [AHR]=1.92 and 1.65, respectively). Conclusions: Men remain susceptible to HPV infections throughout their lifespan, highlighting the need for prevention efforts with long-lasting duration. Keywords: Human papillomavirus, Natural history, Incidence, Clearance, Age-specific, HIM Stud