Manuel Quiterio

The Human Papillomavirus Infection in Men Study: Human Papillomavirus Prevalence and Type Distribution among Men Residing in Brazil, Mexico, and the United States

Male sexual behavior influences the rates of cervical dysplasia and invasive cervical cancer, as well as male human papillomavirus (HPV) infection and disease. Unfortunately, little is known regarding male HPV type distribution by age and across countries. In samples combined from the coronal sulcus, glans penis, shaft, and scrotum of 1,160 men from Brazil, Mexico, and the United States, overall HPV prevalence was 65.2%, with 12.0% oncogenic types only, 20.7% nononcogenic types only, 17.8% both oncogenic and nononcogenic, and 14.7% unclassified infections. Multiple HPV types were detected in 25.7% of study participants. HPV prevalence was higher in Brazil (72.3%) than in the United States (61.3%) and Mexico (61.9%). HPV16 (6.5%), HPV51 (5.3%), and HPV59 (5.3%) were the most commonly detected oncogenic infections, and HPV84 (7.7%), HPV62 (7.3%), and HPV6 (6.6%) were the most commonly detected nononcogenic infections. Overall HPV prevalence was not associated with age. However, significant associations with age were observed when specific categories of HPV, nononcogenic, and unclassified HPV infections were considered. Studies of HPV type distribution among a broad age range of men from multiple countries is needed to fill the information gap internationally with respect to our knowledge of HPV infection in men. (Cancer Epidemiol Biomarkers Prev 2008;17(8):2036–43)

Circumcision and sexual behavior: factors independently associated with human papillomavirus detection among men in the HIM study.

There is growing interest in understanding human papillomavirus (HPV) infection and related disease among men. To date there have been numerous studies reporting HPV DNA prevalence among men from several different countries, however, few have incorporated multivariable analyses to determine factors independently associated with male HPV detection. The purpose of this study was to assess the factors independently associated with HPV detection in men ages 18–70 years residing in Brazil (n = 343), Mexico (n = 312), and the United States (US) (n = 333). In samples combined from the coronal sulcus, glans penis, shaft, and scrotum, we evaluated factors associated with any, oncogenic, and nononcogenic HPV infections. In multivariable analyses, detection of any HPV infection was significantly associated with reported race of Asian/Pacific Islander, lifetime and recent number of sexual partners, and having sex in the past 3 months. Oncogenic HPV detection was independently associated with lifetime and recent number of sexual partners, and having sex in the past 3 months. NonOncogenic HPV infection was independently associated with lifetime number of sexual partners. Circumcision, assessed by clinical examination, was associated with reduced risk of HPV detection across all categories of HPV evaluated. HPV detection in men in the current study was strongly related to sexual behavior and circumcision status. Interventions such as circumcision may provide a low‐cost method to reduce HPV infection.

Six-Month Incidence, Persistence, and Factors Associated With Persistence of Anal Human Papillomavirus in Men: The HPV in Men Study

BACKGROUND Although there are limited numbers of incidence and persistence estimates for anal human papillomavirus (HPV) in women and in men who have sex with men (MSM), there are no such reports for men who have sex with women (MSW). METHODS Genotyping was performed on anal samples from men, aged 18-70, from São Paulo, Brazil; Cuernavaca, Mexico; and Tampa, Florida, who provided specimens at enrollment and the 6-month visit of a 4-year prospective study. Eligibility included no history of genital warts or human immunodeficiency virus. A total of 954 MSW and 156 MSM provided evaluable specimens at both visits. Persistence was defined as type-specific infection at each visit. RESULTS Incident anal infection was common among both MSM and MSW but generally higher for MSM for HPV groups and specific genotypes. A total of 5.1% of MSM and 0.0% of MSW had a persistent HPV-16 infection at the 6-month visit. Cigarette smoking among MSM and age among MSW were associated with persistent infection with any HPV genotype. CONCLUSIONS Although anal HPV infection is commonly acquired by both MSW and MSM, incident events and persistence occurred more often among MSM. Cigarette smoking is a modifiable risk factor that may contribute to HPV persistence among MSM.

Human Papillomavirus (HPV) 6, 11, 16, and 18 Seroprevalence Is Associated with Sexual Practice and Age: Results from the Multinational HPV Infection in Men Study (HIM Study)

Background: Few human papillomavirus (HPV) serology studies have evaluated type-specific seroprevalence of vaccine HPV types in men. This study investigates seroprevalence of HPV 6, 11, 16, and 18, and associated risk factors in men residing in three countries (United States, Mexico, and Brazil). Methods: Data from 1,477 men aged 18 to 70 enrolled in the HPV Infection in Men Study (HIM Study) were analyzed. Serum antibody testing was performed with virus-like particle-based ELISA. Potential risk factors were assessed for individual HPV types by the use of logistic regression. Results: Overall, HPV-6, 11, 16, and 18 seroprevalence was 14.8%, 17.3%, 11.2%, and 5.8%, respectively. Thirty-four percent of men were seropositive to one or more HPV types. When examined by sexual practice, 31.2% of men who had sex with women, 65.6% of men who had sex with men (MSM), and 59.4% of men who had sex with both men and women (MSMW) were seropositive to one or more HPV types. Seroprevalence increased with age among young-to-middle-aged men with significant upward age trends observed for HPV 11, 16, and 18. Men with multiple lifetime male anal sex partners were 2 to 4 times more likely to be HPV 6 or 11 seropositive and 3 to 11 times more likely to be HPV 16 or 18 seropositive. Conclusion: Our data indicate that exposures to vaccine HPV types were common in men and highly prevalent among MSM and MSMW. Impact: Our study provides strong evidence that the practice of same-sex anal intercourse is an independent risk factor for seroprevalence of individual vaccine HPV types. Examination of antibody responses to HPV infections at various anatomic sites in future studies is needed to elaborate on the mechanism. Cancer Epidemiol Biomarkers Prev; 20(5); 990–1002. ©2011 AACR.

The prevalence of genital HPV and factors associated with oncogenic HPV among men having sex with men and men having sex with women and men: The HIM study

Background: Comparative studies of genital human papillomavirus (HPV) among men having sex with men (MSM), men having sex with women and men (MSWM), and men having sex with women (MSW) have not been conducted so far; however, such comparisons may be important for planning prevention strategies like vaccination. Methods: Men, aged 18 to 70 years, were enrolled in a study of genital HPV in São Paulo, Brazil; Cuernavaca, Mexico; and Tampa, FL. Men were classified as MSM (n = 170), MSWM (n = 214), and MSW (n = 3326) based on self-reported sexual behavior. Genotyping for HPV was conducted on cells from the penis and scrotum. Prevalence data were adjusted by country. Factors potentially associated with genital HPV were assessed using multivariable Poisson regression. Results: Genital HPV prevalence was typically higher among MSWM than among MSM or MSW for groups of HPV genotypes including nononcogenic types (51%, 36%, and 42%, respectively), and multiple types (37%, 24%, and 29%, respectively). Age and alcohol consumption in the past month were associated with oncogenic HPV among both MSM and MSWM; however, there were no statistically significant associations between sexual behaviors and genital HPV among MSM or MSWM. Conclusions: Prevalence of genital HPV may be higher among MSWM than among MSW or MSM. Number of female sex partners was associated with genital HPV among MSW, but number of male anal sex partners was not associated with genital HPV among MSM and MSWM.

Prevalent Serum Antibody Is Not a Marker of Immune Protection against Acquisition of Oncogenic HPV16 in Men

In women, naturally induced anti-human papilloma virus (HPV) serum antibodies are a likely marker of host immune protection against subsequent HPV acquisition and progression to precancerous lesions and cancers. However, it is unclear whether the same is the case in men. In this study, we assessed the risk of incident genital infection and 6-month persistent genital infection with HPV16 in relation to baseline serostatus in a cohort of 2,187 men over a 48-month period. Genital swabs were collected every 6 months and tested for HPV presence. Incidence proportions by serostatus were calculated at each study visit to examine whether potential immune protection attenuated over time. Overall, incidence proportions did not differ statistically between baseline seropositive and seronegative men at any study visit or over the follow-up period. The risk of incident and 6-month persistent infection was not associated with baseline serostatus or baseline serum antibody levels in the cohort. Our findings suggest that baseline HPV seropositivity in men is not associated with reduced risk of subsequent HPV16 acquisition. Thus, prevalent serum antibodies induced by prior infection may not be a suitable marker for subsequent immune protection against genital HPV16 acquisition in men.

Incidence and Human Papillomavirus (HPV) Type Distribution of Genital Warts in a Multinational Cohort of Men: The HPV in Men Study

BACKGROUND Data on the natural history of human papillomavirus (HPV)-related genital warts (GWs) in men are sparse. We described the distribution of HPV types in incident GWs and estimated GW incidence and time from type-specific incident HPV infections to GW detection in a multinational cohort of men aged 18-70 years. METHODS Participants included 2487 men examined for GWs and tested for HPV every 6 months and followed up for a median of 17.9 months. Samples were taken from 112 men with incident GWs to test for HPV DNA by polymerase chain reaction. RESULTS Incidence of GWs was 2.35 cases per 1000 person-years, with highest incidence among men aged 18-30 years (3.43 cases per 1000 person-years). HPV 6 (43.8%), HPV 11 (10.7%), and HPV 16 (9.8%) were the genotypes most commonly detected in GWs. The 24-month cumulative incidence of GWs among men with incident HPV 6/11 infections was 14.6% (95% confidence interval [CI], 7.5%-21.1%). Median time to GW detection was 17.1 months (95% CI, 12.4-19.3 months), with shortest time to detection among men with incident infections with HPV 6/11 only (6.2 months; 95% CI, 5.6-24.2 months). CONCLUSIONS HPV 6/11 plays an important role in GW development, with the highest incidence and shortest time to detection among men with incident HPV 6/11 infection.

Seroprevalence of human papillomavirus (HPV) type 6 and 16 vary by anatomic site of HPV infection in men.

Background: It is largely unknown if antihuman papillomavirus (HPV) serum antibody responses vary by anatomic site of infection in men. Methods: This study assessed type-specific anti-HPV serum antibody prevalence associated with corresponding HPV DNA detection in the external genitalia and the anal canal of 1,587 heterosexual men and 199 men who have sex with men (MSM). Results: We observed that HPV 6 and 16 seroprevalence was higher in the presence of same HPV-type infection in the anal canal compared with same HPV-type infection in the external genitalia only, and among MSM compared with the heterosexual men. Seropositivity to HPV 6 was strongly associated with HPV 6 DNA detection in the anal canal but not in the external genitalia alone among both heterosexual men [adjusted prevalence ratio (APR), anal+/genital+ vs. anal−/genital−: 4.2, 95% confidence interval (CI), 11.7–10.5; anal+/genital− vs. anal−/genital−: 7.9 (95% CI, 3.7–17.0)] and MSM [APR, anal+/genital+ vs. anal−/genital−: 5.6 (95% CI, 2.7–11.9); anal+/genital− vs. anal−/genital−: 3.2 (95% CI, 2.1–4.9)]. Similar associations between seropositivity to HPV 16 and anal HPV 16 DNA detection were only observed in MSM [anal+/genital+ vs. anal−/genital−: 3.1 (95% CI, 2.0–5.0); anal+/genital− vs. anal−/genital−: 2.2 (95% CI, 1.3–3.5)]. Conclusion: Our data showed that seroprevalence varied by anatomic site of HPV infection, suggesting differences in epithelium type present at these anatomic sites may be relevant. Impact: Our finding is instrumental in advancing our understanding of immune mechanism involved in anatomic site–specific antibody response. Cancer Epidemiol Biomarkers Prev; 21(9); 1542–6. ©2012 AACR.

Consistent Condom Use Reduces the Genital Human Papillomavirus Burden Among High-Risk Men: The HPV Infection in Men Study

BACKGROUND Data supporting the efficacy of condoms against human papillomavirus (HPV) infection in males are limited. Therefore, we examined the effect of consistent condom use on genital HPV acquisition and duration of infection. METHODS A prospective analysis was conducted within the HPV Infection in Men Study, a multinational HPV cohort study. Men who were recently sexually active (n = 3323) were stratified on the basis of sexual risk behaviors and partnerships. Using Cox proportional hazards regression, type-specific incidence of HPV infection and clearance were modeled for each risk group to assess independent associations with condom use. RESULTS The risk of HPV acquisition was 2-fold lower among men with no steady sex partner who always used condoms, compared with those who never used condoms (hazard ratio, 0.54), after adjustment for country, age, race, education duration, smoking, alcohol, and number of recent sex partners. The probability of clearing an oncogenic HPV infection was 30% higher among nonmonogamous men who always used condoms with nonsteady sex partners, compared with men who never used condoms (hazard ratio, 1.29), after adjustment for country, age, race, education duration, marital status, smoking, alcohol, and number of recent sex partners. No protective effects of condom use were observed among monogamous men. CONCLUSIONS Condoms should be promoted in combination with HPV vaccination to prevent HPV infection in men.

Smoking and Human Papillomavirus (HPV) Infection in the HPV in Men (HIM) Study

Background: The influence of smoking on the natural history of HPV infection in men is not well understood. Smoking could influence the incidence and persistence of HPV infections by suppressing local immune function, increased cellular proliferation, upregulated proinflammatory factors, or induced host DNA damage resulting in increased susceptibility to infection. The purpose of this analysis is to assess prevalent HPV infections by smoking status in men, and to determine baseline risk of HPV infection associated with smoking. Methods: The HPV in Men (HIM) study is a multinational prospective study of the natural history of HPV infections in men. Samples from the coronal sulcus, glans penis, shaft, and scrotum were combined for HPV DNA testing. Multivariable logistic regression was used to assess the association between smoking and any-, oncogenic-, and nononcogenic HPV infections. Results: Our analyses revealed that current smoking was associated with an increased risk of any HPV infection (OR = 1.19; 95% CI: 1.01–1.41) and oncogenic HPV infection (OR = 1.24; 95% CI: 1.05–1.47). However, the association between smoking and any HPV infection (OR = 1.35; 95% CI: 1.05–1.73) and oncogenic HPV infection (OR = 1.46; 95% CI: 1.11–1.92) was only evident among men reporting fewer lifetime sexual partners. Discussion: These results suggest that current smokers with the fewest number of sexual partners are associated with an increased risk for oncogenic HPV infection. Impact: The relationship between smoking and HPV infection remains understudied in men; these data shed new light on the interplay between smoking, sexual activity, and risk of HPV infection. Cancer Epidemiol Biomarkers Prev; 21(1); 102–10. ©2011 AACR.