Martha Abrahamsen

Incidence and clearance of genital human papillomavirus infection in men (HIM): a cohort study

BACKGROUND Human papillomaviruses (HPVs) cause genital warts and cancers in men. The natural history of HPV infection in men is largely unknown, and that information is needed to inform prevention strategies. The goal in this study was to estimate incidence and clearance of type-specific genital HPV infection in men, and to assess the associated factors. METHODS Men (aged 18-70 years), residing in Brazil, Mexico, and the USA, who were HIV negative and reported no history of cancer were recruited from the general population, universities, and organised health-care systems. They were assessed every 6 months for a median follow-up of 27·5 months (18·0-31·2). Specimens from the coronal sulcus, glans penis, shaft, and scrotum were obtained for the assessment of the status of HPV genotypes. FINDINGS In 1159 men, the incidence of a new genital HPV infection was 38·4 per 1000 person months (95% CI 34·3-43·0). Oncogenic HPV infection was significantly associated with having a high number of lifetime female sexual partners (hazard ratio 2·40, 1·38-4·18, for at least 50 partners vs not more than one partner), and number of male anal-sexual partners (2·57, 1·46-4·49, for at least three male partners vs no recent partners). Median duration of HPV infection was 7·52 months (6·80-8·61) for any HPV and 12·19 months (7·16-18·17) for HPV 16. Clearance of oncogenic HPV infection decreased in men with a high number of lifetime female partners (0·49, 0·31-0·76, for at least 50 female partners vs not more than one partner), and in men in Brazil (0·71, 0·56-0·91) and Mexico (0·73, 0·57-0·94) compared with the USA. Clearance of oncogenic HPV was more rapid with increasing age (1·02, 1·01-1·03). INTERPRETATION The data from this study are useful for the development of realistic cost-effectiveness models for male HPV vaccination internationally. FUNDING National Cancer Institute.

Incidence, Prevalence, and Clearance of Type-Specific Human Papillomavirus Infections: The Young Women’s Health Study

The natural history of type-specific human papillomavirus (HPV) infections was examined in a cohort of 331 women aged 18-35 years who self-referred for routine gynecological care. Participants underwent a gynecological examination at baseline and at approximately 4 and approximately 10 months after baseline. Cervical samples were collected for HPV testing and genotyping at each visit, as was information on reproductive, sexual, and medical histories. The rate of new HPV infections was 2.9% per month; the highest rates were observed for HPV types 16, 39, 84, and 51. Among women who tested negative for HPV at baseline, the cumulative probability of acquiring an oncogenic HPV strain during a 12-month follow-up period was 0.32, compared with 0.18 for nononcogenic strains. Women who had had >/=1 new male sex partner in the recent past were significantly more likely to acquire a new HPV infection (relative hazard, 2.39; 95% confidence interval, 1.20-4.76). The median time to clearance of infection was significantly longer for oncogenic strains (9.8 months) than for nononcogenic strains (4.3 months).

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)

The Optimal Anatomic Sites for Sampling Heterosexual Men for Human Papillomavirus (HPV) Detection: The HPV Detection in Men Study

Background. Human papillomavirus (HPV) infection in men contributes to infection and cervical disease in women as well as to disease in men. This study aimed to determine the optimal anatomic site(s) for HPV detection in heterosexual men.Methods. A cross-sectional study of HPV infection was conducted in 463 men from 2003 to 2006. Urethral, glans penis/coronal sulcus, penile shaft/prepuce, scrotal, perianal, anal canal, semen, and urine samples were obtained. Samples were analyzed for sample adequacy and HPV DNA by polymerase chain reaction and genotyping. To determine the optimal sites for estimating HPV prevalence, site-specific prevalences were calculated and compared with the overall prevalence. Sites and combinations of sites were excluded until a recalculated prevalence was reduced by <5% from the overall prevalence.Results. The overall prevalence of HPV was 65.4%. HPV detection was highest at the penile shaft (49.9% for the full cohort and 47.9% for the subcohort of men with complete sampling), followed by the glans penis/coronal sulcus (35.8% and 32.8%) and scrotum (34.2% and 32.8%). Detection was lowest in urethra (10.1% and 10.2%) and semen (5.3% and 4.8%) samples. Exclusion of urethra, semen, and either perianal, scrotal, or anal samples resulted in a <5% reduction in prevalence.Conclusions. At a minimum, the penile shaft and the glans penis/coronal sulcus should be sampled in heterosexual men. A scrotal, perianal, or anal sample should also be included for optimal HPV detection.

Age-Specific Prevalence, Incidence, and Duration of Human Papillomavirus Infections in a Cohort of 290 US Men

BACKGROUND Human papillomavirus (HPV) infections cause disease in men and women, and male-to-female HPV transmission influences the risk of cancer in females. The purpose of the present study was to describe the overall and age-specific incidence and clearance of HPV infections in men. METHODS In a prospective cohort study of 290 men aged 18-44 years, participants were examined at baseline and every 6 months, with a mean duration of follow-up of 15.5 months. RESULTS The period prevalence was 52.8% for any, 31.7% for oncogenic, and 30.0% for nononcogenic HPV infection. The 12-month cumulative risk of acquiring a new HPV infection was 29.2%. Incidences of HPV types 6, 11, 16, and 18 were 2.8, 0.5, 4.8, and 0.8 per 1000 person-months, respectively. The median time to clearance of any HPV infection was 5.9 months (95% confidence interval, 5.7-6.1 months), with comparable times to clearance for oncogenic and nononcogenic infections. Approximately 75% of men tested negative for any HPV 12 months after initial HPV detection. Age was not significantly associated with HPV incidence or duration of infection in men. CONCLUSION HPV infection in men was common, with relatively rapid rates of acquisition and clearance.

Human Papillomavirus Prevalence and Type Distribution in Male Anogenital Sites and Semen

Background: Human papillomavirus (HPV) is sexually transmitted and causes cervical cancer. Although HPV can infect men and women, little is known about infection in men. Specifically, the prevalence of type-specific HPV infection and the distribution of infections by anogenital anatomic site in men are incompletely characterized. Methods: We tested 463 men ages 18 to 40 years for HPV at the glans/corona, penile shaft, scrotum, urethra, perianal area, anal canal, and in a semen sample. Eligible men acknowledged no history of genital warts and had sexual intercourse with a woman within the past year. HPV testing by PCR and reverse line blot genotyping for 37 types was conducted on each of the specimens from the seven sampling sites. Results: When HPV results from any sampling site were considered, 237 (51.2%) men were positive for at least one oncogenic or nononcogenic HPV type, and another 66 (14.3%) men were positive for an unclassified HPV type. The types with the highest prevalence were HPV-16 (11.4%) and 84 (10.6%). External genital samples (glans/corona, shaft, and scrotum) were more likely than anal samples to contain oncogenic HPV (25.1% versus 5.0%). HPV-positive penile shaft and glans/corona samples were also more likely to be infected with multiple HPV types than other sites. Conclusions: More complete anogenital sampling and sensitive detection for 37 HPV types resulted in a higher HPV prevalence in primarily asymptomatic men than reported previously. The penile shaft was the site most likely to be HPV positive and harbored the greatest proportion of multiple type and oncogenic infections. These results have implications for research of HPV among men and transmission between partners. (Cancer Epidemiol Biomarkers Prev 2007;16(6):1107–14)

The Epidemiology of Oral HPV Infection among a Multinational Sample of Healthy Men

Background: Oral human papillomavirus type-16 (HPV16) infection is a risk factor for oropharyngeal cancer. We examined oral HPV infection among healthy men. Methods: Oral rinse/gargle specimens and questionnaire data were collected from 1,688 healthy men aged 18 to 74 (median = 31 years), from the United States, Mexico, and Brazil. HPV16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58 and 59, and noncarcinogenic HPV types were detected using Roche Linear Array. Results: Oral HPV DNA was detected in 67 of 1,680 (4.0%, 95% CI = 3.1%–5.0%) β-globin–positive specimens; carcinogenic HPVs were detected in 1.3% (95% CI = 0.8%–2.0%; n = 22) and HPV16 was the most commonly detected carcinogenic HPV type (0.6%, 95% CI = 0.2%–1.1%; n = 10). The prevalence of oral HPV infection was similar by country except for HPV55, which had notably higher prevalence in Mexico (3.0%) than Brazil (0%) or the United States (0.2%). Oral HPV prevalence nonsignificantly increased over increasing age categories (Ptrend = 0.096). The strongest predictor of oral HPV was current tobacco use, which increased the odds 2.5-fold (95% CI = 1.4–4.4). Oral sexual behaviors were not associated with oral HPV infection. Conclusions: Oral HPV16 infection was rare in healthy men, especially at younger ages, and was positively associated with current tobacco use. Impact: Oral HPV appears to be about 10-fold less prevalent than infection at genital sites in men (4% vs. ∼40%, respectively). It remains unclear whether this reflects reduced exposure or if the oral region is more resistant to HPV infection compared with anogenital sites. Cancer Epidemiol Biomarkers Prev; 20(1); 172–82. ©2011 AACR.

Incidence and clearance of oral human papillomavirus infection in men: the HIM cohort study.

BACKGROUND Oral human papillomavirus (HPV) infection causes a subset of oropharyngeal cancers. These cancers disproportionately affect men, are increasing in incidence, and have no proven prevention methods. We aimed to establish the natural history of oral HPV infection in men. METHODS To estimate incidence and clearance of HPV infections, men residing in Brazil, Mexico, and the USA who were HIV negative and reported no history of anogenital cancer were recruited into the HPV Infection in Men (HIM) cohort study. A subset of the cohort who provided two or more oral rinse-and-gargle samples with valid HPV results and who completed a minimum of 2 weeks of follow-up were included in this analysis. Oral rinse-and-gargle samples and questionnaire data were obtained every 6 months for up to 4 years. Samples were analysed for the presence of oncogenic and non-oncogenic HPV infections by the linear array method. FINDINGS 1626 men aged 18-73 years and with a median follow-up of 12·7 months (IQR 12·1-14·7) were included in the analysis. During the first 12 months of follow-up, 4·4% (95% CI 3·5-5·6; n=115 incident infections) of men acquired an incident oral HPV infection, 1·7% (1·2-2·5; n=53 incident infections) an oral oncogenic HPV infection, and 0·6% (0·3-1·1; n=18 incident infections) an oral HPV 16 infection. Acquisition of oral oncogenic HPV was significantly associated with smoking and not being married or cohabiting, but was similar across countries, age groups, and reported sexual behaviours. Median duration of infection was 6·9 months (95 % CI 6·2-9·3; n=45 cleared infections) for any HPV, 6·3 months (6·0-9·9; n=18 cleared infections) for oncogenic HPV, and 7·3 months (6·0-not estimable; n=5 cleared infections) for HPV 16. Eight of the 18 incident oral HPV 16 infections persisted for two or more study visits. INTERPRETATION Newly acquired oral oncogenic HPV infections in healthy men were rare and most were cleared within 1 year. Additional studies into the natural history of HPV are needed to inform development of infection-related prevention efforts. FUNDING US National Cancer Institute, Merck Sharp & Dohme.

Age-specific prevalence of and risk factors for anal human papillomavirus (HPV) among men who have sex with women and men who have sex with men: the HPV in men (HIM) study.

BACKGROUND An increasing incidence of anal cancer among men suggests a need to better understand anal canal human papillomavirus (HPV) infection among human immunodeficiency virus-negative men. METHODS Genotyping for HPV was conducted on cells from the anal canal among men who have sex with women (MSW) and men who have sex with men (MSM), aged 18-70 years, from Brazil, Mexico, and the United States. Factors associated with anal HPV infection were assessed using multivariable logistic regression. RESULTS The prevalence of any HPV type and oncogenic HPV types did not differ by city. Anal canal HPV prevalence was 12.2% among 1305 MSW and 47.2% among 176 MSM. Among MSW, reporting a lifetime number of ≥ 10 female sex partners, a primary sexual relationship <1 year in duration, and a prior hepatitis B diagnosis were independently associated with detection of any anal HPV in multivariable analysis. Among MSM, a younger age, reporting ≥ 2 male anal sex partners in the past 3 months, and never using a condom for anal sex in the past 6 months were independently associated with detection of any anal HPV in multivariable analysis. CONCLUSIONS Number of sex partners was associated with anal HPV infection in both MSW and MSM. Anal HPV infection in men may be mediated by age, duration of sexual relationship, and condom use.

Condom Use and Other Factors Affecting Penile Human Papillomavirus Detection in Men Attending a Sexually Transmitted Disease Clinic

Background and Objectives: Human papillomavirus (HPV) is the primary cause of cervical, anal, and other anogenital cancers, but risk factors for penile HPV detection in men have not been well-characterized. Goal: The goal of this study was to identify correlates of penile HPV detection in ethnically diverse men attending a sexually transmitted disease clinic. Study: A cross-sectional investigation was conducted among 393 men. Participants completed a risk-factor questionnaire and underwent testing for penile HPV DNA. Presence of HPV DNA was assessed using polymerase chain reaction with PGMY primers and reverse line blot genotyping. Logistic regression analyses were conducted to identify variables associated with any-type, oncogenic, and nononcogenic HPV. Results: Circumcision was associated with reduced risk for oncogenic, nononcogenic, and overall HPV. Regular condom use was associated with reduced risk for oncogenic and overall HPV. Conclusion: These findings, if confirmed by other studies, could impact public health practices and messages regarding HPV.