The HPV in Men (HIM) Study is a multinational prospective study of men aged 18–70 years that examines the natural history of genital HPV infection. A full description of study procedures has been published elsewhere [11
]. In brief, men completed study visits every 6 months for up to 4 years. At each visit a trained clinician examined the external genitalia for condyloma, which was defined as lesions that had a wartlike architecture and did not appear to be related to herpes simplex virus or a benign condition such as cysts or skin tags. Saline-prewetted Dacron swabs were used to sample the surface of condyloma and healthy penile epithelium from the coronal sulcus/glans penis, penile shaft, and scrotum. The 3 samples from healthy epithelium were combined for HPV DNA testing and genotyping. At each visit participants also completed an extensive risk factor questionnaire in their native language (English, Spanish, or Portuguese) administered using computer-assisted self-interviewing to obtain information on sociodemographic factors and lifetime and recent sexual behavior. The current analysis includes the first 2487 men enrolled in the HIM study between July 2005 and January 2009 who had no condyloma detected at enrollment and completed at least one 6-month follow-up visit. All participants provided written informed consent, and study protocols were approved by institutional review boards at each study site.
Polymerase chain reaction (PCR) was used to test for HPV DNA. Following the instructions of the manufacturer (Qiagen), the QIAamp Mini kit was used to extract DNA from skin swabs. The Linear Array HPV Genotyping Test (Roche Diagnostics) was used to test for 37 HPV types, including 13 oncogenic types (16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, and 66) and 24 nononcogenic types (6, 11, 26, 40, 42, 53–55, 61, 62, 64, 67–73, 81–84, IS39, and CP6108). Only samples that tested positive for β-globin were included in the analysis. Samples were considered HPV positive if HPV DNA was detected by PCR or the sample tested positive for at least 1 HPV genotype.
Cox proportional hazard models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for the associations between incident and prevalent HPV infection and condyloma risk. An individual had an incident HPV infection for a specific HPV type if he tested negative for that type at enrollment and subsequently tested positive for the same type at a follow-up visit. Prevalent HPV infections were infections present at enrollment. The reference group for all models assessing the association between HPV infection and condyloma was the group of men who tested HPV negative at all study visits. Person-time was calculated as the months from the enrollment date until the date of the visit that a condyloma was detected or until the date of the last follow-up visit for men who did not develop condyloma.
Cox proportional hazard models were also used to examine crude and multivariable associations between sociodemographic and sexual behavioral factors and the risk of developing condyloma. The backward selection method, with a significance threshold of .05, was used to determine the factors included in the final multivariable model. Variables initially included were race, ethnicity, marital status, education, cigarette smoking status, circumcision status, age at first intercourse with a female, lifetime and recent number of female and male sexual partners, sexual orientation, condom use, frequency of vaginal intercourse, having a steady female partner, ever being diagnosed with an STI, ever having a partner with an STI, ever having a partner with condyloma, and incident infection with HPV 6/11. Country of residence (United States, Brazil, Mexico) and age (18–30, 31–44, and 45–70 years) were study design factors and included in all multivariable models. Covariates that could change over the follow-up period (eg, recent number of female partners) were treated as time-dependent variables.