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Anal and penile high-risk human papillomavirus (HPV) infection is associated with anogenital cancer, which is especially common in HIV-infected MSM. We assessed HPV prevalence and determinants in MSM.Analysis of baseline data from a prospective cohort study.MSM aged 18 years or older were recruited in Amsterdam, the Netherlands. Participants completed risk-factor questionnaires. HPV DNA was analyzed in anal and penile shaft self-swabs and genotyped using a sensitive PCR and reverse line blot assay (SPF10-PCR-DEIA-LiPA25-system). Multivariable logistic regression analyses were performed to assess determinants of high-risk HPV infection.MSM (n = 778) were recruited in 2010–2011, of whom 317 (41%) were HIV-infected. Prevalence of anal high-risk HPV infection was 45% in HIV-negative versus 65% in HIV-infected MSM (P <0.001). HPV-16 was the most frequently detected type and was more common in HIV-infected MSM (13% in HIV-negative and 22% in HIV-infected MSM; P = 0.001). Prevalence of penile high-risk HPV infection was 16% in HIV-negative and 32% in HIV-infected MSM (P <0.001). In multivariable analyses, HIV infection remained associated with anal [adjusted odds ratio (aOR) 2.2; 1.8–2.7] and penile (aOR 2.0; 1.4–2.9) high-risk HPV infection. Higher number of lifetime male sex partners was significantly associated with anal and penile high-risk HPV in HIV-negative, but not HIV-infected MSM. Receptive anal intercourse was associated with anal high-risk HPV in HIV-infected MSM.Anal and penile high-risk HPV infections are very common in MSM. HIV infection is a strong and independent determinant for anal and penile high-risk HPV infection. Determinants for HPV infection appear to differ between HIV-negative and HIV-infected MSM.