Background Infection with human papillomavirus (HPV) is not generally followed by seroconversion for reasons not yet fully understood. This cross-sectional study investigated concordance between high-risk (hr) HPV infections at three anatomical sites and concordant seropositivity, in both HIV-infected and HIV-negative men who have sex with men (MSM).

Methods MSM aged ≥ 18 years were recruited from the Amsterdam Cohort Studies, an STI clinic and an HIV treatment centre in Amsterdam, the Netherlands. The associations between anal, penile, and oral HPV infections and concordant seropositivity of 7 hr-HPV types (16, 18, 31, 33, 45, 52 and 58) were estimated using generalised estimating equations (GEE) regression analyses.

Results Among the 306 HIV-infected MSM 93% were hr-HPV seropositive (i.e. seropositive for at least one of the 7 hr-HPV types) and 69% were infected with at least one anal, penile, or oral hr-HPV infection. Of 441 HIV-negative MSM 74% were hr-HPV seropositive and 41% were infected with one or more hr-HPV infections. Type-specific hr-HPV seropositivity was not more likely for men with concordant infections at multiple anatomical sites (OR 1.58, 95% CI 1.06–1.86) compared to those with concordant infections at only one anatomical site (OR 1.45, 95% CI 1.22–1.73). In multivariable analysis, adjusting for key demographic and sexual behavioural factors, type-specific hr-HPV seropositivity was associated with concordant anal hr-HPV infections (OR 1.60, 95% CI 1.32–1.92), but not with concordant penile (OR 0.79, 95% CI 0.58–1.06) or oral (OR 1.36, 95% CI 0.85–2.17) hr-HPV infections; in stratified analyses, these associations were similar for HIV-infected and HIV-negative men.

Conclusions In both HIV-infected and HIV-negative MSM, anal hr-HPV infections were associated with hr-HPV seropositivity, while penile and oral hr-HPV infections were not. Our findings support the hypothesis that seropositivity differs by the type of epithelium infected, implying that mucosal infection may provide a stronger signal to the immune system.