Objective: To describe effects of HAART on high-risk human papillomavirus (HPV) antibody response in HIV-positive MSM and the meaning of this response for subsequent HPV-related cancer risk. Methods: For each individual, two serum samples, one at HAART initiation (pre-HAART) and another 24 months later (post-HAART), were tested for L1 antibodies to HPV6,11,16,18,31,33,35, 45, 52 and 58, as well as HPV16-E6 antibodies, using a multiplex serology assay. Identification of HPV-related cancer included data linkage with Swiss cancer registries.Results: Pre-HAART, 45.2% were seropositive for any high-risk HPV-L1 and 32.4% for HPV16-L1. Sexual intercourse during the last 6 months was the only evaluated factor associated with L1 seropositivity pre-HAART. Seropositivity increased post-HAART to 60.5% for any high-risk HPV-L1 [prevalence ratio versus pre-HAART ¼ 1.34, 95% confidence interval (CI) 1.14-1.57] and 48.0% for HPV16-L1 (prevalence ratio versus pre-HAART ¼ 1.48, 95% CI 1.20-1.83), and seroconversion was significantly associated with both lower CD4 þ cell count and CD4 þ /CD8 þ ratio (P < 0.01). Only one individual was HPV16-E6-seropositive pre-HAART, but two more seroconverted post-HAART. Anal cancer incidence among the three HPV16-E6-positives post-HAART was significantly increased compared with HPV16-E6-negatives (incidence rate ratio ¼ 63.1, 95% CI 1.1-1211).