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BACKGROUND Men who have sex with men living with human immunodeficiency virus have a high risk of anal cancer. We estimate the likely benefit of human papillomavirus (HPV) vaccination among participants of the Anal Cancer Examination study. METHODS Anal swabs were collected for the detection and genotyping of anal HPV DNA by linear array (Roche Diagnostics) in this 2-year multicenter prospective cohort. We calculated the proportion of men, stratified by age, without detectable vaccine type-specific DNA. RESULTS Overall, 255 men, with a median age of 50 years (interquartile range, 44-56 years) contributed 488.9 person-years of follow-up. After 2 years of follow-up, 149 (58%; 95% confidence interval [CI], 52-65) had at least 1 high-risk HPV (HRHPV), and 71 (28%, 95% CI, 22-34) had HPV types 16/18 detected. Assuming that DNA-negative men would receive vaccine protection, vaccination at baseline could potentially prevent HRHPV infection in 10.2% of men (95% CI, 6.8-14.6, 26 of 255) 2 years later from incident HRHPV covered by the bivalent and quadrivalent vaccine, and 29.4% of men (95% CI, 23.9-35.4, 75/255) from incident HRHPV covered by the nonavalent vaccine. CONCLUSION Though there is high prevalence of anal HPV in men who have sex with men living with human immunodeficiency virus, there was also a high incidence of HRHPV vaccine types in the 2-year follow-up, indicating potential for prevention if these men were not previously infected with HPV vaccine types and were vaccinated at their baseline visit.