BACKGROUND: We assessed human papillomavirus (HPV) vaccine effectiveness (VE) against anal HPV among men who have sex with men (MSM) in 2018-2023. METHODS: Residual anal specimens from MSM without HIV aged 18-45 years were tested for HPV. We calculated adjusted prevalence ratios (aPR) and 95% confidence intervals (CI) for associations between vaccination (≥1 dose) and quadrivalent vaccine (4vHPV)-type prevalence adjusting for city, race/ethnicity, and nonvaccine-type HPV prevalence, stratified by age group (18-26, 27-45 years). VE was calculated as (1 - aPR) × 100. RESULTS: Among 2802 persons aged 18-26, 4vHPV-type prevalence was lower in those vaccinated at age <
18 (aPR = 0.13
95% CI, .08-.22
VE = 87%) and those vaccinated ≥2 years before specimen collection (aPR = 0.52
95% CI, .42-.64
VE = 48%) compared with unvaccinated persons. Among 3548 persons aged 27-45, 4vHPV-type prevalence was lower in those vaccinated at ages 18-26 (aPR = 0.68
95% CI, .57-.82
VE = 32%) and those vaccinated ≥2 years before specimen collection (aPR = 0.66
95% CI, .57-.77
VE = 33%) compared with unvaccinated persons. While we observed no VE in persons vaccinated at age >
26 overall, 4vHPV-type prevalence was lower in the subgroup vaccinated ≥2 years before specimen collection (aPR = 0.71
95% CI, .56-.89
VE = 29%). CONCLUSIONS: We found high VE against anal 4vHPV-type prevalence among MSM aged 18-26 who were vaccinated at age <
18. Lower VE was observed among MSM aged 27-45 who were vaccinated at age 18-26 or ≥2 years before specimen collection. While ideally vaccination should be given at younger ages, vaccination can prevent some future infections in this population.