The Clinical Effects of Off-Label Quadrivalent Human Papillomavirus Vaccination of Men who have Sex with Men: A Non-Concurrent Cohort Study

Background: Industry-sponsored randomized, double-blind, placebo controlled trials of the quadrivalent human papillomavirus (qHPV) vaccine have demonstrated its efficacy against precancerous lesions of the cervix and genital condyloma in young women, against condyloma in older women, and against precancerous lesions of the anus and anogenital condyloma in young men who have sex with men (MSM).;Objective: To determine if the qHPV vaccine, when administered off-label to MSM in a real world setting, is effective against high-grade anal intraepithelial neoplasia (HGAIN) and anogenital condyloma.;Design: A non-concurrent cohort study was performed of 230 HIV-negative MSM who received the full three-dose qHPV vaccine and 313 unvaccinated, HIV-negative MSM. Analysis of vaccine efficacy against HGAIN was conducted for all patients, sub-groups of patients with and without a history of HGAIN, and a sub-group of patients negative for high-risk HPV. Analysis of vaccine efficacy against anogenital condyloma was conducted for all patients and sub-groups of patients with and without a history of anogenital condyloma within the previous five years. Kaplan-Meier plots, Cox Proportional Hazards Ratios of time to event adjusted for potential confounding factors, and logistic regression adjusted for potential confounding factors were performed.;Results: The vaccinated cohort had a mean age of 36.6 years, over half of whom were infected with high-risk HPV prior to vaccination. Over 37% had a history of HGAIN and nearly 75% had a history of anogenital condyloma. Overall, vaccine efficacy was 50.6 (95% confidence interval [CI] 23.8 to 68.0) against HGAIN and 30.4% (95% CI 0.9 to 51.0) against anogenital condyloma. The vaccine proved effective against HGAIN among patients with a history of HGAIN (51.8% [95% CI 17.3 to 68.0]) and against anogenital condyloma among patients with a history of anogenital condyloma (35.7% [95% CI 5.4 to 56.3%]). There were no cases of HGAIN among high-risk HPV negative patients who were vaccinated. The adjusted hazard ratio for unvaccinated patients compared to vaccinated patients was 1.58 (95% CI 0.96 to 2.61) for HGAIN and 2.06 (95% CI 1.10 to 3.85) in the sub-group of patients with a history of HGAIN. Hazard ratios were not significant for anogenital condyloma. The adjusted odds ratio for unvaccinated patients compared to vaccinated patients was 1.78 (95% CI 1.14 to 2.79) for anogenital condyloma and 1.89 (95% CI 1.12 to 3.18) in the sub-group of patients with a history of anogenital condyloma.;Conclusions: The quadrivalent HPV vaccine is effective against HGAIN and anogenital condyloma in older MSM, regardless of past or current HPV infection. The vaccine demonstrated prevention of HGAIN and anogenital condyloma recurrence among patients with history of disease. Vaccinating MSM has the potential for significant public health effect.