HPV vaccination to prevent recurrence of Anal Intraepithelial Neoplasia in HIV+ MSM: a randomised, placebo-controlled multicentre trial

Objective Anal cancer precursor lesions high-grade anal intraepithelial neoplasia (HGAIN) are highly prevalent among HIV+ men-who-have-sex-with-men (MSM). Treatment of HGAIN is frustrated by high recurrence rates. We investigated the efficacy of the quadrivalent human papillomavirus (qHPV) vaccine as post-treatment adjuvant in preventing HGAIN recurrence in HIV+MSM. Design Randomised, double-blind, placebo-controlled, multicentre trial. Setting Three HIV outpatient clinics in Amsterdam, the Netherlands. Subjects HIV+MSM with CD4 count >350 cells/μl, biopsy-proven intra-anal HGAIN successfully treated in the past year, and lesions still in remission at enrolment, as assessed by high-resolution anoscopy (HRA). Intervention Participants were randomised to three doses of qHPV (Gardasil-4®, MSD) or placebo with vaccinations at 0, 2, and 6 months. HRA was repeated at 6, 12 and 18 months. Main outcome measure The primary outcome was cumulative, biopsy-proven HGAIN recurrence rate at 18 months, evaluated in an intention-to-treat (received all vaccinations) and per-protocol analysis (all vaccinations and complete follow-up). Results We randomised 126 participants of which 64 (50.8%) received qHPV and 62 (49.2%) placebo. All participants received three vaccinations and in both groups for two participants follow-up was incomplete. We found no difference (p = 0·38) in cumulative HGAIN recurrence rates between the qHPV (44/64, 68.8%) and placebo group (38/62, 61.3%) in the intention-to-treat analysis (absolute risk reduction -7.5 (95%CI -24.1-9.2)). This was similar in the per-protocol analysis. Conclusions Despite adequate serological responses to qHPV vaccination, short-term recurrence of HGAIN was not prevented. These findings do not support qHPV vaccination as a treatment adjuvant to prevent HGAIN recurrence in HIV+MSM.