Nonavalent HPV vaccine to prevent recurrent anal or vulvar high-grade squamous intraepithelial lesions (VIVA trial): A randomized, double-blind, placebo-controlled trial.

The nonavalent human papillomavirus (9vHPV) vaccine protects against HPV infection and high-grade squamous intraepithelial lesions (HSIL) when administered prior to exposure, but evidence supporting its potential therapeutic benefit has been inconsistent. This randomized, double-blind, placebo-controlled trial evaluated whether the 9vHPV vaccine reduces recurrence of HSIL or HPV persistence in 27-69-year-old persons previously treated for anal or vulvar HSIL. Participants were HSIL-free at enrollment and received 9vHPV or placebo at months 0, 2, and 6. High-resolution anoscopy or vulvoscopy was performed at months 18 and 36, and anal or vulvar swabs were collected at months 0, 18, 24, and 36 for HPV DNA detection. The primary endpoints were HSIL recurrence and HPV persistence (≥2 consecutive positive swabs for the same 9vHPV-type). Of 185 participants included in the intent-to-treat analysis, 91 received vaccine and 94 received placebo. The DSMB recommended early termination for futility. The 9vHPV vaccine was not more effective than placebo in preventing recurrent HSIL, with 16 HSIL among 9vHPV recipients versus 21 HSIL in placebo recipients (incidence 8.1 vs. 10.1/100 person-years; p = .54). HPV persistence was 21% in vaccine versus 31% in placebo recipients (p = .20). The 9vHPV vaccine delivered after treatment of anal or vulvar HSIL did not reduce HSIL recurrence or HPV detection. Our study underlines the importance of HPV vaccine administration prior to HPV exposure and the need for novel treatments for HSIL with high recurrence potential.