Design of a multicenter, randomized, double-blinded, placebo-controlled phase III trial evaluating the 9-valent human papillomavirus (HPV) vaccine to prevent persistent oral HPV infection in men living with human immunodeficiency virus: ULACNet trial 201.

HPV-related oropharyngeal squamous cell carcinoma (OPSCC) has increased significantly among men, especially among men living with HIV. HPV vaccines have proven efficacy in preventing persistent anogenital HPV infections. However, less is known regarding vaccine efficacy against persistent oral HPV infection, the obligate precursor of OPSCC. In 2020, the 9-valent HPV (9vHPV) vaccine received accelerated approval from the FDA for the indication of prevention of HPV-related OPSCC and other head and neck cancers, pending confirmation of clinical benefit in further trials. Currently a Phase III trial is ongoing to evaluate efficacy of the 9vHPV vaccine in preventing persistent oral HPV infection in immunocompetent men (NCT04199689); however, no trials have been conducted in people living with HIV. Here we describe the rationale, design, and study population characteristics of the first randomized (1:1), double-blind, placebo-controlled trial evaluating the efficacy and immunogenicity of the 9vHPV vaccine in preventing persistent oral HPV infection in men aged 20-50 living with HIV. The primary objective is to demonstrate that the 9vHPV vaccine when given in a 3-dose regimen (Day 1, Months 2 and 6) reduces the incidence of persistent (≥6 months) oral HPV infection with 9vHPV vaccine types 6, 11, 16, 18, 31, 33, 45, 52, and 58 in men living with HIV who are oral HPV negative to the relevant HPV type at enrollment, compared with placebo. The trial began in February 2021 and completed enrollment of 700 men at clinical sites in Brazil, Mexico, and Puerto Rico in February 2024. The secondary objectives are to evaluate the vaccine-induced serum anti-HPV 6, 11, 16, 18, 31, 33, 45, 52, and 58 responses, and the safety and tolerability of the 9vHPV vaccine in men living with HIV. Results from this study may inform policy regarding vaccination strategies for people living with HIV. ClinicalTrials.gov Identifier: NCT04255849.