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. 2025 Aug 13:61:127447.
doi: 10.1016/j.vaccine.2025.127447. Epub 2025 Jul 2.

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

Anna R Giuliano  1 , Anna Beltrame  2 , Luisa L Villa  3 , Eduardo Lazcano-Ponce  4 , Jorge Santana-Bagur  5 , Betania Allen-Leigh  4 , Alejandra J Portillo-Romero  4 , Vikrant V Sahasrabuddhe  6 , Margaret G House  6 , Emma Brofsky  6 , Lenice Galan de Paula  3 , Roberto Carvalho da Silva  7 , Michael J Schell  8 , Julie Rathwell  2 , Kimberly Isaacs-Soriano  2 , Wenyi Fan  8 , Caique Mello  9 , Grant B Ellsworth  10 , Timothy Wilkin  9
Affiliations

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

Anna R Giuliano et al. Vaccine. .

Abstract

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.

Keywords: Genotypes; HIV; HPV-16; Oropharyngeal; Prophylactic vaccine; cancer.

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Conflict of interest statement

Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Luisa L. Villa reports financial support was provided by National Cancer Institute. Luisa L. Villa reports a relationship with Merck & Co Inc. that includes fees for travel and talks. Michael J. Schell reports financial support was provided by National Cancer Institute. Betania Allen-Leigh reports financial support was provided by National Cancer Institute. Julie Rathwell reports a relationship with Merck Sharp & Dohme, LLC that includes: consulting or advisory. Moffitt Cancer Center reports financial support was provided by National Cancer Institute. Anna R Giuliano reports financial support was provided by National Cancer Institute. Anna R Giuliano, reports a relationship with Merck & Co Inc. that includes: consulting or advisory, funding grants, and speaking and lecture fees. Anna R Giuliano holds an American Cancer Society Clinical Research Professorship. Anna Beltrame reports financial support was provided by this award. Grant B Ellsworth reports financial support was provided by National Institutes of Health National Cancer Institute. Grant Ellsworth reports financial support was provided by Merck & Co Inc. Grant B Ellsworth reports a relationship with Northeast Carribean AIDS Clinical Training Center that includes: speaking and lecture fees. Grant B Ellsworth reports a relationship with International AIDS Society USA that includes: speaking and lecture fees. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

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