HPV-SAVE_Merck_Sub-Study for Preventing Recurrence of HSIL

Summary

Human papillomavirus (HPV) is the most common sexually transmitted infection (STI) worldwide. Infection by certain high-risk oncogenic types of HPV (HR-HPV) is the major cause of several cancers in men, notably squamous cell carcinoma (SCC) of the anal canal. Rates of anal infection with these HR-HPV strains, and the resultant high-grade anal dysplasia and anal cancer are much higher in men who have sex with men (MSM) than in the general population. Co-infection with human immunodeficiency virus (HIV) further amplifies this burden, making the rates of anal SCC in HIV-positive MSM higher than the historic rates of cervical cancer prior to the adoption of routine cervical cytology screening. Despite these alarming statistics, there are no established protocols for optimal screening and treatment of anal HPV and cancer precursors, nor has there been any widespread rollout of organized screening programs anywhere in Canada. Further, not only does HPV directly cause significant disease in these men, but there is growing epidemiologic evidence that HPV infection may enhance sexual transmission of HIV. These significant knowledge gaps translate into fundamental deficiencies in care for HIV-positive MSM.

The HPV Screening and Vaccine Evaluation in MSM (HPV-SAVE) study team was funded by the Canadian Institutes of Health Research (CIHR) via its Boys' and Men's Health Team Grant Competition. It aims to recruit a large group of MSM from various Ontario and Vancouver clinics, in order to carry out a number of different studies. The HPV-SAVE team brings together community and internationally-recognized experts in HPV and HIV disease and mucosal immunology, to better define the optimal approaches for primary and secondary prevention and treatment of HPV-associated anal disease among HIV-positive MSM, and to explore biological mechanistic evidence regarding the potential role of HPV as a co-factor for HIV transmission. This will yield critical information which can lead to improvement in the health of MSM, and will provide a foundation on which to build large-scale screening and treatment trials on a national level. A key part of this research program involves an analysis of the potential role played by the HPV vaccine in the overall management of HIV-positive MSM.

Planned vaccine-related projects include:

* A mixed-methods analysis of the knowledge, attitudes, and acceptability of HPV vaccination amongst HIV-positive MSM, through quantitative (e.g. cross-sectional survey) and qualitative (e.g. in-depth interviews) means.
* A comprehensive assessment of the 9-valent HPV vaccine in HIV-positive MSM, including safety and immunogenicity, as well as its potential role in secondary prevention of high-grade anal dysplasia. This is the study on which the current proposal is based.

Conditions

• Anal Intraepithelial Neoplasia
• Anal Cancer
• Human Papilloma Virus

Interventions

DRUG

9-valent HPV vaccination

Gardasil-9 is a novel, 9-valent HPV recombinant vaccine, which expands the coverage of oncogenic HPV types, with the addition of HPV types 31, 33, 45, 52, and 58 to the existing quadrivalent vaccine types. The addition of these five oncogenic types is estimated to improve cancer coverage to 90% (versus 70% for the quadrivalent vaccine) \[38\]. With its expanded coverage of oncogenic HPV types, its proven efficacy in primary prevention and its potential role in mitigating HGAIN recurrences.

Sponsors & Collaborators

• Merck Sharp & Dohme LLC

  collaborator INDUSTRY

• University Health Network, Toronto

  lead OTHER

Principal Investigators

• Irving Salit, MD · Toronto General Hospital, University Health Network

Study Design

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

18 Years

Sex

MALE

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2022-09-01

Primary Completion

2026-03-01

Completion

2026-05-01

Countries

• Canada

Study Locations