HPV-SAVE: 9-Valent HPV Vaccine for High-Grade Anal Dysplasia

• Status: Unknown status
• Trial end date: 2020-05-01
• Target enrollment: 0
• Participant gender: Male

Summary

Infection by certain high-risk oncogenic types of Human Papillomavirus (HR-HPV) is the major cause of several cancers in men, notably squamous cell carcinoma (SCC) of the anal canal. Rates of high-grade anal dysplasia and anal cancer are much higher in men who have sex with men (MSM) than in the general population. Rates of anal SCC in HIV-positive MSM are higher than the historic rates of cervical cancer prior to the adoption of routine cervical cytology screening. Despite these statistics, there are no established protocols for optimal screening and treatment of anal cancer precursors. Further, there is growing evidence that HPV may enhance sexual transmission of HIV. These significant knowledge gaps translate into fundamental deficiencies in the care for HIV-positive MSM.

The HPV Screening and Vaccine Evaluation in MSM (HPV-SAVE) study team aims to recruit a large group of MSM from various Ontario and Vancouver clinics in order to carry out 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) 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 b) 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 upon which the current proposal is based.

• Phase: Phase 1
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: University Health Network, Toronto
• Collaborator: Merck Sharp & Dohme Corp.
• Treatments: Vaccines

Criteria

Inclusion Criteria:

1. Males, aged ≥ 18 years at baseline;

2. Laboratory documentation of HIV-1 infection (enzyme-linked immunosorbent assay [ELISA] and Western Blot);

3. AIN-2 or -3 found on biopsy of anal canal lesion(s), and willingness to undergo ablative therapy;

4. History of any sexual activity with men, or both men and women, where sexual activity is defined as oral, vaginal, or anal intercourse;

5. For those on cART, the participant must be on a stable regimen (i.e. virologically suppressed with HIV-1 ribonucleic acid (RNA) below the assay's limit of detection for minimum six months). This will minimize confounding from dramatic shifts in viral load and/or cluster of differentiation 4(CD4) count;

6. For those individuals that are not on cART, there must be no immediate plans to initiate cART in the next six months. There will be no lower limit cut-off for CD4 count;

7. An ability to give informed consent;

8. An ability to attend clinic for all study visits.

Exclusion Criteria:

1. Known hypersensitivity to any component of the HPV vaccine (e.g. Saccharomyces cerevisiae yeast, Amorphous Aluminium Hydroxyphosphate Sulfate adjuvant);

2. Current or prior history of cancer of the anogenital regions (e.g. penile, anal, or rectal) or of the oropharyngeal area (e.g. oral cavity, upper airway).