CTN 324: Assessing the efficacy of an HPV vaccine in preventing anal pre-cancers in men living with HIV

HPV

Co-infections and Related Conditions (CRC)

A multicenter, randomized controlled trial of the efficacy, safety and immunogenicity of the 9-valent human papillomavirus (HPV) vaccination in preventing recurrence of high-grade anal dysplasia in HIV-positive men who have sex with men (MSM)

About The Study

This study will assess how well the HPV vaccine prevents the recurrence of anal pre-cancers in men who have sex with men (MSM) living with HIV. It will measure the recurrence of pre-cancerous lesions, known as high-grade anal intraepithelial neoplasia (HGAIN), in those who have had their HGAIN treated. There will be two groups of men: one receiving an HPV vaccine at the beginning of the study, and one receiving the vaccine after 12 months. HGAINs are known to recur frequently despite ablative therapy treatment (i.e. removal of the lesion with heat) and can progress to cancer. CTN 324 aims to determine whether the HPV vaccine will limit the recurrence of HGAINs, thereby reducing the risk of developing anal cancer. The study will also determine whether HPV vaccines are safe and effective for men living with HIV.

About The Disease

Human papillomavirus (HPV) is the most common sexually transmitted infection worldwide, and has been shown to cause approximately 40–90% of all anal, vulvar, vaginal, penile, and oropharyngeal cancers. In men, HPV infection is the primary cause of a cancer of the anal canal known as squamous cell carcinoma.

Rates of anal infection with HPV, and resultant anal cancers, are much higher in men who have sex with men (MSM) than in the general population. MSM who are living with both HPV and HIV demonstrate the highest anal cancer rates of any population.

Modern HPV vaccinations cover nine types of HPV, protecting against 90% of all HPV-related cancers. While HPV vaccines have been shown to reduce the rates of cervical cancers in women and anal cancers in certain groups of men, little is known about the overall safety and efficacy of HPV vaccines for MSM living with HIV.

Study Approach

A total of 228 MSM who are being treated for HGAIN in Toronto and Vancouver will be randomized into two groups, one receiving the HPV vaccine immediately and another receiving the vaccine 12 months after their initial HGAIN treatment. Participants will be monitored at follow-up visits over the course of 46 months. Each visit will include a complete health history assessment and physical examination, along with blood work and throat and anal swabs to measure HPV prevalence. Rates of HGAIN recurrence will be compared in all groups to determine the overall efficacy of the HPV vaccine.

Eligibility Requirements

Required

Male, aged 18 years or older
HIV-positive
AIN-2 or -3 found on biopsy of anal canal lesion(s), and willingness to undergo ablative therapy
History of any sexual activity with men, or both men and women, where sexual activity is defined as oral, vaginal, or anal intercourse
For those on cART, the participant must be on a stable regimen (i.e. undetectable viral load for a minimum of six months)
For those individuals who 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
An ability to give informed consent
An ability to attend the clinic for all study visits.

Not Allowed

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