The HPV-SAVE Study Team: HPV Screening and Vaccine Evaluation in Men Who Have Sex With Men

NCT02503111 | Terminated DMC

• 1 other identifier: CTN 292B
• Study Type: interventional
• Target: 71
• Locations: 1 country
• Sites: 4

Brief Summary

Human papillomavirus (HPV) is the most common sexually transmitted infection 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 will 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 further, large-scale screening and treatment trials on a national level. The primary aim of the current study is to systematically compare ablative therapy versus intensive observation alone (also known as 'watchful waiting') in outcomes relating to high-grade anal dysplasia.

Conditions

Anal Dysplasia; Human Papillomavirus; Anal Cancer

Keywords

Men who have sex with men; Human immunodeficiency virus; Human papillomavirus; Anal intraepithelial neoplasia; Squamous cell carcinoma; High-resolution anoscopy; Anal cancer; High-risk oncogenic; Intraepithelial lesion; Low-risk non-oncogenic; Dysplasia; High-grade squamous intraepithelial lesion; Low-grade squamous intraepithelial lesion; Ablative therapy; Electrocautery; Infrared coagulation; Active surveillance

Outcome Measures

Primary Outcomes (1)

• Anal dysplasia treatment on a per-patient basis

  Histologic resolution of high-grade AIN after treatment completion, with ablative therapies or surveillance alone. Resolution of high-grade AIN will be defined as histologic diagnosis of AIN-1 or normal at the post treatment HRA.

  Participants will be followed after post-treatment completion, an expected average of 6 months

Secondary Outcomes (4)

• Resolution of high-grade AIN at 3 and 6 months after randomization, on a per-lesion basis

  Participants will be followed after post-treatment completion, an expected average of 6 months

• Recurrence rates of high-grade AIN

  Participants will be followed post-treatment completion, at 12, 24 and 36 months after randomization

• Number of participants with adverse events

  Participants will be followed after post-treatment completion, an expected average of 36 months

• Acceptability of treatment

  Within 6 months of randomization

Study Arms (2)

Ablative therapy

EXPERIMENTAL

Ablative therapy involving electrocautery (EC) will occur for participants with AIN-2 and AIN-3. The Hyfrecator ® 2000 Electrosurgical System will be used for EC therapy.

Device: The Hyfrecator ® 2000 Electrosurgical System

Active Surveillance

ACTIVE COMPARATOR

The control arm includes active surveillance with observation alone; no treatment in AIN-2 and -3.

Other: Observation Alone

Interventions

The Hyfrecator ® 2000 Electrosurgical System DEVICE

Lesion is ablated by the The Hyfrecator ® 2000 Electrosurgical System. During electrocautery (EC) with The Hyfrecator, a gentle brushing technique occurs and the tissue is removed with forceps.

Also known as: EC

Ablative therapy

Observation Alone OTHER

No treatment to AIN-2 or AIN-3, only active surveillance.

Active Surveillance

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Males, aged ≥18 years at baseline;
• Identify as a man who has sex with a men (MSM);
• HIV-positive; laboratory documentation of HIV-1 infection;
• For those on combination antiretroviral therapy (cART), the participant must be on a stable regimen;
• An ability to give informed consent;
• An ability to attend clinic for follow-up, including possible HRA and biopsy;
• AIN-2 or -3 found on biopsy of anal canal lesion(s);
• Willingness to be randomized to undergo ablative therapy or active surveillance.

You may not qualify if:

• Current or prior history of cancer of the anogenital regions (e.g. penile, anal, or rectal).;
• Previous treatment of high grade dysplasia;

Sponsors & Collaborators

• University Health Network, Toronto: lead
• Canadian Institutes of Health Research (CIHR): collaborator
• Ontario HIV Treatment Network: collaborator
• CIHR Canadian HIV Trials Network: collaborator
• Merck Sharp & Dohme LLC: collaborator

Study Sites (4)

BC Centre for Disease Control

Vancouver, British Columbia, V5Z 4R4, Canada

Location

University of British Columbia

Vancouver, British Columbia, V6T 1Z4, Canada

Location

Ottawa Hospital Research Institute

Ottawa, Ontario, K1Y 4E9, Canada

Location

University Health Network - Toronto General Hospital

Toronto, Ontario, M5G 2C4, Canada

Location

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MeSH Terms

Conditions

Anus Neoplasms; Homosexuality; Acquired Immunodeficiency Syndrome; Carcinoma, Squamous Cell; Squamous Intraepithelial Lesions

Interventions

Observation

Condition Hierarchy (Ancestors)

Rectal Neoplasms; Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Diseases; Anus Diseases; Rectal Diseases; Sexuality; Sexual Behavior; Behavior; HIV Infections; Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Slow Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms, Squamous Cell; Morphological and Microscopic Findings; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Methods; Investigative Techniques

Study Officials

• Irving Salit, MD

  Toronto General Hospital, University Health Network

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Immunodeficiency Clinic Director, Toronto General Hospital

Study Record Dates

• First Submitted: July 10, 2015
• First Posted: July 20, 2015
• Study Start: November 1, 2015
• Primary Completion: November 1, 2021
• Study Completion: April 14, 2022
• Last Updated: June 13, 2022

Record last verified: 2022-06

Locations

CA (4)