HPV Vaccine for Anal Cancer Prevention

Recruiting at 3 trial locations

Overseen By Grecia Higuerey

Age: 18+

Sex: Male

Trial Phase: Phase 2

Sponsor: University Health Network, Toronto

Must be taking: cART

Disqualifiers: Hypersensitivity, Anogenital cancer, Previous HPV immunization

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 6

228 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are on cART (HIV treatment), you must be on a stable regimen for at least six months.

What data supports the effectiveness of the 9-valent HPV vaccine treatment for preventing anal cancer?

Research shows that HPV vaccines, including the 9-valent type, are effective in preventing anal HPV infections and related precancerous lesions, which are linked to anal cancer. The 9-valent vaccine covers HPV types found in most anal cancers, suggesting it should effectively prevent anal cancer when given before sexual activity begins. ^{1 2 3 4 5}

Is the 9-valent HPV vaccine safe for humans?

The 9-valent HPV vaccine (9vHPV) has been shown to be safe and well tolerated in clinical studies, with a safety profile comparable to the earlier quadrivalent HPV vaccine. Some local reactions like swelling may occur, especially when given with other vaccines. ^{6 7 8 9 10}

How is the 9-valent HPV vaccine unique for preventing anal cancer?

The 9-valent HPV vaccine is unique because it protects against nine types of HPV, including five additional cancer-causing types not covered by earlier vaccines, potentially preventing up to 95% of HPV-related anal cancers. ^{6 7 11 12 13}

What is the purpose of this trial?

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.

Research Team

Irving Salit, MD

Principal Investigator

Toronto General Hospital, University Health Network

Eligibility Criteria

This trial is for HIV-positive men who have had sexual activity with men or both genders, are at least 18 years old, and have high-grade anal dysplasia (AIN-2 or -3). They must be willing to undergo standard ablative therapy and either be on a stable antiretroviral regimen or not planning to start one within six months. Participants need documented HIV infection and the ability to attend all study visits.

Inclusion Criteria

I have had sexual relations with men or both men and women.

I can go to all required clinic visits for the study.

I have had sexual activity with men or both men and women.

Exclusion Criteria

I have or had cancer in the genital, anal, rectal, or throat areas.

You are allergic to any ingredient in the HPV vaccine, like yeast or aluminum.

I have been vaccinated against HPV.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Immediate Vaccination

Administration of dose #1 of 9-valent HPV vaccination at baseline visit, dose #2 at month 2, and dose #3 at month 6

6 months

3 visits (in-person)

Delayed Vaccination

Administration of dose #1 of 9-valent HPV vaccination at month 12, dose #2 at month 14, and dose #3 at month 18

6 months

3 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including changes in anal carriage of vaccine HPV types and immunogenicity

24 months

Treatment Details

Interventions

• 9-valent HPV vaccination

Trial Overview The trial is testing the safety and effectiveness of the 9-valent HPV vaccine in preventing recurrence of high-grade anal lesions in HIV-positive MSM. It explores how well this vaccine works as part of their overall health management strategy.

Participant Groups

Group I: Immediate Vaccination Experimental Treatment 1 Intervention

Administration of dose #1 of 9-valent HPV vaccination will be given at baseline visit, dose #2 at month 2, and dose #3 at month 6.

Group II: Delayed Vaccination Active Control 1 Intervention

Administration of dose #1 of 9-valent HPV vaccination will be given at month 12, dose #2 at month 14, and dose #3 at month 18.

Who Is Running the Clinical Trial?

University Health Network, Toronto

Lead Sponsor

Trials

1,555

Recruited

526,000+

Merck Sharp & Dohme LLC

Industry Sponsor

Trials

4,096

Recruited

5,232,000+

Chirfi Guindo

Merck Sharp & Dohme LLC

Chief Marketing Officer since 2022

Degree in Engineering from Ecole Centrale de Paris, MBA from New York University Stern School of Business

Robert M. Davis

Merck Sharp & Dohme LLC

Chief Executive Officer since 2021

JD from Northwestern University Pritzker School of Law, MBA from Northwestern University Kellogg Graduate School of Management, Bachelor's in Finance from Miami University

Findings from Research

The nonavalent HPV vaccine (9vHPV) has shown over 90% efficacy in preventing cervical, vulvar, and vaginal precancers caused by HPV types 16, 18, and five additional cancer-causing types (31, 33, 45, 52, 58) in Phase III clinical studies.

9vHPV has the potential to prevent up to 93% of cervical cancer cases and has demonstrated lasting antibody responses for at least five years, indicating its long-term effectiveness in reducing the burden of HPV-related cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recombinant human papillomavirus nonavalent vaccine in the prevention of cancers caused by human papillomavirus. Toh, ZQ., Kosasih, J., Russell, FM., et al.[2020]

The nine-valent HPV (9vHPV) vaccine demonstrated comparable immune responses to the quadrivalent HPV (qHPV) vaccine for HPV types 6/11/16/18, while also effectively eliciting immune responses for five additional oncogenic HPV types (31/33/45/52/58) in a study of 500 men aged 16-26.

Both the 9vHPV and qHPV vaccines exhibited similar safety profiles, indicating that the 9vHPV vaccine is a safe and effective option for preventing a broader range of HPV-related diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase III clinical study to compare the immunogenicity and safety of the 9-valent and quadrivalent HPV vaccines in men. Van Damme, P., Meijer, CJLM., Kieninger, D., et al.[2017]

The 9-valent HPV vaccine (9vHPV) is safe and highly effective, showing over 99.8% seroconversion rates for all vaccine types in both groups of a study involving 1054 participants aged 11-15 years.

Administering the 9vHPV vaccine alongside the REPEVAX vaccine did not interfere with the immune response to either vaccine, indicating that this approach can safely reduce the number of vaccination visits needed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An open-label, randomized study of a 9-valent human papillomavirus vaccine given concomitantly with diphtheria, tetanus, pertussis and poliomyelitis vaccines to healthy adolescents 11-15 years of age. Kosalaraksa, P., Mehlsen, J., Vesikari, T., et al.[2015]

The 9-valent HPV vaccine (9vHPV) is as effective as the quadrivalent HPV vaccine (qHPV) in generating immune responses against HPV types 6, 11, 16, and 18, while also providing a 96.7% risk reduction against high-grade cervical, vulvar, or vaginal diseases related to five additional HPV types in females aged 16-26.

The 9vHPV vaccine has been shown to be safe and well tolerated, with evidence supporting its efficacy in both males and females aged 9-26, indicating its potential to significantly expand protection against HPV infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Human papillomavirus 9-valent vaccine for cancer prevention: a systematic review of the available evidence. Signorelli, C., Odone, A., Ciorba, V., et al.[2022]

The new nonavalent HPV vaccine (9vHPV) shows a very strong immune response with nearly 100% seroconversion rates and has a safety profile similar to the quadrivalent vaccine (qHPV), although it may cause more local reactions like swelling, especially when given with other vaccines.

The 9vHPV vaccine offers additional protection against HPV-related cancers, potentially preventing 8% to 18% more cases compared to previous vaccines, but its overall impact will depend on various factors such as duration of protection and population-specific HPV type distribution.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Spotlight on the 9-valent HPV vaccine. Lopalco, PL.[2018]

The 9-valent HPV vaccine (9vHPV) can potentially increase the prevention of cervical cancer from 70% to 90% by covering additional HPV types (31, 33, 45, 52, and 58) not included in earlier vaccines.

In addition to cervical cancer, the 9vHPV vaccine could prevent 85-95% of HPV-related vulvar, vaginal, and anal cancers, highlighting its broad efficacy in reducing the overall cancer burden associated with HPV.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

9-Valent HPV vaccine for cancers, pre-cancers and genital warts related to HPV. Pitisuttithum, P., Velicer, C., Luxembourg, A.[2022]

The 9-valent HPV vaccine (Gardasil 9®) significantly increases protection against cervical cancer by covering 9 oncogenic HPV types, raising potential protection from about 70% to 90%, based on clinical trials involving young women.

Clinical trials demonstrated that the 9vHPV vaccine has a comparable safety profile and immunogenicity to the original 4-valent vaccine, with a 2-dose regimen showing similar effectiveness in younger boys and girls compared to the standard 3-dose regimen for older women.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Expanded strain coverage for a highly successful public health tool: Prophylactic 9-valent human papillomavirus vaccine. Zhang, Z., Zhang, J., Xia, N., et al.[2019]

References

1. United States pubmed.ncbi.nlm.nih.gov

Bivalent Vaccine Effectiveness Against Anal Human Papillomavirus Positivity Among Female Sexually Transmitted Infection Clinic Visitors in the Netherlands. [2021]

2. United States pubmed.ncbi.nlm.nih.gov

Incidence, Clearance, and Persistence of Anal Human Papillomavirus in Men Who Have Sex With Men Living With Human Immunodeficiency Virus: Implications for Human Papillomavirus Vaccination. [2020]

3. United States pubmed.ncbi.nlm.nih.gov

HPV vaccination and anal high-grade precancerous lesions and cancer: a real-world effectiveness study. [2023]

4. England pubmed.ncbi.nlm.nih.gov

Sexual healthcare professionals' views on HPV vaccination for men in the UK. [2018]

5. United States pubmed.ncbi.nlm.nih.gov

Prophylactic HPV vaccination and anal cancer. [2022]

6. New Zealand pubmed.ncbi.nlm.nih.gov

Recombinant human papillomavirus nonavalent vaccine in the prevention of cancers caused by human papillomavirus. [2020]

7. Netherlands pubmed.ncbi.nlm.nih.gov

A phase III clinical study to compare the immunogenicity and safety of the 9-valent and quadrivalent HPV vaccines in men. [2017]

8. United States pubmed.ncbi.nlm.nih.gov

An open-label, randomized study of a 9-valent human papillomavirus vaccine given concomitantly with diphtheria, tetanus, pertussis and poliomyelitis vaccines to healthy adolescents 11-15 years of age. [2015]

9. England pubmed.ncbi.nlm.nih.gov

Human papillomavirus 9-valent vaccine for cancer prevention: a systematic review of the available evidence. [2022]

10. New Zealand pubmed.ncbi.nlm.nih.gov

Spotlight on the 9-valent HPV vaccine. [2018]

11. England pubmed.ncbi.nlm.nih.gov

9-Valent HPV vaccine for cancers, pre-cancers and genital warts related to HPV. [2022]

12. United States pubmed.ncbi.nlm.nih.gov

A Randomized, Double-Blind, Phase III Study of the Immunogenicity and Safety of a 9-Valent Human Papillomavirus L1 Virus-Like Particle Vaccine (V503) Versus Gardasil® in 9-15-Year-Old Girls. [2015]

13. United States pubmed.ncbi.nlm.nih.gov

Expanded strain coverage for a highly successful public health tool: Prophylactic 9-valent human papillomavirus vaccine. [2019]