Integration of HPV Vaccination and HPV-based Cervical Screening Into ARV Clinics: the H2VICTORY Trial

Summary

A 3-dose HPV vaccination scheme has shown to be safe and immunogenic in people living with HIV (PLWH), although evidence on 1-dose, which is important to improve coverage, is scarce. Available HPV vaccines only prevent new infections. Since a large fraction of WLWH is already infected with HPV (\>50%), vaccines' efficacy to prevent HPV infections (and therefore cervical disease) in this population is limited. Current WHO cervical cancer screening guidelines recommend treatment of the transformation zone (TZ) of WLWH who harbor HPV infections either at initial screening or one year later. Therefore, HPV vaccination at the time of the screening may improve vaccines efficacy conferring protection to newly growing cells of the treated TZ against HPV infections/re-infections. Consequently, a dual-intervention of HPV vaccination and HPV-based cervical screening in WLWH may alleviate the burden of HPV-related disease by improving HPV vaccination efficacy while extending cervical screening intervals. Nevertheless, implementing the dual-intervention may be challenging particularly in some contexts without well-established cervical cancer screening such as sub-Saharan African (SSA) countries. However, in these countries, at least 60% of PLWH regularly attend ARV clinics to be monitored and receive ARV treatment (cART). Therefore, integrating the dual-intervention into ARV clinics seems to be an efficient approach to reduce loss to follow-up while improving overall coverages of HPV vaccination and cervical screening. Such integration may also facilitate the implementation of a platform for the delivery of other HPV-related preventive measures such as HPV therapeutic vaccines.

Nevertheless, little is known about the efficacy of HPV vaccination in WLWH to prevent HPV infections and HPV-related diseases, especially in young adults. Moreover, evidence on how best to conduct cervical cancer prevention, particularly recently released WHO guidelines, through ARV clinics is limited. Therefore, IARC/WHO in collaboration with HRP/WHO and colleagues in SSA proposes to conduct a hybrid effectiveness-implementation trial (H2VICTORY) to evaluate the effectiveness of the dual-intervention of HPV vaccination and HPV-based cervical screening to reduce HPV infections (and therefore, the risk of cervical cancer) in WLWH aged 25-35 years while conducting implementation research to identify facilitators and barriers for adoption and sustainability of proven evidence-based cervical cancer prevention approaches integrated into ARV clinics across sub-Saharan Africa.

Conditions

• HPV Infection

Interventions

BIOLOGICAL

HPV vaccine

Licensed HPV vaccines (bivalent, quadrivalent, or nonvalent) available in the country of the study site

DIAGNOSTIC_TEST

HPV testing

HPV testing with partial genotyping of HPV16/18 (and/or 45) to be used as a primary cervical screening test for all participants regardless of the study arm

BIOLOGICAL

HAV vaccine

Hepatitis A virus (HAV) vaccine to be offered as a placebo

Sponsors & Collaborators

• University of New Mexico

  collaborator OTHER

• University of Stellenbosch

  collaborator OTHER

• University of KwaZulu

  collaborator OTHER

• Coptic Hope Center

  collaborator UNKNOWN

• Emory University

  collaborator OTHER

• Ministry of Health, Swaziland

  collaborator OTHER_GOV

• Baylor College of Medicine Children's Foundation

  collaborator UNKNOWN

• Sefako Makgatho Health Sciences University

  collaborator OTHER

• Aga Khan University

  collaborator OTHER

• World Health Organization

  collaborator OTHER

• International Agency for Research on Cancer

  lead OTHER

Principal Investigators

• Maribel Almonte, MPH, MSc, PhD · International Agency for Research on Cancer

• Armando Baena, MSc, PhD · International Agency for Research on Cancer

• Rolando Herrero, MD, PhD · International Agency for Research on Cancer

• Mathilde Forestier, PhD · International Agency for Research on Cancer

• Joan Valls, MSc, PhD · International Agency for Research on Cancer

• Laura Downham, MSc · International Agency for Research on Cancer

• Prajakta Adsul, MBBS, MPH, PhD · University of New Mexico

• Hennie Botha, MD, PhD · University of Stellenbosch

• Haynes van der Merwe, MD, PhD · University of Stellenbosch

• Motshedisi Sebitloane, MBChB, PhD · University of KwaZulu

• Themba Ginindza, MSc, MPH, PhD · University of KwaZulu

• Samah R Sakr, MBChB · Coptic Hope Center

• Michael H Chung, MD, MPH, PhD · Emory University

• Xolisile Dlamini, MPH · National Cancer Control Unit - Eswatini Ministry of Health

• Florence A Anabwani-Richter, MBChB, MPH · Baylor College of Medicine Children's Foundation

• Lisbeth Lebelo, PhD · Sefako Makgatho Health Sciences University

• Marleen Temmerman, MD, PhD · Aga Khan University

• Jean-Marie Dangou, PhD · World Health Organization (AFRO/WHO)

• Nathalie Broutet, MD, PhD · World Health Organization

• Sami L Gottlieb, PhD · World Health Organization

• Paul Bloem, MSc · World Health Organization

• Soe Soe Thwin, MSc, PhD · World Health Organization

• Ajay Rangaraj, MD, MSc · World Health Organization

Study Design

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

QUADRUPLE

Model

PARALLEL

Eligibility

Min Age

25 Years

Max Age

35 Years

Sex

FEMALE

Healthy Volunteers

No

Timeline & Regulatory

Start

2023-02-01

Primary Completion

2027-06-30

Completion

2027-06-30

FDA Drug

Yes

FDA Device

Yes