Single-dose HPV vaccination efficacy among adolescent girls and young women in Kenya (the KEN SHE Study): study protocol for a randomized controlled trial

Ruanne V Barnabas, Elizabeth R Brown, Maricianah Onono, Elizabeth A Bukusi, Betty Njoroge, Rachel L Winer, Deborah Donnell, Denise Galloway, Stephen Cherne, Kate Heller, Hannah Leingang, Susan Morrison, Elena Rechkina, R Scott McClelland, Jared M Baeten, Connie Celum, Nelly Mugo, KEN SHE Study Team, Ruanne V Barnabas, Elizabeth R Brown, Maricianah Onono, Elizabeth A Bukusi, Betty Njoroge, Rachel L Winer, Deborah Donnell, Denise Galloway, Stephen Cherne, Kate Heller, Hannah Leingang, Susan Morrison, Elena Rechkina, R Scott McClelland, Jared M Baeten, Connie Celum, Nelly Mugo, KEN SHE Study Team

Abstract

Background: HPV infection is the primary cause of cervical cancer, a leading cause of cancer among women in Kenya and many sub-Saharan African countries. High coverage of HPV vaccination is a World Health Organization priority to eliminate cervical cancer globally, but vaccine supply and logistics limit widespread implementation of the current two or three dose HPV vaccine schedule.

Methods: We are conducting an individual randomized controlled trial to evaluate whether a single dose of the bivalent (HPV 16/18) or nonavalent (HPV 16/18/31/33/45/52/58/6/11) HPV vaccine prevents persistent HPV infection, a surrogate marker for precancerous lesions and cervical cancer. The primary objective is to compare the efficacy of immediate, single-dose bivalent or nonavalent vaccination with delayed HPV vaccination. Kenyan women age 15-20 years old are randomized to immediate bivalent HPV and delayed meningococcal vaccine (group 1), immediate nonavalent HPV vaccine and delayed meningococcal vaccine (group 2), or immediate meningococcal vaccine and delayed HPV vaccine (group 3) with 36 months of follow-up. The primary outcome is persistent vaccine-type HPV infection by month 18 and by month 36 for the final durability outcome. The secondary objectives include to (1) evaluate non-inferiority of antibody titers among girls and adolescents (age 9 to 14 years) from another Tanzanian study, the DoRIS Study (NCT02834637), compared to KEN SHE Study participants; (2) assess the memory B cell immune response at months 36 and 37; and (3) estimate cost-effectiveness using the trial results and health economic models.

Discussion: This study will evaluate single-dose HPV vaccine efficacy in Africa and has the potential to guide public health policy and increase HPV vaccine coverage. The secondary aims will assess generalizability of the trial results by evaluating immunobridging from younger ages, durability of the immune response, and the long-term health benefits and cost of single-dose HPV vaccine delivery.

Trial registration: ClinicalTrials.gov NCT03675256 . Registered on September 18, 2018.

Keywords: Human papillomavirus; Multi-age cohort; Randomized controlled trial; Reduced dose schedule; Single-dose vaccination.

Conflict of interest statement

Declaration of interests: RVB reports grants from Bill and Melinda Gates Foundation, grants from National Institutes of Health, grants from Royalty Research Fund (UW), grants from King K. Holmes Professorship in STDs and AIDS, during the conduct of the study; and conference support from Regeneron Pharmaceuticals outside the submitted work. JMB reports grants from Bill & Melinda Gates Foundation during the conduct of the study; grants from BMGF, CDC, NIH, and USAID and personal fees from Gilead Sciences, Merck, and Janssen, outside the submitted work. CC reports grants from BMGF, during the conduct of the study, personal fees from Gilead Sciences, and personal fees from Merck, outside the submitted work. RLW reports grants from NIH and CDC during the conduct of the study. All other co-authors have nothing to disclose.

© 2021. The Author(s).

Figures

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Fig. 1
Participant enrollment, intervention, and assessment

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