KEN SHE Study on HPV-vaccine Efficacy

Research Partners

Protocol Title: Single-dose HPV catch-up vaccination efficacy: A prospective, blinded, randomized study of single-dose HPV vaccination in Kenya


Study Name: KENya Single-dose HPV-vaccine Efficacy – The KEN SHE Study


Protocol co-Chairs:

Ruanne Barnabas, MBChB, MSc, DPhil and Nelly Mugo, MBChB, MMed, MPH

Sample Size: Up to 2,250

Study Population: Adolescent girls and young women age 15-20 years old


Study Sites: 1) Thika, 2) Nairobi, and 3) Kisumu, Kenya

Executive summary

Cervical cancer is the leading cause of new cancer cases among women in Kenya representing a substantial burden of disease for women. HPV infection is a necessary cause of cervical cancer and preliminary evidence suggests a single-dose of the HPV vaccine would provide efficacy in excess of 95%, supporting HPV vaccination as a scaleable intervention for cervical cancer prevention. An evidence gap exists on the efficacy and durability of single-dose HPV vaccine among young women in Africa, particularly as a catch-up vaccination strategy for women age 15-20 years.

The KEN SHE Study is a prospective, blinded randomized study that will test the efficacy of single-dose bivalent and nonavalent HPV vaccination as a catch-up strategy. Women age 15-20 years old will be randomized 1:1:1 to immediate bivalent HPV 16/18 and delayed meningococcal vaccine (arm 1), immediate nonavalent HPV 16/18/31/33/45/52/58/11/6 vaccine and delayed meningococcal vaccine (arm 2), or delayed HPV vaccine and immediate meningococcal vaccine (arm 3) with 36 months of follow-up. The primary study outcome is persistent, incident vaccine type specific HPV infection. Women in this priority group are at risk of incident HPV infection because they have not been vaccinated and are at high risk of acquisition due to sexual debut. Since the HPV vaccine is highly effective and we are likely to see significant impact on the decrease in HPV vaccine type specific infections. Enrollment is anticipated to take 12 months, with 36 months of follow-up for each participant. A formal interim analysis will be conducted after 18 months of follow-up to provide early evidence on single-dose HPV vaccine efficacy. The endpoint-driven trial design among women at risk of HPV acquisition will provide interim results after 18 months of follow-up, and, with the extended follow-up, evidence on durability over three years.

This study design is ethical because HPV vaccination will be available in Kenya for 9-10 year old girls, with the possibility of Global Alliance for Vaccines and Immunization (GAVI) funded catch-up to age 14 years. However, a gap exists in prevention interventions for women age 15-20 years and there is an ethical imperative to identify effective prevention strategies for this priority group. Young women in the study will receive screening, the current standard of care, and have access to research to identify better methods for prevention. Further, the Data Safety and Monitoring Board (DSMB) will review study conduct and data every six months to determine the probability that the study will be able to answer the primary question. Strategies to ensure timely, informative results will be considered at each review, and performance standards for the trial (for recruitment, retention, data quality, and assessment of study endpoints) will be reviewed to assess probability of successful execution of the work. Since both the magnitude and durability of the effect of the single-dose HPV vaccine are critical outcomes, the DSMB will have clear statistical guidelines, based on the expected number of persistent HPV cases, to continue the study as appropriate.

The principal results of the study will demonstrate whether the single-dose HPV vaccine strategy prevents incident persistent HPV vaccine type specific infection among young women, by comparing the rate of new HPV infections among women who receive the vaccine immediately to those receiving delayed vaccination. Further, among the women who receive immediate HPV vaccine, we will estimate the durability of the bivalent and nonavalent HPV vaccines by measuring the antibody response and cumulative incidence of persistent cervical HPV over the duration of follow-up. Specifically, we will compare the incidence of high-risk vaccine HPV types overall and the distribution of HPV types by study arm. We will assess the immunologic response to single-dose HPV vaccination, specifically regarding long lasting B cell responses to support the durability of the single-dose vaccination approach. Data on the magnitude of the antibody response at months 1 and 24 will support immunobridging analyses to young girls and adolescents. The 24 month antibody result will be used to assess durability of the response and will be directly comparable to other studies of the single-dose HPV vaccine, which are uniformly using the month 24 antibody result as the primary outcome. Costing analyses will assess the resources required for scale-up of single-dose HPV vaccination. We will use mathematical modeling to estimate the incident cervical cancer cases and deaths averted through vaccination with the single-dose of these two HPV vaccines over 5, 10, and 15 years, compared to current clinic care (i.e. no catch-up HPV vaccination) and the cost-effectiveness of vaccine scale-up.

The overall aim of the study is to provide timely results of both single-dose HPV vaccine efficacy and estimates of the cost, cost-effectiveness, and budget impact for dissemination and translation to policy. The interim analysis of the impact of the bivalent and nonavalent HPV vaccines at month 18 will inform the (Strategic Advisory Group of Experts on Immunization) SAGE 2021 meeting on single-dose HPV vaccination. If successful, our proposed trial would directly provide robust evidence to support a single-dose HPV vaccination for a SAGE recommendation, by October 2021. The advantage of conducting the costing work in parallel to the efficacy study is that the evidence for impact and data to support implementation are ready at the same time. Throughout the study, the Kenyan Ministry of Health will be engaged to ensure the data and analyses needed to support HPV vaccine scale-up will be available in a timely manner.  


Study Duration: 60 months total


Primary Objectives:


  1. To test the efficacy of immediate single-dose bivalent or nonavalent HPV vaccination to prevent incident persistent HPV 16/18 infection compared to delayed nonavalent HPV vaccination for young women age 15-20 years.


  1. To test the efficacy of immediate single-dose nonavalent HPV vaccination to prevent incident persistent HPV 16/18/31/33/45/52/58 infection compared to delayed nonavalent HPV vaccination for young women age 15-20 years.


  1. To determine whether vaccine-type HPV antibody responses after single-dose bivalent or nonavalent vaccination are noninferior in 9-14 year old girls versus 15-20 year old young women.


Secondary objectives


  1. To assess cost, cost-effectiveness, and budget impact of single-dose HPV vaccination to support implementation strategies for single-dose HPV vaccination following WHO recommendation in high cervical cancer burden settings.


  1. To evaluate B-cell markers as a proxy for immune memory following single-dose bivalent and nonavalent vaccination.


Funder: Bill and Melinda Gates Foundation (OPP1188693)


Overall goal: The overall goal is to identify effective, scaleable cervical cancer prevention strategies.