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Efficacy of Single-Dose Human Papillomavirus Vaccination among Young African Women

  • Ruanne V. Barnabas, M.B.Ch.B., D.Phil.1,2,
  • Elizabeth R. Brown, Ph.D.3,4,5,
  • Maricianah A. Onono, M.B.Ch.B., Ph.D.6,
  • Elizabeth A. Bukusi, M.B.Ch.B., Ph.D.6,7,8,
  • Betty Njoroge, M.B.Ch.B.9,
  • Rachel L. Winer, Ph.D.10,
  • Denise A. Galloway, Ph.D.4,11,
  • Leeya F. Pinder, M.D., M.P.H.8,11,
  • Deborah Donnell, Ph.D.5,7,
  • Imelda Wakhungu6,
  • Ouma Congo, M.B.Ch.B.6,
  • Charlene Biwott, M.B.Ch.B.9,
  • Syovata Kimanthi, M.B.Ch.B.9,
  • Lynda Oluoch, M.B.Ch.B.9,
  • Kate B. Heller, M.S.7,
  • Hannah Leingang, M.P.H.7,
  • Susan Morrison, M.D., M.P.H.7,
  • Elena Rechkina, Ph.D.7,
  • Stephen Cherne, M.S.12,
  • Torin T. Schaafsma, M.S.7,
  • R. Scott McClelland, M.D., M.P.H.7,10,13,
  • Connie Celum, M.D., M.P.H.7,10,13,
  • Jared M. Baeten, M.D., Ph.D.7,10,13,14, and
  • Nelly Mugo, M.B.Ch.B., M.P.H.7,9
for the KEN SHE Study Team*
Published April 11, 2022
NEJM Evid 2022; 1 (5)
DOI:https://doi.org/10.1056/EVIDoa2100056
Issue

Abstract

Background

Single-dose human papillomavirus (HPV) vaccination, if efficacious, would be tremendously advantageous, simplifying implementation and decreasing costs.

Methods

We performed a randomized, multicenter, double-blind, controlled trial of single-dose nonavalent (HPV 16/18/31/33/45/52/58/6/11 infection) or bivalent (HPV 16/18 infection) HPV vaccination compared with meningococcal vaccination among Kenyan women 15 to 20 years of age. Enrollment and 6-monthly cervical swabs and a month 3 vaginal swab were tested for HPV deoxyribonucleic acid (DNA). Enrollment sera were tested for HPV antibodies. The modified intent-to-treat (mITT) cohort comprised participants who had an HPV antibody-negative result at enrollment and an HPV DNA-negative result at enrollment and month 3. The primary outcome was incident persistent vaccine-type HPV infection by month 18.

Results

Between December 2018 and June 2021, 2275 women were randomly assigned and followed. A total of 758 participants received the nonavalent HPV vaccine, 760 received the bivalent HPV vaccine, and 757 received the meningococcal vaccine; retention was 98%. Thirty-eight incident persistent infections were detected in the HPV 16/18 mITT cohort: one each among participants assigned to the bivalent and nonavalent groups and 36 among those assigned to the meningococcal group. Nonavalent vaccine efficacy (VE) was 97.5% (95% confidence interval [CI], 81.7 to 99.7%; P≤0.0001), and bivalent VE was 97.5% (95% CI, 81.6 to 99.7%; P≤0.0001). Thirty-three incident persistent infections were detected in the HPV 16/18/31/33/45/52/58 mITT cohort: four in the nonavalent group and 29 in the meningococcal group. Nonavalent VE for HPV 16/18/31/33/45/52/58 was 88.9% (95% CI, 68.5 to 96.1; P<0.0001). The rate of serious adverse events was 4.5% to 5.2% by group.

Conclusions

Over the 18-month timeframe we studied, single-dose bivalent and nonavalent HPV vaccines were each highly effective in preventing incident persistent oncogenic HPV infection, similar to multidose regimens. (Funded by the National Institutes of Health, the Bill and Melinda Gates Foundation, and the University of Washington; ClinicalTrials.gov number, NCT03675256.)


The KEN SHE Study was funded by the Bill and Melinda Gates Foundation (grant OPP1188693) and by the University of Washington King K. Holmes Endowed Professorship in STD and AIDS (to Dr. Barnabas). Dr. Pinder was supported by a University of Washington T32 Fellowship (5T32CA009515-34). The content is solely the responsibility of the authors and does not necessarily represent the views, decisions, or policies of the institutions with which they are affiliated or the KEN SHE Study funders.

Disclosure forms provided by the authors are available with the full text of this article.

A data sharing statement provided by the authors is available with the full text of this article.

We thank the adolescent girls and young women who participated in this study for their motivation and dedication, and we also thank the parents of minor participants for their support. We are grateful to the members of the trial’s DSMB (Chair Dr. Helen Weiss and Drs. Lynette Denny, Dorothy Mbori-Ngacha, Saidi Kapiga, Fred Were, and Fred Sawe), the community advisory boards at each trial location, and the overseeing ethics review committees for their expertise and guidance. We also thank Dr. Peter Dull and Ms. Carolyn Wendell from the Bill and Melinda Gates Foundation for their attentive oversight. Finally, we are grateful to the KEN SHE Study Team for their dedication and perseverance.

The article is dedicated to Kowselia Ramaswami Ramiah, Sarah Kanyi Mugo, Reginalda Auma Onono, Edwina Muga, Mary Nduta, and all of our mothers.

Dr. Barnabas can be contacted at [email protected] or at Division of Infectious Diseases, Massachusetts General Hospital, 55 Fruit St., Bulfinch 130, Boston, MA 02114.

A complete list of the investigators for the KEN SHE Study is provided in the Supplementary Appendix, available at evidence.nejm.org.

Figures/Media

  • Figure 1. Randomized Trial Profile.
    Figure 1

    Ab denotes antibody, HIV human immunodeficiency virus, HPV human papillomavirus, ITT intention to treat, m month, and mITT modified intention to treat.

    * Of the 419 people who were ineligible for randomization, 132 (32%) had a positive pregnancy test, 51 (12%) were not willing to follow study procedures or be randomly assigned, 34 (8%) had a positive rapid HIV diagnostic test, and 202 (48%) met other exclusion criteria.

    † Complete baseline data include HPV antibody results at month 0 and HPV DNA results at months 0 and 3.

  • Figure 2. Kaplan-Meier Curves for the Primary Modified Intention-to-Treat Analyses.
    Figure 2

    HPV 16/18 infection. HPV denotes human papillomavirus.

  • Figure 3. Kaplan-Meier Curves for the Primary Modified Intention-to-Treat Analyses.
    Figure 3

    HPV 16/18/31/33/45/52/58 infection. HPV denotes human papillomavirus.

  • Table 1. Baseline Characteristics for the mITT Cohort.
  • Table 2. Incidence of Persistent HPV 16/18 Infection and Vaccine Efficacy by Month 18 (mITT Cohort).
  • Table 3. Incidence of Persistent HPV 16/18/31/33/45/52/58 and VE by Month 18 (mITT Cohort).
  • Table 4. Participants Experiencing Adverse Events.