Randomized Controlled Trial

. 2023 Dec;29(12):3224-3232.

doi: 10.1038/s41591-023-02658-0. Epub 2023 Dec 4.

Durability of single-dose HPV vaccination in young Kenyan women: randomized controlled trial 3-year results

Ruanne V Barnabas^{1

2

3}, Elizabeth R Brown^{4

5

6}, Maricianah A Onono⁷, Elizabeth A Bukusi^{7

8

9}, Betty Njoroge¹⁰, Rachel L Winer¹¹, Denise A Galloway¹², Leeya F Pinder^{8

13}, Deborah Donnell^{4

8}, Imelda N Wakhungu⁷, Charlene Biwott¹⁰, Syovata Kimanthi¹⁰, Kate B Heller^{14

8}, Diane G Kanjilal¹⁴, Daniel Pacella¹⁴, Susan Morrison⁸, Elena A Rechkina⁸, Stephen L Cherne¹⁵, Torin T Schaafsma⁸, R Scott McClelland^{8

11

16

17}, Connie Celum^{8

11

16}, Jared M Baeten^{8

16}, Nelly R Mugo^{8

10}; KEN SHE Study Team

Collaborators, Affiliations

Collaborators

KEN SHE Study Team:
Peter Dull, Reena Gulati, Sara Vernam, Abdul Rawuf Yousufzay, Krissa Gunderson, Amra Hercinovic, Lisa Ondrejcek, Gavin Robertson, Angela Williams, Elizabeth Brown, Jody Carter, Denise Galloway, Leeya Pinder, Priya R Prabhu, Robin Smith, Marci Wright, Stephen O Abiero, Maqline A Achola, Meldah O Adipo, Katherine L Amukonyi, Cynthia Akinyi, Teresia O Akinyi, Penina N Amboka, Karl D Arum, Veronica O Atogo, Pius O Atonga, Adero J Cate, Daisy Chepkoros, Oyamo O Christopher, Imelda N Imali, Mildred Imbayi, Lizzie N Kabete, Enericah K Kanampiu, Geoffrey Kebaso, Dennis Kegode, Timothy Kwena, Reina Lenturkana, Celestine Lihavi, David N Marwa, Patricia Matti, Peter O Mboya, Elijah Mbuya, Lyna A Memo, Robai M Mituyi, Benard M Muga, David E Muhoma, Elizabeth L Musi, Gilbert C Mutai, Simon M Muthusi, Ivy M Mutuiri, Catherine W Mwakio, Bill Nyongesa, Maureen A Ochieng, Vincent R Ochuka, Belder A Odedo, Esther A Odeny, Vincent O Odera, Debora A Odhiambo, Perez O Odhiambo, Janet A Okeyo, Linet A Okode, Nollyne A Okuku, Irene Okumu, Lydiah A Okumu, Christine A Olweny, Hellen A Olweyo, George O Omondi, Donnavane A Ondego, Florence A Ondiek, Joan A Ongere, Maricianah Onono, Kevin O Onyango, Annette A Opondo, Millicent A Oronje, Beryl A Osoga, Rebecca A Otieno, Job A Ouma, Mildred A Owenga, Samya S Rashid, Vincent K Salano, Moses O Siaji, Roseline Sikolia, Imelda N Wakhungu, Nicholas Walukana, Nobert B Walusala, Caren A Wemali, Faith Ambiyo, Emily Anyango, Esther K Charles, David Chege, Jane Gacheru, Anne Gaitho, Stephen Gakuo, Zachary Gathu, Mathew Irungu, Vincent Juma, Irene Kamau, Mary Kibatha, Dorcas Kiboi, Francis Khaemba, Hellen W Kimani, Catherine Kiptinness, Caren Koli, Erick Koome, Solomon Maina, Linet Makena, Sarah Mbaire, Veronica Muchoki, Victor Munene, Edwin Mugo, Nelly R Mugo, Umi W Mugo, Faith Munyaka, Paul Mutunga, Margaret Mwangi, Stanley Mwangi, Peter Mwenda, Gladys Namboka, Grace Ndung'u, Rispa Nduuru, Esther Neema, Sammy Ng'ang'a, Josephine Njeri, Irene Njeru, Alice Njoki, John Njoroge, Sarah Njoroge, Peter Nzuve, Fridah Nkatha, Jemimah Nyakio, Edna Nyandiga, Jacinta Nyokabi, Rose Odera, John Okumu, Lynda Oluoch, Linda Orwa, Nina Ouko, Matilda Saina, Agata Thumi, Innes Wambui, Victoria Wambui, Virginia Wangechi, Scholastica Wanjiku, Ruanne Barnabas, Francesca Caramazza, Kate Heller, Diane Kanjilal, Kyle Kennedy, Odunayo Kolawole Talabi, Rukiya Hassan, Emmanuel Kabare, Fatma H Mwidadi, Khamis Mwinyikai, Salwa Mustafa, Juma Shafi, Stephen L Cherne, Daphne Hamilton, Rachel Johnson, John Lin, Justice Quame-Amaglo, Elena A Rechkina, Torin T Schaafsma

Affiliations

¹ Division of Infectious Diseases, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA. rbarnabas@mgh.harvard.edu.
² School of Medicine, Harvard Medical School, Boston, MA, USA. rbarnabas@mgh.harvard.edu.
³ Department of Epidemiology, T. H. Chan Harvard School of Public Health, Boston, MA, USA. rbarnabas@mgh.harvard.edu.
⁴ Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, USA.
⁵ Public Health Sciences, Fred Hutchinson Cancer Center, Seattle, WA, USA.
⁶ Department of Biostatistics, University of Washington, Seattle, WA, USA.
⁷ Center for Microbiology Research, Kenya Medical Research Institute, Kisumu, Kenya.
⁸ Department of Global Health, University of Washington, Seattle, WA, USA.
⁹ Department of Obstetrics and Gynecology, University of Washington, Seattle, WA, USA.
¹⁰ Center for Clinical Research, Kenya Medical Research Institute, Nairobi, Kenya.
¹¹ Department of Epidemiology, University of Washington, Seattle, WA, USA.
¹² Human Biology Division, Fred Hutchinson Cancer Center, Seattle, WA, USA.
¹³ University of Cincinnati, Department of Obstetrics and Gynecology, Cincinnati, OH, USA.
¹⁴ Division of Infectious Diseases, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA.
¹⁵ Department of Laboratory Medicine and Department of Pathology, University of Washington, Seattle, WA, USA.
¹⁶ Division of Allergy and Infectious Diseases, Department of Medicine, University of Washington, Seattle, WA, USA.
¹⁷ East Africa STI Laboratory, University of Washington, Mombasa, Kenya.

PMID: 38049621
PMCID: PMC10719107
DOI: 10.1038/s41591-023-02658-0

Randomized Controlled Trial

Durability of single-dose HPV vaccination in young Kenyan women: randomized controlled trial 3-year results

Ruanne V Barnabas et al. Nat Med. 2023 Dec.

. 2023 Dec;29(12):3224-3232.

doi: 10.1038/s41591-023-02658-0. Epub 2023 Dec 4.

Authors

Collaborators

KEN SHE Study Team:
Peter Dull, Reena Gulati, Sara Vernam, Abdul Rawuf Yousufzay, Krissa Gunderson, Amra Hercinovic, Lisa Ondrejcek, Gavin Robertson, Angela Williams, Elizabeth Brown, Jody Carter, Denise Galloway, Leeya Pinder, Priya R Prabhu, Robin Smith, Marci Wright, Stephen O Abiero, Maqline A Achola, Meldah O Adipo, Katherine L Amukonyi, Cynthia Akinyi, Teresia O Akinyi, Penina N Amboka, Karl D Arum, Veronica O Atogo, Pius O Atonga, Adero J Cate, Daisy Chepkoros, Oyamo O Christopher, Imelda N Imali, Mildred Imbayi, Lizzie N Kabete, Enericah K Kanampiu, Geoffrey Kebaso, Dennis Kegode, Timothy Kwena, Reina Lenturkana, Celestine Lihavi, David N Marwa, Patricia Matti, Peter O Mboya, Elijah Mbuya, Lyna A Memo, Robai M Mituyi, Benard M Muga, David E Muhoma, Elizabeth L Musi, Gilbert C Mutai, Simon M Muthusi, Ivy M Mutuiri, Catherine W Mwakio, Bill Nyongesa, Maureen A Ochieng, Vincent R Ochuka, Belder A Odedo, Esther A Odeny, Vincent O Odera, Debora A Odhiambo, Perez O Odhiambo, Janet A Okeyo, Linet A Okode, Nollyne A Okuku, Irene Okumu, Lydiah A Okumu, Christine A Olweny, Hellen A Olweyo, George O Omondi, Donnavane A Ondego, Florence A Ondiek, Joan A Ongere, Maricianah Onono, Kevin O Onyango, Annette A Opondo, Millicent A Oronje, Beryl A Osoga, Rebecca A Otieno, Job A Ouma, Mildred A Owenga, Samya S Rashid, Vincent K Salano, Moses O Siaji, Roseline Sikolia, Imelda N Wakhungu, Nicholas Walukana, Nobert B Walusala, Caren A Wemali, Faith Ambiyo, Emily Anyango, Esther K Charles, David Chege, Jane Gacheru, Anne Gaitho, Stephen Gakuo, Zachary Gathu, Mathew Irungu, Vincent Juma, Irene Kamau, Mary Kibatha, Dorcas Kiboi, Francis Khaemba, Hellen W Kimani, Catherine Kiptinness, Caren Koli, Erick Koome, Solomon Maina, Linet Makena, Sarah Mbaire, Veronica Muchoki, Victor Munene, Edwin Mugo, Nelly R Mugo, Umi W Mugo, Faith Munyaka, Paul Mutunga, Margaret Mwangi, Stanley Mwangi, Peter Mwenda, Gladys Namboka, Grace Ndung'u, Rispa Nduuru, Esther Neema, Sammy Ng'ang'a, Josephine Njeri, Irene Njeru, Alice Njoki, John Njoroge, Sarah Njoroge, Peter Nzuve, Fridah Nkatha, Jemimah Nyakio, Edna Nyandiga, Jacinta Nyokabi, Rose Odera, John Okumu, Lynda Oluoch, Linda Orwa, Nina Ouko, Matilda Saina, Agata Thumi, Innes Wambui, Victoria Wambui, Virginia Wangechi, Scholastica Wanjiku, Ruanne Barnabas, Francesca Caramazza, Kate Heller, Diane Kanjilal, Kyle Kennedy, Odunayo Kolawole Talabi, Rukiya Hassan, Emmanuel Kabare, Fatma H Mwidadi, Khamis Mwinyikai, Salwa Mustafa, Juma Shafi, Stephen L Cherne, Daphne Hamilton, Rachel Johnson, John Lin, Justice Quame-Amaglo, Elena A Rechkina, Torin T Schaafsma

Affiliations

¹ Division of Infectious Diseases, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA. rbarnabas@mgh.harvard.edu.
² School of Medicine, Harvard Medical School, Boston, MA, USA. rbarnabas@mgh.harvard.edu.
³ Department of Epidemiology, T. H. Chan Harvard School of Public Health, Boston, MA, USA. rbarnabas@mgh.harvard.edu.
⁴ Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, USA.
⁵ Public Health Sciences, Fred Hutchinson Cancer Center, Seattle, WA, USA.
⁶ Department of Biostatistics, University of Washington, Seattle, WA, USA.
⁷ Center for Microbiology Research, Kenya Medical Research Institute, Kisumu, Kenya.
⁸ Department of Global Health, University of Washington, Seattle, WA, USA.
⁹ Department of Obstetrics and Gynecology, University of Washington, Seattle, WA, USA.
¹⁰ Center for Clinical Research, Kenya Medical Research Institute, Nairobi, Kenya.
¹¹ Department of Epidemiology, University of Washington, Seattle, WA, USA.
¹² Human Biology Division, Fred Hutchinson Cancer Center, Seattle, WA, USA.
¹³ University of Cincinnati, Department of Obstetrics and Gynecology, Cincinnati, OH, USA.
¹⁴ Division of Infectious Diseases, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA.
¹⁵ Department of Laboratory Medicine and Department of Pathology, University of Washington, Seattle, WA, USA.
¹⁶ Division of Allergy and Infectious Diseases, Department of Medicine, University of Washington, Seattle, WA, USA.
¹⁷ East Africa STI Laboratory, University of Washington, Mombasa, Kenya.

PMID: 38049621
PMCID: PMC10719107
DOI: 10.1038/s41591-023-02658-0

Abstract

Cervical cancer burden is high where prophylactic vaccination and screening coverage are low. We demonstrated in a multicenter randomized, double-blind, controlled trial that single-dose human papillomavirus (HPV) vaccination had high vaccine efficacy (VE) against persistent infection at 18 months in Kenyan women. Here, we report findings of this trial through 3 years of follow-up. Overall, 2,275 healthy women aged 15-20 years were recruited and randomly assigned to receive bivalent (n = 760), nonavalent (n = 758) or control (n = 757) vaccine. The primary outcome was incident-persistent vaccine type-specific cervical HPV infection. The primary evaluation was superiority analysis in the modified intention-to-treat (mITT) HPV 16/18 and HPV 16/18/31/33/45/52/58 cohorts. The trial met its prespecified end points of vaccine type-specific persistent HPV infection. A total of 75 incident-persistent infections were detected in the HPV 16/18 mITT cohort: 2 in the bivalent group, 1 in the nonavalent group and 72 in the control group. Nonavalent VE was 98.8% (95% CI 91.3-99.8%, P < 0.0001) and bivalent VE was 97.5% (95% CI 90.0-99.4%, P < 0.0001). Overall, 89 persistent infections were detected in the HPV 16/18/31/33/45/52/58 mITT cohort: 5 in the nonavalent group and 84 in the control group; nonavalent VE was 95.5% (95% CI 89.0-98.2%, P < 0.0001). There were no vaccine-related severe adverse events. Three years after vaccination, single-dose HPV vaccination was highly efficacious, safe and conferred durable protection. ClinicalTrials.gov no. NCT03675256 .

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Conflict of interest statement

R.V.B. reports that Regeneron Pharmaceuticals covered the cost of the abstract and manuscript writing, outside the submitted work. She serves on a Gilead Sciences Data Monitoring Committee for which she receives an honorarium, outside the submitted work. J.M.B. reports personal fees from Gilead Sciences, Janssen and Merck, outside the submitted work; and is an employee of Gilead Sciences, outside of the submitted work. C.C. reports personal fees from Gilead Sciences and Merck, outside the submitted work. N.M. reports grant support from Merck Pharmaceuticals, outside the submitted work. D.A.G. reports personal fees from Merck, outside the submitted work. E.A.B. reports personal fees from Gilead Sciences, Merck and ViiV, outside the submitted work. R.S.M. reports personal fees from Lupin Pharmaceuticals and donated testing STI testing supplies from Hologic Corporation, outside of the submitted work. All other coauthors (M.A.O., B.N., R.L.W., D.A.G., L.F.P., D.D., I.W., C.B., S.K., K.B.H., D.G.K., D.P., S.M., E.R., S.C. and T.T.S.) have nothing to disclose.

Figures

**Fig. 1. Randomized trial profile.**
CONSORT diagram for the disposition of KEN SHE Study participants, including primary mITT cohort disposition for HPV 16/18 and HPV 16/18/31/33/45/52/58.

**Fig. 2. Cumulative incidence curves for the incidence of persistent HPV in the modified intention-to-treat primary analyses.**
Cumulative incidence curves were computed by vaccine group using Kaplan–Meier methods. Two-sided log-rank P values were computed for each comparison using the log-rank test. a, Cumulative incidence of persistent HPV 16/18 in the HPV 16/18 mITT cohort (n = 1,458). Four participants in the HPV 16/18 mITT cohort did not contribute a second end-point swab and thus did not contribute time at risk. b, Cumulative incidence of persistent HPV 16/18/31/33/45/52/58 in the HPV 16/18/31/33/45/52/58 mITT cohort (n = 615). One participant in the HPV 16/18/31/33/45/52/58 mITT cohort did not contribute a second end-point swab and thus did not contribute time at risk.

See this image and copyright information in PMC

References

1. Singh, D. et al. Global estimates of incidence and mortality of cervical cancer in 2020: a baseline analysis of the WHO Global Cervical Cancer Elimination Initiative. Lancet Glob. Health11, e197–e206 (2023). 10.1016/S2214-109X(22)00501-0 - DOI - PMC - PubMed
1. Harper, D. M. & DeMars, L. R. HPV vaccines - a review of the first decade. Gynecol. Oncol.146, 196–204 (2017). 10.1016/j.ygyno.2017.04.004 - DOI - PubMed
1. Huh, W. K. et al. Final efficacy, immunogenicity, and safety analyses of a nine-valent human papillomavirus vaccine in women aged 16-26 years: a randomised, double-blind trial. Lancet390, 2143–2159 (2017). 10.1016/S0140-6736(17)31821-4 - DOI - PubMed
1. World Health Organization. A Global Strategy for Elimination of Cervical Cancer www.who.int/activities/a-global-strategy-for-elimination-of-cervical-cancer (2020).
1. Drolet, M., Benard, E., Perez, N. & Brisson, M., H. P. V. Vaccination Impact Study Group. Population-level impact and herd effects following the introduction of human papillomavirus vaccination programmes: updated systematic review and meta-analysis. Lancet394, 497–509 (2019). 10.1016/S0140-6736(19)30298-3 - DOI - PMC - PubMed

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Durability of single-dose HPV vaccination in young Kenyan women: randomized controlled trial 3-year results

Collaborators

Affiliations

Durability of single-dose HPV vaccination in young Kenyan women: randomized controlled trial 3-year results

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