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A randomized trial of single -dose HPV vaccination efficacy
among young women: Month 54 durability results
Ruanne V. Barnabas, MBChB, DPhil
Chief, Division of Infectious Diseases, Massachusetts General Hospital
Department of Medicine, Harvard Medical School
HPV vaccination for all and catch -up vaccination to young adulthood
accelerate the timeline to cervical cancer elimination.
Simms, K. T., Steinberg, J., …, & Canfell , K. (2019). Impact of scaled up human papillomavirus vaccination: A modelling study. The Lancet OncologyPredicted number of cases of cervical cancer globally
We conducted a rigorous randomized trial (the KEN SHE Study) and found that the single
dose HPV vaccination is highly efficacious, with 98% vaccine efficacy for HPV 16/18.
Primary Endpoint Period
Six monthly follow -up visits: clinician collected cervical swabs
Endpoint : Incident, persistent vaccine type -specific infection among participants HPV naïve
at vaccination
Retention was 96% for four or more swab
Duration of follow -up: 36 months
Barnabas, R., Brown, E., and colleagues. KEN SHE Study 36 months VE results. Nature Medicine, Dec. 2023
Young women aged 15-20
N=2,275 participants
Enrolled
n=757 participants
Immediate
meningococcal vaccine
Controln=760 participants
Immediate bivalent
vaccine
2vHPVn=758 participants
Immediate nonavalent
vaccine
9vHPVRandomization
Participants were followed over 36 months.
Physician
collected
cervical swabs
for HPV DNAFollow -up
6 monthly
VE
18 monthsPrimary analysis
Exclude
prevalent
infectionEnrollment and
month 3
Physician collected
cervical swabs for
HPV DNA
Participants
vaccinatedFollow -up
6 monthly
VE
36 monthsFinal analysis
Participants with prevalent HPV infections at enrollment were excluded from
the per protocol/ mITT analysis, because the vaccine is prophylactic only.
mITT HPV 16/18 cohort
•29% (n=661/2,275) prevalent infections → excluded
mITT HPV 16/18/31/33/45/52/58 cohort
•52% (n=792/1,515) prevalent infection → excluded
9v VE= 99% for HPV 16/18 (95% CI: 91 – 100%)
2v VE= 98% for HPV 16/18 (95% CI: 90 – 99%)
VE=96% for HPV 16/18/31/33/45/52/58
(95% CI: 89 – 98%)
Barnabas, R., Brown, E., and colleagues. KEN SHE Study 36 months VE results. Nature Medicine, Dec. 2023Month 36 VE resultsAfter three years, single -dose HPV vaccine efficacy remained high and durable
(VE= 98% for HPV 16/18 and VE= 96% for HPV 16/18/31/33/45/52/58).
n=2
n=1n=72
n=84
n=5
We hypothesized that single -dose vaccination would be effective and durable
over 54 -months based on sustained antibody levels over 16 years.
Joshi, S…Basu, P . Vaccine. 2023 Jan 4;41(1):236 -245.
Porras, C … Kreimer , A. CVT, IPVC, 2023
Participants in the KEN SHE Study were crossed over at month 30/36 while
maintaining the study blind.
Enrollment
Young women aged 15-20 years
Eligibility: 1-5 lifetime partners, HIV RDT
negative, No previous HPV vaccine or
contraindications, Resident
Immediate
meningococcal vaccineImmediate bivalent HPV
vaccineImmediate nonavalent
HPVvaccineRandomized
Delayed nonavalent HPV
vaccineDelayed meningococcal
vaccineDelayed meningococcal
vaccineCrossover vaccination
Primary Endpoint Period
Crossover Period
All Single -dose HPV
Vaccinated Period
Crossover
period
(vaccination at
m 30 or m 36)All single -dose
HPV vaccinated
period
Durability
resultsFinal Endpoint
period
Final RCT VE
results
AIMS
1. To evaluate effectiveness of single -dose HPV vaccination for age 18 -23, we compared the cumulative
incidence of persistent HPV using Kaplan -Meier (cumulative incidence) curves and incident rate
estimates for the immediate and delayed vaccine groups (graphic illustration)
2. To assess durability, vaccine efficacy was evaluated as a function of time since vaccination using a Cox
regression model (accounting for time and time variable covariates)
•Endpoint : Incident persistent vaccine type -specific HPV infection measured at two time points 6
months apart
•Both analyses used the mITT cohorts
We extended the KEN SHE Study in a blinded cross -over trial design to assess
vaccine efficacy and durability at month 54.
There were no differences in baseline characteristics between study groups.
Participants were age 18 -23 years at cross -over vaccination.
Characteristics Nonavalent HPV
(n=758)Bivalent HPV
(n=760)Control
(n=757)
Age group 15 -17 years (%) 60% 56% 56%
Median age (years) 17 17 17
Secondary school (%) 73% 73% 73%
Current steady partner (%) 72% 71% 72%
Chlamydia trachomatis
positive (%)12% 13% 14%
Prevalence of baseline characteristics for the ITT cohort
Retention was 90% for three or more swabs and the median time between endpoint
swab collection was 6.00 months.
Retention 90%
for 3 post -crossover swabs
Median follow -up 53 months2,275 Participants
enrolled
22,124 ( 95% )
Received crossover
vaccine
No diff by study grpRetention 91%
for 5 or more pre -
crossover swabs
151 (6.6%)
exited
The incidence of persistent non -vaccine HPV types was stable across the time
periods and between the study groups, indicating continued HPV exposure.
(26/35/39/40/42/43/44/51/53/54/56/59/61/66/68/69/70/73/82 in HPV 16/18 mITT cohort)
Incidence of persistent
non-vaccine type HPV
per 100 woman -years
(95% CI)Study Group
Delayed HPV
vaccinationImmediate HPV
vaccinationOverall
Primary Endpoint
Period19.5
(15.4 -24.3)20.7
(17.6 -24.2)20.3
(17.8 -23.0)
All Single -dose HPV
Vaccinated Period22.0
(12.0 -36.9)22.5
(14.7 -33.0)22.3
(15.9 -30.3)
Follow -up time amongst women non -vaccine HPV -type DNA negative at month 0 and month 3 (women are excluded if positive at month 0 or
month 3 for any of HPV 26/35/39/40/42/43/44/51/53/54/56/59/61/66/68/69/70/73/82)
Durability and Vaccine Efficacy (VE) Results
Cumulative Incidence of Persistent HPV 16/18 by Original Vaccine Group and Study
Period (HPV 16/18 mITT Cohort)
Pre-crossover n = 4
Post -crossover n = 4
~14 months
Randomized
vaccineBlinded
crossover vaccineCumulative Incidence of Persistent HPV 16/18 by Original Vaccine Group and Study
Period (HPV 16/18 mITT Cohort)
Pre-crossover n = 4
Post -crossover n = 4Pre-crossover n = 89
Post -crossover n = 7
Participants vaccinated at age 18 -23 years, had similar low rates of incident
persistent HPV 16/18 infection compared to vaccination at age 15 -20 years.
VE to prevent HPV 16/18
as a function of time
since HPV Vaccination
(HPV 16/18 mITT Cohort)HPV 16/18 vaccine
efficacy, VE=99.2%
(95% CI 96.1 -99.9%) is
sustained over time
without evidence for
waning immunity.
Cumulative Incidence of Persistent HPV 16/18/31/33/45/52/58 by Original Vaccine
Group and Study Period (HPV 16/18/31/33/45/52/58 mITT Cohort)
Pre-crossover n = 5
Post -crossover n = 5
Cumulative Incidence of Persistent HPV 16/18/31/33/45/52/58 by Original Vaccine
Group and Study Period (HPV 16/18/31/33/45/52/58 mITT Cohort)
~14 monthsBlinded
crossover vaccine
Randomized
vaccine
Pre-crossover n = 5
Post -crossover n = 5Pre-crossover n = 89
Post -crossover n = 9
Participants vaccinated at age 18 -23 years, had similar rates of incident
persistent HPV 16/18/31/33/45/52/58 infection compared to vaccination at
age 15 -20 years.
Vaccine Efficacy to prevent HPV
16/18/31/33/45/52/58 as a function of
time since HPV vaccination (HPV
16/18/31/33/45/52/58 mITT cohort)HPV
16/18/31/33/45/52/
58 vaccine efficacy,
VE=98.9% (95% CI
94.9 -99.8%) is
sustained over time
without evidence for
waning immunity.
Discussion
•Adolescent girls and young women were effectively protected from
HPV infection over the first 54 months post -vaccination
•Rigorous design, high fidelity to the protocol, high retention, clear
ascertainment of outcomes → strong evidence for single -dose HPV
vaccine efficacy for age up to 23 years
•Single -dose VE 16/18 and 16/18/31/33/45/52/58 – lower bound of the
CI is >94% - in keeping with licensure trials for three doses without
evidence of waning
•Adds to the growing body of evidence supporting the efficacy of single -
dose HPV vaccine efficacy
•Next step: Extension to evaluate clinical endpoints
Patient perspectives
Shared Clinical Decision Making Increase Access to Prevention
KEN SHE Study collaborators
Dr. Maricianah Onono Dr. Elizabeth BukusiDr. Betty Njoroge Dr. Nelly MugoKenya Medical Research Institute (KEMRI)
Fred Hutchinson Cancer Center
University of Washington
Dr. Denise GallowayDr. Elizabeth Brown
Dr. Rachel Winer
Grace Umutesi
Christine HathawayMassachusetts General
Hospital
Kate Heller
Jesse Heitner
Meighan Krows
Odun Talabi
Thank you
ClinicalTrials.gov :
NCT03675256•Study Participants
•Bill and Melinda Gates Foundation (Peter Dull, Reena Gulati, Abdul Rawuf Yousufzay , Sara Vernam );Division of Infectious Diseases, Department of Medicine,
Massachusetts General Hospital (Ruanne Barnabas, Kate Heller, Diane Kanjilal ,Meighan Krows , Odunayo Talabi ),Fred Hutchinson Cancer Center (Elizabeth Brown,
Denise Galloway, Jody Carter, Marci Wright, Priya R. Prabhu, Robin Smith, Deborah Donnell, Kidst Zewdie); KEMRI Kisumu (Elizabeth A. Bukusi , Maricianah Onono ,
Samya S. Rashid, Annette A. Opondo, Catherine W. Mwakio , Christine A. Olweny , Cynthia Akinyi , David E. Muhoma , Debora A. Odhiambo, Donnavane A. Ondego ,
Florence A. Ondiek , George O. Omondi, Gilbert C. Mutai, Hellen A. Olweyo , Imelda N. Imali , Imeldah N. Wakhungu , Janet A. Okeyo , Irene Okumu, Joan A. Ongere , Job A.
Ouma , Kevin O. Onyango, Linet A. Okode , Lizzie N. Kabete, Lyna A. Memo, Maqline A. Achola , Meldah O. Adipo , Mildred A. Owenga , Millicent A. Oronje , Moses O. Siaji,
Nobert B. Walusala , Nollyne A. Okuku , Penina N. Amboka , Rebecca A. Otieno, Reina Lenturkana , Robai Mituyi , Simon M. Muthusi , Veronica O. Atogo , Dennis Kegode ,
Daisy Chepkoros , Ivy M. Mutuiri , Benard M. Muga, Caren A. Wemali , Enericah K. Kanampiu , Geoffrey Kebaso , Mildred Imbayi , Teresia O. Akinyi , Rebecca A. Otieno,
Esther A. Odeny , Elijah Mbuya, Stephen O. Abiero , Roseline Sikolia , David N. Marwa, Peter O. Mboya, Elizabeth L. Musi, Beryl A. Osoga , Vincent R. Ochuka , Vincent O.
Odera, Lydiah A. Okumu, Pius O. Atonga , Nollyne A. Okuku , Vincent K. Salano , Adero J. Cate, Nicholas Walukana , Timothy Kwena , Celestine Lihavi , Maureen A. Ochieng,
Robai M. Mituyi , Perez A. Odhiambo, Oyamo O. Christopher, Katherin L. Amukonyi , Patricia Matti, Bill Nyongesa , Belder A. Odedo , Jane A. Odaro , Mathias M. Wakwabi ,
Collins Ochola , Collins I. Mulonga , Nita C. Akech, Synthia Oguna , Grace A. Obinge , Fredrick Ochieng); KEMRI Nairobi (Betty Njoroge, Alice Njoki, Edna Nyandiga , Esther
K. Charles, Esther Neema, Faith Ambiyo , John Okumu, Hellen W. Kimani, Paul Mutunga, Syovata Kimanthi , Umi W. Mugo, Vincent Juma, Umi Mugo, Celina Muthii , Ian
Ng’ang’a , Vallery Obure , Vincent Omondi, Ephraim Njoroge, Florence Thuo );KEMRI Thika (Nelly Mugo, Agata Thumi , Anne Gaitho , Caren Koli, Catherine Kiptinness ,
Charlene Biwott, David Chege, Dorcas Kiboi , Edwin Mugo, Emily Anyango , Erick Koome , Faith Munyaka , Francis Khaemba , Fridah Nkatha , Gladys Namboka , Grace
Ndung’u , Irene Kamau, Irene Njeru, Innes Wambui, Jacinta Nyokabi , Jane Gacheru , Jemimah Nyakio , John Njoroge, Josephine Njeri, Linda Orwa , Linet Makena, Lynda
Oluoch , Margaret Mwangi, Mary Kibatha , Mathew Irungu, Matilda Saina, Nina Ouko, Peter Mwenda, Peter Nzuve , Rispa Nduuru , Rose Odera, Sammy Ng’ang’a , Sarah
Mbaire , Sarah Njoroge, Scholastica Wanjiku, Solomon Maina, Stanley Mwangi, Stephen Gakuo , Veronica Muchoki , Victoria Wambui, Victor Munene, Vincent Juma,
Virginia Wangechi , Zachary Gathu , Jelioth Muthoni, Sabina Ndichu , Faith Rolex); University of Washington, Mombasa (R. Scott McClelland, Emmanuel Kabare , Fatma H.
Mwidadi , Juma Shafi, Khamis Mwinyikai , Rukiya Hassan, Salwa Mustafa); University of Washington, Seattle (Connie Celum , Elena A. Rechkina , Jared M. Baeten, Rachel
Johnson, Rachel L. Winer, Stephen L. Cherne , Susan Morrison, Torin Schaafsma );DF/Net Research, Inc., Seattle (Angela Williams, Amra Hercinovic , Gavin Robertson,
Krissa Gunderson, Lisa Ondrejcek ,). The study is dedicated to Kowselia Ramaswami ( Malitha ) Ramiah , Sarah Kanyi Mugo, Reginalda Auma Onono , Edwina Muga,
Mary Nduta , and all our mothers.
Thank you