Document text
Population -Based Health Impact of
Single -Dose HPV Vaccination
in the United States
Jane J. Kim, Ph.D.
Advisory Committee on Immunization Practices
April 15, 2025
Modeling Teams
Harvard University
•Jane Kim
•Emily Burger
•Nicole Campos
•Mary Caroline Regan
•Jennifer Spencer
•Stephen Sy
Universit é Laval
•Marc Brisson
•Jean -Francois Laprise
•Mélanie Drolet
•Éléonore Chamberland
•Chantal Sauvageau
•Élodie BénardFunding
•PATH Single -Dose HPV Consortium
•NIH/NCI CISNET Consortium (Grant
Number U01 CA253912 )
•Université Laval
•CIHR
•NACI/CCNI
•Digital Research Alliance of Canada
The authors declare no conflicts of interest.Acknowledgments
We would like to acknowledge Lauri
Markowitz, Harrell Chesson, and Mark Jit
for their contributions to related work.
Objectives
Using two independently -developed mathematical models adapted
to the U.S. population:
•To project the long -term health effects of single -dose HPV vaccination ,
taking into account historical HPV vaccination coverage in the U.S.
population.
•To explore key uncertainties of single -dose HPV vaccine efficacy and
duration on the population -level effectiveness.
Harvard1-2 HPV -ADVISE3-5
Model Type Individual -based sexual transmission model (includes herd immunity)
Population Population -based (multi -cohort); females and males by single -year age
Mixing, Risk Groups Heterosexual mixing among 4, age -stratified risk groupsModel Overview
1. Kim, PLOS Med 2021; 2. Burger, JNCI Mono 2024; 3. Brisson, JNCI 2016; 4. Laprise, J Infect Dis 2016; 5. Laprise, Ann Inter n Med 2020.
Harvard1-2 HPV -ADVISE3-5
Model Type Individual -based sexual transmission model (includes herd immunity)
Population Population -based (multi -cohort); females and males by single -year age
Mixing, Risk Groups Heterosexual mixing among 4, age -stratified risk groups
HPV GenotypesHPV -16, -18, -31, -33, -45, -52, -58
(modeled separately) + pooled high -risk
+ pooled low -riskHPV -16, -18, -31, -33, -45, -52, -58, -6,
-11, -35, -39, -51, -56, -59, -66, -68, -73,
and -82 (modeled separately)
HPV TransmissionProbability per month of partnership
duration (sex and genotype -specific)Probability per sexual act (sex and
genotype -specific)
Health StatesNo HPV, HPV, CIN2, CIN3, cervical cancer
(SCC, by stage), deathNo HPV, HPV, CIN1 , CIN2, CIN3, cervical
cancer (SCC, by stage), deathModel Overview
1. Kim, PLOS Med 2021; 2. Burger, JNCI Mono 2024; 3. Brisson, JNCI 2016; 4. Laprise, J Infect Dis 2016; 5. Laprise, Ann Inter n Med 2020.
Model Fit to HPV Prevalence: Harvard
Pre-Vaccine
(2002 -2008)
Post -Vaccine
(2013 -2016)
* Centers for Disease Control and Prevention. National Health and Nutrition Examination Survey (NHANES). http://www.cdc.gov/n chs/nhanes.htm.
Model Fit to HPV Prevalence: HPV -ADVISE (US)
Pre-Vaccine
Post -Vaccine
(2005 -2006) (2013 -2014)
* Centers for Disease Control and Prevention. National Health and Nutrition Examination Survey (NHANES). http://www.cdc.gov/n chs/nhanes.htm.
Model Fit to Median Lifetime Partners
Harvard HPV -ADVISE
2006
2025+2011
2015Change Protection Ages + Doses Population
Vaccine
Introduced;
girls only
3d
9 26 4v GIRLS
9 219 26
4v
3dBoys
addedGIRLS
BOYS
15 9 26 45
15 9 45 269v
3d
2dShared
decision making
for ages 27 -45)GIRLS
BOYS
9 45
9 459v 1dConsidering
one dose*GIRLS
BOYS20199 219 26
9v9v vaccine;
Two doses if < 15GIRLS
BOYS
3d
2d
1515U.S. Vaccination Policy
*1 dose through age 45 years scenario is for illustrative purposes only, to show the maximum possible difference between 1 -dose strategies vs. the current strategy.
Vaccine Assumptions & Justifications
▪Empirical data: VE against persistent HPV16/18 infection = 92 -99%1-4
– Base -case scenario : VE = 98% (Non -inferior VE, based on the KEN SHE trial3)
– Worst -case scenario: VE = 90% (Lower bound 95% CI of the KEN SHE trial3)1-dose vaccine efficacy (VE)
1. Basu, Lancet Oncol 2021; 2. Malvi , JNCI Mono 2024; 3. Barnabas , Nature Med 2023; 4. Barnabas , IPVC 2024; 5. Porras, JNCI Mono 2024 ▪Empirical data: Sustained protection 12-16 years (IARC India Study & CVT)1,2,5
– Base -case scenario: VD = Lifelong
– Worst -case scenario: VD = average 25 years
•Normal distribution (Std Dev = 5 years ) reflects stable efficacy followed by steep drop in protection
•Implies waning starts 15 years after vaccination for some individuals
•Implies no protection for 50% of individuals 25 years after vaccination
•Implies no protection for all individuals 35 -40 years after vaccination
•VD=10 years: excluded from the analysis as waning would have been observed 1-dose vaccine duration (VD)
Brisson, JNCI Mono 2024; IARC ( Malvi , JNCI Mono 2024); KEN SHE (Barnabas, Nature Med 2023 & Barnabas, IPVC 2024); CVT (Porras, JNCI Mono 2024)Worst -case: VE = 90%Vaccine Efficacy Assumptions vs Data for Single -Dose
Vaccine efficacy against persistent HPV -16/18 infection, Vaccine duration (VD) = life
Base case: VE = 98%
Vaccine Duration Assumptions vs Data for Single -Dose
Vaccine efficacy against persistent HPV -16/18 infection, Vaccine efficacy (VE) = 98%
Worst -case: VD = 25and 35years Base case: VD = Lifelong
Brisson, JNCI Mono 2024; IARC ( Malvi , JNCI Mono 2024); KEN SHE (Barnabas, Nature Med 2023 & Barnabas, IPVC 2024); CVT (Porras, JNCI Mono 2024)
RESULTS
What is the impact of switching to 1 -dose
vaccination in the United States?
Year YearHPV -16 Relative Incidence in Females
Cervical Cancer Relative IncidenceResults: Switching to 1 -Dose -Non -inferior 1 -Dose
Gender -neutral 9 -valent vacc , 2-Dose VE=98%, 2 -Dose VD=Life, U.S. coverage
HPV -16 Cervical Cancers
Switch to
1-doseSwitch to
1-dose
Relative incidence calculated against no vaccination.Harvard
Harvard
Laval
Year YearHPV -16 Relative Incidence in Females
Cervical Cancer Relative IncidenceHPV -16
Switch to
1-doseResults: Switching to 1 -Dose -Non -inferior 1 -Dose
Gender -neutral 9 -valent vacc , 2-Dose VE=98%, 2 -Dose VD=Life, U.S. coverage
Cervical Cancers
Switch to
1-dose
Relative incidence calculated against no vaccination.
Harvard
Laval
Year YearHPV -16 Relative Incidence in Females
Cervical Cancer Relative IncidenceHPV -16
Switch to
1-doseResults: Switching to 1 -Dose -Non -inferior 1 -Dose
Gender -neutral 9 -valent vacc , 2-Dose VE=98%, 2 -Dose VD=Life, U.S. coverage
Cervical Cancers
With 2-dose or non -inferior 1 -dose
9-valent HPV vaccination , the
model projects near elimination of
HPV-16 infections and >90%
reduction in cervical cancers.Switch to
1-dose
Relative incidence calculated against no vaccination.
Model Means
Year YearHPV -16 Relative Incidence in Females
Cervical Cancer Relative IncidenceHPV -16
Switch to
1-doseResults: Switching to 1 -Dose -Non -inferior 1 -Dose
Gender -neutral 9 -valent vacc , 2-Dose VE=98%, 2 -Dose VD=Life, U.S. coverage
Cervical Cancers
Switch to
1-dose
Relative incidence calculated against no vaccination; lines represent the mean model projections from the Harvard and HPV -ADVISE US models.
Year YearHPV -16 Relative Incidence in Females
Cervical Cancer Relative IncidenceResults: Switching to 1 -Dose -Lower 1 -Dose VE (90%)
Gender -neutral 9 -valent vacc , 2-Dose VE=98%, 2 -Dose VD=Life, U.S. coverage
Switch to
1-dose
VE=90%HPV -16 Cervical Cancers
Under the worst -case assumption
of vaccine efficacy (90%) , 1-dose
vaccination is projected to produce
similar population -level impacts as
2-dose or non -inferior 1 -dose.Switch to
1-dose
Relative incidence calculated against no vaccination; lines represent the mean model projections from the Harvard and HPV -ADVISE US models.Non -inferior
Results: Switching to 1 -Dose -Waning 1 -Dose VD (25 years)
Gender -neutral 9 -valent vacc , 2-Dose VE=98%, 2 -Dose VD=Life, U.S. coverage
HPV -16
Switch to
1-dose
VD=25 yearsCervical Cancers
Relative incidence calculated against no vaccination; lines represent the mean model projections from the Harvard and HPV -ADVISE US models.Year YearHPV -16 Relative Incidence in Females
Cervical Cancer Relative IncidenceNon -inferior
Even with waning 1 -dose
protection (average of 25 years) ,
1-dose vaccination is projected to
produce similar population -level
impacts as 2 -dose or non -inferior
1-dose.Switch to
1-dose
Results: Switching to 1 -Dose - Lower VE (90%) & Wane (25y)
Gender -neutral 9 -valent vacc , 2-Dose VE=98%, 2 -Dose VD=Life, U.S. coverage
Year YearHPV -16 Relative Incidence in Females
Cervical Cancer Relative IncidenceHPV -16
Switch to
1-doseCervical Cancers
VE=90% and
VD=25 yearsNon -inferior
Assuming both lower VE (90%) and
waning 1 -dose protection (average
25y) , 1-dose vaccination is
projected to produce slight rise in
HPV incidence (~2045) and cervical
cancer incidence (~2060).Switch to
1-dose
Results: Switching to 1 -Dose – Summary
Gender -neutral 9 -valent vacc , 2-Dose VE=98%, 2 -Dose VD=Life, U.S. coverage
Year YearHPV -16 Relative Incidence in Females
Cervical Cancer Relative IncidenceHPV -16
Switch to
1-doseCervical Cancers
Non -inferior
All scenarios result in similar
reductions in HPV -16 and cervical
cancer incidence over time.Switch to
1-dose
VD=25 yearsVE=90%
VE=90% and
VD=25 years
How do these findings compare against
previously published results?
Results Impact of switching to 1 dose –1-dose VD=25 years
Gender -neutral 9 -valent vaccination, 2 -dose VE=98%, 2 -dose VD=Life, VC=85%
HPV-16 new infections among Females
Cervical cancers (SCC)
Brisson JNCI, 2024; the lines are the median result of model projections using 100 parameter sets (50 from HPV -ADVISE US and 50 from HPV -ADVISE Canada); Relative incidence
calculated as % incidence vs no vaccination; HPV infection results excludes reactivation or deposition of HPV infections.
▪What is the impact of 1-dose vaccine efficacy for males?
–In a pessimistic scenario of lower 1 -dose vaccine efficacy (70%) for males only, HPV-ADVISE showed a
similar population -level impact as non -inferior 1-dose for all individuals.
–Herd effects would mitigate a lower vaccine efficacy for males i f gender -neutral vaccination coverage is
high and vaccine efficacy for females is high and long lasting .
▪What is the impact of 1 -dose vaccination on non -cervical HPV -related cancers ?
–More work is required to better understand the natural history of these cancers and the potential
impact of 1 -dose vaccination on their epidemiology.
–Prior analyses suggest more limited/delayed rebound for other HPV -related cancers for all pessimistic
1-dose scenarios given slower progression from infection to cancer.1
▪Can mitigation strategies offset potential rebounds in infection and cancer?
–Both models have shown that if ongoing trial data were to signal waning (i.e., in the next 10 years),
switching back to a 2 -dose regimen would mitigate any rebounds in HPV -16 and cervical cancer.1-3
–Mitigation strategies could be population -level and would not require revaccinating those who received
1 dose to be successful.Other Scenarios Explored in Prior Analyses
1. Drolet, CMAJ 2024; 2. Bénard, Lancet Public Health 2023; 3. Burger, JNCI Mono 2024
Conclusions: 1-Dose HPV Vaccination in the U.S.
▪Switching to 1 -dose HPV vaccination is projected to have similar reductions in
HPV and cervical cancer incidence as continuing with 2 doses in the U.S.
▪Under the pessimistic assumptions of vaccin e efficacy (90%) and vaccine
duration (25 years), a switch to 1 -dose vaccination is projected to have limited
rebound in HPV infection and cervical cancer incidence.
–Switching to 1 -dose vaccination would occur when HPV prevalence is low due to high 2 -dose
vaccination coverage in the U.S.
–Individuals would be protected during their peak ages of sexual activity, providing direct protection
and herd effects to unprotected adults.
▪Continued monitoring of 1 -dose protection over time is required to rapidly
detect any potential signs of waning protection and introduce mitigation
strategies, if needed.
–Under pessimistic assumptions of 1 -dose duration of protection, switching back to 2 -dose vaccination
is projected to mitigate losses in cervical cancer prevention.
References
•Basu P , Malvi SG, Joshi S, Bhatla N, Muwonge R, Lucas E, et al. Vaccine efficacy against persistent human papillomavirus (HPV) 16/18 infection at 10 years afte r
one, two, and three doses of quadrivalent HPV vaccine in girls in India: a multicentre , prospective, cohort study. Lancet Oncol. 2021 Nov;22(11):1518 -1529. doi:
10.1016/S1470 -2045(21)00453 -8. Epub 2021 Oct 8. Erratum in: Lancet Oncol. 2022 Jan;23(1):e16. doi: 10.1016/S1470 -2045(21)00700 -2. PMID: 34634254;
PMCID: PMC8560643.
•Barnabas RV, Brown ER, Onono MA, Bukusi EA, Njoroge B, Winer RL, et al. Durability of single -dose HPV vaccination in young Kenyan women: randomized
controlled trial 3 -year results. Nat Med. 2023 Dec;29(12):3224 -3232. doi: 10.1038/s41591 -023-02658 -0. Epub 2023 Dec 4. PMID: 38049621; PMCID:
PMC10719107.
•Brisson M, Laprise JF, Chesson HW, Drolet M, Malagon T, Boily MC, et al. Health and Economic Impact of Switching from a 4 -Valent to a 9 -Valent HPV Vaccination
Program in the United States. J Natl Cancer Inst. 2016;108(1).
•Burger EA, Laprise JF, Portnoy A, Spencer JC, Sy S, Regan MC, Bénard É, Drolet M, Brisson M, Kim JJ. Population -level health imp act of hypothetical waning 1 -dose
human papillomavirus vaccination and 2 -dose mitigation strategies in a high cervical cancer burden setting. J Natl Cancer Inst Monogr . 2024 Nov 1;2024(67):379 -
386. doi: 10.1093/ jncimonographs /lgae039. PMID: 39529530; PMCID: PMC11555273.
•Kim JJ, Simms KT, Killen J, Smith MA, Burger EA, Sy S, Regan C, Canfell K. Human papillomavirus vaccination for adults aged 3 0 to 45 years in the United States: A
cost-effectiveness analysis. PLoS Med. 2021 Mar 11;18(3):e1003534. doi: 10.1371/journal.pmed.1003534. PMID: 33705382; PMCID: PMC7951902.
•Laprise JF, Markowitz LE, Chesson HW, Drolet M, Brisson M. Comparison of 2 -Dose and 3 -Dose 9 -Valent Human Papillomavirus Vaccine Schedules in the United
States: A Cost -effectiveness Analysis. J Infect Dis. 2016;214(5):685 -8.
•Laprise JF, Chesson HW, Markowitz LE, Drolet M, Martin D, Benard E, et al. Effectiveness and Cost -Effectiveness of Human Papillo mavirus Vaccination Through Age
45 Years in the United States. Ann Intern Med. 2020;172(1):22 -9.
•Malvi SG, Esmy PO, Muwonge R, Joshi S, Poli URR, Lucas E, et al. A prospective cohort study comparing efficacy of 1 dose of q uadrivalent human papillomavirus
vaccine to 2 and 3 doses at an average follow up of 12 years postvaccination. J Natl Cancer Inst Monogr . 2024 Nov 1;2024(67):317 -328. doi:
10.1093/ jncimonographs /lgae042. PMID: 39529521; PMCID: PMC11555276.
•Porras C, Romero B, Kemp T, Fantin R, Herrero R, Hildesheim A, et al. HPV16/18 antibodies 16 -years after single dose of bivalent HPV vaccination: Costa Rica HPV
vaccine trial. J Natl Cancer Inst Monogr . 2024 Nov 1;2024(67):329 -336. doi: 10.1093/ jncimonographs /lgae032. PMID: 39529529; PMCID: PMC11555268.