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Reduced number of doses for HPV vaccination series:
Work Group progress and literature update
Carla L. DeSisto, PhD, MPH
Co-Lead, HPV Vaccines Work GroupNational Center for Immunization and Respiratory Diseases
Advisory Committee on Immunization Practices
April 15, 2025
•PICO and outcomes
•Introduction to systematic review
•Updated data from studies of interest
•Observational studies of HPV vaccine effectiveness
•Outstanding questions for reduced number of HPV vaccine dosesOutline
2
PICOs and outcomes
PICO questions1
Policy question Should 1 dose of HPV vaccine be used for
prevention of HPV infection and HPV attributable
disease, instead of the currently recommended
vaccination schedule? Should 2 doses of HPV vaccine be used
for prevention of HPV infection and
HPV attributable disease, instead of the
currently recommended vaccination
schedule?
Population Persons aged 9 –14 yrs
Except persons with
immunocompromising
conditionsPersons aged 15 –X yrs2
Except persons with
immunocompromising
conditionsPersons aged 15 –X yrs2
Except persons with immunocompromising
conditions
Intervention 1 dose of HPV vaccine 2 doses of HPV vaccine
Comparison
(current
recommendation )2 doses for persons who
initiate at ages 9–14 yrs3 doses for persons who
initiate at age ≥15 yrs3 doses for persons who initiate at age
≥15 yrs
1We are not intending this to change the recommendation of shared clinical decision -making for persons aged 27 -45 years,
although the number of recommended doses in this age group may change.
2Upper age to be discussed by Work Group after we review data
Note: We will review data on 1 vs 2 doses in persons aged 15+, but are focusing PICOs on comparing to current recommendations4
Outcomes
Outcome Importance
HPV -associated cancers Critical
Pre-cancers (CIN2+ or AIN2+) Critical
Serious adverse events related to vaccination Critical
Incident -persistent HPV infection Critical
Prevalent HPV infection Important
Incident HPV infection Important
Immunogenicity Important
Anogenital warts Important
Low -grade histological abnormalities (CIN1 or AIN1) Important
Recurrent respiratory papillomatosis Important
5
Introduction to systematic review
•Cochrane reviewed the global literature on HPV vaccination schedules
with reduced number of doses in 2022
-59 studies (73 publications) were included in review; 49 studies were later
excluded due to serious risk of bias
•We are starting with Cochrane’s review but putting it into U.S. context
-Only including studies of vaccines that are licensed in the United States
-Using 18 publications from Cochrane’s systematic review
•Updated Cochrane’s literature search for publications during 2022 –2024
-Yielded 22 additional publications; 3 excluded due to serious risk of bias
-37 total included publicationsSystematic review of the literature
7
Included studies in alphabetical order
8Study name or first author Study design Population and age at vaccination Vaccine
Batmunkh 2020 (Mongolia) Retrospective cohort Females, 11 -17y 4vHPV
Berenson 2024 (USA) RCT Females, 15 -26y 9vHPV
Bornstein 2021 (global) RCT Girls and boys, 9 -14y 9vHPV
Costa Rica Vaccine Trial (CVT) Post -hoc analysis of RCT Females,18 -25y 2vHPV
CVT/PATRICIA Post -hoc analysis of 2 RCTs Females,15 -25y 2vHPV
DoRIS (Tanzania) RCT Females, 9 -14y 2vHPV and 9vHPV
Hariri 2018 (USA) Retrospective cohort Females, age NR 4vHPV
HOPE (South Africa) Repeat cross -sectional Females, 15 -16y 2vHPV
IARC -India Post -hoc analysis of RCT Females, 10 -18y 4vHPV
Jiamsiri 2024 (Thailand) Repeat cross -sectional Females, 13 -14y 2vHPV
KEN SHE (Kenya) RCT Females,15 -20y 2vHPV and 9vHPV
Klein 2024 (USA) Cohort Girls and boys, 9 -14y 9vHPV
Moss 2024 (USA) Cohort Females, 15 -45y 9vHPV
Reyburn 2023 (Fiji) Retrospective cohort Females, 9 -12y 4vHPV
Wu 2025 (Sweden) Retrospective cohort Females, 10 -35y 4vHPV
Zeng 2023 (USA) Cohort Girls and boys, 9 -11y 9vHPV
Outcome # of studies RCTs Post -hoc analysis of
RCTsObservational
studies
HPV -associated
cancers1 IARC -India (15y; 0 cases)
Pre-cancers (CIN2+
or AIN2+)2 IARC -India (15y) Wu-Sweden (8 -12y)
Incident -persistent
HPV infection3 KEN SHE (4.5y) IARC -India (15y),
CVT/PATRICIA (4y)
Serious adverse
events related to
vaccinationn/a - data to be summarized in narrative review
9Critical outcomes: Studies contributing data and time
since vaccination
Outcome # of
studiesRCTs Post -hoc
analysis of RCTsObservational studies
Prevalent HPV infection 5 CVT (11y) Reyburn -Fiji (8y), Batmunkh -
Mongolia (6y), Jiamsiri -Thailand (4y),
HOPE -South Africa (2y)
Incident HPV infection 2 IARC -India (15y),
CVT (11y)
Immunogenicity 11 DoRIS -Tanzania (5y),
KEN SHE (2y),
Bornstein -global (1y),
Berenson -USA (1m)CVT (16y),
IARC -India (10y)Batmunkh -Mongolia (6y),
Jiamsiri -Thailand (4y),
Zeng -USA (6m), Moss -USA (1m),
Klein -USA (follow -up varied)
Anogenital warts 2 Reyburn -Fiji (8y),
Hariri -USA (follow -up NR)
Low -grade histological
abnormalities (CIN1 or
AIN1)1 IARC -India (15y)
Recurrent respiratory
papillomatosisn/a
10Important outcomes: Studies contributing data and time since vaccination
Updated data from studies of interest
Trial/country Evidence VaccineAge ( yrs) at
vaccinationDescription
CVT
Costa RicaEfficacy/
Immunogenicity2vHPV 18–25 Post -hoc analyses
Original trial: randomized to 3 doses or
control, but analyzed as 1 -, 2-, 3-dose groups
IARC -India
IndiaEfficacy/
Immunogenicity4vHPV 10–18 Post -hoc analyses
Original trial: randomized to 2 or 3 doses
but analyzed as 1 -, 2-, 3-dose groups
KEN SHE
KenyaEfficacy 2vHPV
9vHPV15–20 Randomized trial
1 dose 2vHPV, 9vHPV or MCV
DoRIS
TanzaniaImmunogenicity 2vHPV
9vHPV9–14 Randomized trial
1-, 2-, 3-dose groups
122vHPV, Cervarix; 9vHPV, Gardasil 9; CVT, Costa Rica Vaccine Trial; IARC, International Agency for Research on CancerTrials with data on single -dose HPV vaccination
considered by the World Health Organization in 2022
•Women aged 18 –25 years were randomly assigned to receive 3 doses of
2vHPV or hepatitis A vaccine
•Some women did not receive all 3 doses due to pregnancy, colposcopy
referral, a medical condition, participant refusal, or missing a study visit
-Reasons for receiving fewer doses were balanced within each dosage group
between women receiving the HPV and control vaccines
•Data evaluated as cohort study of women who received 1, 2, or 3 doses
•We previously reviewed data on protection against prevalent infection
and immunogenicity through 11 yearsCosta Rica Vaccine Trial (CVT)
13
•16 years after vaccination, HPV 16/18 seropositivity was very high (>98%)
•During years 11 –16 after vaccination, small but statistically significant
declines in antibodies observed in women who received 3 doses and 1 doseCosta Rica Vaccine Trial (CVT): 2024 update
14 Porras et al 2024 https://academic.oup.com/jncimono/article/2024/67/329/7821493
•Unmarried girls aged 10 –18 years were randomly assigned to receive
either 2 or 3 doses of 4vHPV
•A ministerial decree to halt vaccination in trials resulted in the creation of
cohorts of women who received 1, 2, or 3 doses
•Cervical screening with an HPV test was initiated at age 25 years for
married participants
-Positive screening → colposcopy; negative screening → repeat in 5 years
•Age- and site -matched unvaccinated married women recruited as controls
•We previously reviewed data on protection against persistent infection
through 10 yearsIARC -India Trial
15
•Median follow -up time = 12 years; time since study began = 15 years
-Currently aged 25 –33 years
•VE against persistent HPV 16/18 infection by number of doses:
-1 dose: 92.0% (95% CI: 87.0% –95.0%)
-2 doses: 94.8% (95% CI: 90.0% –97.3%)
-3 doses: 95.3% (95% CI: 90.9% –97.5%)
•No CIN2+ associated with HPV 16/18 detected among vaccinated
participants (compared with 8 among unvaccinated women)
•No cases of invasive cervical cancer associated with HPV 16/18 in studyIARC -India Trial: 2024 update
16 Malvi et al 2024 https://academic.oup.com/jncimono/article/2024/67/317/7821485
•Dose Reduction Immunobridging & Safety Study
•Girls aged 9 –14 years were randomly assigned to 1, 2, or 3 doses of either
2vHPV or 9vHPV
•All participants followed until month 36; 1 - and 2 -dose groups invited to
join long -term extension (through 9 years)
•Objective was to demonstrate noninferiority:
-HPV 16 and 18 antibody response after 1 vs 2 or 3 doses of same vaccine
-HPV 16 and 18 GMCs: 1 dose in DoRIS vs 1 dose in studies that evaluated efficacy
•We previously reviewed data on immunogenicity (seropositivity and
GMCs) and immunobridging to KEN SHE through 2 yearsDoRIS (Tanzania)
17
•Seropositivity:
-HPV 16: 100% seropositive in 1 -dose and 2 -dose arms
-HPV 18: 93% seropositive in 1 -dose arm, 98% seropositive in 2 -dose arm
-Non -inferiority of HPV 18 seropositivity was not metDoRIS : 2025 update (9vHPV results) – 5 years after
vaccination
18 Watson -Jones et al 2025 https://pubmed.ncbi.nlm.nih.gov/39890232/
DoRIS : 2025 update (9vHPV results) – 5 years after
vaccination
19
•GMCs:
-1-dose arm: plateaued at month 12, relatively constant through month 60
-2-dose arm: declined after peak at month 7
-Lower in 1 -dose arm than in 2 -dose arm, as expected
Observational studies of vaccine effectiveness
•Most important sources of bias:
-Differences between dose groups in risk of prevalent infection at time of vaccination
-Differences between dose groups in risk of HPV acquisition during follow -up
-Potential impact of interval between 1st and 2nd dose on vaccine effectiveness
•Serious bias would likely result in lower effectiveness with fewer doses
•Ways investigators attempt to control for biases:
-Using buffer periods to exclude outcomes caused by prevalent infections at vaccination
-Stratifying results for age at vaccination or restricting the population to younger ages
-Adjusting for indicators of sexual activity and socio -demographic characteristics
-Stratifying results for 2 doses by the interval between 1st and 2nd dose (e.g., <5 , ≥5m)Bias in observational studies of HPV vaccine
effectiveness by number of doses
21 Markowitz et al 2022 https://www.sciencedirect.com/science/article/pii/S0264410X22008349?via%3Dihub
•Cohort study of 2.2M females aged 10 –35, residents of Sweden 2006 –2022
•Linked several registries, including vaccination and cervical screening
•Exposure (time -varying): number of doses of 4vHPV
•Outcome: CIN2+
•Used Poisson models to estimate incidence rate ratios (IRR) vs. unvaccinated
-Adjusted for age, calendar year, county of residence, maternal history of high -grade
cervical lesions, mother’s country of birth, parental education, and household income
-1 year buffer
•Median years of follow -up (IQR):
-Unvaccinated: 8.4 (2.3 –15.3); Vaccinated: 12.4 (8.7 –17.0)Wu-Sweden 2025: methods summary
22
Wu-Sweden 2025: CIN2+ by age at vaccination
23 Wu et al https://www.thelancet.com/journals/lanepe/article/PIIS2666 -7762(24)00347 -8/fulltext
Outstanding questions for reduced
number of HPV vaccine doses
▪Longer term efficacy and immunogenicity
▪Protection at sites other than the cervix
▪Efficacy and immunogenicity in males
▪Efficacy and immunogenicity in immunocompromised persons
▪Efficacy and immunogenicity in older age groupsOutstanding questions for reduced number of HPV vaccine doses
25
▪Longer term efficacy and immunogenicity
➢Longest efficacy data: IARC -India (15 years)
➢Longest immunogenicity data: Costa Rica Vaccine Trial (16 years)
▪Protection at sites other than the cervix
➢No data on protection at sites other than the cervix
▪Efficacy and immunogenicity in males
➢13/16 studies include only females
➢No efficacy data in males
➢Some evidence of lower antibody titers in adolescent males versus females after 1 dose
▪Efficacy and immunogenicity in immunocompromised persons
➢Limited data available; not planning to make changes to recommendation
▪Efficacy and immunogenicity in older age groups
➢Limited data available; need to decide appropriate upper age for our PICOs
26Outstanding questions for reduced number of HPV vaccine doses
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TTY: 1 -888-232-6348 www.cdc.gov
The findings and conclusions in this report are those of the authors and do not necessarily represent the official
position of the Centers for Disease Control and Prevention.
Thank you!