Evidence map›Paper›PMID 40481488›Full record

Observational studyBMC medicine2025

The indirect effect of the bivalent human papillomavirus vaccination program: an observational cohort study.

Marit Middeldorp, Janneke W Duijster, Mirjam J Knol, Birgit H B van Benthem, Johannes Berkhof, Audrey J King, Hester E de Melker

Abstract readObservational Study
PubMed Full text at PMC Publisher
In one paragraph

Observational study in BMC medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

5 citing papers in PubMed.

  1. Observational
  2. Article
  3. Review
  4. Article
  5. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors.

Marit MiddeldorpCentre for Infectious Disease Control, National Institute for Public Health and the Environment, Bilthoven, the Netherlands. marit.middeldorp@rivm.nl.
Janneke W DuijsterCentre for Infectious Disease Control, National Institute for Public Health and the Environment, Bilthoven, the Netherlands.
Mirjam J KnolCentre for Infectious Disease Control, National Institute for Public Health and the Environment, Bilthoven, the Netherlands.
Birgit H B van BenthemCentre for Infectious Disease Control, National Institute for Public Health and the Environment, Bilthoven, the Netherlands.
Johannes BerkhofDepartment of Epidemiology and Data Science, Amsterdam, UMC, Location VUmc, Amsterdam, the Netherlands.
Audrey J KingCentre for Infectious Disease Control, National Institute for Public Health and the Environment, Bilthoven, the Netherlands.
Hester E de MelkerCentre for Infectious Disease Control, National Institute for Public Health and the Environment, Bilthoven, the Netherlands.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundThe impact of human papillomavirus (HPV) vaccination programs depends on the degree of indirect protection against new infections achieved among unvaccinated women. We estimated the indirect effect of bivalent HPV vaccination by comparing the HPV-type incidence in unvaccinated female participants between a cohort offered vaccination in 2009/2010 and a cohort of similar-aged women offered vaccination in 2014.

methodsWe compared the incidence rates of HPV types in the HAVANA cohort (follow-up from 2010/2011 until 2015/2016) with those from the HAVANA-2 cohort (2017-2022) using two regression approaches to estimate the indirect effect of HPV vaccination. First, we calculated the incidence ratio (IRR) for a vaccine or cross-protective type in HAVANA-2 versus HAVANA by Poisson regression and compared it to the IRR for a non-cross-protective type. The indirect vaccine effect is defined as 1-ratio of the IRRs. Second, we performed Cox regression with infection by vaccine or cross-protective type as the endpoint and calculated the hazard ratio (HR) for HAVANA-2 versus HAVANA after adjusting for time-varying sociodemographic variables. The indirect effect is defined as 1-HR.

resultsWe included 661 unvaccinated participants in HAVANA and 927 in HAVANA-2. We observed a significant reduction in incident HPV16 infections of 70.9% (95% CI 48.3-83.7%) with Poisson regression and of 73.1% (95% CI 53.3-84.5%) with Cox regression. For HPV45, significant decreases of 67.3% (95% CI 8.8-88.3%) and 69.8% (95% CI 15.2-89.3%) were observed. For HPV18, HPV31, and HPV33, the indirect effect was not statistically significant.

conclusionsLarge indirect effects of the bivalent HPV vaccination program were observed for HPV16 and HPV45 infections.

Indexed as

Immunization ProgramsPapillomavirus InfectionsPapillomavirus VaccinesVaccinationAdolescentAdultCohort StudiesFemaleHuman Papillomavirus VirusesHumansIncidenceMiddle AgedYoung AdultPapillomavirus VaccinesBivalent HPV vaccinationHerd effectsHuman papillomavirusIndirect effects

Identifiers

PMID40481488
PMCPMC12142964

What OpenQuestion holds

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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.