The Differential Risk of Cervical Cancer in HPV-Vaccinated and -Unvaccinated Women: A Mathematical Modeling Study

Emi Naslazi, Jan A. C. Hontelez, Steffie K. Naber, Marjolein van Ballegooijen, Inge M. C. M. de Kok

Research output: Contribution to journalArticleAcademicpeer-review

1 Citation (Scopus)


Background: With increased uptake of vaccination against human papillomavirus (HPV), protection against cervical cancer will also increase for unvaccinated women, due to herd immunity. Still, the differential risk between vaccinated and unvaccinated women might warrant a vaccination-status–screening approach. To understand the potential value of stratified screening protocols, we estimated the risk differentials in HPV and cervical cancer between vaccinated and unvaccinated women.

Methods: We used STDSIM, an individual-based model of HPV transmission and control, to estimate the HPV prevalence reduction over time, after introduction of HPV vaccination. We simulated scenarios of bivalent or nonavalent vaccination in females-only or females and males, at 20% coverage increments. We estimated relative HPV-type–specific prevalence reduction compared with a no-vaccination counterfactual and then estimated the age-specific cervical cancer risk by vaccination status.

Results: The relative cervical cancer risk for unvaccinated compared with vaccinated women ranged from 1.7 (bivalent vaccine for females and males; 80% coverage) to 10.8 (nonavalent vaccine for females-only; 20% coverage). Under 60% vaccination coverage, which is a representative coverage for several western countries, including the United States, the relative risk (RR) varies between 2.2 (bivalent vaccine for females and males) and 9.2 (nonavalent vaccine for females).

Conclusions: We found large cervical cancer risk differences between vaccinated and unvaccinated women. In general, our model shows that the RR is higher in lower vaccine coverages, using the nonavalent vaccine, and when vaccinating females only.

Impact: To avoid a disbalance in harms and benefits between vaccinated and unvaccinated women, vaccination-based screening needs serious consideration.
Original languageEnglish
Pages (from-to)912-919
Number of pages8
JournalCancer Epidemiology Biomarkers & Prevention
Issue number5
Publication statusPublished - May 2021

Bibliographical note

Funding Information: The financial support for this study was provided entirely by a grant from the National Cancer Institute as part of the Cancer Intervention and Surveillance Modeling Network (CISNET), grant number U01CA199334. All authors received funding from this grant. The funding agreement ensured the authors' independence in designing the study, interpreting the data, writing, and publishing the report.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.


Dive into the research topics of 'The Differential Risk of Cervical Cancer in HPV-Vaccinated and -Unvaccinated Women: A Mathematical Modeling Study'. Together they form a unique fingerprint.

Cite this