HPV vaccination is associated with lower risk of cancers among females
Females aged 9–26 who received human papillomavirus vaccination had fewer new cancer diagnoses over 5 years than matched unvaccinated females.
*Retrospective matched cohort study; Level 2b (OCEBM).
*Retrospective matched cohort study; Level 2b (OCEBM).
Citation
Hung YM, Lin TTA, Wang SI, et al. HPV vaccination is associated with lower risk of cancers among females. The American Journal of Medicine. 2026;139:311–320. doi:10.1016/j.amjmed.2025.10.016.
Background
Human papillomavirus vaccines prevent several cancers, but long-term, broad cancer outcomes in real-world settings are less certain. This study examined whether vaccination is linked to lower cancer risk in young females.
Patients
Females aged 9–26 years in a large United States electronic health record network (2013–2022) with at least two visits. Excluded: pregnancy, death, known prior human papillomavirus infection, and any cancer before or at the start date.
Intervention
Completion of a human papillomavirus vaccine series (start date = series completion).
Control
No recorded human papillomavirus vaccination (start date = first visit in the study period). Groups were closely matched on measured baseline factors.
Outcome
First-time diagnosis of any cancer and several cancer categories, counting events from 90 days after the start date.
Follow-up Period
Up to 5 years.
Results
| Outcome (90 days to 5 years) | Hazard ratio (95% confidence interval) |
|---|---|
| Any cancer (primary) | 0.38 (0.34 to 0.43) |
| Breast cancer | 0.21 (0.12 to 0.37) |
| Urinary tract cancers | 0.18 (0.09 to 0.36) |
| Brain and nervous system cancers | 0.26 (0.18 to 0.37) |
| Lymph node and blood cancers | 0.36 (0.29 to 0.46) |
The absolute 5-year risk of any cancer was low (0.11% vs 0.31%); number needed to vaccinate to prevent one cancer diagnosis over 5 years ≈ 503.
Associations were stronger when vaccination started at ages 9–14 than 15–26, and remained directionally similar in multiple sensitivity analyses (including comparisons with influenza-vaccinated controls).
Limitations
Because this was not a randomized study, unmeasured differences between groups could explain some findings (for example, health-seeking behavior or missed infection history). Diagnoses and vaccinations may be incomplete outside participating systems. Despite large relative differences, the short-term absolute cancer reduction was modest because cancers were rare in this age group.
Funding
Government and hospital grants from Taiwan; funders had no role.
Clinical Application
Reinforces recommending early, on-time human papillomavirus vaccination series completion; expect modest short-term absolute cancer reduction, with uncertain applicability to males or older adults.
Discussion
Sign in to join the discussion.
In this retrospective propensity-score–matched cohort using TriNetX EHR data, HPV vaccination (vs no HPV vaccination) was associated with lower 5-year overall cancer incidence (HR 0.38, 95% CI 0.34–0.42; vs influenza-vaccinated comparator HR 0.71): what biases (eg, healthy-user/immortal-time, differential screening, outcome misclassification) could drive this effect, and how should it influence your counseling about “broad cancer prevention” and vaccine timing?