Real-world impact of human papillomavirus vaccination on cervical cancer incidence and prevalence: A large electronic health record analysis.

Abstract

e17521 Background: Human papillomavirus (HPV) vaccination is a key preventive strategy against cervical cancer; however, real-world population-level data comparing cervical cancer burden among vaccinated and unvaccinated individuals remain limited. Large electronic health record databases provide an opportunity to evaluate the epidemiologic impact of HPV vaccination in routine clinical practice. Methods: We conducted a retrospective incidence and prevalence analysis using the TriNetX Global Collaborative Network, comprising de-identified electronic health records from 169 healthcare organizations. Adult female patients (≥9 years) with at least one healthcare encounter between January 1, 2015, and December 21, 2025, were included. Two cohorts were constructed: HPV-vaccinated patients identified by CPT codes 90649, 90650, or 90651, and unvaccinated patients with no record of HPV vaccination. Invasive cervical cancer was identified using ICD-10 codes C53.*, including endocervical and exocervical subtypes. Incidence proportion, prevalence, and incidence rates were calculated using TriNetX’s validated incidence–prevalence framework with an applied lookback period. Analyses were stratified by age, race, and ethnicity. Results: The unvaccinated cohort included 94,899,368 adult women, whereas the vaccinated cohort included 798,346 patients. Among unvaccinated individuals, the incidence proportion of invasive cervical cancer was 0.00163 with a prevalence of 0.00218 and an incidence rate of 1.13×10⁻⁶ cases per person-day. In contrast, HPV-vaccinated individuals demonstrated a substantially lower incidence proportion of 5.54×10⁻⁴, prevalence of 6.50×10⁻⁴, and incidence rate of 1.85×10⁻⁷ cases per person-day. Across both cohorts, cervical cancer incidence increased with age, peaking in middle-aged and older adults. Racial and ethnic disparities persisted in both groups, with higher incidence observed among American Indian or Alaska Native patients. Conclusions: In this large real-world analysis, HPV vaccination was associated with markedly lower incidence and prevalence of invasive cervical cancer compared with unvaccinated populations. These findings provide robust population-level evidence supporting the effectiveness of HPV vaccination in reducing cervical cancer burden while highlighting the continued importance of equitable vaccine uptake and routine screening across demographic groups.