# Extended follow-up of invasive cervical cancer risk after quadrivalent HPV vaccination: nationwide, register based study

## TL;DR

This study shows long-term protection against cervical cancer from the HPV vaccine, with stronger benefits when vaccination occurs before age 17.

## Contribution

The study provides the longest follow-up to date on HPV vaccine effectiveness, showing sustained protection for up to 15 years.

## Key findings

- Vaccination before age 17 reduced cervical cancer risk by 79% compared to unvaccinated individuals.
- Protection remained strong for up to 13-15 years after vaccination.
- School-based vaccination programs were linked to a 72% lower cancer risk compared to earlier opportunistic programs.

## Abstract

To evaluate the long term risk of invasive cervical cancer after receiving the quadrivalent human papillomavirus (HPV) vaccine, how risk varies by time since vaccination, and to assess the population level impact of HPV vaccination programmes.

Nationwide register based cohort study with up to 18 years of follow-up.

Sweden, from 1 January 2006 to 31 December 2023.

926​ 362 girls and women residing in Sweden between 2006 and 2023, born in 1985-88 (opportunistic cohort), 1989-92 (subsidised cohort), 1993-98 (catch-up cohort), or 1999-2001 (school based cohort), and with no previous HPV vaccination or diagnosis of invasive cervical cancer at the start of follow-up.

Incidence rate ratios of invasive cervical cancer among vaccinated women versus unvaccinated women were estimated using Poisson regression, adjusting for age, calendar time, sociodemographic factors, and medical histories. Incidence rate ratios were further assessed by time since vaccination, stratified into three year intervals (eg, 1-3, 4-6 years), and by age at vaccination, as well as additional analyses by birth cohorts.

During follow-up, 365​ 502 (39.5%) girls and women received at least one dose of the quadrivalent HPV vaccine. 930 cases of invasive cervical cancer were identified, including 97 in vaccinated and 833 cases in unvaccinated individuals. Among participants vaccinated before 17 years, the overall fully adjusted incidence rate ratios compared with the unvaccinated group was 0.21 (95% confidence interval (CI) 0.13 to 0.32), with sustained protection for 13-15 years after vaccination (incidence rate ratio 0.23, 95% CI 0.11 to 0.46). For individuals vaccinated at 17 years or older, the overall fully adjusted incidence rate ratio was 0.63 (95% CI 0.49 to 0.81) compared with the unvaccinated group, with significant incidence reductions observed during years 10-12 (incidence rate ratio 0.54, 95% CI 0.33 to 0.86), and years 13-15 (incidence rate ratio 0.23, 95% CI 0.08 to 0.60) after vaccination. Compared with the opportunistic cohort, the school based cohort had a 72% (95% CI 11% to 91%) lower risk of cervical cancer after adjustment for covariates (incidence rate ratio 0.28, 95% CI 0.09 to 0.89).

A significantly reduced risk of invasive cervical cancer following quadrivalent HPV vaccination persisted throughout long term follow-up, with no indication of waning protection. School based cohorts showed lower incidence of cervical cancer at the population level than the opportunistic cohort.