Dose-related effectiveness of quadrivalent human papillomavirus vaccine against cervical intraepithelial neoplasia: A Danish nationwide cohort study

BACKGROUND: A reduced, two-dose schedule of human papillomavirus (HPV) vaccination has been endorsed for preadolescent women on the basis of immunogenicity data from randomised trials, and limited data suggest even one dose may provide sufficient protection. Surveillance of the impact of fewer than three vaccine doses on clinical endpoints in the targeted age group is warranted.

METHODS: We conducted a nationwide cohort study of all women between 17-25 years, living in Denmark between 2006 and 2016. From nationwide registries, we extracted individual-level data on vaccination with the quadrivalent HPV (qHPV) vaccine at 16 years or younger, number of doses administered, diagnoses of cervical intraepithelial neoplasia grade 2 or worse (CIN2+) or grade 3 or worse (CIN3+), and potential confounders. Using Poisson regression, we estimated incidence rate ratios (IRRs) with 95% confidence intervals (CIs) for CIN2+ and CIN3+, according to vaccination status.

RESULTS: The cohort comprised 590,083 women, of which 215,309 (36%) women were vaccinated at ≤16 years, and among these, 40,742 (19%) received fewer than three vaccine doses. A total of 5,561 women had a diagnosis of CIN3+. We find considerable vaccine effectiveness against CIN3+ after three (IRR: 0.37, CI: 0.30-0.45), two (IRR: 0.38, CI: 0.22-0.66), or one (IRR: 0.38, CI: 0.14-0.98) vaccine doses, compared to unvaccinated women. Results were similar for CIN2+.

CONCLUSIONS: We find substantial effectiveness of qHPV vaccination against high-grade cervical precancerous lesions, among women vaccinated with three, two, or one dose at 16 years or younger. One-dose vaccination appears to provide similar protection as three-dose vaccination.