Dose-related Effectiveness of Quadrivalent Human Papillomavirus Vaccine Against Cervical Intraepithelial Neoplasia: A Danish Nationwide Cohort Study

Clin Infect Dis. 2020 Feb 3;70(4):608-614. doi: 10.1093/cid/ciz239.


Background: A reduced, 2-dose schedule of human papillomavirus (HPV) vaccination has been endorsed for preadolescent women on the basis of immunogenicity data from randomized trials, and limited data suggest that even 1 dose may provide sufficient protection. Surveillance of the impact of <3 vaccine doses on clinical endpoints in the targeted age group is warranted.

Methods: We conducted a nationwide cohort study of all women aged 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 <3 vaccine doses. A total of 5561 women had a diagnosis of CIN3+. We found considerable vaccine effectiveness against CIN3+ after 1 (IRR, 0.38 [95% CI, .14-.98]), 2 (IRR, 0.38 [95% CI, .22-.66]), or 3 (IRR, 0.37 [95% CI, .30-.45]) 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 1, 2, or 3 doses at ≤16 years of age. One-dose vaccination appeared to provide similar protection as 3-dose vaccination.

Keywords: HPV vaccination; cervical dysplasia; human papillomavirus; reduced dosing schedule; vaccine effectiveness.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Cervical Intraepithelial Neoplasia* / epidemiology
  • Cervical Intraepithelial Neoplasia* / prevention & control
  • Cohort Studies
  • Denmark / epidemiology
  • Female
  • Humans
  • Papillomavirus Infections* / epidemiology
  • Papillomavirus Infections* / prevention & control
  • Papillomavirus Vaccines*
  • Uterine Cervical Neoplasms* / epidemiology
  • Uterine Cervical Neoplasms* / prevention & control
  • Vaccination
  • Young Adult


  • Papillomavirus Vaccines