Partial Protective Effect of Bivalent Human Papillomavirus 16/18 Vaccination Against Anogenital Warts in a Large Cohort of Dutch Primary Care Patients

Clin Infect Dis. 2021 Jul 15;73(2):291-297. doi: 10.1093/cid/ciaa582.


Background: There is ongoing debate about the possible protective effect of the bivalent human papillomavirus (2vHPV) vaccine, targeting oncogenic types HPV-16/18, against anogenital warts (AGWs), commonly attributed to HPV-6/11. We performed a retrospective registry-based open cohort study to assess the effect of 2vHPV vaccination on AGWs.

Methods: We linked general practice (ie, primary care) data from women born between 1993 and 2002, who had been eligible for HPV vaccination in the Netherlands, to the Dutch national immunization registry on an individual level. Women were followed until their first AGW diagnosis or end of follow-up. Adjusted incidence rate ratios (aIRRs) were estimated using Poisson regression with vaccination status as a time-dependent exposure.

Results: We linked data of 96 468 women with a total of 328 019 years observation time and 613 AGW diagnoses (incidence: 1.87/1000 person-years). At the end of follow-up, 61% were 2vHPV vaccinated (≥ 1 dose) of whom 91% were fully vaccinated. The AGW incidence was lower among those with ≥ 1 dose vs 0 doses (aIRR, 0.75 [95% confidence interval {CI}, .64-.88]). The effect of vaccination was stronger after full vaccination (aIRR, 0.72 [95% CI, .61-.86]) and for women who were offered vaccination at 12-13 years of age (aIRR, 0.69 [95% CI, .51-.93]) vs those at 13-16 years of age (aIRR, 0.77 [95% CI, .64-.93]).

Conclusions: This is the largest population-based study so far to examine the effect of 2vHPV vaccination on AGWs, with reliable individual information on AGW diagnoses and vaccination status. The results indicate that 2vHPV vaccination partially protects against AGWs, especially when administered in early adolescence.

Keywords: anogenital warts; bivalent HPV vaccine; cross-protection; human papillomavirus; vaccine effectiveness.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Cohort Studies
  • Condylomata Acuminata* / epidemiology
  • Condylomata Acuminata* / prevention & control
  • Female
  • Human papillomavirus 16
  • Human papillomavirus 18
  • Humans
  • Netherlands / epidemiology
  • Papillomavirus Infections* / epidemiology
  • Papillomavirus Infections* / prevention & control
  • Papillomavirus Vaccines*
  • Primary Health Care
  • Retrospective Studies
  • Vaccination


  • Papillomavirus Vaccines