Dose-Related Differences in Effectiveness of Human Papillomavirus Vaccination Against Genital Warts: A Nationwide Study of 550,000 Young Girls

Clin Infect Dis. 2015 Sep 1;61(5):676-82. doi: 10.1093/cid/civ364. Epub 2015 May 5.


Background: Reducing the number of doses in the human papillomavirus (HPV) vaccination regimen from 3 to 2 could increase coverage rates. In this cohort study, we assessed the risk of genital warts (GWs) according to timing and number of doses of quadrivalent HPV vaccine.

Methods: From population-based registries, we identified all girls in Denmark born during 1985-1999, for whom information on HPV vaccinations was retrieved. The cohort was followed for GW occurrence during 2006-2012. Incidence rate ratios (IRRs) were calculated by Poisson regression to determine differences in GW rates by number of vaccine doses.

Results: Of the 550,690 girls in the cohort, 361 734 had been vaccinated. Of these, 25.9% had been vaccinated twice and 58.8% 3 times. The risk of GWs decreased significantly with each additional dose of vaccine. For girls who received 2 doses, extension of the interval between doses reduced the incidence of GWs. In comparison with a 2-month interval, the incidence of GWs was reduced by 45% (95% confidence interval [CI], 20%-62%), 55% (95% CI, 35%-69%), and 63% (95% CI, 44%-75%), with an interval of 4, 5, and 6 months, respectively. The IRR of 2 vs 3 doses was close to 1, with an interval of about 6 months between the first 2 doses.

Conclusions: With the original vaccine schedule, completion of 3 doses seems to be required to obtain full protection against GWs. A 2-dose regimen may be as effective if the dosing interval is extended to around 6 months, although the long-term effectiveness of this regimen is unknown.

Keywords: condyloma acuminata; dose–response relationship; genital warts; human papillomavirus; vaccination.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Cohort Studies
  • Condylomata Acuminata / epidemiology*
  • Condylomata Acuminata / prevention & control*
  • Denmark / epidemiology
  • Dose-Response Relationship, Immunologic
  • Female
  • Humans
  • Mass Vaccination / statistics & numerical data
  • Papillomavirus Vaccines / administration & dosage*
  • Papillomavirus Vaccines / immunology*
  • Young Adult


  • Papillomavirus Vaccines