Preterm birth rate after bivalent HPV vaccination: Registry-based follow-up of a randomized clinical trial

A registry-based follow-up of pregnancy data until the end of 2014 was conducted based on a community-randomized trial to assess human papillomavirus (HPV) vaccination strategies and a reference cohort from the same community with no intervention. Our objective was to determine whether prophylactic HPV vaccination (three doses of Cervarix® (AS04-HPV-16/18)-vaccine) affects preterm birth (PTB) rates. All identified 80,272 residents in 1992-95 birth cohorts in Finland were eligible for the trial and 20,513 of 39,420 (51.9%) females consented to participate. The final study population consisted of age-aligned 6226 HPV16/18 vaccinated females and 1770 HBV vaccinated (Engerix® B, hepatitis B-virus vaccine) females that did not receive HPV vaccine at the age of 18 from the 1992-93 birth cohorts, and 19,849 females from the 1990-91 non-vaccinated reference birth cohorts. We compared the rates of preterm (22 + 0-36 + 6 pregnancy weeks) and early preterm (22 + 0-31 + 6) per term (at least 37 + 0) singleton births among the HPV- and non-HPV-vaccinated women, using nationwide Medical Birth Registry data. We observed 409 singleton first pregnancies lasting at least 22 + 0 weeks among 6226 HPV-vaccinated and 1923 among 21,619 non-HPV-vaccinated women. In the first pregnancy the PTB rate was 13/409 (3.2%) among the HPV-vaccinated and 98/1923 (5.1%) among the non-HPV-vaccinated (OR 0.61, 95% CI 0.34-1.09). Early preterm birth rate was 0/409 (0%) in the HPV-vaccinated women and 20/1923 (1.0%) in the non-HPV-vaccinated women (p = 0.04). PTB rate, especially early PTB rate, was lower among the HPV-vaccinated women. Reduction of PTB incidence after prophylactic HPV vaccination would lead to public health benefits globally. Trial Registration:NCT00534638.