Spontaneous preterm birth risk among HPV-vaccinated and -unvaccinated women: a nationwide retrospective cohort study of over 240 000 singleton births.

OBJECTIVE: To determine whether prior human papillomavirus (HPV) vaccination contributes to preterm birth risk. DESIGN: Population-based retrospective cohort study. SETTING: Denmark. POPULATION: A cohort of 243 136 primiparous females born in the period 1961-2004 who had a singleton delivery at >22 weeks of gestation occurring from October 2006 to December 2018. METHODS: High-quality nationwide registries were linked to provide information on demographics, birth outcomes, HPV vaccination status, smoking, body mass index (BMI), and cervical lesions and treatment history. MAIN OUTCOME MEASURES: We assessed the association between HPV vaccination status and spontaneous preterm birth using logistic regression. To address age at vaccination, we performed a stratified analysis by vaccination before and after 17 years of age. RESULTS: In age-adjusted and fully adjusted models, there was a nonsignificant difference in the odds of spontaneous preterm birth between vaccinated and unvaccinated women (OR 1.05 (95% CI 0.99-1.12) and OR 1.04 (95% CI 0.98-1.10), respectively). There was no difference in the odds of spontaneous preterm birth in relation to time between vaccination and pregnancy. In contrast, compared with unvaccinated women, the odds of preterm birth were lower among women vaccinated before the age of 17 years (fully adjusted OR 0.87, 95% CI 0.75-1.00). This association was not present for women vaccinated at ≥17 years of age. CONCLUSIONS: In this large, population-based cohort, we found reduced odds of spontaneous preterm birth among women vaccinated against HPV at an early age compared with women who were unvaccinated. It seems conceivable that HPV vaccination may not only reduce the incidence of cervical cancer and severe precursors, but also reduce the risk of preterm birth related to HPV infection.