quadrivalent human papillomavirus (HPV) vaccination before pregnancy and pregnancy outcomes

A large nationwide Swedish population-based matched case-control study (624,713 singleton births in nulliparous women aged 16–35 years between 2006 and 2023) evaluating the association between pre-pregnancy quadrivalent human papillomavirus (qHPV) vaccination and subsequent obstetric outcomes (1):

• pre-pregnancy qHPV vaccination (92,620 vaccinated women; 14.8%) was associated with a statistically significant reduction in the odds of adverse pregnancy outcomes, particularly preterm-related complications
• findings suggest that the benefits of HPV vaccination extend beyond cervical cancer prevention to confer meaningful reproductive health benefits

Main Clinical Findings and Outcomes

• overall preterm birth reduction: qHPV vaccination before pregnancy was associated with lower adjusted odds of overall preterm birth (<37 weeks) (adjusted odds ratio [aOR] 0.95, 95% confidence interval [CI] 0.91 to 0.99) and spontaneous preterm birth (sPTB) (aOR 0.95, 95% CI 0.91 to 0.99)
• gestational age sub-analyses: significant reductions were observed for very preterm birth (28 to <32 weeks) (aOR 0.85, 95% CI 0.75 to 0.97)
• secondary outcomes: vaccination was associated with significantly reduced odds of preterm prelabour rupture of membranes (pPROM) (aOR 0.93, 95% CI 0.87 to 1.00) and severe small for gestational age (SGA) infants (<3rd centile) (aOR 0.92, 95% CI 0.87 to 0.97)

Impact of Age at Vaccination

• age-dependent benefit: risk reductions were significantly more pronounced among women vaccinated at younger ages (<17 years, prior to median age of sexual debut) compared to those vaccinated at 17 years or older
• early vaccination (<17 years):
  • preterm birth (<37 weeks): aOR 0.90 (95% CI 0.85 to 0.95)
  • spontaneous preterm birth (sPTB): aOR 0.89 (95% CI 0.84 to 0.95)
  • preterm prelabour rupture of membranes (pPROM): aOR 0.86 (95% CI 0.78 to 0.94)
  • severe small for gestational age (SGA) (<3rd centile): aOR 0.91 (95% CI 0.84 to 0.97)
• clinical implication: highlights the importance of timely, early adolescent and school-based routine immunisation programmes before viral exposure

Proposed Biological Mechanisms

• direct prevention of persistent maternal HPV infection, which has been linked to placental dysfunction, trophoblast impairment, and systemic intrauterine inflammation
• indirect reduction in excisional cervical treatments (such as loop electrosurgical excision procedure [LEEP] or cone biopsy for cervical intraepithelial neoplasia grade 2 or worse [CIN2+]), which are known major risk factors for cervical insufficiency and spontaneous preterm delivery

Reference:

1. Zhang Z, Ploner A, Sengpiel V, Kasheshi N, Jacobsson B, Dillner J, Sparén P, Kärrberg C, Lei J. Quadrivalent human papillomavirus vaccination before pregnancy and pregnancy outcomes: nationwide, population based case-control study. BMJ. 2026;395:e100739.