HPV vaccines protect against cancer. Could they benefit pregnancy?

By Dr. Liji Thomas, MDReviewed by Lauren HardakerOct 12 2026

A nationwide study of more than 624,000 births suggests HPV vaccination may offer benefits beyond cancer prevention, with women vaccinated before age 17 showing 10% lower odds of preterm birth and 11% lower odds of spontaneous preterm birth.

Study: Quadrivalent human papillomavirus vaccination before pregnancy and pregnancy outcomes: nationwide, population based case-control study. Image credit: Prostock-studio/Shutterstock.com

Preterm birth is a major contributor to neonatal mortality and later health sequelae in adulthood. A recent nationwide Swedish study in the journal BMJ found that the quadrivalent human papillomavirus (HPV) vaccine was associated with modestly lower odds of several adverse pregnancy outcomes, especially when given earlier in life.

Could HPV vaccination help reduce adverse pregnancy outcomes?

Despite its substantial medical and social burden, preterm birth remains difficult to prevent, with limited effective interventions available. Emerging evidence suggests that human papillomavirus (HPV) infection may contribute to preterm birth and other adverse pregnancy outcomes, raising the possibility of a preventable risk factor.

In addition to the potential effects of infection itself, surgical excision of HPV-related precancerous and early cancerous cervical lesions has been associated with an increased risk of adverse pregnancy outcomes. These procedures are particularly relevant because cervical lesions and their treatment often occur during the reproductive years.

HPV vaccination could therefore offer reproductive health benefits beyond its established role in preventing cervical precancer and cancer. In Sweden, HPV vaccination was introduced in 2006, followed by subsidized vaccination for adolescent girls and, subsequently, a school-based program. Vaccination at younger ages provides particularly strong protection against HPV infection and its associated complications.

Early studies have suggested that HPV vaccination before pregnancy may also reduce the risk of adverse pregnancy outcomes; however, evidence remains limited. Even modest reductions in pregnancy complications could translate into meaningful public health benefits given the widespread uptake of HPV vaccination.

Against this background, the current study examined the association between quadrivalent HPV vaccination before pregnancy and adverse pregnancy outcomes using nationwide Swedish registry data. By linking individual vaccination records with pregnancy outcomes and other maternal characteristics, the researchers sought to provide more robust evidence on these associations, including whether they differed according to age at vaccination.

Swedish study examines HPV vaccination and pregnancy outcomes

The study population included 624,713 nulliparous women aged 16-35 years who gave birth to singleton infants at 22 or more completed weeks of gestation in Sweden between 2006 and 2023. Of these, almost 15% had received the quadrivalent HPV vaccine before pregnancy. Women who immigrated to Sweden after age nine were excluded, as were those whose first recorded HPV vaccination before childbirth involved the bivalent or nonavalent vaccine, those vaccinated after conception, and those with missing gestational age information.

The primary outcomes assessed included preterm birth and spontaneous preterm birth (sPTB). Other secondary outcomes were noted, including preterm prelabor rupture of membranes (pPROM), prelabor rupture of membranes (PROM) at term, small for gestational age (SGA) and severe SGA infant (birth weight below the 10th and 3rd percentiles, respectively, for gestational age and sex), stillbirth, and neonatal mortality.

Preterm birth was stratified by gestational age at birth, as extremely preterm (22-<28 weeks), very preterm (28-<32 weeks), and moderate-to-late preterm (32-<37 weeks).

Cases were matched to up to ten controls by maternal age at childbirth and calendar year of conception, as these factors affected vaccination rates. The researchers compared women who had received at least one dose of quadrivalent HPV vaccination before conception with those who had not.

Confounding factors were adjusted for, including smoking, age at childbirth, body mass index, and assisted reproduction. Details of cervical cancer or precancerous lesions were retrieved from the national registry.

HPV vaccination linked to lower odds of preterm birth

Vaccinated women were more likely to give birth in the most recent years, were younger at the time of childbirth, and were more likely to have Swedish-born mothers.

Among the unvaccinated, 3.7% of mothers had a high-grade cervical lesion diagnosed before childbirth, compared to 0.6% of the vaccinated population.

In the adjusted analyses, vaccination was associated with lower odds of all adverse pregnancy outcomes. However, these associations were statistically significant for only some outcomes. The odds were 5% lower each for preterm birth and sPTB, and 15% lower for very preterm birth.

The odds of secondary outcomes such as pPROM were 7% lower, and the odds of severe SGA were 8% lower. These associations were also statistically significant, although the confidence interval for pPROM reached 1.00 after rounding. The adjusted associations for extremely preterm birth, moderate-to-late preterm birth, PROM at term, SGA, stillbirth, and neonatal mortality did not reach statistical significance.

However, the associations for preterm birth, sPTB, and pPROM were attenuated towards the null when adjusted for history of a high-grade cervical lesion. At the same time, estimates for other outcomes changed minimally. The authors note this is an exploratory analysis, as diagnosis does not imply treatment occurred or define the type and timing of treatment.

Vaccination before age 17 shows stronger protective associations

Women vaccinated before age 17 had lower odds of the primary outcomes, with 10% and 11% lower odds of preterm birth and sPTB, respectively. Among secondary outcomes, statistically significant associations were observed for pPROM and severe SGA, with odds reduced by 14% and 9%, respectively.

For women vaccinated at later ages, statistically significant associations were observed only for severe SGA, by 7%, and stillbirth, by 21%.

Moreover, when earlier versus later vaccination were compared for odds of adverse outcomes, all adjusted odds ratio estimates were lower for the group vaccinated earlier except for SGA and stillbirth, and significantly lower for preterm birth, sPTB, and pPROM.

Swedish findings reinforce earlier evidence on pregnancy outcomes

Sensitivity analyses produced results largely consistent with the main findings. The researchers also estimated the number needed to treat (NNT) using model-based absolute risks from a population-based cohort analysis. The lowest estimates, ranging from 451 to 573, were observed for severe SGA, preterm birth, PROM, sPTB, and SGA, while the highest was 24,116 for neonatal mortality. However, because these estimates were derived from observational data, they do not establish how many women would need to be vaccinated to prevent one adverse outcome.

The findings are consistent with two earlier Finnish studies based on a community-randomized HPV vaccination trial, which reported lower rates of preterm birth among vaccinated women. However, both studies were limited by small numbers of pregnancies and follow-up restricted to early reproductive age.

Evidence from other countries has been mixed. A Danish study found a lower risk of sPTB among women vaccinated before age 17, but not among those vaccinated later. Meanwhile, a Scottish study found no association between HPV vaccination and preterm birth. However, vaccination was linked to lower risks of pPROM, PROM, antepartum hemorrhage, and pre-eclampsia, with considerable variation in effect sizes.

An Australian population-level study also reported 3.2% lower rates of preterm birth and 9.8% lower rates of SGA births among maternal cohorts with HPV vaccination coverage of 60%-80%. However, these findings could not establish a protective effect at the individual level, and residual confounding, particularly from smoking, could not be ruled out.

The current study builds on this evidence by matching women according to maternal age and calendar year of conception. This approach helped account for changes over time in HPV vaccine availability and uptake, cervical screening practices, obstetric care, and the recording of pregnancy outcomes.

HPV prevention may reduce pregnancy complications through two pathways

The proposed mechanisms for the observed protective associations include prevention of HPV infection of the cervix and reduced excisional procedures on the cervix for HPV-related lesions.

Regarding the first, some studies suggest embryonic development is affected by HPV exposure, perhaps contributing to preterm birth risk via poor placental development. Moreover, the risk of sPTB is approximately twice as high among women who had excisional treatment for high-grade cervical lesions.

Meta-analysis findings show increased risks of low birth weight, preterm birth, and PROM after cervical conization is performed. Together, these epidemiological, clinical, and experimental findings provide biologically plausible explanations for the observed associations. However, the present study could not directly establish whether prevention of HPV infection or reduced cervical procedures accounted for the lower odds of adverse pregnancy outcomes.

Limitations

The study's strengths included its large size and high-quality nationwide registry data, long follow-up periods, careful matching by calendar year and maternal age, and adjustment for multiple confounders.

Despite this, the study had several limitations. Residual confounding may have persisted despite extensive adjustments, mainly because the study was observational. Opportunistic or catch-up HPV vaccination may have occurred after HPV infection, potentially weakening the observed associations and contributing to residual confounding.

Other possible issues include the inability to identify differences in health-seeking behavior and reproductive or sexual behavior, as well as differences in the use of cerclage and other interventions to prevent preterm birth.

Spontaneous abortions before 22 weeks were not captured, though they represent competing events for preterm birth and related outcomes, potentially influencing the observed associations. Overlap between intrapartum stillbirth and sPTB remained unresolved.

Finally, post-vaccination HPV infection and cervical treatment were not captured, preventing direct investigation of the proposed biological and clinical mechanisms. Statistical power was also limited for certain rare outcomes, particularly stillbirth and neonatal mortality. Contextual differences in HPV prevalence, infection rates, and high-grade cervical lesions, as well as vaccination programs and obstetric care, may affect the generalizability of the findings.

Early HPV vaccination may offer additional reproductive benefits

The study suggests a modest reduction in the adjusted odds of several adverse pregnancy outcomes after quadrivalent HPV vaccination before pregnancy. The most marked decrease in odds occurred among women vaccinated at earlier ages.

“Together with previous research showing the safety of human papillomavirus vaccination during pregnancy, our results suggest that human papillomavirus vaccination is not only safe with respect to pregnancy outcomes but may also confer additional benefits by reducing the risk of adverse events.” The authors cite this as evidence supporting continued routine HPV vaccination.

Future studies should involve long-term follow-up of vaccinated groups, monitoring pregnancy and birth outcomes, to better assess the actual breadth and magnitude of the impact of these changes and clarify the mechanisms that might explain the observed associations.