TL;DR
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A Swedish case-control study covering 624,713 singleton births found that women vaccinated against HPV before pregnancy had modestly lower odds of preterm, very preterm and spontaneous preterm birth than unvaccinated women. The observational findings do not establish that vaccination caused the differences, and the researchers said the role of cervical lesions and treatment needs further study.
A Swedish study of 624,713 singleton births found that women who had received a quadrivalent HPV vaccine before pregnancy had lower odds of preterm birth, including very preterm and spontaneous preterm birth, than women who were unvaccinated. The observational results, published in The BMJ and reported by MedPage Today, showed stronger associations for some outcomes among women vaccinated before age 17, but do not establish that vaccination caused the differences.
The researchers compared pregnancy outcomes among women aged 16 to 35 who had not previously given birth, using information from Swedish nationwide registers for births between 2006 and 2023. Overall, 14.8% of eligible women had received a quadrivalent HPV vaccine before pregnancy. The study excluded women whose first HPV vaccination was with a bivalent or nonavalent vaccine.
Compared with unvaccinated women, vaccinated women had lower adjusted odds of preterm birth (adjusted odds ratio, or aOR, 0.95; 95% confidence interval 0.91–0.99), very preterm birth (aOR 0.85; 0.75–0.97) and spontaneous preterm birth (aOR 0.95; 0.91–0.99). These are relative odds estimates, not estimates of how many births would be prevented, and the study did not show that the vaccine itself caused the outcomes.
Associations for preterm and spontaneous preterm birth were stronger among women vaccinated before age 17: the aORs were 0.90 (0.85–0.95) and 0.89 (0.84–0.95), respectively. Vaccination was also associated with lower odds of preterm prelabor rupture of membranes and severe small-for-gestational-age birth. The study found no significant overall differences for prelabor rupture of membranes, stillbirth or neonatal mortality.
Possible Benefits Beyond Cancer Prevention
HPV vaccination is used to prevent infections that can lead to cervical and other cancers. The study raises the possibility that vaccination could also be associated with pregnancy outcomes, adding a potential consideration for public health research and economic evaluations. The authors told MedPage Today that the differences were modest at the individual level but could have broader implications if confirmed across populations.
The results do not change what the study can establish: it observed associations in registry data, rather than testing vaccine effects in a randomized trial. They should not be taken as proof that HPV vaccination prevents preterm birth, or as a substitute for established prenatal care. Their relevance is that they identify a possible additional outcome for researchers to examine alongside the vaccine’s established cancer-prevention purpose.
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How Vaccination Timing Relates
The study compared women vaccinated before pregnancy with those who had not received HPV vaccination. The authors reported stronger associations for certain outcomes among women vaccinated before age 17. They suggested that earlier vaccination may occur before HPV exposure and provide protection for longer before reproductive years, but these explanations were not directly established by the study.
The researchers also examined high-grade cervical lesions diagnosed before childbirth. Such lesions were recorded in 0.6% of vaccinated women and 3.7% of unvaccinated women. After adjustment for these diagnoses, associations between vaccination and preterm-birth-related outcomes weakened. The authors said this pattern could be consistent with prevention of lesions and subsequent treatment partly explaining the findings, while cautioning that the analysis was exploratory.
In the United States, the American Academy of Pediatrics recommends a two-dose series of the nine-valent HPV vaccine beginning between ages 9 and 12. The Swedish study examined the quadrivalent vaccine and does not directly determine the pregnancy effects of other vaccine formulations or schedules.
“Our findings highlight the importance of timely HPV vaccination and suggest that its potential benefits may extend beyond cancer prevention to reproductive health.”
— Jiayao Lei, PhD, and Zhongsong Zhang, Karolinska Institute researchers, speaking to MedPage Today
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Causation and Mechanism Remain Unsettled
Because this was an observational case-control study, differences between vaccinated and unvaccinated women may reflect factors other than vaccination. The authors noted possible residual confounding related to catch-up or opportunistic vaccination, prior HPV exposure, and sexual or reproductive behavior, particularly among women vaccinated at age 17 or older. Matching cases with up to 10 controls helped address confounding but cannot remove every source of bias.
The study did not contain detailed information about cervical treatments. Although the association weakened after adjustment for high-grade lesions, that finding cannot establish whether preventing lesions or avoiding treatment explains some of the observed pattern. The researchers also said they could not fully assess differences in preventive interventions for preterm birth.
It remains unclear whether the reported associations would appear in other populations, with other HPV vaccine formulations, or in studies designed to test causation. The results also do not establish a benefit for outcomes where no significant overall difference was found, including stillbirth and neonatal mortality.
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Further Studies Must Test the Findings
The authors said policy and cost-effectiveness analyses should account for HPV vaccination’s cancer-prevention benefits and consider whether pregnancy complications and related healthcare costs are also affected. Those analyses would need to treat the pregnancy findings as uncertain until stronger evidence is available.
Further research could test whether the associations are repeated in other populations and clarify how vaccination timing, prior HPV exposure, cervical lesions and treatment relate to pregnancy outcomes. For now, the Swedish registry study adds an observed association—not proof of a new vaccine effect—and does not by itself change vaccination recommendations.
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Key Questions
What did the Swedish study find?
Among 624,713 singleton births, women vaccinated against HPV before pregnancy had lower adjusted odds of preterm, very preterm and spontaneous preterm birth than unvaccinated women. The study also reported associations with some other outcomes, including severe small-for-gestational-age birth.
Does the study prove HPV vaccination prevents preterm birth?
No. It was an observational study, so it found associations but cannot show that vaccination caused the lower odds. Other differences between vaccinated and unvaccinated women may have contributed.
Did vaccination before age 17 show different results?
The study found stronger associations for preterm and spontaneous preterm birth among women vaccinated before age 17. It did not establish why the associations differed by age.
Did vaccinated women have lower odds of every pregnancy complication studied?
No. The study reported no significant overall differences for prelabor rupture of membranes, stillbirth or neonatal mortality. Results varied by outcome and, in some analyses, by age at vaccination.
Do these findings change HPV vaccine recommendations?
The study does not by itself change recommendations. Its findings concern the quadrivalent vaccine in a Swedish population and do not prove a pregnancy benefit; vaccination guidance remains based on public health recommendations.
Source: rss
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