Study Finds Lower Pregnancy Risks in HPV-Vaccinated Women

Women vaccinated against human papillomavirus (HPV) were significantly less likely to have a range of adverse outcomes during pregnancy, according to a national case-control study from Sweden.

Among nearly 625,000 births from 2006 to 2023, women who had received a quadrivalent HPV shot had significantly lower odds of preterm birth (adjusted odds ratio [aOR] 0.95, 95% CI 0.91-0.99), very preterm birth (aOR 0.85, 95% CI 0.75-0.97), and spontaneous preterm birth (aOR 0.95, 95% CI 0.91-0.99) compared with those who were unvaccinated, reported Jiayao Lei, PhD, of Karolinska Institute in Stockholm, and colleagues in The BMJ.

Links were stronger when HPV vaccination happened before age 17 for both preterm birth (aOR 0.90, 95% CI 0.85-0.95) and spontaneous preterm birth (aOR 0.89, 95% CI 0.84-0.95) compared with those who were unvaccinated.

“Our findings highlight the importance of timely HPV vaccination and suggest that its potential benefits may extend beyond cancer prevention to reproductive health,” Lei and co-author Zhongsong Zhang, a PhD student at Karolinska Institute, told MedPage Today. “Although the observed differences were relatively modest at the individual level, they could translate into meaningful public health and economic benefits at the population level.”

Given the results, policy and cost-effectiveness analyses should include HPV vaccination’s cancer prevention benefits and reductions in pregnancy-related complications and resulting lifelong healthcare costs, they noted.

The potential pregnancy advantages linked to earlier HPV vaccination may show that the shots deliver greater benefits when they’re given before sexual debut and potential HPV exposure, Lei and Zhang noted. “Vaccination at an earlier age may also allow women to benefit from this protection for a longer period before entering their reproductive years,” they said.

The reasons why HPV and pregnancy outcomes may be linked aren’t entirely certain, though Lei and Zhang highlighted two potential explanations.

HPV may interfere with embryonic development, which could lead to placental problems and greater preterm birth risk, they explained. Maternal vaccination could also reduce the risk of embryonic HPV exposure and consequent pregnancy complications.

Research has also linked treatment for HPV-related high-grade cervical lesions with greater risks of preterm birth and other adverse pregnancy outcomes. In the current study population, 0.6% of vaccinated women and 3.7% of unvaccinated women had a diagnosis of high-grade cervical lesion before they gave birth. When the researchers adjusted for high-grade lesions before childbirth, the associations between HPV vaccination and preterm birth-related outcomes weakened.

“This pattern is consistent with the possibility that preventing high-grade cervical lesions and subsequent cervical treatments may partly explain the observed associations,” Lei and Zhang explained. But the study didn’t have detailed information on study participants’ cervical treatment, they cautioned, which means “the analysis should be interpreted as exploratory rather than definitive evidence of an underlying mechanism.”

In the U.S., a two-dose series of the nine-valent HPV vaccine (Gardasil 9) is recommended by the American Academy of Pediatrics starting between the ages of 9 and 12 years, though recent research has suggested a single shot may offer similar levels of protection.

The study included 624,713 singleton births in Sweden among nulliparous women age 16 to 35 years, with data drawn from nationwide registers. Among eligible births, 14.8% of women had quadrivalent HPV vaccination before pregnancy. The researchers excluded births from women whose first HPV vaccination was bivalent or nonavalent. To help counter confounding, the researchers matched each adverse pregnancy outcome case with up to 10 controls without the same adverse outcomes.

Vaccinated women were significantly less likely to have preterm prelabor rupture of membranes (preterm PROM; aOR 0.93, 95% CI 0.87-1.00) or severe small for gestational age infant (aOR 0.92, 95% CI 0.87-0.97), while no significant differences were observed when it came to PROM, stillbirth, or neonatal mortality.

Women who got a shot prior to age 17 were significantly less likely to have preterm PROM (aOR 0.86, 95% CI 0.78-0.94) and severe small for gestational age infants (aOR 0.91, 95% CI 0.84-0.97) compared with the unvaccinated while those vaccinated at age 17 or older had lower odds of severe small for gestational age infants (aOR 0.93, 95% CI 0.87-0.99) and stillbirth (aOR 0.79, 95% CI 0.63-0.99).

Study limitations included potential residual confounding from catch-up or opportunistic vaccination, prior HPV exposure, or sexual or reproductive behavior, particularly in women 17 and older. Differences in preventive interventions for preterm birth couldn’t be fully assessed.