HPV Infections During Pregnancy Associated with Greater Risk of Preterm Birth

Persistence of certain strains of human papillomavirus (HPV) infection during pregnancy was associated with a greater risk of preterm birth, underscoring the importance of vaccination, according to a new study.

The HERITAGE study, published in JAMA Network Open, included 899 pregnant women at three academic hospitals in Canada between November 2010 and October 2016.

“Our study showed a strong association between the persistence of HPV 16-18 during pregnancy and preterm birth,” Helen Trottier, PhD, MSc, assistant professor at the University of Montreal, told Contagion. “Considering that preterm births remain a major cause of perinatal mortality and morbidity, the association that we found is worrisome. We may have just found an explanation for an important part of idiopatic preterm births. If the association is indeed causal, we can expect a significant reduction in preterm birth with HPV mass vaccination against HPV-16/18.”

Among the women with singleton pregnancies included in the study, 378 (42.0%) had HPV DNA detected in vaginal samples collected during the first trimester of pregnancy, and 258 (68.3%) of those also had positive HPV test results in the third trimester. The virus was detected in 11.1% of placentas at birth.

Overall, 55 participants had preterm birth at a median gestational age of 36 weeks, including 38 spontaneous and 17 medically indicated.

Persistent HPV-16/18 infection between the first and third trimester was significantly associated with overall preterm birth (adjusted odds ratio, 3.72; 95% confidence interval, 1.47-9.39) andspontaneous preterm birth (aOR, 3.32; 95% CI, 1.13-9.80).

“No study has shown such an association before,” Trottier said. “We were surprised to see this strong association between preterm birth and persistence of HPV-16 and 18.”

The study controlled for other risk factors for preterm birth, such as young age, tobacco smoking and other genital infection.

Average age of study participants was 31.3 years, most were White (72.3%), had a university education, and did not smoke (90.1%) or drink alcohol (64%). Only 9.3% had received the HPV vaccine and 7.1% had a history of treatment for cervical intraepithelial neoplasia. None of the participants tested positive for Chlamydia trachomatis or Neisseria gonorrhoea in the first trimester.

“It should be remembered that there is no treatment available to eliminate the HPV infection,” Trottier said. “Only the immune system can overcome an HPV infection that is present. The vaccine will be able to prevent infection, but it cannot cure us if we have been infected. It is therefore important to be vaccinated before sexual debut in order to protect ourselves. This study therefore further strengthens the benefits of HPV vaccination.”

More research is needed to understand why the persistent HPV infection was associated with preterm birth. The study authors speculated that overall changes in the vaginal microbiota could be a factor.

Risk of preterm birth was specific to HPV-16/18 and greatest when the infection persisted between the first and third trimesters. The detection of any type of vaginal HPV DNA in the first trimester alone wasn’t associated with an increased risk of preterm birth.

“It is important to continue research on the effects of HPV in pregnancy and on the possible consequences of perinatal HPV transmission in children,” Trottier said. “We’re continuing our research to determine the impact of HPV on other pregnancy outcome and to determine the frequency and short- and long-term consequences of mother-to-child transmission of the virus.”

HPV is the most common sexually transmitted infection in the United States and is associated with anal, cervical, vaginal, vulvar and penile cancers.

A recent study aimed to understand HPV vaccine hesitancy and found that hesitancy increased from 5.3% in 2008 to 26.2% in 2019.

Some concerns arose from anecdotal links between the vaccine and certain autonomic syndromes, such as chronic fatigue syndrome, but a recent study found no such association.