Persistent human papillomavirus infection during pregnancy significantly associated with preterm birth

1. Persistent human papillomavirus-16/18 infection during pregnancy and placental human papillomavirus infection significantly increased the risk of preterm birth compared to infections by other HPV genotypes and separately from a history of cervical dysplasia treatment.

2. The results would support an essential role for community human papillomavirus vaccination programs to help reduce the burden of preterm births.

Evidence Rating Level: 2 (Good)

Study Rundown: Infections of the genital tract can alter protective mechanisms in the cervical epithelium and have been implicated as a possible cause and risk factor associated with preterm birth, although the definitive underlying etiology remains unknown. This prospective cohort study sought to evaluate whether vaginal human papillomavirus (HPV) infections during pregnancy and placental HPV during delivery were independently associated with preterm birth. The main endpoint of the analysis was preterm birth (defined as a live birth or stillbirth between 20-36 weeks of gestation). Logistic regression was used to measure the association between HPV DNA detection and preterm birth and odds ratios (ORs) and 95%CIs were adjusted by inverse probability of treatment weights of the propensity score. Among 899 pregnant women, persistent HPV-16/18 infection during pregnancy was significantly associated with preterm birth. These findings highlighted that persistent HPV-16/18 infection during pregnancy and placental HPV infection significantly increase the risk of preterm birth compared to infections by other HPV genotypes and separately from a history of cervical dysplasia treatment. If confirmed in larger and more diverse study cohorts, the results would support an essential role for community HPV vaccination programs to help reduce the burden of preterm births. A limitation of this study was that the cohort demographics for the HERITAGE study had several characteristics classified as low-risk for preterm birth and thus, not translatable to higher-risk populations.

Click to read the study in JAMA Network Open

Relevant Reading: Association between maternal human papillomavirus infection and adverse pregnancy outcomes: systematic review and meta-analysis

In-Depth [prospective cohort]: This multicenter, prospective HERITAGE cohort study included 899 women (mean [SD] age, 31.3 [4.6] years [range, 19-47 years]) with singleton pregnancies from 3 academic hospitals in Montreal, Québec, Canada, between November 2010 and October 2016. Follow-up was completed through June 2017, with statistical analysis completed in January 2021. The main exposure was defined as HPV DNA detection in vaginal samples collected during the first and third trimesters of pregnancy and placental HPV infection. In total, 378 women (42.0%) had vaginal HPV DNA detected during the first trimester, where it was also detected in 91 of 819 placentas (11.1%) at delivery. Fifty-five participants experienced preterm birth (38 spontaneous and 17 medically indicated). The study found that persistent HPV-16/18 detected on vaginal samples was significantly associated with all preterm births (adjusted OR [aOR], 3.72; 95%CI, 1.47-9.39) and spontaneous preterm births (aOR, 3.32; 95%CI, 1.13-9.80). Furthermore, placental HPV infection was significantly associated with all preterm births (aOR, 2.53; 95%CI, 1.06-6.03) and spontaneous preterm births (aOR, 2.92; 95%CI, 1.09-7.81). To limit confounding factors, results remained similar after including only participants without a history of cervical intraepithelial neoplasia treatment.

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