Introduction: To determine whether maternal human papillomavirus (HPV) infection is associated with preterm premature rupture of membranes (PPROM). Materials and Methods: We conducted a retrospective cohort study of singleton deliveries at our institution from 2010 to 2015. Women, ages 16-49, with HPV genotyping or cervical cytology results 3 years before delivery were included. Chi-squared and logistic regression analyses were used. Results: In our cohort of 2153 women, 38.5% were HPV positive. PPROM was observed in 2.88% of women. HPV infection (p = 0.02), history of PPROM (p < 0.001), history of cervical conization or loop electrical excision procedure (LEEP) (p < 0.05), parity (p = 0.001), maternal body mass index at delivery (p < 0.001), drug use or smoking (p < 0.001), and ethnicity (p = 0.01) were associated with PPROM. HPV infection (odds ratio [OR] = 2.07, 95% confidence interval [CI]: 1.03-4.14) remained associated with PPROM when adjusting for history of PPROM, cervical conization, drug use or smoking, parity, ethnicity, and insurance. PPROM was associated with preterm delivery (OR = 105.50, 95% CI: 29.49-377.46) when adjusting for HPV infection, pregnancy-related hypertension, diabetes, placenta previa and abruption, cervical conization, smoking or drug use, ethnicity, and history of PPROM. HPV infection was associated with preterm delivery (p = 0.04) in univariate analysis, but not after adjusting for PPROM (p = 0.13). HPV infection had a univariate association with newborn septicemia (p = 0.02), respiratory distress syndrome (RDS) (p = 0.01), neonatal intensive care unit (NICU) admission (p = 0.001), and low birthweight (p = 0.03). Conclusions: HPV infection was associated with an increased risk of PPROM in this cohort. However, maternal HPV infection does not increase the risk of preterm delivery beyond those caused by PPROM. The observed association between maternal HPV infection and neonatal morbidity is likely due to the relationship between PPROM and preterm delivery.

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