Placental infection with human papillomavirus is associated with spontaneous preterm delivery

BACKGROUND: We sought to determine if human papillomavirus (HPV) infection of extravillous trophoblast cells reduces cell invasion and if placental infection is associated with adverse reproductive outcomes attributed to placental dysfunction. METHODS: We conducted apoptosis and invasion assays using extravillous trophoblast (HTR-8/SVneo) cells that were transfected with a plasmid (pAT-HPV-16) containing the entire HPV-16 genome. In order to associate HPV infection with reproductive outcomes, we conducted a case-control study to detect HPV DNA in the extravillous trophoblast region of placentas from cases of spontaneous preterm delivery, severe pre-eclampsia requiring delivery at < 37 weeks and controls who delivered at term. RESULTS: Rates of apoptosis were 3- to 6-fold greater in transfected cells than in non-transfected cells or cells transfected with an empty plasmid. Invasion of transfected cells through extracellular matrices was 25-58% lower than that of the controls. HPV was detected more frequently in placentas from spontaneous preterm deliveries than in placentas from controls (P = 0.03). Identification of HPV in placentas from cases of pre-eclampsia was not significantly different to controls. CONCLUSIONS: HPV infection of extravillous trophoblast induces cell death and may reduce placental invasion into the uterine wall. Thus, HPV infection may cause placental dysfunction and is associated with adverse pregnancy outcomes, including spontaneous preterm delivery.