Abstract
Overview: Human papillomavirus (HPV) is well known as the leading cause of cervical cancer worldwide. Whether HPV also contributes to other adverse effects such as those associated with pregnancy is unclear. Higher incidences of HPV DNA were previously found in placentas of women presenting with birth complications such as preeclampsia and with placental pathology such as lymphohistiocytic villitis. Little is understood about the function of HPV in the placenta including the types of HPV present, and whether HPV genes capable of altering cell function are expressed such as E6 and E7. This study investigated if HPV 18 was present in placentas associated with preeclampsia and if HPV E6/E7 and E4 were expressed in the placenta. With HPV linked to impaired fertility, the prevalence of HPV in individuals undergoing assisted reproduction in New Zealand was also explored.
Methods: Thirteen placental cases with nine associated with preeclampsia were collected as part of the Otago Placental Study and Hippop study based at Queen Mary Maternity Centre (Dunedin Hospital) and tested for the presence of DNA from five high risk HPV types (16, 18, 31, 33, and/or 51) by in situ hybridisation (ISH). Six cases were tested for HPV 18 DNA specifically by ISH. Gene expression of HPV E6/E7 and E4 was identified using RNA in situ hybridisation (RNAscope®). To test the frequency of HPV in a cohort of men and women undergoing assistant reproduction technologies high vaginal swabs (n=19), endometrium (n=19), and paternal first catch urine (n=17) samples were collected by Fertility Associates, Christchurch and tested for the presence of pan HPV types and HPV 18 using PCR. Sixteen endometrial tissues were tested for the presence of five high risk HPV types (16, 18, 31, 33, and/or 51) by ISH.
Results: Ten placental cases were high risk HPV (16, 18, 31, 33, and/or 51) DNA positive (77%). Three out of six placentas (50%) were HPV 18 DNA positive. Expression of high risk E6/E7 was seen in five placental cases (41.7%) within the decidua basalis and foetal villous trophoblast regions. Human papillomavirus E4 expression was found in two placental cases also positive for E6/E7 expression within the decidua basalis.
Human papillomavirus 18 DNA was detected in 74% of high vaginal swabs, 16% of endometrium, and in no first catch urine samples using endpoint PCR. Endometrial tissue was identified as positive for high risk HPV types (16, 18, 31, 33, and/or 51) in 62.5% of cases.
Conclusion: Human papillomavirus 18 was common in the placenta and the reproductive tract of women undergoing assisted reproduction. Human papillomavirus E6/E7 and E4 were transcribed in the placenta, suggesting active transcription of HPV genes including those that can alter cell function. This data supports future studies aimed at identifying HPV as a causative factor towards adverse pregnancy complications such as preeclampsia and infertility.