The HiPPiE study- Human Papilloma virus in Pregnancy

The HiPPiE-study- Human Papillomavirus (HPV) in PregnancyHPV infection is one of the most common infections of the genital tract in women’s reproductive years. The HiPPiE study addresses the possible role of HPV infection during pregnancy, determined by HPV detection and genotyping in pregnant women at week 18 of gestation (urine) and at birth (urine/placenta), on adverse pregnancy and neonatal outcomes.About 40 HPV types have been found to infect the mucosa of the genital tract. The peak prevalence of infection is seen in women younger than 25 years of age. Most infections regress spontaneously, but long-lasting persistent infection with 12 HPV types, classified as high-risk (HR) types, is associated with the development of precancerous and cancerous lesions in the cervix. The mechanism for HPV persistence involves impairment of immunological processes in infected epithelium. We hypothesize that HR-HPV may lead to placental dysfunction in pregnant women and cause adverse pregnancy and neonatal outcomes. The participants included in The HiPPiE study were recruited from the large multi-center population based prospective cohort PrenventADALL (Preventing Atopic dermatitis and ALLergies) study in Norway and Sweden, from Oslo University Hospital, Østfold Hospital Trust and Karolinska Institute. Recruitment of pregnant women in PreventADALL at week 18 of gestation started in December 2014 and ended in October 2016. Urine samples for HPV detection were collected at two time points (mid-gestation and delivery) from 757 pregnant women. Placenta samples were taken for about two third of the women as well and consist of swabs from both sides of the placenta, and 3 punch biopsies. Birth data (gestational age at delivery, mode of delivery, newborn weight/height and health) and data from pregnancy (blood pressure, diseases of pregnancy and treatments given during pregnancy) were registered, and all data were curated in 2019. HPV detection on nucleic acid eluates from urine and placenta samples was performed, using a commercial kit that detects, genotypes, and partly quantifies 28 genital HPV types, An in-house protocol was used for genotyping from placentas samples. HPV (any of the 28 types detected in the assay) was detected in 38% and 28% of the study cohort at mid-gestation and delivery respectively. The corresponding prevalence for HR-HPV was of 24% and 16% respectively, Type-specific HPV persistence from mid-gestation to delivery was of 52%, for both the overall HPV 28 types group, and the HR-HPV. A short pre-conception relationship with the child’s father and alcohol intake during pregnancy were associated with higher HPV prevalence. This study was published in 2021 (Int J Infect Dis 2021 Jul;108:574-581. doi: 10.1016/j.ijid.2021.05.064). In a second study that is about to be sent for peer review, the association between human papillomavirus infections detected in urine samples and adverse pregnancy outcomes was investigated. In the general pregnant population in PreventADALL with an overall low prevalence of adverse outcomes, there was no evidence for an association of HPV infection at mid-gestation, persisting infection or multiple HPV infections and adverse outcomes. The third study of the PhD student will describe the prevalence of HPV in placenta, investigate association with risk factors, and adverse pregnancy outcomes. All HPV genotype analyses have been performed, and the statistical work is ongoing. The PhD student has completed all the courses and PhD educational part and has started to write her thesis. The PhD student applied UiO for an extension of her PhD period due to delay in progression related to the pandemic situation in 2020-2021, that was granted until 27.08.2025. The PhD student is now working full-time on her research project until July 2023, and submission of her thesis in scheduled for June/July 2023.

The HiPPiE-study- Human Papillomavirus (HPV) in PregnancyHPV infection is one of the most common infections of the genital tract in women’s reproductive years. The HiPPiE study addresses the possible role of HPV infection during pregnancy, determined by HPV detection and genotyping in pregnant women at week 18 of gestation (urine) and at birth (urine/placenta), on adverse pregnancy and neonatal outcomes.About 40 HPV types have been found to infect the mucosa of the genital tract. The lifetime risk for HPV infection is estimated to 70% with a peak prevalence of the infection seen in women younger than 25 years of age. Most infections regress spontaneously, but long-lasting persistent infection with 12 HPV types, classified as high-risk (HR) types, is associated with the development of precancerous and cancerous lesions in the cervix. The mechanism for HPV persistence involves impairment of immunological processes in infected epithelium. We hypothesize that HR-HPV may lead to placental dysfunction in pregnant women and cause adverse pregnancy and neonatal outcomes. The HiPPiE study is a multi-center population based prospective cohort study. The participants included in The HiPPiE study were recruited from the large PrenventADALL (Preventing Atopic dermatitis and ALLergies) study in Norway and Sweden, from Oslo University Hospital, Østfold Hospital Trust and Karolinska Institute. Recruitment of pregnant women in PreventADALL at week 18 of gestation started in December 2014 and ended in October 2016. The last baby was born in April 2017. Urine samples for HPV detection were collected at two time points (week 18 of gestation and at birth) from 757 pregnant women, approximately equally distributed from each of the three recruiting hospitals. Placenta samples were taken from about two third of the women as well, and consist of swabs from both sides of the placenta, and 3 punch biopsies. Birth data, including gestational age at delivery, mode of delivery, newborn weight/height and health, have been registered. Data from pregnancy, including, blood pressure, diseases of pregnancy and treatments given during pregnancy, were registered in 2018/2019, and pregnancy and birth data were curated in 2019 for the whole PreventADALL cohort. HPV detection on nucleic acid eluates from urine samples was performed, using a commercial kit that detects, genotypes, and partly quantifies 28 genital HPV types. HPV (any of the 28 types detected in the assay) was detected in 38% and 28% of the study cohort at mid-gestation and delivery respectively. The corresponding prevalence for HR-HPV was of 24% and 16% respectively, the most prevalent type being HPV16 (6% and 4% at mid-gestation and delivery respectively). Type-specific HPV persistence from mid-gestation to delivery was of 52%, when considering both the overall HPV 28 types group, and the HR-HPV. A short pre-conception relationship with the child’s father and alcohol intake during pregnancy were associated with higher HPV prevalence. This study was published in 2021 (Int J Infect Dis 2021 Jul;108:574-581. doi: 10.1016/j.ijid.2021.05.064. The PhD student has completed all the courses and educational part of her PhD, and is now finalizing the analyses of the relation of prevalence and persistence of HPV in pregnancy with pregnancy and birth outcomes. The third work of the PhD thesis will address the relation between HPV prevalence at mid-gestation and biomarkers of placental function. Due to COVID-19 pandemics with closed schools and day care centers during 2020, as well as numerous quarantine periods in 2021, the PhD student has been delayed a few months in her project.

The HiPPiE-study- Human Papillomavirus (HPV) in PregnancyHPV infection is one of the most common infections of the genital tract in women’s reproductive years. The HiPPiE study addresses the possible role of HPV infection during pregnancy, determined by HPV detection and genotyping in pregnant women at week 18 of gestation (urine) and at birth (urine/placenta), on adverse pregnancy and neonatal outcomes.About 40 HPV types have been found to infect the mucosa of the genital tract. The lifetime risk for HPV infection is estimated to 70% with a peak prevalence of the infection seen in women younger than 25 years of age. Most infections regress spontaneously, but long-lasting persistent infection with 12-15 HPV types, classified as high-risk (HR) types, is associated with the development of precancerous and cancerous lesions in the cervix. The mechanism for HPV persistence involves impairment of immunological processes in infected epithelium. We hypothesize that HR-HPV may lead to placental dysfunction in pregnant women and cause adverse pregnancy and neonatal outcomes. The HiPPiE study is a multi-center population based prospective cohort study. The participants included in The HiPPiE study were recruited from the large PrenventADALL (Preventing Atopic dermatitis and ALLergies) study in Norway and Sweden, from Oslo University Hospital, Østfold Hospital Trust and Karolinska Institute. Recruitment of pregnant women in PreventADALL at week 18 of gestation started in December 2014 and ended in October 2016. The last baby was born in April 2017. Urine samples for HPV detection were collected at two time points (week 18 of gestation and at birth) from 757 pregnant women, approximately equally distributed from each of the three recruiting hospitals. Placenta samples were taken for about two third of the women as well, and consist of swabs from both sides of the placenta, and of 3 punch biopsies. Birth data, including gestational age at delivery, mode of delivery, newborn weight/height and health, have been registered. Data from pregnancy, including, blood pressure, diseases of pregnancy and treatments given during pregnancy, were registered in 2018/2019, and pregnancy and birth data were curated in 2019 for the whole PreventADALL cohort. DNA extraction from urine samples and HPV analyses, using a commercial kit that detects, genotypes, and partly quantifies 28 genital HPV types, are complete. Our results show a relatively high prevalence of HPV from urine samples in pregnant women, both at week 18 and, to a lesser extent, at birth. Several factors have been identified, that are related to HPV prevalence and persistence in pregnancy, and the PhD candidate has been working with finalizing the first manuscript, that is about to be sent for publication. The PhD student has also been involved in completing the curation of all pregnancy and birth data relevant for the next part of the study, addressing the relation of prevalence and persistence of HPV in pregnancy with pregnancy and birth outcomes. The PhD student has worked with a Statistical Analysis Plan for this part of the study. The PhD student completed the half-way evaluation mid-April 2020. Due to COVID-19 pandemics, and cancellation of all planned HPV conferences, there were no opportunities for the PhD student to present data internationally in 2020. In addition to the above mentioned, due to closed schools and day care centers during 2020, the PhD student has been delayed in her project.

The HiPPiE-study- Human Papillomavirus (HPV) in PregnancyHPV infection is one of the most common infections of the genital tract in women’s reproductive years. The HiPPiE study addresses the possible role of HPV infection during pregnancy, determined by HPV detection and genotyping in pregnant women at week 18 of gestation and at delivery on adverse pregnancy and neonatal outcomes.About 40 HPV types have been found to infect the mucosa of the genital tract. The lifetime risk for HPV infection is estimated to 70% with a peak prevalence of the infection seen in women younger than 25 years of age. Most infections regress spontaneously, but long lasting persistent infection with 12-15 HPV types, classified as high-risk (HR) types, is associated with the development of precancerous and cancerous lesions of the cervix. The mechanism for HPV persistence involves impairment of immunological processes in infected epithelium. We hypothesize that HR-HPV may lead to placental dysfunction in pregnant women and cause adverse pregnancy and neonatal outcomes. The HiPPiE study is a multi-center population based prospective cohort study. The participants included in The HiPPiE study were recruited from the large PrenventADALL (Preventing Atopic Dermatitis and ALLergies) study in Norway and Sweden, from Oslo University Hospital, Østfold Hospital Trust and Karolinska Institute. Recruitment of pregnant women in PreventADALL at week 18 of gestation started in December 2014 and ended in October 2016. The last baby was born in April 2017. Urine samples for HPV detection were collected at two time points (week 18 of gestation and at delivery) from 757 pregnant women, approximately equally distributed from each of the three recruiting hospitals. Placenta samples were taken for about two third of the women as well, and consist of swabs from both sides of the placenta, and of 3 punch biopsies. Birth data, including gestational age at delivery, mode of delivery, newborn weight/height and health, have been registered. Data from pregnancy, including, blood pressure, diseases of pregnancy and treatments given during pregnancy, were registered in 2018/2019, and pregnancy and birth data were curated in 2019 for the whole PreventADALL cohort. DNA extraction from urine samples and HPV analyses, using a commercial kit that detects, genotypes, and partly quantifies 28 genital HPV types, are complete. Our results show a relatively high prevalence of HPV from urine samples in pregnant women, both at week 18 and, to a lesser extent, at delivery. Type-specific persistence from week 18 to birth is related to high-risk types and high viral loads at week 18. The PhD candidate has been involved in curating pregnancy and birth data in 2019, has performed statistical analyses on prevalence and persistence for HPV in pregnant women and associated factors, and has drafted the first paper for publication. Results have been presented at the Eurogin (European Research Organisation on Genital Infection and Neoplasia) 2019-conference as well as the yearly conference for the Norwegian Society of Gynecology and Obstetrics.

The HiPPiE-study- Human Papillomavirus (HPV) in PregnancyHPV infection is one of the most common infections of the genital tract in women’s reproductive years. The HiPPiE study addresses the possible role of HPV infection during pregnancy, determined by HPV detection and genotyping in pregnant women at week 18 of gestation (urine) and at birth (urine/placenta), on adverse pregnancy and neonatal outcomes.About 40 HPV types have been found to infect the mucosa of the genital tract. The lifetime risk for HPV infection is estimated to 70% with a peak prevalence of the infection seen in women younger than 25 years of age. Most infections regress spontaneously, but long lasting persistent infection with 12-15 HPV types, classified as high-risk (HR) types, is associated with the development of precancerous and cancerous lesions in the cervix. The mechanism for HPV persistence involves impairment of immunological processes in infected epithelium. We hypothesize that HR-HPV may lead to placental dysfunction in pregnant women and cause adverse pregnancy and neonatal outcomes. The HiPPiE study is a multi-center population based prospective cohort study. The participants included in The HiPPiE study were recruited from the large PrenventADALL (Preventing Atopic dermatitis and ALLergies) study in Norway and Sweden, from Oslo University Hospital, Østfold Hospital Trust and Karolinska Institute. Recruitment of pregnant women in PreventADALL at week 18 of gestation started in December 2014 and ended in October 2016. The last baby was born in April 2017. Urine samples for HPV detection have been collected at two time points (week 18 of gestation and at birth) from about 750 pregnant women, approximately equally distributed from each of the three recruiting hospitals. Placenta samples have been taken for about two third of the women as well, and consist of swabs from both sides of the placenta, and of 3 punch biopsies. Birth data, including gestational age at delivery, mode of delivery, newborn weight/height and health, have been registered. Data from pregnancy, including blood pressure, diseases of pregnancy and treatments given during pregnancy, were registered in 2018, and this work is still ongoing, DNA extraction from urine samples and HPV analyses, using a commercial kit that detects, genotypes, and partly quantifies 28 genital HPV types, are complete. Preliminary data show a relatively high prevalence of HPV from urine samples in pregnant women, both at week 18 and at birth. DNA extraction protocols have been established for placenta samples for further HPV testing. Currently, the PhD candidate is compiling dataset of variables and has started on her first paper with analyses on prevalence and persistence of HPV infection in pregnant women.

The HiPPiE-study- Human Papillomavirus (HPV) in PregnancyHPV infection is one of the most common infections of the genital tract in women’s reproductive years. We address in the HiPPiE study the possible role of HPV infection during pregnancy, determined by HPV detection and genotyping from urine samples of pregnant women at week 18 of gestation and at birth, on adverse pregnancy and neonatal outcomes.About 40 HPV types have been found to infect the mucosa of the genital tract. The lifetime risk for HPV infection is estimated to 70% with a peak prevalence of the infection seen in women younger than 25 years of age. Most infections regress spontaneously, but long lasting persistent infection with 12-15 HPV types, classified as high-risk (HR) types, is associated with the development of precancerous and cancerous lesions in the cervix. The mechanism for HPV persistence involves impairment of immunological processes in infected epithelium. We hypothesize that HR-HPV may lead to placental dysfunction in pregnant women and cause adverse pregnancy and neonatal outcomes. The HiPPiE study is a multi-center population based prospective cohort study. The participants included in The HiPPiE study are recruited from the large PrenventADALL (Preventing Atopic dermatitis and ALLergies) study in Norway and Sweden, from Oslo University Hospital, Østfold Hospital Trust and Karolinska Institute. Recruitment of pregnant women in PreventADALL at week 18 of gestation started in December 2014 and ended in October 2016. The last baby was born in April 2017. Urine samples for HPV detection have been collected at two time points (both at week 18 of gestation and at birth) from more than 800 pregnant women, approximately equally distributed from each of the three recruiting hospitals. Placenta samples have been taken for about two third of the women as well, and consist of swabs from both sides of the placenta, and from 3 punch biopsies. Data from pregnancy and birth data have been registered, including gestastional age at delivery, mode of delivery, newborn health and weight. An application to the Regional Committees for Medical and Health Research Ethics (REK) in this substudy, in addition to the main PreventADALL REK approval, was required, sought for and approved in 2017. DNA extraction from urine samples and HPV analyses, using a commercial kit that detects, genotypes, and partly quantifies 28 genital HPV types, are in progress. Preliminary data show a relatively high prevalence of HPV from urine samples in pregnant women. Currently, the PhD candidate is compiling dataset of variables.