Severien Van Keer assistant professor - senior researcher

Research Severien Van Keer

Research team

Expertise

Severien Van Keer graduated in 2014 as Master in Biomedical Sciences, major 'Infectious and Tropical Diseases' and minor 'Molecular and Cellular Biomedical Sciences'. Since July 2014, she has been working at the Centre for the Evaluation of Vaccination (CEV – VAXINFECTIO). In May 2019, she successfully defended her PhD thesis entitled ‘First-void urine as a biomarker source for primary and secondary cervical cancer prevention’ (FWO Ph.D fellowship 2015-2019). This thesis was established under supervision of Prof. Pierre Van Damme, Dr. Alex Vorsters, Prof. Xaveer Van Ostade, Prof. Wiebren Tjalma, and Prof. Margareta Ieven. To date, Severien is continuing her work as FWO junior postdoctoral researcher at the University of Antwerp. This UROSCREEN (a home-based first-void Urine One-step triage option for cervical cancer SCREENing) project focuses on translational research to demonstrate the clinical accuracy of Human Papillomavirus (HPV) testing in first-void urine with host cell methylation marker triage.

Reaching more women in cervical cancer screening with a better prediction of their cancer risk. 01/01/2023 - 31/12/2024

Abstract

Cervical cancer is a major impact on public health, causing approximately 150 deaths in Belgium each year. Despite that there is a screening program in Flanders, 37% of the population eligible for cervical cancer screening is not reached by the current program that is based on analysing cervical smears (pap smears). Here, self-sampling, potentially done at home, could pose an alternative strategy for this hard-to-reach population. Infection with the human papillomavirus (HPV) is the cause of nearly all cervical cancer cases. Consequently, HPV detection is currently implemented as screening test. In case HPV is detected, an additional test (triage) is necessary to avoid overtreatment as the majority of HPV infections are spontaneously cleared and do not result in cervical cancer. For this triage the presence of aberrant cells in the pap smear is assessed. HPV detection performs well on self-samples, however, triage by detecting aberrant cells is not possible in this sample type. We will develop a test in which the detection of HPV and triage can be performed in one step on self-samples (as well as traditional cervical samples). As such we hope to reach more women and disturb less. Indeed, fewer women will need to be referred for follow-up causing less (emotional) distress. Thus, in this project we aim to reach more women in cervical cancer screening and give them a better prediction of their cancer risk.

Researcher(s)

Research team(s)

Project type(s)

  • Research Project

Developing a combined screening and molecular triage approach for cervical cancer based on HPV detection, quantification, genotyping and DNA methylation in self-samples. 01/11/2022 - 31/10/2026

Abstract

37% of the population eligible for cervical cancer screening in Flanders is not reached by the current program. Here, self-sampling could pose an alternative strategy for this hard-to-reach population. Persistent infection with the human papillomavirus (HPV) is the cause of nearly all cervical cancer cases. Consequently, HPV DNA detection is considered the superior screening test to date due to its increased sensitivity as compared to cytology. However, it is associated with a lower clinical specificity as the majority of HPV infections are spontaneously cleared and do not result in clinically relevant disease. Thereby an additional triage step is necessary to prevent over-referral and potentially overtreatment which can be done by cytology. HPV DNA-based screening can already be performed on self-samples, however, this is not the case for cytology. By developing a fully molecular, combined screen and triage approach (one-step) based on HPV DNA detection, quantification, genotyping, and DNA methylation and that can be applied on self-samples (as well as cervical samples), we will provide a solution for the current screen and triage challenges. This will avoid over referral and allow better guided management of women needing treatment, while simultaneously increasing the participation rate. As such, the morbidity and mortality of cervical cancer could be reduced and both the health of the patients as well as the costs for the healthcare system would be positively affected.

Researcher(s)

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  • Research Project

Cervical cancer screening based on first-void urine self-sampling to reach screening non-responders: ScreenUrSelf trial. 01/10/2021 - 30/09/2025

Abstract

The goal of the ScreenUrSelf trial is to increase cervical cancer screening attendance and compliance to follow-up by offering a first-void urine self-sampling alternative to women who are currently not participating in the organized screening program (non-responders). Offering a cost-effective, fully molecular (primary high-risk Human Papillomavirus (hrHPV) testing, and if positive methylation marker triage) first-void urine self-test with high preference and compliance to follow-up has the potential to increase screening coverage among non-responders whilst reducing cervical cancer related morbidity and mortality. If embedded in the organized cervical cancer screening program, this could positively impact both the patient's health as well as reduce costs for the Flemish healthcare system. Thus, the primary scientific goal of this project is to evaluate the (cost-)effectiveness of four different self-sampling strategies (first-void urine vs vaginal self-sampling, via an opt-in or opt-out strategy) to women who do not participate in the Flemish organized cervical screening program, compared to the standard recall letter and no intervention. Secondly, a novel follow-up "reflex" test will be evaluated in self-samples that tested positive for hrHPV.

Researcher(s)

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Project type(s)

  • Research Project

Evaluating the predictive value of a primary high-risk HPV DNA and reflex methylation marker test strategy in first-void urine to identify women with clinically relevant cervical disease in need of referral. 01/04/2022 - 31/03/2023

Abstract

Cervical cancer remains a significant problem worldwide, in Belgium, yearly over 200 women die from this disease. Almost all cervical cancer cases are caused by an infection with high-risk (hr) types of the Human Papillomavirus (HPV). Traditional screening programs based on cervical smear taking (Pap smear) detecting abnormal cells face limitations – including suboptimal cervical cancer screening coverage (approximately 65% in Flanders), urging the need for alternative screening approaches. Detection of primary hrHPV DNA in combination with more specific biomarkers such as methylation of host cell genes offer the opportunity to be detected in self-collected samples, like first-void urine. Within this project, we aim to provide data on the predictive value of primary hrHPV DNA and reflex methylation marker testing in first-void urine to identify cervical cancer precursor lesions that have a high short-term progression risk to cancer. Offering a fully molecular screen and triage strategy applicable on non-invasive, easily to collect first-void urine samples has the potential to increase screening participation among women currently not reached by the organized screening programs for cervical cancer.

Researcher(s)

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Project type(s)

  • Research Project

UROSCREEN: a home-based first-void URine One-step triage option for cervical cancer SCREENing. 01/10/2019 - 30/09/2023

Abstract

Cervical cancer remains a significant problem worldwide, in Belgium, yearly over 200 women die from this disease. Almost all cervical cancer cases are caused by an infection with high risk (HR) types of the Human Papillomavirus (HPV). Traditional screening programs based on cervical smear taking (pap smear) detecting abnormal cells face numerous limitations, urging the need for alternative screening approaches. Detection of highly sensitive HR-HPV DNA in combination with more specific biomarkers such as methylation of host cell genes offer the opportunity to be detected in self-collected samples, like first-void urine. Therefore, we aim to demonstrate the clinical accuracy of HPV testing in first-void urine (WP2), in combination with triage markers (WP3). Followed by a population based pilot study to evaluate the performance of this novel screen and triage algorithm compared to self- and clinician-collected samples (WP4). And hereto offer a highly-accepted screening solution to women, especially benefitting hard-to-reach populations. And by means of this, decreasing the burden of cervical cancer associated disease and mortality.

Researcher(s)

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Project type(s)

  • Research Project

Biomarkers in first-void urine for improved diagnosis and monitoring of cervical (pre)cancer. 01/10/2017 - 30/09/2019

Abstract

Cervical cancer remains a significant problem worldwide, in Belgium, yearly over 200 women die from this disease. Almost all cervical cancer cases are caused by an infection with high-risk (hr) types of the Human Papillomavirus (HPV). Traditional screening programs based on cervical smear taking (pap smear) detecting abnormal cells face numerous limitations, urging the need for alternative screening approaches. Detection of hrHPV DNA instead of abnormal cervical cells has proven more sensitive in detecting cervical cancer cases, however, it lacks clinical specificity, i.e. the ability to detect solely those women who require follow-up or immediate referral for colposcopy. Therefore, the major objective of this study is to analyse candidate biomarkers for diagnosis of cervical (pre)cancer and disease monitoring in home-collected first-void (FV) urine samples, followed by translation of the presence of (1) hrHPV DNA and (2) these biomarkers into a novel screening algorithm for cervical cancer. Hereto, we will conduct two clinical trial studies, where women (=30 years) diagnosed with an abnormal pap smear will be asked to provide a FV morning urine sample. In the first study, we aim to identify accurate biomarkers for respectively low-, and high-grade squamous intraepithelial lesions. In a second study, multiple samples will be collected over time (longitudinal sample collection) to identify biomarkers that can predict pro- or regression of HPV infection/precancerous lesions.

Researcher(s)

Research team(s)

Project type(s)

  • Research Project

Biomarkers in first-void urine for improved diagnosis and monitoring of cervical (pre)cancer. 01/10/2015 - 30/09/2017

Abstract

Cervical cancer remains a significant problem worldwide, in Belgium, yearly over 200 women die from this disease. Almost all cervical cancer cases are caused by an infection with high-risk (hr) types of the Human Papillomavirus (HPV). Traditional screening programs based on cervical smear taking (pap smear) detecting abnormal cells face numerous limitations, urging the need for alternative screening approaches. Detection of hrHPV DNA instead of abnormal cervical cells has proven more sensitive in detecting cervical cancer cases, however, it lacks clinical specificity, i.e. the ability to detect solely those women who require follow-up or immediate referral for colposcopy. Therefore, the major objective of this study is to analyse candidate biomarkers for diagnosis of cervical (pre)cancer and disease monitoring in home-collected first-void (FV) urine samples, followed by translation of the presence of (1) hrHPV DNA and (2) these biomarkers into a novel screening algorithm for cervical cancer. Hereto, we will conduct two clinical trial studies, where women (=30 years) diagnosed with an abnormal pap smear will be asked to provide a FV morning urine sample. In the first study, we aim to identify accurate biomarkers for respectively low-, and high-grade squamous intraepithelial lesions. In a second study, multiple samples will be collected over time (longitudinal sample collection) to identify biomarkers that can predict pro- or regression of HPV infection/precancerous lesions.

Researcher(s)

Research team(s)

    Project type(s)

    • Research Project