Article • Prediction for breast, ovarian, cervical, and endometrial carcinoma

New test detects four women’s cancers from cervical screening samples

What if a test analysing cervical cells from a gynaecological swab could be used to detect four different female cancers at an early stage and also predict cancer risk over a healthy woman's lifetime? Researchers at the European Translational Oncology Prevention and Screening (EUTOPS) Institute in Innsbruck, Austria, are developing tests to do just that for breast, ovarian, cervical, and endometrial cancer detection.

Report: Cynthia E. Keen

© EUTOPS/Uni Innsbruck

These four cancers account for more than 50% of all cancers in women in Europe. Globally, the World Health Organization’s International Agency for Research on Cancer reports that breast cancer was the world’s leading cause of cancer incidence in 2020, with an estimated 2.3 million new cases and 685,000 deaths. It also estimated 604,000 new cases of cervical cancer, 417,000 of endometrial cancer, and 314,000 of ovarian cancer. 

Ovarian cancer is especially deadly because it tends to be asymptomatic until reaching an advanced stage, when the cancer has spread within the abdominal cavity or beyond. Over half of ovarian cancer patients die within five years after their initial diagnosis. Once fully developed and clinically approved, the Women’s risk IDentification for Ovarian Cancer Test (WID-OC-Test) has the potential to change these sobering statistics by using DNA methylation analysis from a single cervical smear sample taken during a routine screening. 

portrait of Martin Widschwendter
Prof Dr Martin Widschwendter

Photo: supplied

Prof Dr Martin Widschwendter, principal investigator and director of the EUTOPS Institute, says: ‘The identity of a cell is defined by its epigenome, which consists of thousands of tags on the DNA called DNA methylation.’ These tags integrate all factors a cell has been exposed to over a lifetime, leaving a unique “footprint” on the DNA. Examples are hormonal exposures due to childbirth and environmental factors including diet and exercise, the expert explains. ‘Changes in the epigenome can increase or reduce the risk of developing cancer. The WID-Test analyses DNA methylation footprints, which can indicate increased cancer risk during a women’s lifetime.’ 

The researchers explain in detail how they developed and validated each test in articles published in Nature Communications.* Samples were assessed from over 3,000 women with and without breast/ovarian cancer from 15 centres in Europe. They obtained samples from women over the age of 18 years and evaluated the performance of the WID-Test in different age groups, including pre- and post-menopausal women. Their studies are evaluating an individual’s risk for more than one cancer by assessing several different epigenetic footprints in a single cervical screening sample. 

‘The results were much better than we hoped for,’ said Prof Dr Widschwendter. ‘The WID-OC methylation test allowed us to identify 71.4% of women under 50 years of age and 54.5% of women over 50 with ovarian cancers with 75% specificity. The fact that the test is not driven by the presence of tumour DNA in the sample suggests that the WID-OC test would have identified women well in advance of their diagnosis.’ 

Samples were evaluated with the WID-BC test and with a current method for determining breast cancer risk that combines information on genetic variants. The WID test identified 76.6% of women in the highest risk group, compared with 47.5% using the current method. 

Prof Dr Widschwendter tells Healthcare-in-Europe that ‘the next research steps will be to demonstrate that the WID-OC and WID-BC tests are able to identify healthy women at risk of developing ovarian or breast cancer in future years. The only way to achieve this is to collect thousands of cervical samples from an entire population, test them, and assign a risk score. After waiting for a number of years to identify women in the study cohort who had developed ovarian or breast cancer, we would analyse samples of these women and a control group of samples of healthy women to determine if our test could have predicted which women developed cancer.’ Currently, the team is working on the logistics and funding for this large-scale initiative, he reports. 

‘Our goal is to identify women at risk for cancer independently of a BRCA mutation, so that they can take preventative measures potentially decades before they would develop cancer. This could include lifestyle changes as well as regularly scheduled screening tests and preventative medication like tamoxifen for women with breast cancer risk,’ Widschwendter adds. ‘We also will be conducting research to determine if the WID-Test can be used to monitor cancer risk over time.’ 


Profile: 

Prof Dr Martin Widschwendter is Director of the EUTOPS Institute and Professor for Cancer Prevention and Screening at the Leopold-Franzens-University of Innsbruck. He is a Consultant Gynaecological Oncology Surgeon and also holds the position of Professor in Women’s Cancer at University College London. In July 2020, he was conferred a Guest Professorship at the Karolinska Institutet in Stockholm. Dr Widschwendter has spent decades researching the role of early detection, risk prediction and prevention of breast and gynaecological cancers. 


*Publications: 

Barrett et al.: The WID-BC-index identifies women with primary poor prognostic breast cancer based on DNA methylation in cervical samples; Nature Communications 2022

Barrett et al.: The DNA methylome of cervical cells can predict the presence of ovarian cancer; Nature Communications 2022

20.10.2022

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