Epigenetic test identifies cervical cancer precursor cells

A simple test can identify those who will develop potentially dangerous cervical cell changes up to four years in advance.

Researchers in London, Sweden and Austria developed the test which looks at DNA methylation to identify cells with potentially precancerous changes. It detected patients who would go on to have changes in the next four years in 11-38 percent more cases than traditional cytology (a trained person looking at cells under a microscope) or several newer molecular tests.

'Building new, holistic, risk-predictive screening programmes around existing, effective cervical sample collection offers real potential for cancer prevention in the future,' said study author Professor Martin Widschwendter, from the University of Innsbruck's Cancer Prevention and Screening Department and University College London's (UCL) EGA Institute for Women's Health and the European Translational Oncology Prevention and Screening Institute at University of Innsbruck, Austria.

The research, published in Genome Medicine, used samples taken during standard cervical screening programmes.

The teams at UCL and Innsbruck performed an epigenome-wide analysis of DNA methylation at 850,000 sites in the genome, across over 1254 samples from patients with confirmed cervical intraepithelial neoplasias (CINs): cells with changes that have a higher risk of becoming cancerous.

From this, they identified the 5000 most variable sites and used these to create the index, named WID-CN. Collaborators at the Karolinska Institutet in Stockholm, Sweden tested WID-CN on 1254 cervical screening samples from Stockholm women, showing it was able to identify advanced CIN in 90 percent of cases overall, and more in samples from women over the age of 30.

In England, the samples collected at these screenings are tested for the human papillomavirus (HPV), which causes 99.8 percent of cervical cancers. If HPV is detected, the samples are further analysed to look for CINs, and if they are detected further investigation takes place.

Overall, the index identified 55 percent of HPV-positive patients who did not have CINs but who developed them in the next four years. It was also able to identify patients with advanced cell changes (CIN3) at much higher rates than current, more manually intensive methods.

Population-level cervical screening is the UK's most successful cancer prevention strategy. Vaccination against HPV is now widespread in the UK, and the rates and types of circulating HPV will change with time.

The researchers' next steps will be to test the WID-CIN in individuals who have received the HPV vaccine, and in samples collected at home (as opposed to in clinics), to understand how the index can be used for population screening going forward.

'Our approaches to cervical screening must adapt so that programmes continue to deliver benefit,' said Professor Widschwendter.