Research project will use cervical cells to predict risk of cancers

A European research project is aiming to develop new ways for testing cervical endothelial cells, collected during cervical screening tests, to predict women’s risk of breast, endometrial, and ovarian cancer as well as cervical cancer.

The FORECEE (4C) project involves 14 European research partners and has been awarded a €7.9m (£5.7m; $8.7m) grant by the European Commission and £1m by the Eve Appeal charity to enable it to use “multi-omics” to identify markers for the most aggressive types of the four cancers affecting women. Multi-omics means that the researchers use genome, epigenome (environmental factors that turn genes on and off and affect how cells read genes), and metagenome (through study of uncultured micro-organisms) analysis to come up with a model for estimating women’s risk of breast, endometrial, ovarian, and cervical cancer.

A 10th of women who develop breast or ovarian cancer carry the BRCA1 and BRCA2 mutations, and these mutations are known to raise the lifetime risk of breast cancer and ovarian cancer to 80% and 65%, respectively. Many women with the mutations opt for radical surgery because they are aware of their risk. However, 90% of women who develop the four cancers do not carry these germline mutations, explained Martin Widschwendter, head of the department of women’s cancer at University College London’s Institute for Women’s Health and the project’s lead researcher. He told The BMJ, “We would like to predict the risk with as high as possible sensitivity and specificity of developing breast, endometrial, cervical, and ovarian cancer and particularly those cancers which we know are very difficult to treat.” These include basal breast cancer, high grade serous ovarian cancer, and clear cell endometrial cancer.

“We feel that if we are able to detect those women who would eventually develop those cancers we could interfere very early on and actually prevent those cancers from developing,” Widschwendter said. Screening strategies could be tailored to risk, and women most at risk could be offered more aggressive prevention strategies such as hormone therapies or surgery.

The project will analyse cervical epithelial cells collected from women who have recently been given a diagnosis of one of the four cancers and then compare them with those from a high number of control women to develop a risk stratification model. The model will then be validated against cervical epithelial cells collected from a cohort of women in Sweden since 2010.

Only 3-5% of cervical epithelial cells collected in smear tests are currently used. Epithelial cells are superior to blood cells for predicting cancer risk because they are hormone sensitive, so DNA methylation provides an indication of long term exposure to hormones—exposure that can be implicated in cancer development.

Around 100 single nucleotide polymorphisms linked to the four cancers (around 70 for breast, 30 for ovarian, and a few for endometrial cancer) will be targeted, and the researchers will then look for evidence of DNA methylation (a mechanism for controlling gene expression). They will also look at the metagenome, because chlamydia infection and pelvic inflammatory disease are known to contribute to disease progression in cervical and ovarian cancer, respectively.