The vast majority of epithelial ovarian cancer arises from tissues that are embryologically derived from the Müllerian Duct. Here, we demonstrate that a DNA methylation signature in easy-to-access Müllerian Duct-derived cervical cells from women with and without ovarian cancer (i.e. referred to as the Women's risk IDentification for Ovarian Cancer index or WID-OC-index) is capable of identifying women with an ovarian cancer in the absence of tumour DNA with an AUC of 0.76 and women with an endometrial cancer with an AUC of 0.81. This and the observation that the cervical cell WID-OC-index mimics the epigenetic program of those cells at risk of becoming cancerous in BRCA1/2 germline mutation carriers (i.e. mammary epithelium, fallopian tube fimbriae, prostate) further suggest that the epigenetic misprogramming of cervical cells is an indicator for cancer predisposition. This concept has the potential to advance the field of risk-stratified cancer screening and prevention.

Centre for Cancer Biomarkers CCBIO Department of Clinical Science University of Bergen Bergen Norway

Centre for Prevention Detection and Diagnosis Wolfson Institute of Population Health Queen Mary University of London London EC1M 6BQ UK

Department of Gynaecological Oncology Barts Health NHS Trust Royal London Hospital London E1 1BB UK

Department of Health Sciences University of Leicester Leicester LE1 7RH UK

Department of Health Services Research The London School of Hygiene and Tropical Medicine London WC1E 7HT UK

Department of Non communicable Disease Epidemiology The London School of Hygiene and Tropical Medicine London WC1E 7HT UK

Department of Obstetrics and Gynaecology Haukeland University Hospital Bergen Norway

Department of Obstetrics and Gynecology General University Hospital Prague 1st Faculty of Medicine Charles University Prague Czech Republic

Department of Women's and Children's Health Karolinska Institutet Stockholm Sweden

Department of Women's Cancer UCL EGA Institute for Women's Health University College London 74 Huntley Street London WC1E 6AU UK

European Translational Oncology Prevention and Screening Institute 6060 Hall in Tirol Austria

Hospital Na Bulovce Prague Czech Republic

Research Institute for Biomedical Aging Research Universität Innsbruck 6020 Innsbruck Austria

UCL Genomics Zayed Centre for Research into Rare Disease in Children University College London London WC1N 1DZ UK

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