# The cervico‐vaginal DNA methylation WID‐qEC test: An epigenetic marker associated with ovarian cancer in the absence of endometrial and cervical cancer

## TL;DR

A DNA methylation test originally for cervical and endometrial cancers also shows potential for detecting ovarian cancer in some cases.

## Contribution

The study identifies a link between WID-qEC test positivity and ovarian cancer risk in the absence of other gynecological cancers.

## Key findings

- WID-qEC positivity was associated with ovarian cancer (adjusted OR 2.93).
- Positivity was also linked to more lifetime ovulatory cycles (adjusted OR 2.67).
- WID-qEC could be used in a two-step triage approach for ovarian cancer detection.

## Abstract

The DNA methylation‐based WID‐qEC test, applied to cervico‐vaginal samples, has been validated for the accurate detection of endometrial and cervical cancers. However, a small proportion of women test positive despite the absence of these cancers. The aim of this study was to explore the biological and clinical characteristics associated with such WID‐qEC‐positive cases to inform potential follow‐up strategies. We analyzed 1269 cervico‐vaginal samples from women without endometrial or cervical cancer, including healthy controls (n = 624), women with benign gynecological conditions (n = 324), and ovarian cancer cases (n = 321). Of the 80 WID‐qEC‐positive results, 43 (54%) were from women with ovarian cancer. WID‐qEC positivity was associated with the presence of ovarian cancer (adjusted odds ratio [OR] 2.93; 95% CI 1.75–4.95) and with a higher number of lifetime ovulatory cycles (adjusted OR 2.67; 95% CI 1.06–7.50), a known ovarian cancer risk factor. Both associations were independent of age, menopausal status, hormone replacement therapy usage, or family history of breast or ovarian cancer. Our findings suggest that in the absence of endometrial or cervical cancer, WID‐qEC positivity may indicate an elevated risk or presence of ovarian cancer. While the standalone positive predictive value (PPV) for ovarian cancer detection remains low in the general population, we outline how WID‐qEC could be used in a two‐step triage approach. In women presenting with abnormal bleeding, combining WID‐qEC positivity with a highly specific plasma‐based cell‐free DNA methylation test (e.g., with 60%–80% sensitivity and ~98.4% specificity) could theoretically yield a PPV of around 30%–40%. This hypothetical modeling is intended solely to illustrate how WID‐qEC positivity might inform future triage research, rather than to propose a clinical diagnostic algorithm.

The DNA methylation‐based WID‐qEC test has been validated for the accurate detection of endometrial and cervical cancers using cervico‐vaginal samples. However, a small proportion of women test positive despite the absence of these cancers. This study explored the associated biological and clinical characteristics to inform potential follow‐up strategies. The results showed that in the absence of endometrial or cervical cancer, WID‐qEC test positivity may indicate an elevated risk or the presence of ovarian cancer. While the standalone positive predictive value for ovarian cancer detection remains low in the general population, WID‐qEC could potentially be used in future two‐step triage approaches.