Endometriosis and ovarian cancer risk by histotype: a pooled analysis from the Ovarian Cancer Cohort Consortium

Holly Harris*, Kara L. Cushing‐Haugen, Naoko Sasamoto, Kathryn Terry, Leslie Farland
In: Epidemiology · 2026 · vol. 37(S2) · doi:10.1097/01.ede.0001280116.05658.c3 · W7221509660
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A pooled analysis of 725,122 participants demonstrated that endometriosis is associated with a significantly higher risk of invasive epithelial ovarian cancer across all major histotypes, including high-grade serous, mucinous, endometrioid, low-grade serous, and clear cell subtypes.

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This pooled analysis from the Ovarian Cancer Cohort Consortium examined the association between self-reported endometriosis and invasive epithelial ovarian cancer risk across ten prospective cohorts comprising over 725,000 participants. The study found that individuals with endometriosis had a 64% higher overall risk of developing ovarian cancer compared to those without the condition. Significant increased risks were observed for all major histotypes, including clear cell, endometrioid, low-grade serous, mucinous, and high-grade serous cancers. This paper is centrally about endometriosis — specifically its role as a risk factor for various subtypes of ovarian cancer.

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Background

Endometriosis is a common inflammatory condition that is characterized by the presence of endometrial-like tissue outside the uterine cavity. People with endometriosis have approximately a two to three-fold increased risk of endometrioid and clear cell ovarian cancer. However, the associations with other histotypes are less certain given the potential for detection bias as well as small sample sizes.

Methods

Our objective was to examine the association between endometriosis and invasive epithelial ovarian cancer risk in 10 prospective cohorts in the Ovarian Cancer Cohort Consortium (n=725,122 total participants). Endometriosis was self-reported in most of the studies. We used pooled logistic regression with time divided into two-year intervals. This approach estimates beta coefficients interpreted as log ORs that are analogous to cause-specific HRs.

Results

7.1% of participants reported an endometriosis diagnosis. During follow-up 4,327 incident ovarian cancer cases were diagnosed, with 380 cases among those with endometriosis and 3,947 cases among those without. We observe a 64% higher risk of ovarian cancer (95% CI=1.47-1.82) in those with endometriosis compared to those without endometriosis. We observed a higher risk of all major ovarian cancer histotypes among those with endometriosis with ORs (95% CI) of 1.23 (1.05-1.45) for high-grade serous, 2.09 (1.30-3.35) for mucinous, 2.24 (1.65-3.03) for endometrioid, 3.02 (1.63-5.57) for low-grade serous, and 4.21 (3.00-5.89) for clear cell.

Conclusions

This prospective consortium analysis is one of the largest to demonstrate associations with high grade serous and mucinous ovarian cancer histotypes as well as endometrioid, clear cell, and low-grade serous. Given the distinctive cell of origins proposed for distinct ovarian cancer histotypes, this may indicate that pathways linking endometriosis to ovarian cancer may differ across histotypes.

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