A large population-based cohort study found that women with endometriosis have a 4.2-fold increased risk of ovarian cancer compared to women without endometriosis. The risk was even higher for women with deep-infiltrating endometriosis and/or ovarian endometriomas, who had a 9.66-fold increased risk of ovarian cancer overall, an 18.96-fold increased risk of type I ovarian cancer, and a 3.72-fold increased risk of type II ovarian cancer, specifically.

The study, published in JAMA, analyzed data from nearly 451,000 women in the Utah Population Database. Researchers categorized endometriosis cases into subtypes and evaluated associations with ovarian cancer histotypes.

Methods

Researchers identified 78,476 women with endometriosis diagnoses from electronic health records between 1992 and 2019. They were matched 1:5 to 372,430 women without endometriosis. Endometriosis subtypes in the analysis included deep-infiltrating endometriosis and/or ovarian endometriomas (n = 21,379), superficial peritoneal endometriosis (n = 39,277), and other types of endometriosis (n = 18,237).

Ovarian cancers diagnosed from 1992-2019 (n = 597) were identified via the Utah Cancer Registry. Cancers were classified as type I (endometrioid, clear cell, mucinous, low-grade serous) or type II (high-grade serous).

Cox proportional hazards models were used to estimate adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs). Models accounted for birth year, birth state, age at endometriosis diagnosis, and parity.

In the cohort, mean age at first endometriosis diagnosis was 36 years. The mean follow-up time was 12 years. Seventy-five percent of women were parous; 6% underwent bilateral oophorectomy during follow-up. Women with endometriosis were more likely to be nulliparous (31% vs 24%) and to have undergone hysterectomy (39% vs 6%) during follow-up compared to women without endometriosis.

Results

Women with any endometriosis subtype had an increased risk of developing ovarian cancer compared to women without endometriosis, for all types of ovarian cancer (aHR = 4.20; 95% CI, 3.59-4.91), type I ovarian cancer (aHR = 7.48; 95% CI, 5.80-9.65) and type II ovarian cancer (aHR = 2.70, 95% CI, 2.09-3.49).

The risk of ovarian cancer was highest for women with deep-infiltrating endometriosis and/or ovarian endometriomas:

• All ovarian cancer (aHR = 9.66; 95% CI, 7.77-12.00)
• Type I ovarian cancer (aHR = 18.96, 95% CI, 13.78-26.08)
• Type II ovarian cancer (aHR = 3.72, 95% CI, 2.31-5.98).

Women with superficial peritoneal endometriosis had a lower—but still elevated—risk for developing all ovarian cancers (aHR = 2.82, 95% CI, 2.27-3.51).

By specific ovarian cancer histotypes, the strongest associations were seen for clear cell carcinoma (aHR =  11.15, 95% CI, 6.19-20.10), endometrioid (aHR = 7.96, 95% CI, 5.59-11.34), and low-grade serous (aHR = 8.12, 95% CI, 2.67-24.73).

The absolute risk difference for ovarian cancer in women with vs without endometriosis was 9.90 cases per 10,000 women over a mean follow-up of 12 years (95% CI, 7.22-12.57).

Strengths of the study included the large sample size, medical record–confirmed endometriosis diagnoses, and the ability to evaluate endometriosis subtypes and ovarian cancer histotypes. Limitations included potential misclassification of endometriosis subtypes and ovarian cancer histotypes, though sensitivity analyses suggested bias toward the null. The study also lacked data on oral contraceptive use, which may have led to underestimation of the true associations.

Conclusions

This study found a markedly increased ovarian cancer risk among women with endometriosis, particularly those with deep-infiltrating disease and/or ovarian endometriomas. The authors suggest this population may benefit from ovarian cancer risk counseling and could be an important group for targeted screening and prevention studies.

Conflict of interest disclosures can be found in the study.