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Women with endometriosis, particularly those with more severe subtypes, have an increased risk of ovarian cancer, according to results from a population-based cohort study.

The risk for ovarian cancer was higher among women with endometriosis compared with those without endometriosis (adjusted HR 4.20, 95% CI 3.59-4.91), with an especially high risk for type I ovarian cancer, such as endometrioid, clear cell, mucinous, and low-grade serous cancers (aHR 7.48, 95% CI 5.80-9.65), reported Karen C. Schliep, PhD, of University of Utah Health in Salt Lake City, and colleagues in .

Of note, ovarian cancer risk was highest in women with deep infiltrating endometriosis and/or ovarian endometriomas for all ovarian cancers (aHR 9.66, 95% CI 7.77-12.00).

When endometriosis subtypes and ovarian cancer histotypes were evaluated together, the strongest association was between deep infiltrating endometriosis and/or ovarian endometriomas and type I ovarian cancer (aHR 18.96, 95% CI 13.78-26.08).

However, "risks were elevated for all endometriosis subtypes for both type I and type II ovarian cancer [high-grade serous]," the authors noted.

"Given the rarity of ovarian cancer, the excess risk was relatively small, with 10-20 additional cases per 10,000 women. Nevertheless, women with endometriosis, notably the more severe subtypes, may be an important population for targeted cancer screening and prevention studies," Schliep said in a press release. "Precision medicine is more than just genetics. Clinical features, including a woman's history of endometriosis and type of endometriosis, may inform ovarian cancer risk prediction models."

Schliep and colleagues suggested that there are a number of mechanisms that could explain the association between endometriosis subtypes and ovarian cancer histotypes. For example, they said that endometriosis is believed to be a tissue of origin for both endometrioid and clear cell ovarian cancer.

"Additionally, there is emerging evidence of an overlapping genetic predisposition for both endometriosis and endometrioid and clear cell ovarian cancer," they wrote.

On the other hand, they suggested that oral contraceptives -- commonly used as a first-line treatment for endometriosis -- may serve to protect women.

In an , Michael T. McHale, MD, of the University of California San Diego, pointed out that "early detection [of ovarian cancer] continues to be elusive and screening strategies inadequate, even in women at high risk. Women continue to be diagnosed with advanced-stage disease, which portends a poor prognosis, despite improved outcomes in women treated with a [PARP] inhibitor for maintenance therapy, particularly those with germline or somatic BRCA1 or BRCA2 sequence variations."

While McHale agreed with the study authors that the excess risk in terms of absolute numbers of ovarian cancers is limited, "the increased risk is significant." He suggested that more definitive surgery should be discussed and considered in women who have completed childbearing or who have other fertility options.

"This study also provides important new information identifying an increased risk with particular phenotypes of endometriosis, such as deep infiltrating and/or ovarian," he added. "It is imperative that future investigations explore the biology of this association and mechanisms contributing to malignant transformation."

For this study, Schliep and colleagues used data from the Utah Population Database, which utilizes linked vital records, health facility records, the Utah Cancer Registry, and University of Utah and Intermountain Health records. They enrolled a cohort of 450,906 women -- 78,476 with endometriosis and 372,430 without. Over the period of 1992-2019, there were 597 diagnosed ovarian cancers identified via the Utah Cancer Registry.

The mean age at endometriosis diagnosis was 36 years, and follow-up time was a mean of 12 years. The majority of women were parous (75%), and 6% underwent a bilateral oophorectomy during follow-up.

Women with endometriosis were more likely to be nulliparous (31% vs 24% of those without) and to have undergone a hysterectomy during follow-up (39% vs 6%).

Risk differences showed that the excess risk of ovarian cancer among women with endometriosis was 9.90 cases per 10,000 women (95% CI 7.22-12.57) over a mean of 12 years, and risks were highest in women with deep infiltrating endometriosis and/or ovarian endometriomas for all ovarian cancers (adjusted risk difference [aRD] 26.71, 95% CI 20.01-33.41) and type I ovarian cancer (aRD 19.57, 95% CI 13.80-25.35).

Schliep and colleagues noted that misclassification of endometriosis was possible, due to the lack of a biomarker for diagnosing endometriosis, changes in the procedures to diagnose subtypes (i.e., operation vs MRI), and the difficulty in diagnosing endometriosis in women without symptoms or access to care.

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