In a Utah population–based cohort study reported in JAMA Network Open, Barnard et al found that women with ovarian endometriomas and/or deep-infiltrating endometriosis had a markedly increased risk of developing ovarian cancer. Those with such severe subtypes may represent an important population for targeted cancer screening and prevention studies.

“Endometriosis has [previously] been associated with an increased risk of ovarian cancer,” the investigators commented. “[However, prior to this study,] associations between endometriosis macrophenotypic subtypes—superficial peritoneal endometriosis, ovarian endometriomas, and deep-infiltrating endometriosis—and ovarian cancer had not been adequately explored.”

Study Details

The investigators assembled a retrospective population-based cohort using data gathered between 1992 and 2019 from the Utah Population Database. Women with a history of endometriosis (n = 78,893) were matched in a 1:5 ratio to those without the condition (n = 379,043) by birth year and birthplace (Utah or other). All unaffected women were reportedly living in Utah as of the diagnosis date of their matched endometriosis case.

Endometriosis cases were categorized as superficial peritoneal endometriosis (n = 39,277; 49.8%), ovarian endometriomas (n = 18,977; 24.1%), deep-infiltrating endometriosis (n = 1,028; 1.3%), ovarian endometriomas and concurrent deep-infiltrating endometriosis (n = 1,374; 1.7%), or other (n = 18,237; 23.1%). For the main analyses, the investigators grouped ovarian cancer cases into the commonly used classifications of type I (endometrioid, clear cell, mucinous, and low-grade serous) and type II (high-grade serous).

Ovarian Cancer Risk

The study population had a mean age at first endometriosis diagnosis of 36 years and a mean follow-up duration of 12 years. A total of 597 women were diagnosed with ovarian cancer.

Overall, women with vs without endometriosis appeared to have a higher risk of developing ovarian cancer (adjusted hazard ratio [aHR] = 4.20; adjusted risk difference [aRD] = 9.90); a 7.48-fold higher risk of developing a type I histotype was reported (aRD = 7.53). The risk of developing ovarian cancer was found to be the highest in women with deep-infiltrating endometriosis and/or ovarian endometriomas (all histotypes: aHR = 9.66, aRD = 26.71; type I: aHR = 18.96, aRD = 19.57; type II: aHR = 3.72, aRD = 2.42).

The investigators concluded, “Studies that can better characterize the biology underlying these associations are urgently needed to guide improved ovarian cancer screening and prevention strategies among women with severe endometriosis, with or without other important ovarian cancer risk factors (eg, BRCA1/2 variations), and to inform novel molecular targets for ovarian cancer treatments.”

Karen C. Schliep, PhD, of University of Utah Health, Salt Lake City, is the corresponding author of the JAMA Network Open article.

Disclosure: The study was funded by the National Cancer Institute and others. For full disclosures of the study authors, visit jamanetwork.com.