Does endometriosis increase risk of ovarian cancer?

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Patients with endometriosis are twice as likely to develop ovarian cancer, according to results of a meta-analysis.

But endometriosis does not necessarily pose an increased risk for endometrial cancer, and definitely does not increase the likelihood of cervical cancer.

The study in Archives of Gynecology and Obstetrics sought to determine the influence of endometriosis on the risk for the three gynecologic cancers.

Chinese investigators conducted a comprehensive search of several medical literature electronic databases, including PubMed, Embase and the Cochrane Library. Of 8,538 articles identified, 25 published between 1997 and 2017 were selected for analysis: 15 cohort studies and 10 case–control studies. 

Patients with endometriosis had an overall risk ratio (RR) of 1.964 (95% CI 1.685-2.290) for ovarian cancer, compared to 1.176 for endometrial cancer (95% CI 0.878-1.575) and 0.670 for cervical cancer (95% CI 0.537-0.838).

Although endometriosis is benign, it manifests some characteristics similar to malignancy, including tissue invasion, angiogenesis and development of local and distant foci. Therefore, the authors advocate that women with endometriosis be closely observed and rechecked routinely to prevent malignant changes.

“A growing number of recent studies have supported the notion that endometriosis represents the initial stage of tumor progression,” the authors wrote.

They also noted that endometriosis and gynecologic cancer share common risk factors, such as obesity, type 2 diabetes, hyperestrogenism and reproductive characteristics.

Of the 25 studies in the meta-analysis, four were conducted in Taiwan, eight in the United States, three in Australia, three in Sweden and two in Denmark. The Netherlands, Japan, Canada and Spain each contributed a single study, and the remaining study enlisted multiple countries.

Six studies assessed the effects of age on ovarian, endometrial, and cervical cancer in patients with endometriosis.

Concerning type of gynecologic cancer, 23 studies provided risk estimates for endometriosis and ovarian cancer, nine studies for endometriosis and endometrial cancer, three studies for endometriosis and cervical cancer, five studies for endometriosis and endometriod ovarian cancer, six studies for endometriosis and clear-cell type ovarian cancer and one study for endometriosis and epithelioid ovarian cancer.

“The ovary is the major target organ for the malignant transformation of endometriosis, although the extragonadal may also be one of its origins,” the authors wrote. “Endometriosis increased susceptibility to developing some subtypes of epithelial ovarian cancer and exhibits some molecular similarities with cancer. This finding shows that endometriosis played a role in the process of tumorigenesis.”

One of the limitations of the meta-analysis was that the eligible manuscripts used four different effect size estimates: odds ratio (OR), RR, hazard ratio (HR) and standard incidence ratio (SIR). Because different effect sizes represent different meanings, coupled with the fact that absolute risk of ovarian cancer and endometrial cancer is low, the investigators combined the four effect size estimates into RR estimates.

“However, SIR corresponds to RR estimates only for age and calendar time adjustments, usually leading to overestimation of cancer risk,” the authors wrote.