Endometriosis is a benign disease, however, does its presence increase the risk of ovarian cancer? Or, to ask differently, do ovarian cancers in women with endometriosis arise from the malignant transformation of endometriosis foci or not?

A large number of studies has been published on this topic. One of the most interesting has been published recently, indicating that in women with endometriosis, the risk of epithelial ovarian cancers is higher, mostly for the clear-cell and endometrioid type¹. The risk of malignant transformation of an endometriosis cyst is around 0.5 to 1%², whilst the lifetime risk of ovarian cancer in the average woman (with no endometriosis) is estimated to be 1 in 76³.

The term ‘’atypical endometriosis’’ suggests that endometriosis could be a precursor to cancer⁴, and surgical removal could have a protective effect⁵. However, the idea of ‘’screening’’ (use of imaging or blood tests) or ‘’risk-reducing surgery’’ (removal of the ovaries and fallopian tubes) has not gained widespread acceptance^1,6.  

We should mention, at this point, the protective role of anovulation (lack of ovulation during the menstrual cycle) in the pathogenesis of ovarian cancer. The risk increases with the number of ovulatory cycles⁷. Therefore, the long-term use of combined hormonal contraception or progestogens (that causes anovulation) can play a protective role that may be maintained for years after cessation of use.

In summary, endometriosis increases the risk of 2 types of ovarian cancer (clear-cell and endometrioid) that, compared with other types, remain rare. The lifetime risk increases from 1.3% (1/76) to 1.8% (1/55), therefore, remains small. The long-term use of combined hormonal contraception or progestogens (a common medical approach for the management of symptomatic endometriosis) can, through anovulation, reduce the risk of developing ovarian cancer.

References:

1. Kvaskoff M, Mahamat-Saleh Y, Farland LV, Shigesi N, Terry KL, Harris HR, Roman H, Becker CM, As-Sanie S, Zondervan KT, Horne AW, Missmer SA. Endometriosis and cancer: a systematic review and meta-analysis. Hum Reprod Update. 2021 Feb 19;27(2):393-420.
2. Stamp JP, Gilks CB, Wesseling M, Eshragh S, Ceballos K, Anglesio MS, Kwon JS, Tone A, Huntsman DG, Carey MS. BAF250a Expression in Atypical Endometriosis and Endometriosis-Associated Ovarian Cancer. Int J Gynecol Cancer. 2016 Jun;26(5):825-32.
3. Lifetime risk estimates calculated by the Statistical Information Team at Cancer Research UK. Based on Office for National Statistics (ONS) 2016-based Life expectancies and population projections. Accessed December 2017, and Smittenaar CR, Petersen KA, Stewart K, Moitt N. Cancer Incidence and Mortality Projections in the UK Until 2035(link is external). Brit J Cancer 2016.
4. Karnezis AN, Cho KR, Gilks CB, Pearce CL, Huntsman DG. The disparate origins of ovarian cancers: pathogenesis and prevention strategies. Nat Rev Cancer. 2017 Jan;17(1):65-74.
5. Rossing MA, Cushing-Haugen KL, Wicklund KG, Doherty JA, Weiss NS. Risk of epithelial ovarian cancer in relation to benign ovarian conditions and ovarian surgery. Cancer Causes Control. 2008;19(10):1357-1364.
6. Hermens M, van Altena AM, Nieboer TE, Schoot BC, van Vliet HAAM, Siebers AG, Bekkers RLM. Incidence of endometrioid and clear-cell ovarian cancer in histological proven endometriosis: the ENOCA population-based cohort study. Am J Obstet Gynecol. 2020 Jul;223(1):107.e1-107.e11.
7. Trabert B, Tworoger SS, O’Brien KM, Townsend MK, Fortner RT, Iversen ES, Hartge P, White E, Amiano P, Arslan AA, Bernstein L, Brinton LA, Buring JE, Dossus L, Fraser GE, Gaudet MM, Giles GG, Gram IT, Harris HR, Bolton JH, Idahl A, Jones ME, Kaaks R, Kirsh VA, Knutsen SF, Kvaskoff M, Lacey JV, Lee IM, Milne RL, Onland-Moret NC, Overvad K, Patel AV, Peters U, Poynter JN, Riboli E, Robien K, Rohan TE, Sandler DP, Schairer C, Schouten LJ, Setiawan VW, Swerdlow AJ, Travis RC, Trichopoulou A, van den Brandt PA, Visvanathan K, Wilkens LR, Wolk A, Zeleniuch-Jacquotte A, Wentzensen N; Ovarian Cancer Cohort Consortium (OC3). The Risk of Ovarian Cancer Increases with an Increase in the Lifetime Number of Ovulatory Cycles: An Analysis from the Ovarian Cancer Cohort Consortium (OC3). Cancer Res. 2020 Mar 1;80(5):1210-1218.
8. Collaborative Group on Epidemiological Studies of Ovarian Cancer, Beral V, Doll R, Hermon C, Peto R, Reeves G. Ovarian cancer and oral contraceptives: collaborative reanalysis of data from 45 epidemiological studies including 23,257 women with ovarian cancer and 87,303 controls. Lancet. 2008 Jan 26;371(9609):303-14.