Pelvic inflammatory disease and risk of epithelial ovarian cancer. A national population-based case-control study in Sweden.

BACKGROUND: Epithelial ovarian cancer is an insidious disease, and women are often diagnosed when the disease is beyond curative treatment. Accordingly, identifying modifiable risk factors is of paramount importance. Inflammation predisposes an individual to cancer in various organs, but whether pelvic inflammatory disease is associated with an increased risk of epithelial ovarian cancer has not been fully determined.

OBJECTIVE: The aim of the present study was to investigate a possible association between clinically verified pelvic inflammatory disease and risk of epithelial ovarian cancer.

STUDY DESIGN: In this national population-based case-control study, we identified all women in Sweden diagnosed with epithelial ovarian cancer between 1999 and 2020 and ten controls for each, matched for age and residential district. Using several Swedish nationwide registers, we retrieved data on previous pelvic inflammatory disease and potential confounding factors (age, parity, educational level, and previous gynecological surgery). Adjusted odds ratios and 95% confidence intervals were estimated using conditional logistic regression. We performed histotype-specific analyzes for the subgroup of women diagnosed with epithelial ovarian cancer between 2015 and 2020. Hormonal contraceptives and menopausal hormone therapy were also adjusted for in addition to the aforementioned confounders.

RESULTS: We included 15,072 women with epithelial ovarian cancer and 141,322 controls. A majority had serous carcinoma (n=9102, 60.4%). In a subgroup of cases diagnosed between 2015 and 2020 we identified high-grade serous carcinoma (n=2319, 60.0%). A total of 1.1% (n=168) of cases and 0.9% (n=1270) of controls were diagnosed with pelvic inflammatory disease. Previous pelvic inflammatory disease was associated with increased risk of epithelial ovarian cancer (adjusted odds ratio, 1.39; 95% confidence interval, 1.17-1.66) and serous carcinoma (adjusted odds ratio, 1.46; 95% confidence interval, 1.18-1.80) for the entire study population. For the subgroup of women diagnosed in 2015-2020, pelvic inflammatory disease was associated with high-grade serous carcinoma (adjusted odds ratio, 1.43; 95% confidence interval, 1.01-2.04). Odds ratios of the other histotypes were as follows: endometrioid (adjusted odds ratio, 0.13; 95% confidence interval, 0.02-1.06); mucinous (adjusted odds ratio, 1.55; 95% confidence interval, 0.56-4.29); and clear cell carcinoma (adjusted odds ratio, 2.30; 95% confidence interval, 0.90-5.86). A dose-response relationship was observed between the number of pelvic inflammatory disease episodes and risk of epithelial ovarian cancer (Ptrend <0.001).

CONCLUSIONS: A history of pelvic inflammatory disease is associated with an increased risk of epithelial ovarian cancer and a dose-response relationship is evident. Histotype-specific analyzes show an association with increased risk of serous epithelial ovarian cancer and high-grade serous carcinoma, and potentially also with clear cell carcinoma, but no significant association with other histotypes. In conclusion, infection and inflammation of the upper reproductive tract might have serious long-term consequences, including epithelial ovarian cancer.