Abstract
A substantial proportion of epithelial ovarian cancer (EOC) arises in the fallopian tube and other epithelia of the upper genital tract; these epithelia may incur damage and neoplastic transformation after sexually transmitted infections (STI) and pelvic inflammatory disease. We investigated the hypothesis that past STI infection, particularly Chlamydia trachomatis, is associated with higher EOC risk in a nested case-control study within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort including 791 cases and 1669 matched controls. Serum antibodies against C. trachomatis, Mycoplasma genitalium, herpes simplex virus type 2 (HSV-2) and human papillomavirus (HPV) 16, 18 and 45 were assessed using multiplex fluorescent bead-based serology. Conditional logistic regression was used to estimate relative risks (RR) and 95% confidence intervals (CI) comparing women with positive vs. negative serology. A total of 40% of the study population was seropositive to at least one STI. Positive serology to C. trachomatis Pgp3 antibodies was not associated with EOC risk overall, but with higher risk of the mucinous histotype (RR = 2.30 [95% CI = 1.22-4.32]). Positive serology for chlamydia heat shock protein 60 (cHSP60-1) was associated with higher risk of EOC overall (1.36 [1.13-1.64]) and with the serous subtype (1.44 [1.12-1.85]). None of the other evaluated STIs were associated with EOC risk overall; however, HSV-2 was associated with higher risk of endometrioid EOC (2.35 [1.24-4.43]). The findings of our study suggest a potential role of C. trachomatis in the carcinogenesis of serous and mucinous EOC, while HSV-2 might promote the development of endometrioid disease.
Highlights
Epithelial ovarian cancer (EOC) is a heterogeneous disease, with distinct histologic subtypes hypothesized to arise via different pathways of carcinogenesis.[1]
The findings of our study suggest a potential role of C. trachomatis in the carcinogenesis of serous and mucinous epithelial ovarian cancer (EOC), while herpes simplex virus type 2 (HSV-2) might promote the development of endometrioid disease
Individual C. trachomatis antibodies were associated with higher risk of EOC, in particular, cHSP60 antibodies were associated with EOC overall and the serous subtype, while Pgp[3] was associated with the mucinous subtype, in this large, prospective study
Summary
Epithelial ovarian cancer (EOC) is a heterogeneous disease, with distinct histologic subtypes hypothesized to arise via different pathways of carcinogenesis.[1]. Transmitted infections (STIs) are associated with a range of gynecologic sequelae including pelvic inflammatory disease (PID),[6,7] PID has been associated with EOC risk,[8,9] though data to date suggest strongest associations with borderline tumors.[10] Chlamydia trachomatis and Mycoplasma genitalium are two sexually transmitted bacterial causes of PID. Transmitted infections (STI) have been linked with pelvic inflammatory disease but their association with ovarian cancer remains unclear. In this large prospective study, serum antibodies against Chlamydia trachomatis were associated with higher epithelial ovarian cancer risk, though some associations were limited to select histotypes. Aim of our study was to assess the association between STI serostatus, analyzed in prospectively collected blood samples, and EOC risk, overall and by histologic subtype, in a case-control study nested in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort
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