Sexually transmitted infections and risk of ovarian cancer

A European nested case-control study suggests that Chlamydia trachomatis and herpes simplex virus 2 (HSV-2) may play a role in development of certain types of ovarian cancer. The authors caution, however, that their results require confirmation in other large prospective cohorts.

Published in the International Journal of Cancer, the research was an outgrowth of the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, and included 791 cases and 1,669 matched controls. The authors hypothesized that risk of epithelial ovarian cancer would be higher in women with a history of sexually transmitted infection, particularly C. trachomatis.

With more than a half million participants from 10 European countries, nearly 400,000 of whom are women, EPIC is an ongoing prospective cohort. The individuals being studied are from the general population, range in age from 25 to 70, and were enrolled at 23 centers from 1992 to 2000.

For their study of STI risk and epithelial ovarian cancer, the researchers used multiplex fluorescent bead-based serology to assess serum antibodies against C. trachomatis, Mycoplasma genitalium, HSV-2, and human papillomavirus 16, 18 and 45 prior to diagnosis. Relative risks (RR) and 95% confidence intervals (CIs) were estimated for positive versus negative serology using conditional logistic regression. Of the ovarian cancers seen in the women in the cases, 54.7% were serous, 16.7% not otherwise specified, 11.8% endometrioid, 7.3% mucinous, and 4.7% clear cell.

Overall, 40% of the study population was seropositive for at least one STI. Testing positive for C trachomatis antibodies was not linked with a higher risk of epithelial ovarian cancer overall, but it was linked with a higher risk of the mucinous histotype (RR = 2.30; 95% CI 1.22-4.32), which was robust to adjustment for smoking (RR = 2.49; 95% CI, 1.29-4.79). Positive serology for chlamydia heat shock protein 60 (cHSP60-1) was associated with higher risk of epithelial ovarian cancer overall (RR = 1.35; 95% CI, 1.13-1.64) and with the serous subtype (RR = 1.44; 95% CI, 1.12-1.85).

None of the other STIs that the authors evaluated were associated with elevated risk overall but HSV-2 was associated with a higher risk of endometrioid epithelial ovarian cancer (RR = 2.35; 95% CI, 1.24-4.43).

The authors noted that when the analysis was restricted to parous women, the results were not materially different and limited heterogeneity was seen in associations by age at blood collection (<60 years vs ≥ 60 years).

Commenting on the fact that their results with a European population differ from those seen in two prospective US studies, the researchers posited that “one explanation may be regional differences in C. trachomatis strains, with different strains possibly having different downstream impacts on the genital tract epithelium.” They concluded that “history of STIs might be of importance in the etiology of serous, mucinous and endometrioid ovarian cancer.”