Abstract 4941: Sexually transmitted infections and risk of epithelial ovarian cancer: Results from the Nurses' Health Studies

Abstract

Abstract Introduction: Sexually transmitted infections (STIs) including bacterial infections Chlamydia trachomatis and Mycoplasma genitalium and infections with the human papillomavirus (HPV), and the herpes simplex virus type 2 (HSV-2), may induce persistent changes in the female genital tract increasing risk of epithelial ovarian cancer (OC). For example, C. trachomatis and M. genitalium infections are associated with pelvic inflammatory disease (PID), salpingitis, and tubal factor infertility. STI-induced tubal pathologies may be relevant to OC development given mounting evidence showing that a proportion of OCs originate in the fallopian tube. Epidemiologic data on STIs and OC risk are sparse. Methods: A case-control study was nested in the Nurses' Health Study (NHS) and NHSII including 338 cases individually matched to 338 controls. Antibodies indicating past infection with C. trachomatis (pGP3), M. genitalium (MgPa N-Terminus + rMgPa), HPV (E6+E7 oncoproteins of types 16, 18, and 45), and HSV-2 (mgGunique) were measured using validated serological multiplex assays in pre-diagnosis plasma samples. Multivariable conditional logistic regression was used to estimate relative risks (RR) and 95% confidence intervals [CI] comparing seropositive vs. seronegative for the individual infections for OC overall, as well as invasive OC and invasive serous OC. We further cross-classified the infections, comparing women seropositive for C. trachomatis plus any other STI to women seronegative for all STIs. Results: Study participants were median age 60 years (range: 34-81) at blood collection. The majority were parous (87%) and ever oral contraceptive users (54%), and 19% reported tubal ligation. Of the 338 OC cases, 257 were diagnosed with invasive disease and 156 were diagnosed with invasive serous disease. Cases were diagnosed median 7 years (range: 0.1-25) after blood collection. Seropositivity was observed in 20% of cases (12% of controls) for C. trachomatis, 5% (3%) for M. genitalium and 12% (9%) for HSV-2. Prevalence of infection with HPV ranged from 4% of cases (4% of controls) for HPV18 E6+E7 to 14% (14%) for HPV16 E6+E7. C. trachomatis infection was associated with increased risk of OC overall (RR: 1.98 [1.21-3.26]), invasive OC (1.81 [1.12-2.93]) and invasive serous OC (2.14 [1.23-3.75]). We observed no association between the other STIs and OC risk. Seropositivity to C. trachomatis plus any other STI was associated with a 3-fold increased risk of OC, relative to seronegativity to all infections (3.19 [1.41-7.21]). Discussion: We provide the first large-scale epidemiologic study on common STIs and OC risk, and show a significant positive association between C. trachomatis infection and OC, and a potentially synergistic effect of infection with multiple STIs. These results suggest STI prevention efforts, including vaccine development, represent an opportunity to reduce OC risk. Citation Format: Renee Turzanski Fortner, Kathryn L. Terry, Noemi Bender, Tim Waterboer, Shelley S. Tworoger. Sexually transmitted infections and risk of epithelial ovarian cancer: Results from the Nurses' Health Studies [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4941.