Sexually transmitted infections and risk of epithelial ovarian cancer: results from the Nurses’ Health Studies

Abstract

BACKGROUND: Sexually transmitted infections (STIs) are associated with pelvic inflammatory disease and tubal pathologies. Given the tubal origin of a proportion of ovarian cancers, STIs may be relevant in their aetiology. METHODS: Antibodies indicating past infection with Chlamydia trachomatis, Mycoplasma genitalium, herpes simplex virus type 2, and against human papillomavirus oncogenes (L1 and E6+E7 oncoproteins of types 16, 18, 45) were measured in prediagnosis plasma samples in a nested case-control study in the Nurses' Health Studies (n = 337 cases 1:1 matched to controls). Logistic regression was used to estimate multivariable-adjusted relative risks (RRs) and 95% confidence intervals [CIs] comparing women seropositive vs. seronegative among all cases (invasive and borderline), invasive (n = 257), and invasive serous ovarian cancers; n = 170), and borderline ovarian tumours (n = 80). RESULTS: C. trachomatis seropositivity was associated with higher risk of ovarian cancer overall (RR = 2.07 [1.25-3.43]); results were similar for invasive, invasive serous, and borderline tumours. We observed no associations for the other STIs. Relative to women seronegative to all infections, strongest associations were observed for seropositivity to C. trachomatis plus another STI (2.74 [1.20-6.27]; C. trachomatis alone, 1.88 [1.03-3.42]; all cases); however, the RRs were not significantly different. CONCLUSIONS: C. trachomatis infection may increase ovarian cancer risk; additional studies are required.

Serologic markers of Chlamydia trachomatis and other sexually transmitted infections and subsequent ovarian cancer risk: Results from the EPIC cohort

“…We observed limited heterogeneity in associations by age at blood collection (<60 vs ≥60 years; Table S5). In the analysis considering "high" and "low" positive antibody levels to C. trachomatis cHSP60-1 antibodies and EOC risk, women with high positive antibody levels had higher risk of EOC only among women <60 at blood collection (P het = 0.04; <60 years, Our findings of positive associations between select C. trachomatis antibodies and EOC risk are in line with the results of three previous studies 18,19,25 ; however, others have observed no association. 20,22,24 Previous studies have predominantly analyzed ovarian cancer as a single disease, with small sample size precluding analyses by subtype beyond serous vs nonserous disease.…”

“…20,22,24 Previous studies have predominantly analyzed ovarian cancer as a single disease, with small sample size precluding analyses by subtype beyond serous vs nonserous disease. [18][19][20]22,24,25 In the current study, we provide a detailed investigation by histotype, observing suggestive heterogeneity by tumor histology. Pgp3 serology indicating current or past infection with C. trachomatis was not associated with EOC risk overall in contrast to two recent studies, 18,25 but was associated with significantly higher risk of mucinous EOC; this has not previously been described.…”

“…Serum antibodies to M. genitalium were not associated with EOC overall or any histotypes in our study, in line with the findings of prospective studies, 18,22 although an association was reported in a retrospective case-control study population 18 and parous women in another study. 25 Positive HSV-2 serostatus was associated with a higher risk of endometrioid EOC. A higher, but not statistically significant, risk of EOC overall was also found in the recent study by Trabert et al 18 Women with positive serology for HSV-2 had higher risk of endometrial (uterine) cancer in the NHANES (National Health and Nutrition Examination Survey).…”

“…History of infection with different STIs could potentially lead to worse tissue damage, and a tendency toward higher risk of EOC with antibodies to C. trachomatis plus a second infection was found in one study. 25 We investigated STIs and EOC overall, by tumor histology (serous, mucinous, endometrioid, clear cell and NOS), and for HGSC disease (tumor grades 2 or 3). Heterogeneity in the associations between the STIs and EOC risk by disease subtype was assessed comparing models assuming the same association across subtypes to a model assuming different associations across subtypes using the likelihood ratio test.…”

“…16 Similarly, the distal end of the fallopian tubes harbors the potentially vulnerable junction of the fallopian tubal epithelium and the peritoneal mesothelium. 17 Epidemiologic data on STIs and EOC risk are limited and the results divergent, [18][19][20][21][22][23][24][25] and few studies are prospective. 18,22,25,26 The largest and most recent prospective study (n = 337 cases) observed a twofold higher risk of EOC among women seropositive to chlamydial Pgp3 antibodies, 25 with similar associations between relatively high circulating antibodies in another recent prospective study 18 ; no associations were observed for M. genitalium, the investigated HPV types (L1 proteins of types 16, 18 and 45), or HSV-2.…”