Circulating biomarkers of infection and endometrial cancer risk

TL;DR

This study explores if genital infections are linked to endometrial cancer risk, finding some associations with herpes and chlamydia.

Contribution

The study identifies potential infection-related risk factors for specific subtypes of endometrial cancer.

Findings

Seropositivity for Herpes simplex virus 2 was associated with low-grade endometrial tumors.

Chlamydia trachomatis antigens showed increased risk for type II endometrial cancers.

Infection-related mechanisms may contribute to endometrial cancer, particularly for type II tumors.

Abstract

Incidence and mortality rates for endometrial cancer are rising. We need to better understand the etiology of this disease and identify new risk factors. We examined whether common genital infections are associated with endometrial cancer.

Using serum samples from The Polish Endometrial Cancer Study (443 cases, 443 controls), we measured antibodies against microbial antigens with a multiplex fluorescent bead-based assay. We estimated adjusted odds ratios (OR) and 95% confidence intervals (CI), comparing women with positive versus negative serology.

Most antibodies were not associated with endometrial cancer overall, but seropositivity for Herpes simplex virus 2 was associated with low-grade tumors (OR 1.43 CI 1.02, 2.00). While increased risks for type II, but not type I tumors, were consistently indicated for multiple Chlamydia trachomatis antigens, most estimates did not reach statistical significance (e.g., Pgp3 seropositivity and type I cancers: OR 0.97 CI 0.73, 1.31; and type II: OR 2.96 CI 0.85, 10.31; heterogeneity p-value = 0.03). The strongest associations for type II tumors were observed with seropositivity for Chlamydial stress response proteins.

Reproductive tract infections may increase risk for endometrial cancer, but the biologic mechanisms are likely both microbe- and histology-specific. Some C. trachomatis infections may be a risk factor for type II endometrial cancers. Given that so few risk factors for type II endometrial cancers are identified, infection-related mechanisms of carcinogenesis in the endometrium merit continued investigation.

The online version contains supplementary material available at 10.1007/s10552-025-02080-6.