Investigation of the Association Between HSV-2 Virus and the Risk of Ovarian Cancer

Abstract

Ovarian cancer is among the most lethal gynecologic malignancies, and its etiology remains poorly understood. Viral infections, including herpes simplex virus type 2 (HSV-2), have been hypothesized as potential risk factors. This study aimed to evaluate the association between HSV-2 infection and ovarian cancer risk in an Iranian population. A case-control study was conducted at Fatemieh Hospital, Hamadan, Iran, from 2021 to 2022, involving 38 women with histologically confirmed ovarian cancer and 38 age- and marital status-matched healthy controls. Data on demographic characteristics, obstetric history, sexually transmitted diseases (STDs), and family history of genital cancers were collected. HSV-2 serology was assessed using enzyme-linked immunosorbent assay (ELISA). Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using univariate and multivariate logistic regression.  A post-hoc power analysis was performed. Baseline characteristics were similar between cases and controls. Among cases, 52.6% had epithelial ovarian cancer, 26.3% serous tumors, and 21.1% borderline tumors. Univariate analysis indicated increased odds of ovarian cancer with Chlamydia trachomatis (OR 4.2, 95% CI: 1.04-16.6), HSV-2 (OR 3.1, 95% CI: 0.7-12.8), and STDs overall (OR 4.8, 95% CI: 1.8-12.7). In multivariate analysis adjusting for age, menopausal status, family history, and urban residence, STDs remained significantly associated (adjusted OR 4.8, 95% CI: 1.7-13.2, P=0.003). No significant associations were observed between infections and cancer subtypes. Post-hoc power analysis indicated approximately 35% power to detect the observed HSV-2 difference. Sexually transmitted infections may contribute to ovarian cancer etiology. However, due to low statistical power, the non-significant finding for HSV-2 should be interpreted with caution. Further studies with larger sample sizes are needed to clarify the role of HSV-2 infection.