Tehran University of Medical Sciences Acta Medica Iranica 0044-6025 64 6 2026 07 09 350 354 Nada Shafie Department of Obstetrics and Gynecology, Guilan University of Medical Sciences, Rasht, Iran. Mahdie Mirahmadi Department of Obstetrics and Gynecology, Hamadan University of Medical Sciences, Hamadan, Iran. 2025 12 23 2026 05 06 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. https://acta.tums.ac.ir/index.php/acta/article/view/11955 https://acta.tums.ac.ir/index.php/acta/article/download/11955/6062