Investigation of the Association Between HSV-2 Virus and the Risk of Ovarian Cancer
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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.
2. Hobeika E, Armouti M, Kala HS, Stocco C. Ovarian hormones. In: Hormonal Signaling in Biology and Medicine. Elsevier; 2020:565-83.
3. Berek JS, Renz M, Kehoe S, Kumar L, Friedlander M. Cancer of the ovary, fallopian tube, and peritoneum: 2021 update. Int J Gynecol Obstet 2021;155:61-85.
4. Ali AT, Al-Ani O, Al-Ani F. Epidemiology and risk factors for ovarian cancer. Menopause Rev 2023;22:93-104.
5. Momenimovahed Z, Tiznobaik A, Taheri S, Salehiniya H. Ovarian cancer in the world: epidemiology and risk factors. Int J Womens Health 2019;11:287-99.
6. Fu Z, Brooks MM, Irvin S, Jordan S, Aben KK, Anton-Culver H, et al. Lifetime ovulatory years and risk of epithelial ovarian cancer: a multinational pooled analysis. J Natl Cancer Inst 2023;115:539-51.
7. Michels KA, Jin D, Jeske R, Lissowska J, Pepłońska B, Wentzensen N, et al. Circulating biomarkers of infection and endometrial cancer risk. Cancer Causes Control 2025;36:1-8.
8. Hill BT, Shah H, Winter A. Etiology of cancer. In: Clinical Ophthalmic Oncology: Basic Principles. Springer; 2025:17-22.
9. Piao J, Lee EJ, Lee M. Association between pelvic inflammatory disease and risk of ovarian cancer: an updated meta-analysis. Gynecol Oncol 2020;157:542-8.
10. Zhou Z, Zeng F, Yuan J, Tang J, Colditz GA, Tworoger SS, et al. Pelvic inflammatory disease and the risk of ovarian cancer: a meta-analysis. Cancer Causes Control 2017;28:415-28.
11. Hosseininasab-Nodoushan SA, Ghazvini K, Jamialahmadi T, Keikha M, Sahebkar A. Association of Chlamydia and Mycoplasma infections with susceptibility to ovarian cancer: a systematic review and meta-analysis. Semin Cancer Biol 2022;86:993-1001.
12. Zayyan MS, Ahmed SA, Oguntayo AO, Kolawole AO, Olasinde TA. Epidemiology of ovarian cancers in Zaria, Northern Nigeria: a 10-year study. Int J Womens Health 2017;9:855-60.
13. Jindal D, Sahasrabhojanee M, Jindal M, D'Souza J. Epidemiology of epithelial ovarian cancer: a tertiary hospital based study in Goa, India. Int J Reprod Contracept Obstet Gynecol 2017;6:2541-6.
14. Trabert B, Waterboer T, Idahl A, Brenner N, Brinton LA, Butt J, et al. Antibodies against Chlamydia trachomatis and ovarian cancer risk in two independent populations. J Natl Cancer Inst 2019;111:129-36.
15. Fortner RT, Terry KL, Bender N, Brenner N, Hufnagel K, Butt J, et al. Sexually transmitted infections and risk of epithelial ovarian cancer: results from the Nurses' Health Studies. Br J Cancer 2019;120:855-60.
16. Idahl A, Le Cornet C, González Maldonado S, Waterboer T, Bender N, Tjønneland A, et al. Serologic markers of Chlamydia trachomatis and other sexually transmitted infections and subsequent ovarian cancer risk: results from the EPIC cohort. Int J Cancer 2020;147:2042-52.
17. Idahl A, Lundin E, Jurstrand M, Kumlin U, Elgh F, Ohlson N, et al. Chlamydia trachomatis and Mycoplasma genitalium plasma antibodies in relation to epithelial ovarian tumors. Infect Dis Obstet Gynecol 2011;2011:824627.
18. Perrott SL, Kar SP. Appraisal of the causal effect of Chlamydia trachomatis infection on epithelial ovarian cancer risk: a two-sample Mendelian randomisation study. medRxiv 2024.
19. Kuchenbaecker KB, Hopper JL, Barnes DR, Phillips KA, Mooij TM, Roos-Blom MJ, et al. Risks of breast, ovarian, and contralateral breast cancer for BRCA1 and BRCA2 mutation carriers. JAMA 2017;317:2402-16.
20. Stewart C, Ralyea C, Lockwood S. Ovarian cancer: an integrated review. Semin Oncol Nurs 2019;35:151-6.
21. Janbabaei G, Sarmadi Kia M, Kardan Souraki M, Moosazadeh M, Khani S, Janbaz M. Epidemiology of ovarian cancer in Sari Imam Khomeini Hospital, Iran 2006-2014. J Mazandaran Univ Med Sci 2018;28:151-6.
22. Tingulstad S, Skjeldestad FE, Halvorsen TB, Hagen B. Survival and prognostic factors in patients with ovarian cancer. Obstet Gynecol 2003;101:885-91.
23. Rodriguez-Velazquez A, Velez R, Lafontaine JC, Colon-Echevarria CB, Lamboy-Caraballo RD, Ramirez I, et al. Prevalence of breast and ovarian cancer subtypes in Hispanic populations from Puerto Rico. BMC Cancer 2018;18:1177.
| Files | ||
| Issue | Vol 64 No 6 (2026) | |
| Section | Original Articles | |
| DOI | https://doi.org/10.18502/acta.v64i6.22317 | |
| Keywords | ||
| Ovarian neoplasms Herpes simplex virus type 2 Sexually transmitted diseases Case-control studies Iran | ||
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