Human papillomavirus infection beyond the cervix: Implications for the endometrium, ovary and fertility

Maryam Falahatzadeh; Hamed  Hekmat Nejad; Zahra  Ranjbari; Mohammad Saadatmand Jobijarkoli; Ali  Emami

doi:10.66224/jcbior.7.2.363

Authors

Maryam Falahatzadeh Department of Biotechnology, School of Pharmacy, Shiraz University of Medical Science, Shiraz, Iran
Hamed Hekmat Nejad Department of Basic Sciences, Sari Agricultural Sciences and Natural Resources University, Sari, Iran https://orcid.org/0000-0002-5716-9240
Zahra Ranjbari Department of Basic Science, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran
Mohammad Saadatmand Jobijarkoli School of Medicine, Guilan University of Medical Science, Rasht, Iran
Ali Emami Department of Epidemiology and Biostatistics, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran

DOI:

https://doi.org/10.66224/jcbior.7.2.363

Keywords:

HPV, Cervical cancer, Pregnancy, Ovarian reserve, Female reproductive health

Abstract

Human papillomavirus (HPV) is a major sexually transmitted infection and an established cause of cervical cancer and several other anogenital and oropharyngeal malignancies. Increasing evidence has raised questions regarding the presence of HPV beyond the cervix and its potential relevance to female reproductive health. This critical narrative review examines current evidence concerning HPV detection in the endometrium and ovary and evaluates its potential associations with endometrial and ovarian pathology, ovarian reserve, infertility, assisted reproductive technology outcomes, implantation, and pregnancy loss. HPV DNA has been detected in some endometrial and ovarian specimens; however, reported findings are highly heterogeneous and are influenced by tissue sampling, specimen handling, population characteristics, histopathology, and molecular detection methods. Importantly, detection of HPV DNA does not necessarily indicate productive or persistent infection and should not be interpreted as evidence of tissue-specific causality. Observational studies have reported possible associations between HPV positivity and altered ovarian-reserve measures, reproductive outcomes, and pregnancy complications, while experimental evidence suggests that inflammatory signaling, immune modulation, oxidative stress, and viral oncoprotein activity may provide biologically plausible mechanisms. Nevertheless, the available clinical evidence remains insufficient to establish HPV as a direct cause of ovarian dysfunction, endometrial impairment, infertility, or adverse pregnancy outcomes. Overall, HPV should currently be regarded as a potential reproductive-health correlate rather than an established determinant of female reproductive dysfunction. Standardized tissue sampling, type-specific molecular testing, longitudinal designs, and well-defined reproductive endpoints are needed to clarify the biological and clinical significance of HPV beyond the cervix.

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