Molecular Detection and Oncogenic Association of Human Herpesvirus 8 (HHV-8) in Breast Cancer: Evidence from a Case Control Study in Iran

Ramezani, Ali; Azaran, Azarakhsh; Mirzaei, Habibollah; Jailian, Shahram; Pirmoradi, Roya; Bagheri, Shahram; Khoramkouhi, Zahra; Mohammadi, Armin

doi:10.66224/ari.2026.371886.4012

Molecular Detection and Oncogenic Association of Human Herpesvirus 8 (HHV-8) in Breast Cancer: Evidence from a Case Control Study in Iran

Articles in Press

Document Type : Original Articles

Authors

¹ Infectious and Tropical Diseases Research Center, Health Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran

² Department of Pathology, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran

³ Department of Surgery, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran

10.66224/ari.2026.371886.4012

Abstract

Introduction: Breast cancer remains the most prevalent malignancy among women globally. The oncogenic role of human herpesvirus 8 (HHV-8) in breast pathology remains controversial and underexplored. Existing literature offers conflicting data on HHV-8 prevalence in breast tissue, and there is a paucity of research correlating viral presence with specific histological subtypes, such as ductal carcinoma in situ (DCIS), or molecular biomarkers within the Iranian population. This study investigates the "hit-and-run" viral hypothesis by comparing viral prevalence between pre-invasive (DCIS) and invasive (IDC) stages, while also providing a phylogenetic analysis of Iranian HHV-8 strains.
Objective: This study aimed to detect HHV-8 DNA in breast tissue samples and evaluate its association with malignancy, tumor grade, and clinicopathological characteristics.
Materials and Methods: A case-control study was conducted using 201 formalin-fixed, paraffin-embedded (FFPE) tissue blocks (110 malignant, 91 benign). HHV-8 DNA was identified via nested PCR targeting the ORF26 gene, followed by sequencing and phylogenetic tree construction.
Results: HHV-8 DNA was significantly more frequent in malignant tissues (7.27%) than in benign lesions (1.10%; p = 0.038). Notably, viral prevalence was higher in pre-invasive DCIS (22.22%) than in invasive carcinoma (4.55%). HHV-8-positive cases exhibited elevated lymph node involvement (62.5%). Phylogenetic analysis clustered the Iranian sequences with East Asian strains.
Conclusion: HHV-8 is significantly associated with breast malignancy, particularly in the pre-invasive stage, which supports a transient oncogenic role. The virus correlates with aggressive clinical features, suggesting it may influence tumor progression during early carcinogenesis via inflammatory pathways and immune evasion mechanisms.

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