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Analysis of Hpv-16 Viral Load, Integration Status, and P16 Expression in Relation to Ebv Co-Infection and Cervical Lesion Severity Publisher Pubmed



Khamseh A1, 2 ; Farhadi A3, 4 ; Jalilvand S5 ; Yarandi F6 ; Izadimood N7 ; Ghorbani S1 ; Saadati H8 ; Shirali E9 ; Jazayeri SM2, 5 ; Sarvari J1, 10
Authors
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Authors Affiliations
  1. 1. Department of Bacteriology and Virology, School of Medicine, Shiraz University of Medical Science, Shiraz, Iran
  2. 2. Research Center for Clinical Virology, Tehran University of Medical Sciences, Tehran, Iran
  3. 3. Department of Medical Laboratory Sciences, School of Paramedical Sciences, Shiraz University of Medical Sciences, Shiraz, Iran
  4. 4. Diagnostic Laboratory Sciences and Technology Research Center, School of Paramedical Sciences, Shiraz University of Medical Sciences, Shiraz, Iran
  5. 5. Department of Virology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
  6. 6. Department of Obstetrics and Gynecology, Yas Hospital, Tehran, Iran
  7. 7. Department of Pathology, Yas Hospital, Tehran University of Medical Sciences, Tehran, Iran
  8. 8. Department of Epidemiology and Biostatistics, School of Health, North Khorasan University of Medical Sciences, Bojnurd, Iran
  9. 9. Yas Hospital, Tehran University of Medical Sciences, Tehran, Iran
  10. 10. Gastroenterohepatology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran

Source: Scientific Reports Published:2025


Abstract

Cervical cancer, one of the most common cancers in women, is primarily driven by high-risk human papillomaviruses (HPV) infections, particularly HPV-16. Co-infection with Epstein-Barr virus (EBV) has been reported to exacerbate disease progression by influencing HPV genome integration. This study examines HPV-16 integration status, p16INK4a expression, and their relationship with EBV co-infection and viral load in cervical cancer cases. In this study, 134 HPV-16-positive formalin-fixed, paraffin-embedded cervical samples were collected and analyzed for HPV-16 viral load, genome integration and EBV co-infection, followed by p16INK4a immunohistochemistry. Statistical analysis was performed to examine the association between viral markers and cervical cancer progression. HPV-16 viral loads varied significantly by histological grade, with the highest loads observed in cervical intraepithelial neoplasia 2 (CIN 2) lesions. HPV integration status revealed episomal forms in 32.8% of samples, mixed forms in 56%, and fully integrated forms in 11.2%. p16INK4a expression correlated with disease progression, increasing with CIN grade and in squamous cell carcinoma (SCC). EBV was detected in 13.4% of samples, but no significant associations were found between EBV infection and HPV integration, viral load, or p16INK4a expression levels. HPV-16 viral load and integration status are strongly associated with cervical lesion severity, while p16INK4a expression increases with lesion grade, indicating its utility as a diagnostic marker. EBV co-infection did not significantly impact lesion progression, suggesting that its role in cervical cancer remains unclear. © The Author(s) 2025.