Human Papillomavirus Type 16 Integration Analysis by Real-time PCR Assay in Associated Cancers

Human papillomavirus (HPV) is a common viral infection worldwide associated with a variety of cancers. The integration of the HPV genome in these patients causes chromosomal instability and triggers carcinogenesis. The aim of this study was to investigate the HPV-16 genome physical status in four major cancers related to HPV infection. Formalin-fixed paraffin-embedded blocks from our previous projects on head and neck, colorectal, penile, and cervical cancers were collected, and HPV-16-positive specimens were used for further analysis. The DNA extraction copy number of E2 and E7 genes was calculated by qualitative real-time PCR method. Serially diluted standards that were cloned in PUC57 plasmid were used. Standard curve and melting curve analysis was used for quantification. Of the 672 specimens studied, 76 (11.3%) were HPV-16 positive. We found that 35.6% (16/45) were integrated. Statistical analysis showed that there were significant correlations between integration of HPV-16 and cervical cancer end-stage carcinogenesis (P < .0001), episomal form, and ASCUS lesions (P = .045). Significant correlation in penile cancer patients was seen between the episomal form and high-grade cancer stage (P = .037). Integration is a major factor in the carcinogenesis mechanism of HPV and has different prevalence in various cancers with a higher rate in progression except in penile cancer.

Translational oncology. 2018 Mar 13 [Epub ahead of print]

Mohammad Hadi Karbalaie Niya, Hossein Keyvani, Fahimeh Safarnezhad Tameshkel, Mostafa Salehi-Vaziri, Sedigheh Teaghinezhad-S, Farah Bokharaei Salim, Seyed Hamid Reza Monavari, Davod Javanmard

Department of Virology, Iran University of Medical Sciences, Tehran, Iran., Department of Virology, Iran University of Medical Sciences, Tehran, Iran; Gastrointestinal and Liver Diseases Research Center, Iran University of Medical Sciences, Tehran, Iran. Electronic address: ., Gastrointestinal and Liver Diseases Research Center, Iran University of Medical Sciences, Tehran, Iran., Research Centre for Emerging and Reemerging Infectious Diseases, Pasteur Institute of Iran; Department of Arboviruses and Viral Hemorrhagic Fevers (National Reference Laboratory), Pasteur Institute of Iran., Department of Microbiology, Faculty of Basic Sciences, Science and Research Branch, Islamic Azad University, Tehran, Iran., Department of Virology, Iran University of Medical Sciences, Tehran, Iran; HIV Laboratory of National Center, Deputy of Health, Iran University of Medical Sciences, Tehran, Iran.