en Infectious disease (Molecular and Cellular aspects) Infectious disease (Molecular and Cellular aspects) Original Article Original Article <span style="font-size:12px;"><span style="line-height:150%"><span new="" roman="" times=""><span style="line-height:150%">Human papillomavirus (HPV) is recognized as a most important risk factor in oral cavity cancer and</span> <span style="line-height:150%">pre-malignant lesions; however,</span> <span style="line-height:150%">etiological association of concomitant infection with other oncogenic viruses as a co-factor</span> <span style="line-height:150%">has not been definitively proven. The present study aimed to determine the prevalence of co-infection with HPV, Epstein&ndash;Barr virus (EBV) and Merkel Cell PolyomaVirus (MCPyV) in oral cavity lesions in Iranian patients.<b> </b>One hundred and fourteen</span> <span style="line-height:150%">oral cavity samples, including 33 oral squamous cell carcinoma, 28</span> <span style="line-height:150%">oral lichen planus, 16 oral epithelial dysplasia and 37 oral irritation fibromas were analyzed for the HPV, EBV and MCPyV infection by quantitative real-time PCR. According to histological features 32.5% and 28.9% of cases were oral irritation fibroma and oral squamous cell carcinoma, respectively. <span class="fontstyle01" new="" roman="" times=""><span style="color:black"><span style="font-weight:bold"><span style="font-style:normal"><span style="line-height:150%"><span style="font-weight:normal">Infection with at least two viruses was detected in 21.1% of patients. In this group, co-infection with HPV/EBV was identified in 37.5% of cases, HPV/MCPyV in 29.2%, EBV/MCPyV in 12.5%, and HPV/EBV/MCPyV in 20.8%. There was no statistically significant difference between multiple infections and anatomical locations of cancer. The prevalence of triple viral infection (HPV/EBV/MCPyV) in well differentiated tumors was higher than EBV or MCPyV single infection.</span></span></span></span></span></span><b> </b>This study revealed that co-infection of HPV, EBV and MCPyV can be detected in both malignant and non-malignant oral cavity tissues, and <span class="fontstyle01" new="" roman="" times=""><span style="color:black"><span style="font-weight:bold"><span style="font-style:normal"><span style="line-height:150%"><span style="font-weight:normal">co-infection with all three viruses in well differentiated tumors </span></span></span></span></span></span>can be shown as a synergistic hypothesis of the pathogenic role of these viruses in oral malignant transformation.</span></span></span><br> &nbsp;</span> Co-infection, human papillomavirus (HPV), Merkel cell polyomavirus (MCPyV), Epstein–Barr virus (EBV), oral lesions 64 77 http://ijmcmed.org/browse.php?a_code=A-10-100-3&slc_lang=en&sid=1 Sagahr Saber Amoli sagharsaberamoli2@gmail.com 100319475328460026126 100319475328460026126 No Department of Medical Microbiology, Faculty of Medicine, Babol University of Medical Sciences, Babol, Iran. Ali Hasanzadeh ali72hassanzadeh@gmail.com 100319475328460026127 100319475328460026127 No Department of Medical Microbiology, Faculty of Medicine, Golestan University of Medical Sciences, Gorgan, Iran. Farzin Sadeghi sadeghi.farzin@yahoo.com 100319475328460026128 100319475328460026128 No Cellular and Molecular Biology Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran. Mohammad Chehrazi mohamadchehrazi@gmail.com 100319475328460026129 100319475328460026129 No Department of Biostatistics and Epidemiology, School of Public Health, Babol University of Medical Sciences, Babol, Iran. Maryam Seyedmajidi ms_majidi79@yahoo.com 100319475328460026130 100319475328460026130 No Dental Materials Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran. Arghavan Zebardast arqavan9372@gmail.com 100319475328460026131 100319475328460026131 No Department Medical Virology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran. Yousef Yahyapour uyahyapoor@yahoo.com 100319475328460026132 100319475328460026132 Yes Cancer Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran.