HUMAN PAPILLOMA VIRUS INFECTION AND CORRELATION WITH EXPRESSION OF P16 GENE IN ORAL POTENTIALLY MALIGNANT DISORDERS AND ORAL CANCER

Abstract

<h3>Background</h3> Human papilloma virus (HPV) infection has been increasingly recognized as a major etiologic factor for a subset of oral squamous cell carcinoma (OSCC) and oral potentially malignant disorders (OPMDs). The <i>p16^INK4A</i> gene is usually inactivated in many cancers. HPV leads to an increase in p16^INK4a levels. <h3>Objective</h3> To investigate the presence of E7 and E6 oncogenes of HPV and the expression of p16^INK4a in OSCC and OPMDs. <h3>Methods</h3> Twelve OSCC, 71 OPMD, and 30 normal oral mucosal tissues were used. Of the OPMD samples there were 24 cases of oral submucous fibrosis (OSF), 26 cases of oral lichen planus (OLP), and 21 cases of oral leukoplakia (OL). Expression of p16 was investigated by immunohistochemistry. E7 and E6 oncogenes were detected using polymerase chain reaction. <h3>Results</h3> Twenty-two cases were positive for p16 gene expression (26.5%). Expression of p16 in OLP was observed in 7 cases (8.4%), followed by 10 cases of OSF (12.1%) and 4 cases of OL (4.8%). One OSCC case was positive for p16 (1.2%), and HPV E7 was detected in same specimen (8.4%). Of OSF cases, 1 was positive for HPV (4.2%) and the same specimen was positive for P16. For HPV E7 overall positivity was 2.4% and HPV E6 was negative for all cases. All positive HPV cases were among male patients and positive for p16 gene expression. <h3>Conclusions</h3> A significant correlation between HPV gene positivity and p16 gene expression was observed in OSCC and OPMD. The findings also suggest that inactivation of p16 occurs at the early stage of multistep carcinogenesis before the acquisition of an invasive phenotype.