**4. Human papillomavirus and carcinogenesis**

A systematic review by Kriemer et al. has described the presence of HPV DNA in head and neck cancers [7]. Approximately 150 HPV subtypes have been reported. HPV 16 is associated with >90% of HPV associated oropharyngeal cancers [7]. HPV is a circular, double stranded DNA virus of 55 nm. Multiple sexual partners and/ or higher frequency of oral sex may increase the risk of HPV infection and later malignant transformation. Tonsillar crypts provide large epithelial surface and deep invaginations of the mucosal surface are thought to favor the capture and processing of viral antigens. The epithelial basal cells are the target cells of the virus, where the viral DNA undergoes uncoating and is transported to the nucleus. In high risk HPV infection E6 and E7 proteins are produced from the supra basal layers. In HPV induced carcinogenesis, E6 and E7 oncoproteins deregulates cell cycle and apoptosis by acting on p53 [8]. P53 is a tumor suppressor gene which controls G1 transition to S phase in the cell cycle at G1 check point by inducing the expression of cyclin inhibitors p16, p21 and p27 which in turn will block cyclin dependent kinases and progression of the cell cycle at G1/S transition. Inactivation, of p53 gene causes increased cell proliferation. Rb family of proteins governs the check point between G1 and S Phase. In normal cell cycle hypo phosphorylated Rb forms a complex with E2F and makes it unavailable for the DNA synthesis. E7 oncoprotein inactivate Rb family of proteins that causes over expression of E2F thereby produces increased cell proliferation [9].
