Anal human papilloma viral infection and squamous cell carcinoma: Need objective biomarkers for risk assessment and surveillance guidelines

Figure 1 Human papilloma viral oncogenes and cell cycle in carcinogenesis. The tumor suppressors are depicted in green and the oncogenes are depicted in pink color. The cell cycle is in blue color. Human papilloma viral (HPV) targets actively proliferating basal cells in the anogenital mucosa. E6 and E7 are HPV viral oncogenes and up-regulate cellular proliferation resulting in increased numbers of infected cells with infectious virions. E6 and E7 viral oncoproteins inactivate a number of the host’s cells tumor suppressor proteins such as P53, P21 and pRb (retinoblastoma) respectively. These tumor suppressor genes have key functions in regulation from a G1 to S phase of the cell cycle. P53 is also called the guardian of the genome with mechanisms for DNA repair and in inducing apoptosis. PRb is also referred to as the gatekeeper of the genome. P16 is a tumor suppressor protein which is a marker for increased HPV related cell proliferative state. It inhibits the cyclin D and CDK4/6 proteins. It is also a marker for cell stress and senescence. P16 positivity in HPV infected cells suggests a proliferative state with deregulatory mechanisms in effect. It is thus a surrogate marker for high risk HPV infections. HPV: Human papilloma viral.