Cervical cancer remains a major public health problem for women in the world and developing countries, especially in Indonesia. Cervical cancer is caused by persistent infection of high risk human papillomavirus (HPV) that causes for more than 500.000 new cases worldwide and reach almost 300.000 deaths each year. However, most infections will be eradicated by the immune response and only 1% of HPV infections will develop into cancer. The role of HPV in cervical carcinogenesis is explored using literature review from the last ten years. This review aimed to determine the HPV escaping process in carcinogenesis and apoptosis modulation of cells caused by viral oncogene expression.
The mechanism of HPV evades immune response involves the role of HPV oncoproteins e.g. early protein E6 and E7. These protein dysregulate the interferon signaling pathways, therefore, the proinflammatory cytokines can not be produced. Furthermore, early protein E5 and E7 interfere the process of antigen presentation by suppressing the expression of proteosome subunits LMP2 and LMP7, transporters subunits TAP1 and TAP2, and decreased MHC expression. The HPV oncoprotein E5, E6, and E7 also play a role in modulating apoptotic cells and regulate cells proliferation. HPV E7 protein binds to Rb thereby activating the S phase of cells. HPV E6 protein binds to p53 to prevent apoptosis of cells and HPV E5 inhibits TRIAL-mediated apoptotic.
Human papillomavirus infection plays a significant role in cervical carcinogenesis. Exploring the mechanism of HPV escaping mechanism is of great interest in the development of effective new therapies and vaccine in the future. |