Review Article: CarcinogenesisReview of the current knowledge on the epidemiology, pathogenesis, and prevention of human papillomavirus infectionAsiaf, Asiaa; Ahmad, Shiekh T.b; Mohammad, Sheikh O.c; Zargar, Mohammad A.a Author Information aDepartment of Biochemistry, Faculty of Biological Science, University of Kashmir, Srinagar bInstitute for Stem Cell Biology & Regenerative Medicine, NCBS (TIFR) Campus, Bangalore cDepartment of Biochemistry and Molecular Biology, School of life Sciences, Pondicherry University, Puducherry, India Correspondence to Mohammad A. Zargar, PhD, Department of Biochemistry, Faculty of Biological Science, University of Kashmir, Srinagar 190006, India Tel: +91 194 242 8723; fax: +91 194 242 1353; e-mail: [email protected] Received April 4, 2013 Accepted June 25, 2013 European Journal of Cancer Prevention 23(3):p 206-224, May 2014. | DOI: 10.1097/CEJ.0b013e328364f273 Buy Metrics Abstract Human papillomavirus (HPV) infection is a central and necessary, although not sufficient, cause of cervical cancer. Besides HPV, the additional multiple risk factors related with the onset of cervical cancer are early-age sexual activities; high number of sexual partners, which is the most salient risk factor; suppression and alteration of the immune status; long-term use of oral contraceptives; and other hormonal influences. The tumor-suppressor proteins p53 and pRb are degraded and destabilized through ubiquitination by viral oncoproteins E6 and E7. Over 95% of cervical cancer cases worldwide test positive for oncogenic HPV DNA. Although cervical screening procedures have been successful in reducing the disease burden associated with HPV infection because of lack of resources or inadequate infrastructure many countries have failed to reduce cervical cancer mortality. Therefore, prevention may be a valuable strategy for reducing the economic and disease burden of HPV infection. At present, two successful prophylactic HPV vaccines are available, quadrivalent (HPV16/18/6/11) ‘Gardasil’ and bivalent (HPV16/18) ‘Cervarix’ for vaccinating young adolescent girls at or before the onset of puberty. Recent data indicate that vaccination prevents the development of cervical lesions in women who have not already acquired the vaccine-specific HPV types. Moreover, several therapeutic vaccines that are protein/peptide-based, DNA-based, or cell-based are in clinical trials but are yet to establish their efficacy; these vaccines are likely to provide important future health benefits. The therapeutic vaccination mode of prevention is a promising area of research, as revealed in preclinical trials; however, clinical trials based on large populations are warranted before reaching a valid conclusion. This review summarizes the studies on the epidemiology of HPV infection, the pathogenesis of viral oncoproteins in the oncogenesis of cervical cancer, the economic and health burden of HPV-related diseases, and, finally, focuses on the results of recent clinical vaccination trials. © 2014 Lippincott Williams & Wilkins, Inc.