The mechanisms of HPV-induced carcinogenesis and the HPV vaccine

Abstract

Human Papillomavirus (HPV) is the most common sexually transmitted virus. It is estimated that 75% of sexually active adults transmit HPV at some instance during their life. It has long since been known that infection with particular genotypes of this virus is a necessary factor for the development of cervical cancer. In fact, the DNA of this virus is found in 100% of histologically-confirmed cervical cancers. Cervical cancer is a frequent cause of female morbidity and mortality, especially in developing counties. The first part of this study will focus on the way in which infection with specific genotypes of this virus can lead to the development of neoplasia. This will be done in part by explanation of the life cycle of this virus as well as by clarification of the function of the 2 oncogenes E6 and E7 that this virus possesses as part of its genome. It must be kept in mind that not all genotypes of this virus are carcinogenic. In fact, the genotypes that are most strongly associated with cervical cancer are HPV-16 and HPV-18, 2 genotypes that were described by the International Association of Research on Cancer (IARC) as definite human carcinogens. These two genotypes also fall under the heading of high-risk viruses, also because of their oncogenic potential. Given the fact that infection with HPV is an essential step in the development of cervical cancer, prevention of infection by vaccination can reduce the incidence of this cancer. In June 2006, the Food and Drug Administration (FDA) approved an HPV vaccine, Gardasil, for clinical use in females aged 9-26. This vaccine protects against 4 genotypes of HPV, two of which are the above-mentioned HPV-16 and HPV-18. These 2 genotypes together are responsible for over 70% of cervical cancers. It is thus, hoped that this vaccine will have major benefit on a global scale. The 2nd part of this review will focus on diverse issues related to the HPV vaccine. A brief review of the experiments.