Genomics of Human Papillomavirus-induced Cervical Cancer

Abstract

Human papillomavirus (HPV) induced cervical cancer is a serious health issue among most women from the least developed countries of the world due to scarcity of resources. HPVs have evolved a masterly infectious cycle that grabs the advantage of the self-renewal property of stratified cutaneous and mucosal epithelia. Firstly, the viral genome replicates episomally at a low copy number in the epithelial basal layers cells, with minimum viral transcription and translation. After that, when the infected cells are transmitted through the differentiation process maximum viral DNA synthesis and gene expression occur. The two major oncoproteins - E6 and E7, are responsible for inactivating the important tumor suppressor proteins, retinoblastoma (pRb) and p53. Due to the inactivation of these proteins, disruption occurs in the DNA replication, DNA repair mechanisms, oxidative induced damage (8-oxoguanine), aneuploidy, and apoptosis, leading to tumorigenesis. Hence, manipulation of E6 and E7 genes shows a successful result in the treatment of cervical cancer. The diagnosis tests include liquid-based preparations to improve the standard of the Pap smear; computer-based screening methods to improve Pap smear interpretation; and HPV testing methods that may be beneficial in triaging patients with untypical squamous cells of unknown significance or low grade squamous intraepithelial lesions (SILs). The continued studies of the molecular biology of HPVs are necessary to develop advanced screening techniques for testing and prophylactic vaccines for the elimination of HPV infection, also better therapeutic vaccines for the treatment of various HPVs infections.