Genetic Insight of Oncogenic Potential of Human Papilloma Virus

Cervical cancer (CC), fourth-ranked cancer worldwide, affecting women of different age groups. Human papilloma virus (HPV) is an etiological cause in virtually all CC by infecting mucosal or cutaneous stratified epithelia. Enormously published studies on pathogenesis, gene expression, and epidemiological studies have proved beyond doubt the etiology of the high-risk (HR)-HPV genotypes in CC. HPV genotypes, namely, 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, and 68, are considered as HR-HPV among which HPV-16 majorly responsible for 60–80% of CC. Since HPV is sexually transmitted, there are also multiple risk factors other than HPV genomic factors for progression of CC, such as sexual activities and pregnancies at early teenage age, multiple sex partners/parity, infection of Herpes simplex virus, human immunodeficiency infection, smoking, oral contraceptives, hormone replacement therapy, and immune system deficiency. Various HPV genetic factors associated with crucial events of prolonged viral persistence enhance the oncogenic progress of premalignant cervical intraepithelial neoplasia stages 1–3 to transform into invasive cervical carcinoma. Host immunity plays an important role, as in many cases, HPV infection is clinically not manifested and subsided in a time period of up to 3 years, whereas, in others, it may lead to various benign or malignant lesions transforming into invasive CC. Since the pathogenesis of HPV infection progressing to CC is a complex, multifaceted mechanism, this chapter, therefore, aims to provide an update on genomic insight, especially in the context of HPV-16 to illustrate various viral factors facilitating viral replication, immune evasion, degradation of tumor suppressor gene pRB and p53, PDZ-binding domain protein, and infected cell immortalization all eventually leading to malignant cervical lesion progression.