THE CARCINOGENIC POTENTIAL OF E6 & E7 GENES OF HIGH-RISK HPV COMPARED WITH E6, E7 GENES OF LOW-RISK HPV IN HUMAN CERVICAL CANCER: A REVIEW

Human papillomavirus is one of the most common causes of sexually transmitted disease in both men and women worldwide. Genital HPV types are divided into high and low-risk types, on the basis of oncogenic gene potential. Molecular & epidemiologic studies have confirmed the interaction between high risk HPV types (especially HPV-16 & 18) and cervical squamous cell low risk strain. In high grade Intra epithelial neoplasias & invasive cancers, generally integration of HPV-DNA into the host genome disrupts or deletes the E2 region, which results in loss of its expression. The E6 and E7 gene deregulate the host cell growth cycle by binding and inactivating two tumor suppressor proteins: the tumor suppressor protein (p53) and retinoblastoma gene (pRb). The HPV E6 gene binds to p53 and targets it for rapid degradation leads to an increased expression of E6 and E7 genes. The inactivations of p53 & pRb proteins can increased proliferation rate & genomic instability. In addition, the potential of activated oncogenes cause chromosome instability may transformed in the host genome such as methylation of viral, cellular DNA, telomerase activation, hormonal & immunogenetic factors.  As a result, the host cells accumulate more damage DNA that cannot be repaired, leading to cancerous cells. Low-risk HPV E6 proteins do not bind p53 at detectable levels and have no effect on p53 protein stability in vitro. The E7 protein of low-risk HPV types binds pRb with decreased affinity.