Intervention targeting viral E6/E7 oncogenes
The development of cervical cancer from the initial establishment to subsequent progression is entirely dependent on two major hrHPV oncogenes, E6 and E7, whose overexpression leads to tumorigenesis.15-16 Therefore, targeting E6 and E7 oncogenes is the most promising strategy for developing therapeutic drugs or vaccines to eliminate persistent hrHPV infection and promote regression of cervical intraepithelial neoplasia.17Generally, hrHPV persists in infected host cells as a circular episome, but can also linearize and integrate into the host genome. High-risk HPV genome integration can lead to disruption of the E2 open reading frame, causing loss of expression of the E2 gene that represses the viral oncogenes, E6 and E7,18 resulting in overexpression of viral E6 and E7 oncoproteins, which disrupt the functions of the tumor suppressor p53 and retinoblastoma protein pRB, damage host cell DNAs, and inhibit the host’s innate immune system. Therefore, E6 and E7 are the most effective therapeutic targets.17