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