Introduction
High-risk human papillomavirus (hrHPV) infection is responsible for
approximately 5% of all human cancers, and nearly all cases of cervical
cancer are initiated by persistent hrHPV infection. According to the
2020 Global Cancer Statistics,1 there are
approximately 600,000 new cases of cervical cancer and 340,000 deaths
worldwide annually. A large-scale epidemiological study of 138,000
Chinese women in 2020 revealed that the HPV infection rate in
gynecological clinics was approximately 23.5%, of which hrHPV infection
accounted for 19.4%.2 Despite the implementation of
standardized cervical cancer screening, persistent hrHPV infections
remain extremely common in the clinic.2-3 During
persistent hrHPV infection, if the viral DNA becomes integrated into the
host genome, constitutive overexpression of viral E6 and E7 oncoproteins
induces the degradation of tumor suppressor p53 and pRb1, leading to
cervical intraepithelial lesions and carcinogenesis.4Therefore, urgent clinical intervention is needed to eliminate
persistent hrHPV infection and promote regression of HPV-associated
high-grade squamous intraepithelial lesions (HSIL).
In recent years, HPV preventive vaccines have been applied clinically to
prevent HPV infection; however, these vaccines do not generate strong
therapeutic effects against existing HPV infections and established
lesions.5 Studies have demonstrated that 99% of
cervical cancers harbor the hrHPV E6 and E7 oncogenes, making the E6/E7
viral oncogene an attractive target for the development of anti-hrHPV
drugs or therapeutic vaccines.6-7 The major difference
between a therapeutic vaccine and
a preventive vaccine is that the former confers cell-mediated immunity
to kill infected cells instead of introducing neutralizing antibodies
into the system. Some HPV therapeutic vaccines, such as VGX 3100,
GX-188E, pNGVL4a-CRT/E7 (detox), and PepCan + Candin ADXS11-OO1, have
undergone clinical trials, and some therapeutic modalities, such as
genome editing and immunity therapy for E6/E7, have also been
explored.8-11
REBACIN® is an innovative anti-HPV biologic. In 2010,
we reported for the first time that the viral E6/E7 oncogenes were the
target of REBACIN® in clearing persistent hrHPV
infection.12 In vitro, REBACIN®significantly inhibited the expression of HPV E6 and E7 oncogenes in
TC-1 and HeLa cells. In vivo, REBACIN® can effectively
inhibit viral E6/E7-induced tumor growth in severe combined
immunodeficiency disease (SCID) mice, and the experimental data in both
cells and animals are shown in a dose-dependent
manner.13 Our clinical studies demonstrated that
REBACIN® significantly eliminates persistent hrHPV
infection and promotes regression of the associated intraepithelial
neoplasia.13-14 This review summarizes the progress of
REBACIN® in clearing persistent hrHPV infection and
promoting the regression of HPV-associated cervical precancerous
lesions, with the aim of providing a new non-invasive clinical
intervention option to clear persistent hrHPV infection and associated
cervical lesions.