Overview of genetic and epigenetic regulation of human papillomavirus and apoptosis in cervical cancer

Cervical cancer is the fourth most common cancer affecting women worldwide after breast, colorectal and lung cancers. Owing to a lack of awareness and resources, low- and middle-income countries bear most of the burden of cervical cancer. In developed countries, the incidence rate has been halved over the past three decades due to robust screening and implementation of vaccine programs. HPV is not the sole cause of cervical cancer but acts as a principal factor in the pathogenesis of cervical cancer. By integrating into the host genome, its oncogenic proteins (E6 and E7) alter and interfere with the standard signal transduction machinery of the host. Apoptosis is a key pathway affected by aberrant genetic mutations, polymorphisms and epigenetic mechanisms during cervical carcinogenesis. Along with DNA methylation and histone modifications, non-coding RNAs have also been implicated as epigenetic modulators in various malignancies and are being explored for reversing disease severity. This review emphasizes various genetic and epigenetic approaches regulating apoptotic pathways and HPV E6 and E7 genes that can be targeted to overcome the challenges in cervical cancer treatment. In addition, it also discusses the apoptosis targeting novel drug molecules in cervical cancer which are currently undergoing clinical and pre-clinical trials.

Automated summary

Cervical cancer is a common cancer in women worldwide, particularly in low- and middle-income countries. HPV plays a crucial role in its development by interfering with the host's signaling pathways. Aberrant genetic mutations, polymorphisms, and epigenetic mechanisms affect the apoptotic pathways involved in cervical carcinogenesis. Non-coding RNAs have also been implicated in epigenetic regulation of various malignancies, including cervical cancer. This review focuses on genetic and epigenetic approaches to target apoptosis and HPV genes, as well as novel drug molecules currently in clinical trials for cervical cancer treatment.