Recent Topics of Human Papillomavirus and Cervical Cancer

Human papillomavirus (HPV) infection is the leading cause of cervical cancer, resulting in a significant global disease burden. HPV consists of a large family of small DNA viruses; with a limited protein-coding capacity due to its ~8000-bp genome, HPV relies heavily on host cell proteins to support the viral life cycle, both productive and persistent phases of infection. Although the viral oncoproteins E6 and E7 (targeting TP53 and RB1, respectively) play critical roles in cervical carcinogenesis, accumulation of somatic mutations in the host genome is required for cancer progression. With regard to this latter point, APOBEC3 cytosine deaminases, which are upregulated by E6/E7, are a major mutagenic source of the HPV-related cancer genome. Moreover, deep sequencing of HPV genomes has shown high levels of variability in the viral genomic sequences in clinical specimens, and elucidated evolutionary pressures on the HPV genome. Cellular mechanisms hijacked by HPV include the intracellular transport pathways for infectious cell entry, DNA damage responses and homologous recombination repair for viral genome replication, and double-strand DNA break repair for viral integration into the host genome. These novel insights pave the way for the development of promising anti-HPV therapeutics to treat and eliminate HPV-infected lesions.