APOBEC-mediated genomic alterations link immunity and viral infection during human papillomavirus-driven cervical carcinogenesis.

Cervical cancer is one of the most frequently diagnosed cancers and is a major cause of death from gynecologic cancers worldwide; the cancer burden from cervical cancer is especially heavy in less developed countries. Most cases of cervical cancer are caused by persistent infection with carcinogenic human papillomavirus (HPV) genotypes 16 and 18. Non-resolving inflammation caused by HPV infection provides a microenvironment that facilitates cancer development. Molecular alterations during the process of HPV-induced carcinogenesis are characterized by DNA methylation within the HPV genome, promoter hypermethylation of tumor suppressor genes in the host genome, as well as genomic instability caused by viral DNA integrating into the host genome. Catalytic polypeptide-like apolipoprotein B mRNA editing enzymes (APOBECs) normally function as part of the innate immune system. APOBEC expression is stimulated upon viral infection and plays an important role in HPV-induced cervical cancer. APOBECs catalyze the deamination of cytosine bases in nucleic acids, which leads to a conversion of target cytosine (C) to uracil (U) and consequently a change in the single-stranded DNA/RNA sequence. APOBEC proteins mediate the complex interactions between HPV and the host genome and link immunity and viral infection during HPV-driven carcinogenesis. Understanding the effects of APOBECs in HPV-induced cervical carcinogenesis will enable the development of better tools for HPV infection control and personalized prevention and treatment strategies.