HPV-driven oncogenesis-much more than the E6 and E7 oncoproteins

High-risk human papillomaviruses are well-established drivers of several cancer types including cervical, head and neck, penile as well as anal cancers. While the E6 and E7 viral oncoproteins have proven to be critical for malignant transformation, evidence is also beginning to emerge suggesting that both host pathways and additional viral genes may also be pivotal for malignant transformation. Here, we focus on the role of host APOBEC genes, which have an important role in molecular editing including in the response to the viral DNA and their role in HPV-driven carcinogenesis. Further, we also discuss data developed suggesting the existence of HPV-derived miRNAs in HPV + tumors and their potential role in regulating the host transcriptome. Collectively, while recent advances in these two areas have added complexity to the working model of papillomavirus-induced oncogenesis, these discoveries have also shed a light onto new areas of research that will be required to fully understand the process.