Editorial - ONCOGENIC HUMAN PAPILLOMAVIRUSES - High-Risk Human Papillomaviruses: Towards a Better Understanding of the Mechanisms of Viral Transformation, Latency and Immune-Escape

Abstract

High-risk human papillomaviruses (HR-HPVs) cause mucosal epithelial malignancies, most notably cervical intraepithelial neoplasia (CIN) and cancer of the uterine cervix. Prophylactic vaccines based on the L1 capsid proteins of the most prevalent HR-HPV types have been commercialized, and recent studies have shown that cross-neutralization epitopes are present in the L2 minor capsid protein of HR-HPVs, thus giving hope for the prevention of many HPV-associated cancers. However, the high prevalence of HPV infections worldwide and the morbidity and mortality associated with them warrant further research to improve our understanding of HPV pathogenesis, and to develop new generations of prophylactic vaccines and effective immunotherapy strategies. Furthermore, there is a need for a better understanding of the virus life cycle and how this is influenced by the epithelial site, the mechanisms of viral persistence, regression and reactivation, and for detailed molecular studies that clarify the cellular pathways altered by the viral oncoproteins. This special issue was aimed to underline some of those aspects of current HPV research. The E2 gene product of oncogenic HPVs is a transcriptional repressor that controls expression of the viral oncogenes. Integration of the viral DNA in the host genome resulting in disruption of the sequence encoding E2 was postulated more than two decades ago to be critical in the progression from premalignant lesions to cancer. However, further studies have shown that the viral DNA can be found in episomal as well as integrated state in HPV-associated cancers. Using E2-immunohistochemistry and NanoString technology to quantify E2 transcripts Xue et al. [1] show in their article that integration of the viral DNA in the host genome does not always cause disruption of the E2 gene and