HPV E6 oncoprotein as a potential therapeutic target in HPV related cancers

Introduction: Human Papillomaviruses (HPVs) are the main etiological agents for the development of most ano-genital cancers and for a subset of head and neck neoplasias. The oncogenic capacity of HPV is due to the combined activity of the viral oncoproteins E6 and E7. A defining feature of all HPV associated cancers is the continued retention and expression of these two viral oncoproteins throughout the development of the disease, and this highlights their value as potential targets for therapeutic intervention, in HPV-induced malignancies. Areas covered: In this review, the authors focus on the HPV E6 oncoprotein functions and its interactions with cellular targets containing either LxxLL motifs or PDZ domains. New approaches leading to the prevention such interactions are described, showing the advantage of E6 as a target for therapeutic intervention against malignant transformation and cancer. Expert opinion: The high degree of conservation in E6-LxxLL interactions across multiple HPV types makes this a compelling therapeutic target for pathologies caused by diverse HPV types. Combining this with therapeutics directed against E6-PDZ interactions offers great promise for the treatment of malignancies caused by high-risk HPV types.