Human Papillomavirus (HPV)-Positive Head and Neck Cancer and the Wnt Signaling Pathway

All known human papillomaviruses (HPVs) are exclusively epitheliotropic. Upon entry into populations of stratified epithelial cells, the E6 and E7 oncoproteins encoded by high-risk HPV variants establish a productive infection by manipulating signaling processes in the host environment, leading ultimately to production of infectious particles in the upper epithelial layers. The mechanisms by which E6 and E7 promote cell-cycle progression and viral DNA replication are well established, and involve E6-dependent ubiquitination and degradation of the p53 tumor suppressor, and E7- and cullin 2-dependent ubiquitination and degradation of the retinoblastoma (Rb) tumor suppressor protein. Recent experimental work provides evidence that high-risk HPVs also manipulate the underlying differentiation status of cells by targeting the Wnt pathway to ensure progression of the viral replication cycle. This chapter summarizes the possible cell pathways involved in the activation of Wnt signaling in HPV-positive head and neck cancer.