HPV Mediated Antagonism of the IL-18 Proinflammatory Pathway in Head and Neck Cancer
Abstract
In this thesis, I examined the effect of human papillomavirus (HPV) on the proinflammatory IL-18 cytokine pathway in head and neck cancers. I investigated the expression and methylation of genes associated with this pathway using The Cancer Genome Atlas (TCGA) data. In HPV+ cancers, IL18, CASP1, and AIM2 were downregulated, while IL18BP was upregulated compared to HPV- cancers and adjacent non-cancerous tissues, and IL18’s promoter was significantly more methylated. I compared HPV+ and HPV- head and neck cancer cell lines for expression of RNA and protein levels of IL-18 and IL-18BP by qPCR, western blot, and ELISA. IL-18 mRNA and protein levels were lower in HPV+ cells, while IL-18BP mRNA was higher. The E7 protein from most HPV types repressed an IL18 luciferase reporter and this required conserved region 3 of HPV16. Repression of IL-18 mediated inflammation may help HPV evade the immune system and contribute to chronic infection.