Investigation of human papillomavirus pathogenesis in the head and neck using novel

A large proportion of head and neck cancers that arise in the oropharynx are caused by infection with the human papillomavirus (HPV). The incidence of this HPV-driven cancer is increasing very rapidly and has been referred to as an "emerging epidemic". However, there is a distinct lack of information on how the virus replicates in the oropharynx and on how these infections convert to cancer. To understand the interaction between the virus and the oropharynx, we have developed a unique model of HPV infection within the tonsil that recapitulates the molecular phenotype of the site of HPV-driven oropharyngeal cancer; the tonsil crypt. The aim of the studentship is to utilise the model to understand how HPV contributes to early disease progression at this body site. In-depth investigation of the model grown in 2- and 3-dimensional tissue culture will link virus-driven changes in biology to changes in virus genomic structure and the tonsil transcriptome. Also, the role of potential oncogenic drivers in the development HPV associated oropharyngeal cancer will be examined by using different technologies including CRISPR/Cas9 technology. Understanding HPV pathogenesis at this body site will be important in the design of novel early diagnostic and prognostic tools, and therapeutics for HPV-driven oropharyngeal cancer.