Date of Award


Document Type

Open Access Dissertation


Biomedical Science


School of Medicine

First Advisor

Lucia Pirisi-Creek


The anatomy of the head and neck is closely associated with the nervous system which plays an important role in the prognosis of head and neck cancer (HNC). However, the molecular interactions between these compartments and HNC remain poorly understood. We present a novel big data approach utilizing clinical data, sequencing, and machine learning to identify and validate potential molecular pathways by which the nervous system affects the development and progression of HNC. Our studies demonstrate across multiple datasets that perineural invasion (PNI) frequently occurs in HPV+ HNC. Furthermore, we show novel activating and missense mutations and pathways that may play important roles in the progression of HNC. We hypothesized that HPV+ cancers might be driven by different neurotrophic-associated genes and programs. We observed that neuroendocrine and neurotrophin signaling through the nerve growth factor receptor (NGFR) can be observed in differentiating HPV+ versus HPV- and PNI+ versus PNI- HNC. These observations may provide significant therapeutic targets for HNC.


© 2018, Christian A. Graves