Title: An Immunocompetent Mouse Model of HPV16(+) Head and Neck Squamous Cell Carcinoma.

Authors: Carper, Miranda B; Troutman, Scott; Wagner, Bethany L; Byrd, Kevin M; Selitsky, Sara R; Parag-Sharma, Kshitij; Henry, Erin C; Li, Weimin; Parker, Joel S; Montgomery, Stephanie A; Cleveland, John L; Williams, Scott E; Kissil, Joseph L; Hayes, David N; Amelio, Antonio L

Published In Cell Rep, (2019 11 05)

Abstract: The incidence of human papilloma virus (HPV)-associated head and neck squamous cell carcinoma (HNSCC) is increasing and implicated in more than 60% of all oropharyngeal carcinomas (OPSCCs). Although whole-genome, transcriptome, and proteome analyses have identified altered signaling pathways in HPV-induced HNSCCs, additional tools are needed to investigate the unique pathobiology of OPSCC. Herein, bioinformatics analyses of human HPV(+) HNSCCs revealed that all tumors express full-length E6 and identified molecular subtypes based on relative E6 and E7 expression levels. To recapitulate the levels, stoichiometric ratios, and anatomic location of E6/E7 expression, we generated a genetically engineered mouse model whereby balanced expression of E6/E7 is directed to the oropharyngeal epithelium. The addition of a mutant PIK3CAE545K allele leads to the rapid development of pre-malignant lesions marked by immune cell accumulation, and a subset of these lesions progress to OPSCC. This mouse provides a faithful immunocompetent model for testing treatments and investigating mechanisms of immunosuppression.

PubMed ID: 31693903

MeSH Terms: No MeSH terms associated with this publication