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

Cell Rep. 2019 Nov 5;29(6):1660-1674.e7. doi: 10.1016/j.celrep.2019.10.005.


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.

Keywords: GEMM, human papilloma virus; HNSCC; HPV; HPV16; LumiFluor; OPSCC; genetically engineered mouse model; head and neck squamous cell carcinoma; immunocompetent; oncogene; oropharyngeal squamous cell carcinoma; tumor suppressor; tumorigenesis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carcinogenesis / genetics
  • Carcinogenesis / metabolism
  • Cell Line, Tumor
  • Class I Phosphatidylinositol 3-Kinases / genetics
  • Class I Phosphatidylinositol 3-Kinases / metabolism
  • Disease Models, Animal*
  • Female
  • Gene Expression
  • Head and Neck Neoplasms / genetics
  • Head and Neck Neoplasms / immunology
  • Head and Neck Neoplasms / metabolism
  • Head and Neck Neoplasms / virology*
  • Humans
  • Immunocompetence
  • Internal Ribosome Entry Sites / genetics
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Natural Killer T-Cells / immunology
  • Natural Killer T-Cells / metabolism
  • Oncogene Proteins, Viral / genetics
  • Oncogene Proteins, Viral / metabolism*
  • Oropharyngeal Neoplasms / genetics
  • Oropharyngeal Neoplasms / immunology
  • Oropharyngeal Neoplasms / metabolism
  • Oropharyngeal Neoplasms / virology*
  • Papillomavirus E7 Proteins / genetics
  • Papillomavirus E7 Proteins / metabolism*
  • RNA Splicing / genetics
  • RNA-Seq
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism*
  • Squamous Cell Carcinoma of Head and Neck / genetics
  • Squamous Cell Carcinoma of Head and Neck / immunology
  • Squamous Cell Carcinoma of Head and Neck / metabolism
  • Squamous Cell Carcinoma of Head and Neck / virology*
  • T-Lymphocytes, Regulatory / immunology
  • T-Lymphocytes, Regulatory / metabolism


  • E6 protein, Human papillomavirus type 16
  • Internal Ribosome Entry Sites
  • Oncogene Proteins, Viral
  • Papillomavirus E7 Proteins
  • Repressor Proteins
  • oncogene protein E7, Human papillomavirus type 16
  • Class I Phosphatidylinositol 3-Kinases
  • Pik3ca protein, mouse