HPV-negative HNSCC – USA


United States

Organ System:

Head and Neck

Funding Organizations:

  • Cancer Prevention Institute of Texas, USA
  • National Cancer Institute, USA
  • Robert and Janice McNair Foundation, USA
  • Translational Breast Cancer Research Training Program, USA

Research Organizations:

  • Baylor College of Medicine, USA
  • Brigham Young University, USA
  • Broad Institute of MIT and Harvard, USA
  • Fred Hutchinson Cancer Research Center, USA
  • Icahn School of Medicine at Mount Sinai, USA
  • Johns Hopkins University, USA
  • National Cancer Institute, USA
  • New York University School of Medicine, USA
  • Pacific Northwest National Laboratory, USA
  • University of Michigan, USA
  • Washington University in St. Louis, USA

Principal Investigators:

  • Bing Zhang
  • Daniel W. Chan
  • Hui Zhang


External Links:

We present a proteogenomic study of 108 human papilloma virus (HPV)-negative head and neck squamous cell carcinomas (HNSCCs). Proteomic analysis systematically catalogs HNSCC-associated proteins and phosphosites, prioritizes copy number drivers, and highlights an oncogenic role for RNA processing genes. Proteomic investigation of mutual exclusivity between FAT1 truncating mutations and 11q13.3 amplifications reveals dysregulated actin dynamics as a common functional consequence. Phosphoproteomics characterizes two modes of EGFR activation, suggesting a new strategy to stratify HNSCCs based on EGFR ligand abundance for effective treatment with inhibitory EGFR monoclonal antibodies. Widespread deletion of immune modulatory genes accounts for low immune infiltration in immune-cold tumors, whereas concordant upregulation of multiple immune checkpoint proteins may underlie resistance to anti-programmed cell death protein 1 monotherapy in immune-hot tumors. Multi-omic analysis identifies three molecular subtypes with high potential for treatment with CDK inhibitors, anti-EGFR antibody therapy, and immunotherapy, respectively. Altogether, proteogenomics provides a systematic framework to inform HNSCC biology and treatment.