Integrative analysis of head and neck cancer identifies two biologically distinct HPV and three non-HPV subtypes.

Serdal Aktolga, Tanguy Y Seiwert, Everett E Vokes, Kevin P White, Ezra E W Cohen, K Kian Ang, Michael D Story, Mark W Lingen, Ralph R Weichselbaum, Ravi Salgia, Steve G Rozen, Patrick Tan, Zhengdeng Lei, Michaela K Keck, Mohamed El-Dinali, Rebecca DeBoer, Johannes Brägelmann, Petra Fang, Katharina Endhardt, Damian Rieke, Matin Imanguli, Christopher D Brown, Thomas P Stricker, Arun Khattri, Zhixiang Zuo

Journal: Clinical cancer research : an official journal of the American Association for Cancer Research 2015;21(4):870-81

PMID: 25492084

Full Text on Silverchair Information Systems View on PubMed

Abstract

PURPOSE

Current classification of head and neck squamous cell carcinomas (HNSCC) based on anatomic site and stage fails to capture biologic heterogeneity or adequately inform treatment.

EXPERIMENTAL DESIGN

Here, we use gene expression-based consensus clustering, copy number profiling, and human papillomavirus (HPV) status on a clinically homogenous cohort of 134 locoregionally advanced HNSCCs with 44% HPV(+) tumors together with additional cohorts, which in total comprise 938 tumors, to identify HNSCC subtypes and discover several subtype-specific, translationally relevant characteristics.

RESULTS

We identified five subtypes of HNSCC, including two biologically distinct HPV subtypes. One HPV(+) and one HPV(-) subtype show a prominent immune and mesenchymal phenotype. Prominent tumor infiltration with CD8(+) lymphocytes characterizes this inflamed/mesenchymal subtype, independent of HPV status. Compared with other subtypes, the two HPV subtypes show low expression and no copy number events for EGFR/HER ligands. In contrast, the basal subtype is uniquely characterized by a prominent EGFR/HER signaling phenotype, negative HPV-status, as well as strong hypoxic differentiation not seen in other subtypes.

CONCLUSION

Our five-subtype classification provides a comprehensive overview of HPV(+) as well as HPV(-) HNSCC biology with significant translational implications for biomarker development and personalized care for patients with HNSCC.

Address: Department of Medicine, The University of Chicago, Chicago, Illinois. Institute of Biological Chemistry and Nutrition, The University of Hohenheim, Stuttgart, Germany.; Department of Medicine, The University of Chicago, Chicago, Illinois.; Department of Pathology, The University of Chicago, Chicago, Illinois.; Department of Human Genetics, The University of Chicago, Chicago, Illinois.; Medical Center, Department of Otolaryngology-Head and Neck Surgery, The University of Texas Southwestern, Dallas, Texas.; Duke-NUS Graduate Medical School, Singapore.; Duke-NUS Graduate Medical School, Singapore. Genome Institute of Singapore, Singapore.; Department of Medicine, The University of Chicago, Chicago, Illinois. The University of Chicago Comprehensive Cancer Center, Chicago, Illinois.; Department of Pathology, The University of Chicago, Chicago, Illinois. The University of Chicago Comprehensive Cancer Center, Chicago, Illinois.; Southwestern Medical Center, Department of Radiation Oncology, The University of Texas, Dallas, Texas.; MD Anderson Cancer Center, The University of Texas, Houston, Texas.; University of California San Diego, La Jolla, California.; The University of Chicago Comprehensive Cancer Center, Chicago, Illinois. Institute for Genomics and Systems Biology, The University of Chicago, Chicago, Illinois.; Department of Medicine, The University of Chicago, Chicago, Illinois. The University of Chicago Comprehensive Cancer Center, Chicago, Illinois. Institute for Genomics and Systems Biology, The University of Chicago, Chicago, Illinois. [email protected].

DOI: 10.1158/1078-0432.CCR-14-2481