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

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

Research output: Contribution to journalArticlepeer-review

199 Scopus citations


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 sub-type-specifi c, 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 fi ve-subtype classifi cation 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. Clin Cancer Res.

Original languageEnglish (US)
Pages (from-to)870-881
Number of pages12
JournalClinical Cancer Research
Issue number4
StatePublished - Feb 15 2015
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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