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

268 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

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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