Details

Autor(en) / Beteiligte

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

Titel

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

Ist Teil von

• Clinical cancer research, 2015-02, Vol.21 (4), p.870-881

Ort / Verlag

United States

Erscheinungsjahr

2015

Link zum Volltext

Quelle

Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals

Beschreibungen/Notizen

• 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. 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. 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. 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.