TY - JOUR
T1 - Integrative analysis of head and neck cancer identifies two biologically distinct HPV and three non-HPV subtypes
AU - Keck, Michaela K.
AU - Zuo, Zhixiang
AU - Khattri, Arun
AU - Stricker, Thomas P.
AU - Brown, Christopher D.
AU - Imanguli, Matin
AU - Rieke, Damian
AU - Endhardt, Katharina
AU - Fang, Petra
AU - Gelmann, Johannes Bra
AU - DeBoer, Rebecca
AU - El-Dinali, Mohamed
AU - Aktolga, Serdal
AU - Lei, Zhengdeng
AU - Tan, Patrick
AU - Rozen, Steve G.
AU - Salgia, Ravi
AU - Weichselbaum, Ralph R.
AU - Lingen, Mark W.
AU - Story, Michael D.
AU - Ang, K. Kian
AU - Cohen, Ezra E W
AU - White, Kevin P.
AU - Vokes, Everett E.
AU - Seiwert, Tanguy Y.
N1 - Publisher Copyright:
© 2015 American Association for Cancer Research.
PY - 2015/2/15
Y1 - 2015/2/15
N2 - 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.
AB - 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.
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U2 - 10.1158/1078-0432.CCR-14-2481
DO - 10.1158/1078-0432.CCR-14-2481
M3 - Article
C2 - 25492084
AN - SCOPUS:84923172078
SN - 1078-0432
VL - 21
SP - 870
EP - 881
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 4
ER -