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

Publication ,  Journal Article
Keck, MK; Zuo, Z; Khattri, A; Stricker, TP; Brown, CD; Imanguli, M; Rieke, D; Endhardt, K; Fang, P; Brägelmann, J; DeBoer, R; El-Dinali, M ...
Published in: Clin Cancer Res
February 15, 2015

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.

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Published In

Clin Cancer Res

DOI

EISSN

1557-3265

Publication Date

February 15, 2015

Volume

21

Issue

4

Start / End Page

870 / 881

Location

United States

Related Subject Headings

  • Squamous Cell Carcinoma of Head and Neck
  • Papillomavirus Infections
  • Papillomaviridae
  • Oncology & Carcinogenesis
  • Humans
  • Head and Neck Neoplasms
  • Carcinoma, Squamous Cell
  • 3211 Oncology and carcinogenesis
  • 3202 Clinical sciences
  • 1112 Oncology and Carcinogenesis
 

Citation

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MLA
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Keck, M. K., Zuo, Z., Khattri, A., Stricker, T. P., Brown, C. D., Imanguli, M., … Seiwert, T. Y. (2015). Integrative analysis of head and neck cancer identifies two biologically distinct HPV and three non-HPV subtypes. Clin Cancer Res, 21(4), 870–881. https://doi.org/10.1158/1078-0432.CCR-14-2481
Keck, Michaela K., Zhixiang Zuo, Arun Khattri, Thomas P. Stricker, Christopher D. Brown, Matin Imanguli, Damian Rieke, et al. “Integrative analysis of head and neck cancer identifies two biologically distinct HPV and three non-HPV subtypes.Clin Cancer Res 21, no. 4 (February 15, 2015): 870–81. https://doi.org/10.1158/1078-0432.CCR-14-2481.
Keck MK, Zuo Z, Khattri A, Stricker TP, Brown CD, Imanguli M, et al. Integrative analysis of head and neck cancer identifies two biologically distinct HPV and three non-HPV subtypes. Clin Cancer Res. 2015 Feb 15;21(4):870–81.
Keck, Michaela K., et al. “Integrative analysis of head and neck cancer identifies two biologically distinct HPV and three non-HPV subtypes.Clin Cancer Res, vol. 21, no. 4, Feb. 2015, pp. 870–81. Pubmed, doi:10.1158/1078-0432.CCR-14-2481.
Keck MK, Zuo Z, Khattri A, Stricker TP, Brown CD, Imanguli M, Rieke D, Endhardt K, Fang P, Brägelmann J, DeBoer R, El-Dinali M, Aktolga S, Lei Z, Tan P, Rozen SG, Salgia R, Weichselbaum RR, Lingen MW, Story MD, Ang KK, Cohen EEW, White KP, Vokes EE, Seiwert TY. Integrative analysis of head and neck cancer identifies two biologically distinct HPV and three non-HPV subtypes. Clin Cancer Res. 2015 Feb 15;21(4):870–881.

Published In

Clin Cancer Res

DOI

EISSN

1557-3265

Publication Date

February 15, 2015

Volume

21

Issue

4

Start / End Page

870 / 881

Location

United States

Related Subject Headings

  • Squamous Cell Carcinoma of Head and Neck
  • Papillomavirus Infections
  • Papillomaviridae
  • Oncology & Carcinogenesis
  • Humans
  • Head and Neck Neoplasms
  • Carcinoma, Squamous Cell
  • 3211 Oncology and carcinogenesis
  • 3202 Clinical sciences
  • 1112 Oncology and Carcinogenesis