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 Lim Seiwert

Research output: Contribution to journalArticle

Abstract

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
Volume21
Issue number4
DOIs
StatePublished - Feb 15 2015
Externally publishedYes

Fingerprint

Head and Neck Neoplasms
Neoplasms
Phenotype
Cluster Analysis
Cell Biology
Cations
Patient Care
Research Design
Biomarkers
Carcinoma, squamous cell of head and neck
Lymphocytes
Ligands
Gene Expression

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Integrative analysis of head and neck cancer identifies two biologically distinct HPV and three non-HPV subtypes. / Keck, Michaela K.; Zuo, Zhixiang; Khattri, Arun; Stricker, Thomas P.; Brown, Christopher D.; Imanguli, Matin; Rieke, Damian; Endhardt, Katharina; Fang, Petra; Gelmann, Johannes Bra; 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.; Lim Seiwert, Tanguy.

In: Clinical Cancer Research, Vol. 21, No. 4, 15.02.2015, p. 870-881.

Research output: Contribution to journalArticle

Keck, MK, Zuo, Z, Khattri, A, Stricker, TP, Brown, CD, Imanguli, M, Rieke, D, Endhardt, K, Fang, P, Gelmann, JB, 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 & Lim Seiwert, T 2015, 'Integrative analysis of head and neck cancer identifies two biologically distinct HPV and three non-HPV subtypes', Clinical Cancer Research, vol. 21, no. 4, pp. 870-881. https://doi.org/10.1158/1078-0432.CCR-14-2481
Keck, Michaela K. ; Zuo, Zhixiang ; Khattri, Arun ; Stricker, Thomas P. ; Brown, Christopher D. ; Imanguli, Matin ; Rieke, Damian ; Endhardt, Katharina ; Fang, Petra ; Gelmann, Johannes Bra ; 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. ; Lim Seiwert, Tanguy. / Integrative analysis of head and neck cancer identifies two biologically distinct HPV and three non-HPV subtypes. In: Clinical Cancer Research. 2015 ; Vol. 21, No. 4. pp. 870-881.
@article{8e4966e156f74aa2abfcc9a15a3cc96b,
title = "Integrative analysis of head and neck cancer identifies two biologically distinct HPV and three non-HPV subtypes",
abstract = "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.",
author = "Keck, {Michaela K.} and Zhixiang Zuo and Arun Khattri and Stricker, {Thomas P.} and Brown, {Christopher D.} and Matin Imanguli and Damian Rieke and Katharina Endhardt and Petra Fang and Gelmann, {Johannes Bra} and Rebecca DeBoer and Mohamed El-Dinali and Serdal Aktolga and Zhengdeng Lei and Patrick Tan and Rozen, {Steve G.} and Ravi Salgia and Weichselbaum, {Ralph R.} and Lingen, {Mark W.} and Story, {Michael D.} and Ang, {K. Kian} and Cohen, {Ezra E.W.} and White, {Kevin P.} and Vokes, {Everett E.} and {Lim Seiwert}, Tanguy",
year = "2015",
month = "2",
day = "15",
doi = "10.1158/1078-0432.CCR-14-2481",
language = "English (US)",
volume = "21",
pages = "870--881",
journal = "Clinical Cancer Research",
issn = "1078-0432",
publisher = "American Association for Cancer Research Inc.",
number = "4",

}

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 - Lim Seiwert, Tanguy

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.

UR - http://www.scopus.com/inward/record.url?scp=84923172078&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84923172078&partnerID=8YFLogxK

U2 - 10.1158/1078-0432.CCR-14-2481

DO - 10.1158/1078-0432.CCR-14-2481

M3 - Article

C2 - 25492084

AN - SCOPUS:84923172078

VL - 21

SP - 870

EP - 881

JO - Clinical Cancer Research

JF - Clinical Cancer Research

SN - 1078-0432

IS - 4

ER -