Integrative analysis of head and neck cancer identifies two biologically distinct HPV and three non-HPV subtypes.
Clin Cancer Res, 2015/2/15;21(4):870-81.
Keck MK[1], Zuo Z[2], Khattri A[2], Stricker TP[3], Brown CD[4], Imanguli M[5], Rieke D[2], Endhardt K[2], Fang P[2], Brägelmann J[2], DeBoer R[2], El-Dinali M[2], Aktolga S[2], Lei Z[6], Tan P[7], Rozen SG[6], Salgia R[8], Weichselbaum RR[8], Lingen MW[9], Story MD[10], Ang KK[11], Cohen EE[12], White KP[13], Vokes EE[8], Seiwert TY[14]
Affiliations
PMID: 25492084DOI: 10.1158/1078-0432.CCR-14-2481
Impact factor: 13.801
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 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.
MeSH terms
Carcinoma, Squamous Cell; Head and Neck Neoplasms; Humans; Papillomaviridae; Papillomavirus Infections; Squamous Cell Carcinoma of Head and Neck
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