Data from Integrative Analysis of Head and Neck Cancer Identifies Two Biologically Distinct HPV and Three Non-HPV Subtypes

Abstract

<div>Abstract<p><b>Purpose:</b> 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.</p><p><b>Experimental Design:</b> 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<sup>+</sup> tumors together with additional cohorts, which in total comprise 938 tumors, to identify HNSCC subtypes and discover several subtype-specific, translationally relevant characteristics.</p><p><b>Results:</b> We identified five subtypes of HNSCC, including two biologically distinct HPV subtypes. One HPV<sup>+</sup> and one HPV<sup>−</sup> subtype show a prominent immune and mesenchymal phenotype. Prominent tumor infiltration with CD8<sup>+</sup> 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.</p><p><b>Conclusion:</b> Our five-subtype classification provides a comprehensive overview of HPV<sup>+</sup> as well as HPV<sup>−</sup> HNSCC biology with significant translational implications for biomarker development and personalized care for patients with HNSCC. <i>Clin Cancer Res; 21(4); 870–81. ©2014 AACR</i>.</p></div>