Emerging biomarkers in head and neck cancer in the era of genomics

Key Points

  • Epstein–Barr virus in nasopharyngeal carcinoma, human papillomavirus (HPV) in head and neck squamous-cell carcinoma (HNSCC), and PET-imaging features provide robust prognostic biomarkers that are actively being incorporated into clinical trials

  • HPV-positive HNSCCs, most-commonly occurring in the oropharynx, have a better prognosis than HPV-negative tumours; HPV-positive status as a biomarker has facilitated efforts to de-intensify therapy in a subset of patients with a favourable prognosis

  • Comprehensive genomic analyses of HNSCC show loss-of-function in tumour suppressor genes is more common compared with gain-of-function in oncogenes due to genetic aberrations or viral oncoproteins

  • Although overall rates of DNA mutation and copy-number variation are low, HPV-positive tumours have a relatively higher rate of oncogene mutations than HPV-negative tumours

  • For HNSCC, prognostic biomarkers are limited in their utility, and development of predictive biomarkers is desired

  • Novel drug and biomarker developments have been focused on oncogenes, but more-common aberrations in tumour suppressors need to be further exploited

Abstract

Head and neck cancer (HNC) broadly includes carcinomas arising from the mucosal epithelia of the head and neck region as well as various cell types of salivary glands and the thyroid. As reflected by the multiple sites and histologies of HNC, the molecular characteristics and clinical outcomes of this disease vary widely. In this Review, we focus on established and emerging biomarkers that are most relevant to nasopharyngeal carcinoma and head and neck squamous-cell carcinoma (HNSCC), which includes primary sites in the oral cavity, oropharynx, hypopharynx and larynx. Applications and limitations of currently established biomarkers are discussed along with examples of successful biomarker development. For emerging biomarkers, preclinical or retrospective data are also described in the context of recently completed comprehensive molecular analyses of HNSCC, which provide a broad genetic landscape and molecular classification beyond histology and clinical characteristics. We will highlight the ongoing effort that will see a shift from prognostic to predictive biomarker development in HNC with the goal of delivering individualized cancer therapy.

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Figure 1: Molecular pathogenesis of EBV-related NPC.
Figure 2: Schematic diagram of molecular pathogenesis of HPV-related OPC.
Figure 3: Genomic testing using clinical specimens.

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Acknowledgements

This Review is dedicated to our beloved colleague and friend, Dr K. Kian Ang, who had been a pioneer in clinically relevant biomarker development and dedicated his career to improving the care of patients with head and neck cancer.

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Correspondence to Christine H. Chung.

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Kang, H., Kiess, A. & Chung, C. Emerging biomarkers in head and neck cancer in the era of genomics. Nat Rev Clin Oncol 12, 11–26 (2015). https://doi.org/10.1038/nrclinonc.2014.192

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