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Head and neck squamous cell carcinoma

Nature Reviews Disease Primers volume 6, Article number: 92 (2020) Cite this article

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An Author Correction to this article was published on 19 January 2023

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Abstract

Most head and neck cancers are derived from the mucosal epithelium in the oral cavity, pharynx and larynx and are known collectively as head and neck squamous cell carcinoma (HNSCC). Oral cavity and larynx cancers are generally associated with tobacco consumption, alcohol abuse or both, whereas pharynx cancers are increasingly attributed to infection with human papillomavirus (HPV), primarily HPV-16. Thus, HNSCC can be separated into HPV-negative and HPV-positive HNSCC. Despite evidence of histological progression from cellular atypia through various degrees of dysplasia, ultimately leading to invasive HNSCC, most patients are diagnosed with late-stage HNSCC without a clinically evident antecedent pre-malignant lesion. Traditional staging of HNSCC using the tumour–node–metastasis system has been supplemented by the 2017 AJCC/UICC staging system, which incorporates additional information relevant to HPV-positive disease. Treatment is generally multimodal, consisting of surgery followed by chemoradiotherapy (CRT) for oral cavity cancers and primary CRT for pharynx and larynx cancers. The EGFR monoclonal antibody cetuximab is generally used in combination with radiation in HPV-negative HNSCC where comorbidities prevent the use of cytotoxic chemotherapy. The FDA approved the immune checkpoint inhibitors pembrolizumab and nivolumab for treatment of recurrent or metastatic HNSCC and pembrolizumab as primary treatment for unresectable disease. Elucidation of the molecular genetic landscape of HNSCC over the past decade has revealed new opportunities for therapeutic intervention. Ongoing efforts aim to integrate our understanding of HNSCC biology and immunobiology to identify predictive biomarkers that will enable delivery of the most effective, least-toxic therapies.

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Fig. 1: Anatomical sites of HNSCC development.
Fig. 2: Global incidence of HNSCC.
Fig. 3: Progression of HNSCC and key genetic events.
Fig. 4: Development of carcinogen-associated, HPV-negative HNSCC.
Fig. 5: HPV infection of the tonsil crypt and development of HPV-positive HNSCC.
Fig. 6: Histopathology of HNSCC.
Fig. 7: Algorithm for treatment decision-making for recurrent and/or metastatic HNSCC.

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Acknowledgements

This work was supported by the following: NIH R35CA231998 (J.R.G.), U54CA209891 (J.R.G.), R01DE023685 (J.R.G. and D.E.J.), R01DE028289 (D.E.J. and J.R.G.), NET-QUBIC–Dutch Cancer Society grant VU 2013-5930 (C.R.L.), General Research Fund no. 17121616 and no. 14168517 (V.W.Y.L.), Research Impact Fund R4015-19F and R4017-18 (V.W.Y.L.), the Health and Medical Research Fund by the Food and Health Bureau, the Government of the Hong Kong Special Administrative Region no. 15160691 (V.W.Y.L.), University–Industry Collaboration Program UIM/329 by the Innovation and Technology Fund, Hong Kong Government, Hong Kong SAR (V.W.Y.L.), the Hong Kong Cancer Fund, Hong Kong SAR (V.W.Y.L.), NIH/NCI UG1CA242596 (J.E.B.), and NIH/NCI P30CA023074 (J.E.B.).

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Authors and Affiliations

  1. Department of Otolaryngology-Head and Neck Surgery, University of California at San Francisco, San Francisco, CA, USA

    Daniel E. Johnson & Jennifer R. Grandis

  2. Department of Medicine, Yale University School of Medicine and Yale Cancer Center, New Haven, CT, USA

    Barbara Burtness

  3. Department of Otolaryngology-Head and Neck Surgery, Amsterdam University Medical Center, Vrije Universiteit Amsterdam, Cancer Center Amsterdam, Amsterdam, Netherlands

    C. René Leemans

  4. School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, Hong Kong SAR

    Vivian Wai Yan Lui

  5. Department of Medicine-Hematology/Oncology, University of Arizona, Tucson, AZ, USA

    Julie E. Bauman

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  1. Daniel E. Johnson
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  2. Barbara Burtness
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  3. C. René Leemans
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  4. Vivian Wai Yan Lui
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  6. Jennifer R. Grandis
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Contributions

Introduction (J.R.G.); Epidemiology (V.W.Y.L.); Pathophysiology/mechanisms (D.E.J.); Diagnosis, screening and prevention (J.E.B.); Management (B.B.); Quality of life (C.R.L.); Outlook (D.E.J. and J.R.G.).

Corresponding author

Correspondence to Jennifer R. Grandis.

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Competing interests

D.E.J. and J.R.G. are co-inventors of cyclic STAT3 decoy and have financial interests in STAT3 Therapeutics. STAT3 Therapeutics holds an interest in cyclic STAT3 decoy. B.B. has received honoraria for consulting from Merck and AstraZeneca. C.R.L. serves on the Advisory Board of Merck & Co. and Rakuten Medical. V.W.Y.L. receives grant support from Lee’s Pharmaceutical, Hong Kong Limited, via the University–Industry Collaboration Program (UIM/329; from the Innovation and Technology Fund, Hong Kong Government; in 2018–2020), and served as a scientific consultant for Novartis Pharmaceutical (Hong Kong) Limited (Oct 2015–Oct 2016). J.E.B. serves as a scientific consultant to CUE Pharmaceuticals and AstraZeneca and has research grant support from the IST programmes of Aveo and Novartis.

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Nature Reviews Disease Primers thanks C. Chung, C. Van Waes, A. Dietz, J. Hess, C. Bradford and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Johnson, D.E., Burtness, B., Leemans, C.R. et al. Head and neck squamous cell carcinoma. Nat Rev Dis Primers 6, 92 (2020). https://doi.org/10.1038/s41572-020-00224-3

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