Review Article | Published:

The changing therapeutic landscape of head and neck cancer

Abstract

Head and neck cancers are a heterogeneous collection of malignancies of the upper aerodigestive tract, salivary glands and thyroid. In this Review, we primarily focus on the changing therapeutic landscape of head and neck squamous cell carcinomas (HNSCCs) that can arise in the oral cavity, oropharynx, hypopharynx and larynx. We highlight developments in surgical and non-surgical therapies (mainly involving the combination of radiotherapy and chemotherapy), outlining how these treatments are being used in the current era of widespread testing for the presence of human papillomavirus infection in patients with HNSCC. Finally, we describe the clinical trials that led to the approval of the first immunotherapeutic agents for HNSCC, and discuss the development of strategies to decrease the toxicity of different treatment modalities.

Key points

  • Current treatments for human papillomavirus-driven (HPV+) oropharyngeal squamous cell carcinoma (OPSCC), primarily derived from those for the more aggressive HPV head and neck squamous cell carcinoma (HSNCC), might be more intensive than necessary for patients with favourable risk features and an excellent prognosis.

  • Multiple prospective studies have investigated various treatment de-intensification strategies with promising early results; however, pending definitive conclusions, HPV+ OPSCC should continue to be treated with established standard-of-care therapies, known to yield very high survival.

  • Minimally invasive transoral surgical techniques provide an alternative treatment option for OPSCC; retrospective evidence is promising, but results from prospective randomized trials are required to fully integrate these approaches into the treatment armamentarium.

  • More-precisely targeted radiotherapy (with incorporation of intensity-modulated radiation therapy, molecular imaging-guided therapy, adaptive therapy and proton beam therapy) has the potential to decrease the long-term toxicity of radiotherapy.

  • Anti-EGFR therapy with cetuximab improves survival in the curative and recurrent and/or metastatic settings; however, no other molecularly targeted approach has prolonged survival in HNSCC.

  • Anti-programmed cell death 1 (PD-1) therapies, currently approved for platinum-refractory recurrent and/or metastatic HNSCC, offer the prospect of long-term remissions with fewer toxicities than traditional cytotoxic chemotherapy for a minority of patients, and are expected to advance to earlier lines of therapy.

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Acknowledgements

The work of R.L.F. was supported by the US NIH grant P50 CA097190 and the University of Pittsburgh Cancer Center support grant P30CA047904.

Reviewer information

Nature Reviews Clinical Oncology thanks A. Eisbruch and the other anonymous reviewer(s), for their contribution to the peer review of this work.

Author information

All authors made a substantial contribution to all aspects of the preparation of the manuscript.

Competing interests

B.B. has received compensation for consulting from Aduro, Alligator Biosciences, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, DebioPharma, Genentech–Roche, Merck and TRM Oncology, has been a non-paid consultant of Adlai Norte and Celldex, has received compensation for serving on data safety monitoring committees for IDDI (AstraZeneca–Medimmune) and VentiRx, and for medical education activities from CCO, Chemo Advisor, PER, Peerview, Practice Update, Prime Oncology and OncLive, and has received travel support from Boehringer Ingelheim and Merck. Q.T.L. has received travel support for serving on the advisory board of Bristol-Myers Squibb, serves as a non-paid consultant of Merck, and serves on the data safety monitoring committee for a clinical trial sponsored by Pfizer. R.L.F. has received compensation for consulting and/or advisory board membership from AstraZeneca–Medimmune, Bristol-Myers Squibb, Merck, PER, Pfizer, Regeneron, Tesaro and TTMS Therapeutics. Through contracts with the UPMC Hillman Cancer Center, his laboratory has also been funded to perform sponsored research by AstraZeneca–Medimmune, Bristol-Myers Squibb and Tesaro. J.D.C. declares no competing interests.

Correspondence to Robert L. Ferris.

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Fig. 1: Incidence rates and mortality for patients with head and neck squamous carcinoma
Fig. 2: Therapeutic targets and potential driver oncogenes in head and neck squamous carcinoma according to The Cancer Genome Atlas Network.
Fig. 3: Timeline showing the main therapeutic advances for patients with head and neck squamous carcinoma.