Please cite this article in press as: S.S. Subramaniam, C. Paterson and J.A. McCaul. Immunotherapy in the management of squamous cell carcinoma of the head and neck. Br J Oral Maxillofac Surg (2019), https://doi.org/10.1016/j.bjoms.2019.08.002 ARTICLE IN PRESS YBJOM-5751; No. of Pages 10 British Journal of Oral and Maxillofacial Surgery xxx (2019) xxx–xxx Available online at www.sciencedirect.com ScienceDirect Review Immunotherapy in the management of squamous cell carcinoma of the head and neck S.S. Subramaniam a,∗ , C. Paterson b , J.A. McCaul a a Department of Maxillofacial Surgery, Queen Elizabeth University Hospital, 1345 Govan Rd, Glasgow, UK b Beaston West of Scotland Cancer Centre, 1053 Great Western Rd, Glasgow, UK Received 16 August 2018; accepted 5 August 2019 Abstract Despite many advances in surgery, radiotherapy, and systemic treatments, only modest improvements in survival, function, and quality of life have been achieved after treatment of squamous cell carcinoma (SCC) of the head and neck. With a better understanding of the biology and genetics of tumours, the emergence of a paradigm shift towards the further development of non-surgical treatments may result in less morbidity and better outcomes than are seen currently. SCC of the head and neck is known to be a complex disease that has a sophisticated interaction with the human immune system. At the forefront of emerging treatments is immunotherapy, which has already been established in many other areas of oncology. The rapidly evolving nature of immunotherapeutic agents and, sometimes, their complex mechanisms can make the understanding of these concepts challenging, and could discourage clinicians from engaging in clinical trials. The aim of this paper therefore was to review the current premise for immunotherapeutic approaches, and to provide a contemporary evidence-based rationale for their use. © 2019 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved. Keywords: head and neck squamous cell carcinoma; oral squamous cell carcinoma; immunotherapy Introduction Despite advances in the management of squamous cell carci- noma (SCC) of the head and neck, multimodal therapy such as surgery, radiotherapy, and cytotoxic chemotherapy still often result in permanent toxicity, impaired function, and decreased quality of life. Whilst there have been improve- ments in survival, the morbidity of current treatments and the poor outcomes for advanced local, recurrent and metastatic disease 1,2 have prompted the search for less toxic and more effective methods. ∗ Corresponding author. Present address: Canberra Hospital, Yamba Drive, ACT 2605, Australia. E-mail addresses: shivassubramaniam@gmail.com (S.S. Subramaniam), Claire.paterson2@ggc.scot.nhs.uk (C. Paterson), mccaulsurgery@gmail.com (J.A. McCaul). As part of this search, immunotherapeutic agents have increasingly been investigated in recurrent and metastatic disease and, more recently, as “up-front” methods of treat- ment. The safety and efficacy of some agents – for example, nivolumab, have already been shown in the palliative treat- ment of SCC of the head and neck, 3 whilst other agents (somewhat unusually) have moved directly to early-phase trials in the radical setting. 4,5 In some patients, immunotherapeutic agents induce improvements in tumour control and survival. SCC of the head and neck is an obvious area in which to investigate these immune-modulating agents in window of opportunity trials, as ease of access to tumour tissue (both through biopsy and at definitive resection) facilitates much-needed translational research, which will hopefully also identify the patholog- ical or molecular biomarkers that are associated with the response. Ultimately, success with these new agents may https://doi.org/10.1016/j.bjoms.2019.08.002 0266-4356/© 2019 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.