Head and neck cancers are a diverse group of malignancies that includes an increasing number of virally mediated cancers in addition to tumors caused by tobacco and alcohol use. In both cases, tumor development is intimately related to the host immune system, and the status of an endogenous antitumor response is likely prognostic. Virally mediated cancers provide unique targets for preventive vaccines that generate immune responses directed against virus-associated antigens. Once head and neck tumors develop, they are commonly treated with surgery, radiotherapy, and/or chemotherapy. These treatments are associated with significant toxicities, and despite this, subgroups of patients respond poorly and are likely to relapse and die of their disease. Tumor immunotherapy may allow for improvements in both treatment-associated toxicity and outcome. In addition to providing specific targets for therapeutic vaccines and adoptive therapy, virally associated cancers may also be particularly dependent on immune checkpoints; therefore, immune checkpoint inhibitors are being actively tested for these diseases. Cancers that are not virally mediated may also respond to immunotherapies, and biomarkers that could predict response to immunotherapy irrespective of viral status are being evaluated. Multiple ongoing studies are testing benefits of immunotherapy in the management of metastatic squamous cell carcinoma of the head and neck. Early promising results pave the way for future studies that will expand testing to nonmetastatic diseases and other types of head and neck cancers. Prospects of combining various immunotherapies and more established treatments such as chemotherapy and radiotherapy are very intriguing and may provide synergistic benefits.
©2015 American Association for Cancer Research.