Head and neck squamous cell carcinoma (HNSCC) is the 6th most common cancer globally, originating from the epithelial surface of the upper aerodigestive tract from the lips to the larynx. It commonly presents with locally advanced disease, with a recurrence rate of around 50% despite aggressive multimodality treatment involving surgery, radiotherapy and chemotherapy or EGFR inhibition as appropriate. Improvements in understanding the underlying cancer biology and its evolution within the complex interactions of the tumor microenvironment, there is gathering interest in and evidence for the use of immunomodulating agents in the management of HNSCC. Immune checkpoint inhibitors, primarily programmed cell death protein 1 (PD-1) inhibitors to date, which inhibit the inhibitory interaction between PD-1 and its ligand PD-L1, have demonstrated durable improvements in patient outcomes in advanced/metastatic HNSCC, with both nivolumab and pembrolizumab being granted FDA approval in 2016.
There are numerous clinical trials ongoing exploring the role of checkpoint inhibitors both as single agents and in combination, administered with established modalities such as chemotherapy and radiotherapy, as well as alongside other novel immune modulators. These trials are not limited to advanced/ metastatic HNSCC, but also explore neoadjuvant or adjuvant settings. As studies complete and more data become available, immunotherapy agents are likely to have expanding roles within the treatment algorithms of HNSCC, and with greater biomarker development have the potential to further improve patient outcomes via a personalized therapy approach.
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