Recent Advances and Future Directions in Clinical Management of Head and Neck Squamous Cell Carcinoma

Abstract

Head and neck squamous cell carcinoma (HNSCC) is the most common cancer arising in the head and neck region. The most common risk factors are smoking, excessive drinking, and human papillomavirus (HPV) infection. While the overall incidence of smoking is decreasing, the incidence of HPV-related HNSCC is increasing in the United States and Western Europe, which led to a shift in understanding of the pathophysiology, treatment, and prognosis of this disease. The outcomes for non-metastatic HNSCC remains very encouraging and continues to improve. Advances in radiation technology and techniques, better organ preserving surgical options, and multidisciplinary treatment modalities have improved cure rates for locally advanced HNSCC patients. The treatment of metastatic disease, however, remains an area of need. The advancement of immune checkpoint inhibitors has provided significantly better outcomes, but only a small proportion of patients obtain benefits. Most recurrent and/or metastatic HNSCC patients continue to have poor survival. This has led to the vigorous investigation of new biomarkers and biomarker-based therapies. Novel therapeutic options including adaptive cellular therapy and therapeutic vaccines are also on the horizon. In this review, we highlight the latest advances in the field of HNSCC and the future direction of research.

Keywords: biomarkers; cisplatin; clinical trials; head and neck squamous cell carcinoma; human papillomavirus; immunotherapy; induction chemotherapy; programmed cell death protein 1 inhibitors; radiation therapy; smoking.

Figure 1

Major pathways dysregulated in HNSCC with approved and investigational therapeutic agents and their sites of activity. Derivative of original figure from Alsahafi et al. [103] licensed under CC BY 4.0 https://creativecommons.org/licenses/by/4.0/. HGF: hepatocyte growth factor, EGFR: epidermal growth factor receptor, JAK: Janus kinase, PIP: prolactin induced protein, ERK: extracellular-signal-regulated kinase, PTEN: Phosphatase and tensin homolog, STAT: signal transducer and activator of transcription, MDM2: Mouse double minute 2 homolog, mTOR: mechanistic target of rapamycin