Head and neck cancer: Current challenges and future perspectives.

Head and neck cancers are a heterogeneous, aggressive and genetically complex collection of malignancies of the oral cavity, nasopharynx, oropharynx, hypopharynx, larynx, paranasal sinuses and salivary glands, which are difficult to treat. About 90% of all head and neck cancers are squamous cell carcinomas (HNSCC). Larynx and Oral cavity carcinomas are generally related with tobacco consumption, alcohol abuse (or both), but pharynx carcinomas are generally associated with infection of human papillomavirus (HPV), especially HPV-16 subtype. Thus, usually HNSCC can be separated into HPV-negative and HPV-positive categories. Despite substantial efforts invested into therapeutic development of HNSCC, the 5-year survival rate of patients with HNSCC still remains dismal. The primary reason being late diagnosis, recurrent metastasis, relapse and resistance to therapies. Currently surgery and radiotherapy represent the baseline treatment options for most initial stage HNSCC patients, but these treatments are associated with significant morbidity and poor prognosis. Moreover, the issue of resistance to both radiotherapy/chemotherapy and recurrent relapse are common in HNSCC. Elucidation of the genetic landscape, tumor microenvironment and aberrant signaling pathways have generated new insights into the molecular pathogenesis of this disease. Thus, the scientific research has therefore been focused on the understanding of HNSCC biology and immunobiology to identification of predictive/prognostic biomarkers, which will be key to develop more effective targeted therapies with less toxicity and high specificity.