Head and Neck Cancers

Head and neck cancers are a group of malignancies arising from the head and neck region and include head and neck squamous cell carcinoma (HNSCC), skin cancers, thyroid cancers, adenocarcinomas, sarcomas, and lymphomas. Since HNSCC is the most common head and neck cancer, most recent molecular advances occurred in the HNSCC. While chromosomal copy number abnormalities are common in both groups, different genetic alterations drive the development of HPV+ve and HPV-ve HNSCC; HPV+ tumors depend on helical domain mutations of PIK3CA, loss of TRAF3, and amplification of E2F1, whereas HPV-ve tumors carry frequent TP53 (83%) and CDKN2A (58%) mutations in addition to co-amplifications of 11q13 (CCND1, FADD and CTTN) and 11q22 (BIRC2 and YAP1), recurrent focal amplifications of genes encoding receptor tyrosine kinases, and focal deletions in the nuclear set domain gene (NSD1) and tumor suppressor genes. As deletion and inactivation of tumor suppressor genes are the main drivers of HNSCC development, there remains a lack of effective targeted therapy for HNSCC. A precision pathologist should provide all the potential therapeutic targets to the clinicians and be actively involved in clinical trials.