Head Neck Squamous Cell Cancer Genomics: Oncogenes, Tumor Suppressor Genes and Clinical Implications

Abstract

Head Neck Squamous Cell Cancer is genomically heterogenous. Common somatic mutations involve TP53, CDKN2A, FAT1, NOTCH1, PIK3CA, KMT2D and NSD1, less frequently others. Epigenetic changes also contribute to HNSCC biology. Alterations in tumor suppressor genes is a major oncogenic event in HNSCC. Genomic heterogeneity exists between different subsites within head neck region and also between the primary and metastatic disease. Intratumor heterogeneity has also been recognized. Based on key genomic alterations, four major molecular subtypes have been identified. Multi-omics analysis has provided further insights into HNSCC biology and shed light on EGFR pathway and immunogenomics. Corelative genomics of tumor cells, stromal cells and immune cells have led to emergence of distinct immune molecular subtypes of HNSCC. Major tumor suppressor genes and oncogenes have a correlation with prognosis, survival and treatment resistance. EGFR pathway is in focus for renewed understanding of resistance to EGFR targeted treatments and novel ways to target EGFR pathways. Increasingly genomic data is being leveraged towards clinical use including HNSCC prevention, prediction of metastases, survival and prognostication, fine tuning use of surgery, chemotherapy and radiation therapy, identifying patients for using immunotherapy, predicting drug resistance and gaining new information from radiological studies. Several novel targeted therapies are being pursued in clinical trials. Molecular co targeting strategies are being developed. Understanding the way tumor suppressor genes and oncogenes shape HNSCC biology and clinical behavior is bringing the much-needed therapeutic breakthrough in this tough to treat disease.