Review
Copyright ©2013 Baishideng Publishing Group Co., Limited. All rights reserved.
World J Med Genet. Nov 27, 2013; 3(4): 22-33
Published online Nov 27, 2013. doi: 10.5496/wjmg.v3.i4.22
Genetic alterations in head and neck squamous cell carcinoma: The next-gen sequencing era
Thien Khanh Nguyen, N Gopalakrishna Iyer
Thien Khanh Nguyen, Duke-NUS Graduate Medical School, Singapore 169857, Singapore
N Gopalakrishna Iyer, Department of Surgical Oncology, Principal Investigator, Cancer Therapeutics Research Laboratory, National Cancer Centre, Singapore 169610, Singapore
Author contributions: Nguyen TK and Iyer NG solely contributed to this paper.
Correspondence to: N Gopalakrishna Iyer, MBBS (Hons) (Singapore), PhD (Cantab), FRCS (Gen), FAMS, Senior Consultant, Head and Neck Surgeon and Director of Research, Department of Surgical Oncology, Principal Investigator, Cancer Therapeutics Research Laboratory, National Cancer Centre, 11 Hospital Dr, Singapore 169610, Singapore. gopaliyer@nccs.com.sg
Telephone: +65-6426-8000 Fax: +65-6225-6283
Received: June 28, 2013
Revised: October 28, 2013
Accepted: November 7, 2013
Published online: November 27, 2013
Abstract

Head and neck squamous cell carcinoma is the sixth most common cancer in the world with approximately 650000 new cases diagnosed annually. Next-generation molecular techniques and results from phase 2 of the Cancer Genome Atlas becoming available have drastically improved our current knowledge on the genetics basis of head and neck squamous cell carcinoma. New insights and new perspectives on the mutational landscape implicated in head and neck squamous cell carcinoma provide improved tools for prognostication. More importantly, depend on the patient’s tumor subtypes and prognosis, deescalated or more aggressive therapy maybe chosen to achieve greater potency while minimizing the toxicity of therapy. This paper aims to review our current knowledge on the genetic mutations and altered molecular pathways in head and neck squamous cell carcinoma. Some of the most common mutations in head and neck squamous cell carcinoma reported by the cancer genome atlas including TP53, NOTCH1, Rb, CDKN2A, Ras, PIK3CA and EGFR are described here. Additionally, the emerging role of epigenetics and the role of human papilloma virus in head and neck squamous cell carcinoma are also discussed in this review. The molecular pathways, clinical applications, actionable molecular targets and potential therapeutic strategies are highlighted and discussed in details.

Keywords: Head and neck squamous cell carcinoma, TP53, Ras/PIK3CA, NOTCH1/p63, HPV/E6/E7/Rb/CDKN2A

Core tip: Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer in the world with approximately 650000 new cases diagnosed annually. Understanding the molecular pathways that are implicated in the pathogenesis of HNSCC enable clinicians to be able to classify and to prognosticate the disease based on subtypes, such as human papilloma virus (HPV)-positive vs HPV-negative HNSCC. More importantly, patients may be placed on de escalated or more aggressive therapies depend on their tumor subtypes and prognosis. This paper aims to review our current knowledge of the most common genetic alterations in HNSCC.