A Pilot Study Comparing HPV-Positive and HPV-Negative Head and Neck Squamous Cell Carcinomas by Whole Exome Sequencing

Anthony C Nichols; Michelle Chan-Seng-Yue; John Yoo; Wei Xu; Sandeep Dhaliwal; John Basmaji; Christopher C T Szeto; Samuel Dowthwaite; Biljana Todorovic; Maud H W Starmans; Philippe Lambin; David A Palma; Kevin Fung; Jason H Franklin; Bret Wehrli; Keith Kwan; James Koropatnick; Joe S Mymryk; Paul Boutros; John W Barrett

doi:10.5402/2012/809370

A Pilot Study Comparing HPV-Positive and HPV-Negative Head and Neck Squamous Cell Carcinomas by Whole Exome Sequencing

ISRN Oncol. 2012:2012:809370. doi: 10.5402/2012/809370. Epub 2012 Dec 12.

Affiliation

¹ Department of Otolaryngology-Head and Neck Surgery, Western University, Victoria Hospital, London Health Science Centre, Room B3-431A, 800 Commissioners Road East, London, ON, Canada N6A 5W9 ; London Regional Cancer Program, London, ON, Canada N6A 4L6 ; Lawson Health Research Institute, London, ON, Canada N6C 2R5 ; Department of Oncology, Western University, London, ON, Canada N6A 4L6 ; Department of Pathology, Western University, London, ON, Canada N6A 5C1.

Abstract

Background. Next-generation sequencing of cancers has identified important therapeutic targets and biomarkers. The goal of this pilot study was to compare the genetic changes in a human papillomavirus- (HPV-)positive and an HPV-negative head and neck tumor. Methods. DNA was extracted from the blood and primary tumor of a patient with an HPV-positive tonsillar cancer and those of a patient with an HPV-negative oral tongue tumor. Exome enrichment was performed using the Agilent SureSelect All Exon Kit, followed by sequencing on the ABI SOLiD platform. Results. Exome sequencing revealed slightly more mutations in the HPV-negative tumor (73) in contrast to the HPV-positive tumor (58). Multiple mutations were noted in zinc finger genes (ZNF3, 10, 229, 470, 543, 616, 664, 638, 716, and 799) and mucin genes (MUC4, 6, 12, and 16). Mutations were noted in MUC12 in both tumors. Conclusions. HPV-positive HNSCC is distinct from HPV-negative disease in terms of evidence of viral infection, p16 status, and frequency of mutations. Next-generation sequencing has the potential to identify novel therapeutic targets and biomarkers in HNSCC.