title: Gene Expression Characterization of HPV Positive Head and Neck Cancer to Predict Response to Chemoradiation.
abstract: Human papillomavirus (HPV) has been shown to have a causal role in the development of head and neck squamous cell carcinoma. While HPV-positive head and neck cancer is associated with a better response to treatment in the majority of patients, there is a subset who does not respond favorably to current therapy. Identification of these patients could prevent unnecessary morbidity and indicate the need for alternative therapeutic options. Tissue samples were obtained from 19 patients with HPV-positive head and neck squamous carcinoma treated with chemoradiation therapy. HPV status was confirmed by polymerase chain reaction analysis through detection of HPV16 E7 in both DNA and RNA. RNA was isolated from tissue samples and subjected to microarray gene expression analysis. In addition to identification of potential genetic biomarkers (including LCE3D, KRTDAP, HMOX1, KRT19, MDK, TSPAN1), differentially expressed genes associated with genomic stability, cell cycle, and DNA damage were detected between responders and non-responders. These results were further validated with publicly available gene expression studies. This pilot study suggests prospective biomarkers that predict response to therapy. The importance of genes involved with genomic stability is highlighted in both development and progression of head and neck squamous cell carcinoma but also recurrence. Potential development of an assay may prove beneficial to clinicians, assisting them to provide alternative care sooner thus lowering morbidity.
authors.affiliation: Beaumont BioBank, Beaumont Health System, 3811 West 13 Mile Road, 105-RI, Royal Oak, MI, 48073, USA, bryan.thibodeau@beaumont.edu.
authors.forename: Bryan J
authors.initials: BJ
authors.lastname: Thibodeau
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Geddes
authors.forename: Laura E
authors.initials: LE
authors.lastname: Fortier
authors.forename: Samreen
authors.initials: S
authors.lastname: Ahmed
authors.forename: Barbara L
authors.initials: BL
authors.lastname: Pruetz
authors.forename: Jessica
authors.initials: J
authors.lastname: Wobb
authors.forename: Peter
authors.initials: P
authors.lastname: Chen
authors.forename: George D
authors.initials: GD
authors.lastname: Wilson
authors.forename: Jan A
authors.initials: JA
authors.lastname: Akervall
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000628:therapy / Q000821:virology*; D059248:Chemoradiotherapy; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000032:analysis; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006258:Head and Neck Neoplasms / Q000235:genetics* / Q000628:therapy / Q000821:virology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D030361:Papillomavirus Infections / Q000150:complications; D011836:Radiation Tolerance / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000077195:Squamous Cell Carcinoma of Head and Neck; D059467:Transcriptome
chemical_list: D014408:Biomarkers, Tumor; D019941:Cyclin-Dependent Kinase Inhibitor p16