Genetic Signatures of HPV-related and Unrelated Oropharyngeal Carcinoma and Their Prognostic Implications

• Published in: Clinical cancer research 2009-03, Vol.15 (5), p.1779-1786
• Main Authors: KLUSSMANN, Jens P, MOOREN, Jeroen J, MANNI, JohannesJ, HOPMAN, Anton H. N, SPEEL, Ernst-Jan M, LEHNEN, Martin, CLAESSEN, Sandra M. H, STERNER, Markus, HUEBBERS, Christian U, WEISSENBORN, Soenke J, WEDEMEYER, Inga, PREUSS, Simon F, STRAETMANS, Jos M. J. A. A
• Format: Article
• Language: English
• Subjects: Alcohol Drinking; Antineoplastic agents; Biological and medical sciences; Carcinoma, Squamous Cell - genetics; Carcinoma, Squamous Cell - metabolism; Carcinoma, Squamous Cell - virology; chromosomal alterations; Chromosome Aberrations; Chromosomes, Human, Pair 16 - genetics; Chromosomes, Human, Pair 3 - genetics; Comparative Genomic Hybridization; comparative genomic hybridization (CGH); Cyclin-Dependent Kinase Inhibitor p16 - metabolism; Feasibility Studies; Gene Dosage; Gene Expression Profiling; human papillomavirus (HPV); Human papillomavirus 16 - genetics; Human papillomavirus 16 - isolation & purification; Humans; Immunoenzyme Techniques; In Situ Hybridization, Fluorescence; Medical sciences; Neoplasm Staging; Oropharyngeal Neoplasms - genetics; Oropharyngeal Neoplasms - metabolism; Oropharyngeal Neoplasms - virology; oropharyngeal squamous cell carcinomas (OSCC); Papillomavirus Infections - genetics; Papillomavirus Infections - metabolism; Papillomavirus Infections - virology; Pharmacology. Drug treatments; Polymerase Chain Reaction; Prognosis; Risk Factors; Smoking; Survival Rate
• ISSN: 1078-0432; 1557-3265
• DOI: 10.1158/1078-0432.CCR-08-1463

Purpose: Patients with human papillomavirus (HPV)-containing oropharyngeal squamous cell carcinomas (OSCC) have a better prognosis than patients with HPV-negative OSCC. This may be attributed to different genetic pathways promoting cancer. Experimental Design: We used comparative genomic hybridization to identify critical genetic changes in 60 selected OSCC, 28 of which were associated with HPV-16 as determined by HPV-specific PCR and fluorescence in situ hybridization analysis and positive p16 INK4A immunostaining. The results were correlated with HPV status and clinical data from patients. Results: Two thirds of OSCC harbored gain at 3q26.3-qter irrespective of HPV status. In HPV-negative tumors this alteration was associated with advanced tumor stage ( P = 0.013). In comparison with HPV-related OSCC, the HPV-negative tumors harbored: ( a ) a higher number of chromosomal alterations and amplifications ( P = 0.03 and 0.039, respectively); ( b ) significantly more losses at 3p, 5q, 9p, 15q, and 18q, and gains/amplifications at 11q13 ( P = 0.002, 0.03;