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Patients with human papillomavirus (HPV)-containing oropharyngeal squamous cell carcinoma (OSCC) generally have a better disease-specific survival than patients with HPV-lacking OSCC. These differences in survival may reflect different genetic pathways leading to carcinoma: one caused by oncogenic HPV, such as HPV-16, and one induced by environmental carcinogens as a result of, e.g., tobacco and alcohol consumption.

To identify critical DNA copy number changes that occur in these pathways, we used comparative genomic hybridization (CGH) to analyze 63 OSCC, 33 of which harbored HPV-16 as determined by PCR and FISH analysis and stained positive for p16INK4A.

Comparison of HPV/p16-positive with negative OSCC by CGH revealed that: a) amplifications were less frequent in HPV/p16-positive tumors (22% versus 78%; P=0.02), b) losses of 3p, 9p and 18q and gains/amplifications of 11q13 were significantly less frequent detected in HPV/p16-positive tumors (P=0.009, <0.001, 0.007 and 0.003, respectively); c) 16q losses and Xp gains were more likely in HPV/p16 positive tumors (P=0.019, 0.025) d.) losses of 3p, 4q and 13q and gains of 3q, 8q, 17q and 20q were altered at a frequency of more than 33% in both groups. Interestingly, two third of OSCC in both groups harbored 3q gains with 3 amplifications observed per group at 3q26.3-qter. Prognostic significance was found after stratification for total number of amplifications, 17q gains and 16q losses.

Our data show that there are specific chromosomal alterations that discriminate HPV-containing from -lacking OSCC, most likely reflecting differences in the carcinogenesis of these tumor groups and implicating prognostic significance.

98th AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA