Abstract
Tonsillar squamous cell carcinoma (TSCC) is frequently associated with oncogenic human papillomavirus (HPV). Data on chromosomal alterations in these lesions in relation to HPV, however, are scarce. The aim of this study was to assess chromosome 1 and 7 copy number changes in relation to the presence of HPV as well as the prognosis of TSCCs. Seventy TSCCs with known clinical outcome and cell cycle protein expression profiles, and of which 36% showed HPV16 integration, were analyzed by double-target fluorescence in situ hybridization (FISH) using chromosome 1- and 7-specific centromere DNA probes. In addition, 6 HPV-positive, tumor-adjacent dysplasias were analyzed by FISH. Disomy for chromosome 1 and 7 was present in 26 out of 70 TSCCs (37%) and strongly associated with HPV presence (16 out of 26; p=0.001). Aneusomies for both chromosomes were observed in the remaining TSCCs, of which 24 tumors showed balanced and 20 unbalanced copy numbers (19 cases with higher chromosome 7 copy numbers). Aneusomies correlated significantly with tobacco- and alcohol consumption (p=0.001 and p=0.007, respectively) and a higher T-stage (p=0.03). Both HPV-positivity and chromosome disomy were significantly associated with favorable prognosis (p=0.003 and p=0.011, respectively). Five out of 6 HPV-positive, tumor-adjacent dysplasias also showed disomy for chromosomes 1 and 7. In conclusion, HPV-positive TSCCs and their precursor lesions are genetically more stable than HPV-negative lesions, suggesting that HPV integration preferentially occurs in (near) diploid lesions. The high chromosome 7 copy numbers in HPV-negative tumors may point to oncogene involvement such as EGFR, which is inversely related to HPV presence. Furthermore, HPV-positivity and chromosome disomy are favorable prognosticators in TSCC.
Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 1858.
100th AACR Annual Meeting-- Apr 18-22, 2009; Denver, CO
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