Genomic and transcriptomic profiling of Human Papilloma Virus (HPV)-positive head and neck squamous cell carcinomas (HNSCC) identifies a genetically distinct subgroup of head and neck cancers

Abstract

5507 Background: HPV is recognized as an important etiologic agent in a subset of HNSCC. HPV-positive cancers tend to be clinically distinct from HPV-negative ones in several ways, including a more favorable prognosis for patients with HPV-positive HNSCC. These different clinical characteristics imply an underlying biologic difference between the two tumor types. Methods: DNA and RNA samples from 24 HNSCC tumors and genetically matched normal tissues were analyzed. Oligonucleotide microarrays (Affymetrix, Santa Clara, CA) were used for genomic and transcriptomic profiling to determine global patterns of allelic imbalance (loss-of heterozygosity or amplification) and gene expression. Tumors were also examined for HPV status as well as genetic and epigenetic alterations in the CDKN2A/p16 and TP53/p53 tumor suppressor genes. HPV-positive (at both the DNA and RNA level) tumors were compared with HPV-negative tumors to identify HPV-related differences in patterns of gene expression and DNA alterations. Results: In total, 180 genes were found to show statistically significant differential expression between HPV-positive and HPV-negative tumors. These included immunomodulatory genes, and known tumor suppressor genes and oncogenes. Interestingly, HPV-negative tumors showed more genome-wide DNA alterations than HPV-positive tumors, most notably in a novel 3-Mb region in chromosome 9q where allelic imbalances occurred statistically significantly more often in HPV-negative tumors. Conclusions: HPV-positive tumors are genetically distinct from HPV-negative tumors, likely reflecting different mechanisms of oncogenesis. This has significant implications for the treatment and prevention of these different subgroups of HNSCC. No significant financial relationships to disclose.