5-year survival for head and neck squamous cell carcinoma (HNSCC) is only 50%, and very variable. Survival cannot be accurately predicted through standard histopathology. Recently, a subset of approximately 30% of the HNSCC has been shown to contain HPV. In comparison to HPV-negative tumors, HPV-positive HNSCCs are more likely to be located within the oral cavity/pharynx, poorly differentiated, and diagnosed at a late stage. The HPV DNA (overwhelmingly genotype 16, a high-risk type also found in cervical cancer) in these tumors is present at high copy numbers, is frequently integrated, and is often transcriptionally active (e.g., expression of the viral oncoproteins E6 and E7). Surprisingly, despite being more advanced at diagnosis, HPV-positive HNSCC is associated with better response to therapy and longer survival than HPV-negative tumors. Thus, HPV-positive and-negative HNSCC appear to be clinically and biologically distinct. The differences in in clinical and biologic characteristics that distinguish HPV-positive and-negative HNSCC are likely to be explained by differences in RNA expression. Our proposed study will be the first to compare and contrast gene expression in HPV-positive and-negative HNSCC. Specifically, under this application frozen tumor samples from 112 HNSCC patients undergoing surgery at Montefiore Medical Center, New York, will be assessed for presence of HPV DNA on a type-specific basis using a well established sensitive PCR assay, and the expression of the viral oncoproteins E6 and E7 using RT-PCR. This project exploits ongoing (currently funded research) to characterize gene expression patterns in HNSCC tumors using a novel high-throughput microarray method with 28,000 cDNA clones developed and previously validated by our team. Detailed? data on clinical characteristics are being collected prospectively following an approved study design and standardized clinical review criteria. This data will be used to study: (i) the association of HPV with characteristics of HNSCC; (ii) differences in gene expression profiles between HPV-positive and-negative HNSCC; and (iii) the relation of these gene expression profiles with disease free and overall survival.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Small Research Grants (R03)
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Special Emphasis Panel (ZCA1-SRRB-Q (J1))
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Starks, Vaurice
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Albert Einstein College of Medicine
Public Health & Prev Medicine
Schools of Medicine
United States
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Ben-Dayan, Miriam M; MacCarthy, Thomas; Schlecht, Nicolas F et al. (2015) Cancer as the Disintegration of Robustness: Population-Level Variance in Gene Expression Identifies Key Differences Between Tobacco- and HPV-Associated Oropharyngeal Carcinogenesis. Arch Pathol Lab Med 139:1362-72
Schlecht, Nicolas F; Ben-Dayan, Miriam; Anayannis, Nicole et al. (2015) Epigenetic changes in the CDKN2A locus are associated with differential expression of P16INK4A and P14ARF in HPV-positive oropharyngeal squamous cell carcinoma. Cancer Med 4:342-53
Salazar, Christian R; Anayannis, Nicole; Smith, Richard V et al. (2014) Combined P16 and human papillomavirus testing predicts head and neck cancer survival. Int J Cancer 135:2404-12
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Schlecht, Nicolas F; Brandwein-Gensler, Margaret; Smith, Richard V et al. (2012) Cytoplasmic ezrin and moesin correlate with poor survival in head and neck squamous cell carcinoma. Head Neck Pathol 6:232-43
Schlecht, Nicolas F; Brandwein-Gensler, Margaret; Nuovo, Gerard J et al. (2011) A comparison of clinically utilized human papillomavirus detection methods in head and neck cancer. Mod Pathol 24:1295-305
Childs, Geoffrey; Fazzari, Melissa; Kung, Gloria et al. (2009) Low-level expression of microRNAs let-7d and miR-205 are prognostic markers of head and neck squamous cell carcinoma. Am J Pathol 174:736-45
Schlecht, N F; Burk, R D; Adrien, L et al. (2007) Gene expression profiles in HPV-infected head and neck cancer. J Pathol 213:283-93
Madan, Rashna; Brandwein-Gensler, Margaret; Schlecht, Nicolas F et al. (2006) Differential tissue and subcellular expressionof ERM proteins in normal and malignant tissues: cytoplasmic ezrin expression has prognostic signficance for head and neck squamous cell carcinoma. Head Neck 28:1018-27

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