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Grant Details

Grant Number: 5R03CA115243-02 Interpret this number
Primary Investigator: Schlecht, Nicolas
Organization: Albert Einstein College Of Medicine
Project Title: HPV Induced Pathogenesis in Head and Neck Cancer
Fiscal Year: 2006
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Abstract

DESCRIPTION (provided by applicant): 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.

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Publications

Association between pretreatment obesity, sarcopenia, and survival in patients with head and neck cancer.
Authors: Fattouh M. , Chang G.Y. , Ow T.J. , Shifteh K. , Rosenblatt G. , Patel V.M. , Smith R.V. , Prystowsky M.B. , Schlecht N.F. .
Source: Head & neck, 2019 Mar; 41(3), p. 707-714.
EPub date: 2018-12-23.
PMID: 30582237
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Cancer as the Disintegration of Robustness: Population-Level Variance in Gene Expression Identifies Key Differences Between Tobacco- and HPV-Associated Oropharyngeal Carcinogenesis.
Authors: Ben-Dayan M.M. , MacCarthy T. , Schlecht N.F. , Belbin T.J. , Childs G. , Smith R.V. , Prystowsky M.B. , Bergman A. .
Source: Archives of pathology & laboratory medicine, 2015 Nov; 139(11), p. 1362-72.
EPub date: 2015-07-01.
PMID: 26132601
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Epigenetic changes in the CDKN2A locus are associated with differential expression of P16INK4A and P14ARF in HPV-positive oropharyngeal squamous cell carcinoma.
Authors: Schlecht N.F. , Ben-Dayan M. , Anayannis N. , Lleras R.A. , Thomas C. , Wang Y. , Smith R.V. , Burk R.D. , Harris T.M. , Childs G. , et al. .
Source: Cancer medicine, 2015 Mar; 4(3), p. 342-53.
EPub date: 2015-01-26.
PMID: 25619363
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Combined P16 and human papillomavirus testing predicts head and neck cancer survival.
Authors: Salazar C.R. , Anayannis N. , Smith R.V. , Wang Y. , Haigentz M. , Garg M. , Schiff B.A. , Kawachi N. , Elman J. , Belbin T.J. , et al. .
Source: International journal of cancer, 2014-11-15; 135(10), p. 2404-12.
EPub date: 2014-04-17.
PMID: 24706381
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Human papillomavirus-associated head and neck squamous cell carcinoma survival: a comparison by tumor site and initial treatment.
Authors: Salazar C.R. , Smith R.V. , Garg M.K. , Haigentz M. , Schiff B.A. , Kawachi N. , Anayannis N. , Belbin T.J. , Prystowsky M.B. , Burk R.D. , et al. .
Source: Head and neck pathology, 2014 Mar; 8(1), p. 77-87.
EPub date: 2013-09-04.
PMID: 24002971
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Comorbidity, human papillomavirus infection and head and neck cancer survival in an ethnically diverse population.
Authors: Ankola A.A. , Smith R.V. , Burk R.D. , Prystowsky M.B. , Sarta C. , Schlecht N.F. .
Source: Oral oncology, 2013 Sep; 49(9), p. 911-917.
EPub date: 2013-07-25.
PMID: 23891528
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Cytoplasmic ezrin and moesin correlate with poor survival in head and neck squamous cell carcinoma.
Authors: Schlecht N.F. , Brandwein-Gensler M. , Smith R.V. , Kawachi N. , Broughel D. , Lin J. , Keller C.E. , Reynolds P.A. , Gunn-Moore F.J. , Harris T. , et al. .
Source: Head and neck pathology, 2012 Jun; 6(2), p. 232-43.
EPub date: 2012-01-07.
PMID: 22228071
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A comparison of clinically utilized human papillomavirus detection methods in head and neck cancer.
Authors: Schlecht N.F. , Brandwein-Gensler M. , Nuovo G.J. , Li M. , Dunne A. , Kawachi N. , Smith R.V. , Burk R.D. , Prystowsky M.B. .
Source: Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc, 2011 Oct; 24(10), p. 1295-305.
EPub date: 2011-05-13.
PMID: 21572401
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Low-level expression of microRNAs let-7d and miR-205 are prognostic markers of head and neck squamous cell carcinoma.
Authors: Childs G. , Fazzari M. , Kung G. , Kawachi N. , Brandwein-Gensler M. , McLemore M. , Chen Q. , Burk R.D. , Smith R.V. , Prystowsky M.B. , et al. .
Source: The American journal of pathology, 2009 Mar; 174(3), p. 736-45.
EPub date: 2009-01-29.
PMID: 19179615
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Gene expression profiles in HPV-infected head and neck cancer.
Authors: Schlecht N.F. , Burk R.D. , Adrien L. , Dunne A. , Kawachi N. , Sarta C. , Chen Q. , Brandwein-Gensler M. , Prystowsky M.B. , Childs G. , et al. .
Source: The Journal of pathology, 2007 Nov; 213(3), p. 283-93.
PMID: 17893858
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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.
Authors: Madan R. , Brandwein-Gensler M. , Schlecht N.F. , Elias K. , Gorbovitsky E. , Belbin T.J. , Mahmood R. , Breining D. , Qian H. , Childs G. , et al. .
Source: Head & neck, 2006 Nov; 28(11), p. 1018-27.
PMID: 16783828
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Prognostic value of human papillomavirus in the survival of head and neck cancer patients: an overview of the evidence.
Authors: Schlecht N.F. .
Source: Oncology reports, 2005 Nov; 14(5), p. 1239-47.
PMID: 16211291
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