Defining molecular phenotypes of human papillomavirus-associated oropharyngeal squamous cell carcinoma

Validation of three-class hypothesis

Paul Maurice Weinberger, Ziwei Yu, Panteleimon Kountourakis, Clarence Sasaki, Bruce G. Haffty, Diane Kowalski, Mark A. Merkley, David L. Rimm, Robert L. Camp, Amanda Psyrri

Research output: Contribution to journalArticle

40 Citations (Scopus)

Abstract

Objective: The purpose of this study was to determine if oropharyngeal squamous cell carcinoma (OSCC) classified into three groups based on human papillomavirus (HPV) 16 DNA presence and p16 expression display different protein expression patterns. Study Design: Cross-sectional study. Setting: A laboratory-based study of patients with OSCC treated at a tertiary care academic medical center. Subjects and Methods: Paraffin-embedded OSCC specimens from 77 patients classified into the three-class model (HPV negative, HPV inactive [HPV16+/p16-], and HPV active [HPV16+/p16+]) were queried for the expression of 14 tumor progression proteins using AQUA (HistoRx, New Haven CT). Protein expression between groups was assessed by analysis of variance. Global expression patterns were determined by unsupervised hierarchical clustering. Results: There were significant differences in expression of β-catenin (P = 0.009), epidermal growth factor receptor (P = 0.009), and vascular endothelial growth factor (P = 0.028) between groups. HPV-active tumors had overexpression of β-catenin. Hierarchical clustering showed HPV-negative and HPV-inactive tumors displayed association patterns distinct from HPV-active tumors. Conclusions: Tumors classified by HPV DNA presence and p16 expression have different molecular phenotypes. This is the first demonstration of overexpression of β-catenin (also found in HPV-caused cervical cancer) in HPV-active OSCC. HPV-active OSCC may share a similar ontogeny to HPV-caused cervical cancer.

Original languageEnglish (US)
JournalOtolaryngology - Head and Neck Surgery
Volume141
Issue number3
DOIs
StatePublished - Jan 1 2009

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Squamous Cell Carcinoma
Phenotype
Catenins
Neoplasms
Uterine Cervical Neoplasms
Cluster Analysis
Proteins
Human papillomavirus 16
DNA
Tertiary Healthcare
Epidermal Growth Factor Receptor
Paraffin
Vascular Endothelial Growth Factor A
Analysis of Variance
Cross-Sectional Studies

ASJC Scopus subject areas

  • Surgery
  • Otorhinolaryngology

Cite this

Defining molecular phenotypes of human papillomavirus-associated oropharyngeal squamous cell carcinoma : Validation of three-class hypothesis. / Weinberger, Paul Maurice; Yu, Ziwei; Kountourakis, Panteleimon; Sasaki, Clarence; Haffty, Bruce G.; Kowalski, Diane; Merkley, Mark A.; Rimm, David L.; Camp, Robert L.; Psyrri, Amanda.

In: Otolaryngology - Head and Neck Surgery, Vol. 141, No. 3, 01.01.2009.

Research output: Contribution to journalArticle

Weinberger, PM, Yu, Z, Kountourakis, P, Sasaki, C, Haffty, BG, Kowalski, D, Merkley, MA, Rimm, DL, Camp, RL & Psyrri, A 2009, 'Defining molecular phenotypes of human papillomavirus-associated oropharyngeal squamous cell carcinoma: Validation of three-class hypothesis', Otolaryngology - Head and Neck Surgery, vol. 141, no. 3. https://doi.org/10.1016/j.otohns.2009.04.014
Weinberger, Paul Maurice ; Yu, Ziwei ; Kountourakis, Panteleimon ; Sasaki, Clarence ; Haffty, Bruce G. ; Kowalski, Diane ; Merkley, Mark A. ; Rimm, David L. ; Camp, Robert L. ; Psyrri, Amanda. / Defining molecular phenotypes of human papillomavirus-associated oropharyngeal squamous cell carcinoma : Validation of three-class hypothesis. In: Otolaryngology - Head and Neck Surgery. 2009 ; Vol. 141, No. 3.
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