Defining molecular phenotypes of human papillomavirus-associated oropharyngeal squamous cell carcinoma: validation of three-class hypothesis.
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.


METHODS
Cross-sectional study.


METHODS
A laboratory-based study of patients with OSCC treated at a tertiary care academic medical center.


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 beta-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 beta-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 beta-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.
Weinberger
Paul M
PM
Department of Otolaryngology, Medical College of Georgia, Augusta, GA, USA.
Yu
Ziwei
Z
Kountourakis
Panteleimon
P
Sasaki
Clarence
C
Haffty
Bruce G
BG
Kowalski
Diane
D
Merkley
Mark A
MA
Rimm
David L
DL
Camp
Robert L
RL
Psyrri
Amanda
A
D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000473:pathology / Q000821:virology*; D015344:DNA Probes, HPV; D004279:DNA, Viral / Q000235:genetics*; D005260:Female; D052162:Human papillomavirus 16 / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009959:Oropharyngeal Neoplasms / Q000378:metabolism / Q000473:pathology / Q000821:virology*; D030361:Papillomavirus Infections / Q000235:genetics / Q000473:pathology / Q000821:virology*; D010641:Phenotype; D011379:Prognosis; D015203:Reproducibility of Results; D012189:Retrospective Studies
D014408:Biomarkers, Tumor; D015344:DNA Probes, HPV; D004279:DNA, Viral