title: Prognostic impact of p16, p53, epidermal growth factor receptor, and human papillomavirus in oropharyngeal cancer in a betel nut-chewing area.
abstract: OBJECTIVE
  To evaluate the prevalence of human papillomavirus (HPV) and the prognostic significance of epidermal growth factor receptor (EGFR), p53, and p16 among patients with oropharyngeal carcinoma.
  
  
  METHODS
  Retrospective study.
  
  
  METHODS
  Academic Institute of Otolaryngology, Kaohsiung, Taiwan.
  
  
  METHODS
  Two hundred seventy-four patients who were diagnosed as having oropharyngeal carcinoma underwent testing for the presence of the HPV genome in the nuclei of their tumor cells from January 1, 1992, through March 31, 2008.
  
  
  METHODS
  The HPV genome was detected by performing polymerase chain reaction-based assays and in situ hybridization on tumor tissue from paraffin blocks. Immunohistochemistry staining for p16, p53, and EGFR was also performed.
  
  
  METHODS
  We used the Fisher exact test to evaluate the correlation between the clinicopathological variables and the presence of HPV in tumor cells. Survival analysis was based on the Kaplan-Meier method.
  
  
  RESULTS
  We detected HPV in 45 of the 274 patients (16.4%); of these, HPV-16 and -18 were identified in 42 (93.3%) of the HPV-positive tumors. The HPV-positive oropharyngeal cancers were more likely to occur in females, nonsmoking individuals, and those who did not chew betel quid. The HPV-positive tumors significantly expressed p16 and were inversely associated with EGFR and p53 expression (all, P < .001). In addition, patients with tumor tissue that was positive for HPV (P = .008) and had negative expression of EGFR (P = .01), low expression of p53 (P = .01), and high expression of p16 (P = .04) had a better prognosis.
  
  
  CONCLUSIONS
  Our results suggest that HPV, EGFR, p53, and p16 are useful biomarkers in predicting the clinical outcomes of oropharyngeal cancer.
authors.affiliation: Department of Otolaryngology, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan.
authors.forename: Jamil N
authors.initials: JN
authors.lastname: Al-Swiahb
authors.forename: Chao-Cheng
authors.initials: CC
authors.lastname: Huang
authors.forename: Fu-Min
authors.initials: FM
authors.lastname: Fang
authors.forename: Hui-Ching
authors.initials: HC
authors.lastname: Chuang
authors.forename: Hsuan-Ying
authors.initials: HY
authors.lastname: Huang
authors.forename: Sheng-Dean
authors.initials: SD
authors.lastname: Luo
authors.forename: Chang-Han
authors.initials: CH
authors.lastname: Chen
authors.forename: Ching-Mei
authors.initials: CM
authors.lastname: Chen
authors.forename: Chih-Yen
authors.initials: CY
authors.lastname: Chien
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001114:Areca; D014408:Biomarkers, Tumor / Q000378:metabolism; D019941:Cyclin-Dependent Kinase Inhibitor p16; D005260:Female; D052162:Human papillomavirus 16 / Q000378:metabolism; D052161:Human papillomavirus 18 / Q000378:metabolism; D006801:Humans; D017403:In Situ Hybridization; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000378:metabolism*; D009367:Neoplasm Staging; D009959:Oropharyngeal Neoplasms / Q000453:epidemiology / Q000378:metabolism / Q000473:pathology / Q000821:virology*; D030361:Papillomavirus Infections / Q000453:epidemiology*; D016133:Polymerase Chain Reaction; D015995:Prevalence; D011379:Prognosis; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D012307:Risk Factors; D015996:Survival Rate; D013624:Taiwan; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; C000614131:CDKN2A protein, human; D019941:Cyclin-Dependent Kinase Inhibitor p16; D009363:Neoplasm Proteins; D016159:Tumor Suppressor Protein p53