title: Association between p53 and human papillomavirus in head and neck cancer survival.
abstract: BACKGROUND
  High-risk human papillomavirus (HPV-HR) is a significant risk factor for head and neck cancer (HNC), abrogating normal p53 function. In addition, HPV and p53 have been associated with prognosis of these tumors but the findings have been inconsistent. We examined p53 expression and HPV-HR individually and jointly for differences in predicting HNC survival.
  
  
  METHODS
  HNC patients (n = 294) were evaluated for p53 by immunohistochemical staining. HPV was detected by PCR/dot blot hybridization and sequencing.
  
  
  RESULTS
  HNC tumors showed 48% with p53 overexpression and 27% with HPV-HR. Multivariate analyses showed that p53 positivity was significantly associated with higher risk of disease-specific [hazard ratio (HR); 2.0; 95% confidence interval (95% CI), 1.1-3.7] and recurrence-free mortality (HR, 2.8; 95% CI, 1.4-5.3). HPV- cases had significantly worse disease-specific survival (HR, 2.8; 95% CI, 1.3-6.3) compared with HPV-HR cases. When analyzed jointly, with p53(-)/HPV-HR tumors as the reference group, p53(+)/HPV(-) patients had the worst disease-specific (HR, 5.3; 58% versus 15%, P = 0.006) and recurrence-free survival rates (HR, 9.5; 17% versus 89%, P = 0.001), in contrast to the p53(-)/HPV(-) and p53(+)/HPV-HR groups, which had less elevated and different risks for disease-specific survival (HR, 2.5 and 1.7, respectively) and recurrence-free survival (HR, 4.2 and 7.2, respectively).
  
  
  CONCLUSIONS
  Joint assessment of p53/HPV status provides different HRs for each clinical outcome in the four biomarker groups that are distinct from the individual biomarkers. These findings suggest that joint assessment of p53/HPV provides a better indicator of prognosis and potentially different types of treatments.
authors.affiliation: Department of Epidemiology, College of Public Health, University of Iowa, Iowa City, IA 52242, USA. elaine-smith@uiowa.edu
authors.forename: Elaine M
authors.initials: EM
authors.lastname: Smith
authors.forename: Donghong
authors.initials: D
authors.lastname: Wang
authors.forename: Linda M
authors.initials: LM
authors.lastname: Rubenstein
authors.forename: William A
authors.initials: WA
authors.lastname: Morris
authors.forename: Lubomir P
authors.initials: LP
authors.lastname: Turek
authors.forename: Thomas H
authors.initials: TH
authors.lastname: Haugen
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics; D005260:Female; D006258:Head and Neck Neoplasms / Q000235:genetics* / Q000401:mortality / Q000821:virology*; D052162:Human papillomavirus 16 / Q000235:genetics* / Q000302:isolation & purification; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000235:genetics; D030361:Papillomavirus Infections / Q000150:complications*; D011379:Prognosis; D016016:Proportional Hazards Models; D012307:Risk Factors; D016019:Survival Analysis; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
chemical_list: D014408:Biomarkers, Tumor; D016159:Tumor Suppressor Protein p53