title: EGFR, p16, HPV Titer, Bcl-xL and p53, sex, and smoking as indicators of response to therapy and survival in oropharyngeal cancer.
abstract: OBJECTIVE
  To prospectively identify markers of response to therapy and outcome in an organ-sparing trial for advanced oropharyngeal cancer.
  
  
  METHODS
  Pretreatment biopsies were examined for expression of epidermal growth factor receptor (EGFR), p16, Bcl-xL, and p53 as well as for p53 mutation. These markers were assessed for association with high-risk human papillomavirus (HPV), response to therapy, and survival. Patient variables included smoking history, sex, age, primary site, tumor stage, and nodal status.
  
  
  RESULTS
  EGFR expression was inversely associated with response to induction chemotherapy (IC) (P = .01), chemotherapy/radiotherapy (CRT; P = .055), overall survival (OS; P = .001), and disease-specific survival (DSS; P = .002) and was directly associated with current smoking (P = .04), female sex (P = .053), and lower HPV titer (P = .03). HPV titer was significantly associated with p16 expression (P < .0001); p16 was significantly associated with response to IC (P = .008), CRT (P = .009), OS (P = .001), and DSS (P = .003). As combined markers, lower HPV titer and high EGFR expression were associated with worse OS (rho(EGFR) = 0.008; rho(HPV) = 0.03) and DSS (rho(EGFR) = 0.01; rho(HPV) = 0.016). In 36 of 42 biopsies, p53 was wild-type, and only one HPV-positive tumor had mutant p53. The combination of low p53 and high Bcl-xL expression was associated with poor OS (P = .005) and DSS (P = .002).
  
  
  CONCLUSIONS
  Low EGFR and high p16 (or higher HPV titer) expression are markers of good response to organ-sparing therapy and outcome, whereas high EGFR expression, combined low p53/high Bcl-xL expression, female sex, and smoking are associated with a poor outcome. Smoking cessation and strategies to target EGFR and Bcl-xL are important adjuncts to the treatment of oropharyngeal cancer.
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, University of Michigan Comprehensive Cancer Center Head and Neck Cancer Program, Ann Arbor, MI 48109, USA.
authors.forename: Bhavna
authors.initials: B
authors.lastname: Kumar
authors.forename: Kitrina G
authors.initials: KG
authors.lastname: Cordell
authors.forename: Julia S
authors.initials: JS
authors.lastname: Lee
authors.forename: Francis P
authors.initials: FP
authors.lastname: Worden
authors.forename: Mark E
authors.initials: ME
authors.lastname: Prince
authors.forename: Huong H
authors.initials: HH
authors.lastname: Tran
authors.forename: Gregory T
authors.initials: GT
authors.lastname: Wolf
authors.forename: Susan G
authors.initials: SG
authors.lastname: Urba
authors.forename: Douglas B
authors.initials: DB
authors.lastname: Chepeha
authors.forename: Theodoros N
authors.initials: TN
authors.lastname: Teknos
authors.forename: Avraham
authors.initials: A
authors.lastname: Eisbruch
authors.forename: Christina I
authors.initials: CI
authors.lastname: Tsien
authors.forename: Jeremy M G
authors.initials: JM
authors.lastname: Taylor
authors.forename: Nisha J
authors.initials: NJ
authors.lastname: D'Silva
authors.forename: Kun
authors.initials: K
authors.lastname: Yang
authors.forename: David M
authors.initials: DM
authors.lastname: Kurnit
authors.forename: Joshua A
authors.initials: JA
authors.lastname: Bauer
authors.forename: Carol R
authors.initials: CR
authors.lastname: Bradford
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Carey
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis*; D001706:Biopsy; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000378:metabolism*; D004252:DNA Mutational Analysis; D004279:DNA, Viral / Q000235:genetics / Q000378:metabolism; D066246:ErbB Receptors / Q000378:metabolism*; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D008875:Middle Aged; D009959:Oropharyngeal Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000532:radiotherapy*; D027383:Papillomaviridae / Q000302:isolation & purification; D011446:Prospective Studies; D012737:Sex Factors; D012907:Smoking / Q000009:adverse effects*; D018709:Statistics, Nonparametric; D016019:Survival Analysis; D016896:Treatment Outcome; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*; D051020:bcl-X Protein / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; D019941:Cyclin-Dependent Kinase Inhibitor p16; D004279:DNA, Viral; D016159:Tumor Suppressor Protein p53; D051020:bcl-X Protein; D066246:ErbB Receptors