EGFR, p16, HPV Titer, Bcl-xL and p53, sex, and smoking as indicators of response to therapy and survival in oropharyngeal cancer

J Clin Oncol. 2008 Jul 1;26(19):3128-37. doi: 10.1200/JCO.2007.12.7662. Epub 2008 May 12.


Purpose: To prospectively identify markers of response to therapy and outcome in an organ-sparing trial for advanced oropharyngeal cancer.

Patients and 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).

Conclusion: 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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Aged
  • Biomarkers, Tumor / analysis*
  • Biopsy
  • Cyclin-Dependent Kinase Inhibitor p16 / metabolism*
  • DNA Mutational Analysis
  • DNA, Viral / genetics
  • DNA, Viral / metabolism
  • ErbB Receptors / metabolism*
  • Female
  • Humans
  • Immunoenzyme Techniques
  • Male
  • Middle Aged
  • Oropharyngeal Neoplasms / drug therapy*
  • Oropharyngeal Neoplasms / metabolism
  • Oropharyngeal Neoplasms / radiotherapy*
  • Papillomaviridae / isolation & purification
  • Prospective Studies
  • Sex Factors
  • Smoking / adverse effects*
  • Statistics, Nonparametric
  • Survival Analysis
  • Treatment Outcome
  • Tumor Suppressor Protein p53 / genetics
  • Tumor Suppressor Protein p53 / metabolism*
  • bcl-X Protein / metabolism*


  • Biomarkers, Tumor
  • Cyclin-Dependent Kinase Inhibitor p16
  • DNA, Viral
  • Tumor Suppressor Protein p53
  • bcl-X Protein
  • ErbB Receptors