JCO Early Release, published online ahead of print May 12 2008
Journal of Clinical Oncology, 10.1200/JCO.2007.12.7662
Received May 23, 2007
Accepted October 30, 2007
EGFR, p16, HPV Titer, Bcl-xL and p53, Sex, and Smoking As Indicators of Response to Therapy and Survival in Oropharyngeal Cancer
Bhavna Kumar, Kitrina G. Cordell, Julia S. Lee, Francis P. Worden, Mark E. Prince, Huong H. Tran, Gregory T. Wolf, Susan G. Urba, Douglas B. Chepeha, Theodoros N. Teknos, Avraham Eisbruch, Christina I. Tsien, Jeremy M.G. Taylor, Nisha J. D'Silva, Kun Yang, David M. Kurnit, Joshua A. Bauer, Carol R. Bradford, and Thomas E. Carey*
From the Department of Otolaryngology–Head and Neck Surgery, Department of Periodontics and Oral Medicine, Department of Pathology, Comprehensive Cancer Center, Department of Internal Medicine, Division of Hematology-Oncology, Department of Radiation Oncology, Department of Biostatistics, Department of Pediatrics, and Department of Pharmacology, University of Michigan, Ann Arbor, MI.
* To whom correspondence should be addressed. E-mail: careyte{at}umich.edu
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 ( EGFR = 0.008; HPV = 0.03) and DSS (EGFR = 0.01; 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.
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