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.
 CiteULike  Complore  Connotea  Del.icio.us  Digg  Facebook  Reddit  Technorati  Twitter What's this?
Related Article
- Chemoselection As a Strategy for Organ Preservation in Advanced Oropharynx Cancer: Response and Survival Positively Associated With HPV16 Copy Number
Francis P. Worden, Bhavna Kumar, Julia S. Lee, Gregory T. Wolf, Kitrina G. Cordell, Jeremy M.G. Taylor, Susan G. Urba, Avraham Eisbruch, Theodoros N. Teknos, Douglas B. Chepeha, Mark E. Prince, Christina I. Tsien, Nisha J. D’Silva, Kun Yang, David M. Kurnit, Heidi L. Mason, Tamara H. Miller, Nancy E. Wallace, Carol R. Bradford, and Thomas E. Carey
JCO 2008 26: 3138-3146
[Abstract]
[Full Text]
Related Editorials
- Individualized Treatment Selection in Patients With Head and Neck Cancer: Do Molecular Markers Meet the Challenge?
Bhuvanesh Singh and David G. Pfister
JCO 2008 26: 3114-3116
[Full Text]
- Redefining the Role of Induction Chemotherapy in Head and Neck Cancer
David J. Adelstein
JCO 2008 26: 3117-3119
[Full Text]
This article has been cited by other articles:
|
|
|
|
 
E. A. Mroz and J. W. Rocco
Functional p53 Status As a Biomarker for Chemotherapy Response in Oral-Cavity Cancer
J. Clin. Oncol.,
February 10, 2010;
28(5):
715 - 717.
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Tandon, C. Tudur-Smith, R. D. Riley, M. T. Boyd, and T. M. Jones
A Systematic Review of p53 as a Prognostic Factor of Survival in Squamous Cell Carcinoma of the Four Main Anatomical Subsites of the Head and Neck
Cancer Epidemiol. Biomarkers Prev.,
February 1, 2010;
19(2):
574 - 587.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. S. Kies, F. C. Holsinger, J. J. Lee, W. N. William Jr, B. S. Glisson, H. Y. Lin, J. S. Lewin, L. E. Ginsberg, K. A. Gillaspy, E. Massarelli, et al.
Induction Chemotherapy and Cetuximab for Locally Advanced Squamous Cell Carcinoma of the Head and Neck: Results From a Phase II Prospective Trial
J. Clin. Oncol.,
January 1, 2010;
28(1):
8 - 14.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. Klinghammer, M. Knodler, A. Schmittel, V. Budach, U. Keilholz, and I. Tinhofer
Association of Epidermal Growth Factor Receptor Polymorphism, Skin Toxicity, and Outcome in Patients with Squamous Cell Carcinoma of the Head and Neck Receiving Cetuximab-Docetaxel Treatment
Clin. Cancer Res.,
January 1, 2010;
16(1):
304 - 310.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
W. Shi, H. Kato, B. Perez-Ordonez, M. Pintilie, S. Huang, A. Hui, B. O'Sullivan, J. Waldron, B. Cummings, J. Kim, et al.
Comparative Prognostic Value of HPV16 E6 mRNA Compared With In Situ Hybridization for Human Oropharyngeal Squamous Carcinoma
J. Clin. Oncol.,
December 20, 2009;
27(36):
6213 - 6221.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N.P. Nguyen, A. Chi, L.M. Nguyen, B.H. Ly, U. Karlsson, and V. Vinh-Hung
Human papillomavirus-associated oropharyngeal cancer: a new clinical entity
QJM,
December 16, 2009;
(2009)
hcp176v1.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. H. Chung and M. L. Gillison
Human Papillomavirus in Head and Neck Cancer: Its Role in Pathogenesis and Clinical Implications
Clin. Cancer Res.,
November 15, 2009;
15(22):
6758 - 6762.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. C. Shonka Jr, A. N. Shoushtari, C. Y. Thomas, C. Moskaluk, P. W. Read, J. F. Reibel, P. A. Levine, and M. J. Jameson
Predicting Residual Neck Disease in Patients With Oropharyngeal Squamous Cell Carcinoma Treated With Radiation Therapy: Utility of p16 Status
Arch Otolaryngol Head Neck Surg,
November 1, 2009;
135(11):
1126 - 1132.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. J. Jaber, J. Moreira, W. J. Canar, and C. M. Bier-Laning
A 25-Year Analysis of Veterans Treated for Tonsillar Squamous Cell Carcinoma
Arch Otolaryngol Head Neck Surg,
November 1, 2009;
135(11):
1147 - 1153.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. M. Chen, G. Li, L. R. Reitzel, K. B. Pytynia, M. E. Zafereo, Q. Wei, and E. M. Sturgis
Matched-Pair Analysis of Race or Ethnicity in Outcomes of Head and Neck Cancer Patients Receiving Similar Multidisciplinary Care
Cancer Prevention Research,
September 1, 2009;
2(9):
782 - 791.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. Lassen, J. G. Eriksen, S. Hamilton-Dutoit, T. Tramm, J. Alsner, and J. Overgaard
Effect of HPV-Associated p16INK4A Expression on Response to Radiotherapy and Survival in Squamous Cell Carcinoma of the Head and Neck
J. Clin. Oncol.,
April 20, 2009;
27(12):
1992 - 1998.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P.T. Hennessey, W.H. Westra, and J.A. Califano
Human Papillomavirus and Head and Neck Squamous Cell Carcinoma: Recent Evidence and Clinical Implications
Journal of Dental Research,
April 1, 2009;
88(4):
300 - 306.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. T. Wolf
Tradition, Teamwork, and Tailored Treatment: Surgical Oncology in the Genomic Era
Arch Otolaryngol Head Neck Surg,
April 1, 2009;
135(4):
337 - 341.
[Full Text]
[PDF]
|
|
|
|
|
|
|
W. A. Michaud, A. C. Nichols, E. A. Mroz, W. C. Faquin, J. R. Clark, S. Begum, W. H. Westra, H. Wada, P. M. Busse, L. W. Ellisen, et al.
Bcl-2 Blocks Cisplatin-Induced Apoptosis and Predicts Poor Outcome Following Chemoradiation Treatment in Advanced Oropharyngeal Squamous Cell Carcinoma
Clin. Cancer Res.,
March 1, 2009;
15(5):
1645 - 1654.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. Singh and D. G. Pfister
Individualized Treatment Selection in Patients With Head and Neck Cancer: Do Molecular Markers Meet the Challenge?
J. Clin. Oncol.,
July 1, 2008;
26(19):
3114 - 3116.
[Full Text]
[PDF]
|
|
|
|
