PROGNOSTIC FACTORS IN HPV NEGATIVE OROPHARYNGEAL CANCER

 Cancer. 2011 Aug 25. doi: 10.1002/cncr.26485. [Epub ahead of print]

Novel biomarker panel predicts prognosis in human papillomavirus-negative
oropharyngeal cancer: An analysis of the TAX 324 trial.

Wu Y, Posner MR, Schumaker LM, Nikitakis N, Goloubeva O, Tan M, Lu C, Iqbal S,
Lorch J, Sarlis NJ, Haddad RI, Cullen KJ.

Experimental Therapeutics Program, University of Maryland Marlene and Stewart
Greenebaum Cancer Center, Baltimore, Maryland.

BACKGROUND: New treatment strategies for locally advanced head and neck squamous 
cell carcinoma combine induction chemotherapy and chemoradiation. Identifying the
predictors of outcome in sequentially treated patients is critical for focusing
therapeutic research. In this analysis, the authors evaluated human
papillomavirus type 16 (HPV-16) status and the expression levels of a defined set
of biomarkers to identify predictors of response to this treatment modality.
METHODS: In total, 114 patients with oropharyngeal cancer (OPC) who were treated 
on the TAX 324 trial (cisplatin and fluorouracil with or without docetaxel in
patients with locally advanced head and neck squamous cell carcinoma) had
pretreatment biopsy specimens that were evaluable for HPV-16 DNA and
immunohistochemical expression of the following biomarkers: beta-tubulin II
(βT-II), glutathione S-transferase (GST-π), p53, and B-cell lymphoma 2 (Bcl-2).
Patients were categorized into risk groups based on their HPV status and
biomarker expression levels. RESULTS: Patients with high-risk OPC were defined by
HPV-negative status and either elevated expression of βT-II or levels of at least
2 of the other 3 adverse markers (elevated GST-π, elevated p53, or low Bcl-2).
All other HPV-negative patients were categorized as moderate risk. In total, 55
patients were HPV-positive, and 59 patients were HPV-negative, with 34 were
categorized as high risk and 25 categorized as moderate risk. The median survival
for HPV-positive patients was not reached. The median survival was 44.2 months
for moderate-risk patients (95% confidence interval, 20.9 months to not reached) 
and 12.1 months for high-risk patients (95% confidence interval, 7.5-19.7
months). The 24-month survival rate was 89% for HPV-positive patients, 67% for
moderate-risk patients, and 29% for high-risk patients (P < .0001). CONCLUSIONS: 
The molecular data set in this study readily differentiated between 2 distinct
groups of patients with locally advanced, HPV-negative OPC. This
risk-stratification strategy may serve as a guide for treatment selection.