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

Yin Wu, Marshall R. Posner, Lisa M. Schumaker, Nikolaos Nikitakis, Olga Goloubeva, Ming Tan, Changwan Lu, Sana Iqbal, Jochen Lorch, Nicholas J. Sarlis, Robert I. Haddad, Kevin J. Cullen*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

25 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1811-1817
Number of pages7
JournalCancer
Volume118
Issue number7
DOIs
StatePublished - Apr 1 2012
Externally publishedYes

Keywords

  • In human papilloma virus
  • Negative
  • Oropharyngeal cancer
  • Prognostic markers

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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