Background:
Oropharyngeal squamous cell carcinoma (OPSCC) comprises one of the main cancers of the head and neck area and displays distinct clinicopathologic features such as high frequency of human papillomavirus (HPV). Despite many efforts, molecular pathogenesis of OSCC has not been fully elucidated, therefore, therapeutic strategies based on molecular tumor profiling leaves much to be desired.
Aim:
The aim of this study was to explore a potential molecular therapeutic target of OPSCC.
Methods:
Formalin-fixed paraffin- embedded tumor samples from ninety-seven cases of OPSCC were included in this study. Association of HPV was tested by immunohistochemistry for P16, in situ hybridization (ISH), and HPV DNA chip based microarray. Gene copy number status for EGFR and FGFR1 was examined by fluorescence in situ hybridization (FISH). Clinicopathologic correlation and prognostication was statistically analyzed.
Results:
HPV was detected in 47 of 97 patients (48.5%), most of them carried high risk HPV, especially HPV 16. Amplification of EGFR or FGFR1 gene was found in 6.3% (5/79) and 11.4% (9/79), respectively. Amplification of EGFR or FGFR1 was found to be mutually exclusive, and most of them were HPV-negative / P16-negative cases (no EGFR amplification in HPV+ tumor, and 2 FGFR1 of 9 in HPV+ cases) (p<0.05) In univariate analysis, HPV association or P16 positivity (p=0.001) was associated with better overall survival (OS) and progression free survival (PFS) (all p<0.05). Amplification of EGFR was related to better PFS (p<0.01) and FGFR1 amplification showed better PFS with borderline significance (p=0.068). In multivariate analysis, only P16 indicated to be an independent prognostic factor of OS and PFS, whereas EGFR amplification to be another independent predictor of prolonged PFS with borderline significance (p=0.084).
Conclusions:
These findings suggest that EGFR or FGFR1 may be used as a potential molecular therapeutic target in a subset of HPV negative patients with OPSCC.