Plasma biomarkers and long-term survival in head and neck squamous cell carcinoma patients: insights from EGF, VEGF, IL-4, IL-6, IL-8 and MCP-1 at diagnosis

Abstract Background The acute-phase cascade (APC) has been correlated with outcome in many different cancers, including head and neck squamous cell carcinoma (HNSCC). A main driver of the APC is cytokines. We have studied systemic acute-phase soluble cytokine and growth factor profiles in the serum of HNSCC patients at diagnosis and their correlation with prognosis. Methods Long-term HNSCC-specific survival was analyzed from blood samples obtained at diagnosis from 115 patients at diagnosis treated with curative intent. Following observation for up to 10 years, HNSCC-specific survival was determined. The cytokines were determined by enzyme-linked immunosorbent assay (ELISA). Results Increased levels Interleukin 4 (IL-4) predicted better survival among HPV(−), whereas high IL-6 levels were negative survival predictor among all patients. Increased levels of the chemokines IL-8 and MCP-1 predicted worse prognosis among HPV(+) patients. High levels of growth factor VEGF at diagnosis showed a trend towards worse outcomes for among HPV(+) patients. High levels of EGF predicted decreased both overall and HNSCC-specific survival among HPV(+). ROC analysis demonstrated that clinically, EGF levels above 2.3 pg/ml yielded more than 75% sensitivity and specificity for long-term HNSCC specific survival in HPV(+) patients. Conclusion High plasma levels of IL-6 predicted worse survival among all patients, whereas IL-8, MCP-1, EGF and VEGF predicted worse survival among HPV(+) patients only. High levels of IL-4 predicted better survival in HPV(−) patients.