Abstract
OBJECTIVE: EGFR, cyclin D1, and Bcl-2 are proteins involved in different stages of tumorigenesis which have all been associated with poor prognosis in head and neck squamous cell carcinoma (HNSCC). In this systematic review and meta-analysis, we aim to measure the association of each protein with survival in HNSCC. DATA SOURCES: PubMed, Scopus, and Cochrane databases. REVIEW METHODS: A systematic review of EGFR, cyclin D1, and Bcl-2 was conducted to determine the association between overexpression and survival in HNSCC. A weighted random-effects meta-analysis then measured pooled rates of overall, disease-free, and disease-specific survival for each protein. RESULTS: Overexpression of EGFR was associated with worse overall mortality (HR = 1.52, P = .01), disease-related mortality (HR = 1.33, P = .02), and disease progression (HR = 1.99, P < .001). Overexpression of cyclin D1 was also associated with worse overall mortality (HR = 1.93, P < .001), disease-related mortality (HR = 1.57, P = .01), and disease-specific mortality (HR = 1.93, P = .01). The association between cyclin D1 and overall mortality also remained significant in papers examining only oropharynx cancer (HR = 2.66, P = .03). Overexpression of Bcl-2 was associated with worse overall mortality (HR = 1.92, P = .002). CONCLUSION: These findings support EGFR, cyclin D1, and Bcl-2 as biomarkers which portend worse prognosis in HNSCC. Further work will be needed to understand whether measurement of these proteins can be useful in tailoring treatment strategies, and whether they can be used as targets for novel therapies.