Lower circulating platelet counts and antiplatelet therapy independently predict better outcomes in patients with head and neck squamous cell carcinoma.

Saleh Rachidi,Zihai Li,Terry A Day,Kristin Wallace,Anthony J Alberg

doi:10.1186/s13045-014-0065-5

Abstract

BackgroundHead and neck squamous cell carcinoma (HNSCC) mortality rates have not shown significant reduction in decades. Platelets are being implicated in having cancer-promoting roles, an observation supported by the adverse outcomes associated with thrombocytosis in many malignancies associated with thrombocytosis. However, the prognostic significance of platelet counts in HNSCC is unknown. Here, we comprehensively investigate the predictive value of platelet counts at diagnosis and post-diagnosis antiplatelet treatment in the overall survival of HNSCC patients.MethodsThe study population consists of 1051 pathologically confirmed HNSCC cases diagnosed between years 2000 and 2012 in a tertiary medical center. Platelet count was investigated as a predictor of survival by fitting Cox Proportional Hazards (CPH) regression models to generate Hazard Ratios (HR) and 95% confidence intervals (CI), while adjusting for age, sex, race, stage, treatment and smoking status. Finally, we evaluated the association between overall survival and antiplatelet medication intake after diagnosis.ResultsMultivariable analysis showed an increased death rate in patients with thromobocytosis [HR 2.37, 95% CI 1.60-3.50)] and high normal platelet counts [HR 2.20, 95% CI 1.58-3.05] compared to the reference middle normal group. Post-diagnosis treatment with antiplatelet medications was inversely associated with death rate [HR 0.76, 95% CI 0.58-0.99].ConclusionsHigher platelet counts were associated with poorer prognosis in HNSCC patients, whereas antiplatelet agents were associated with better prognosis. Antiplatelet agents warrant evaluation in preclinical and clinical settings as a way to improve survival in HNSCC.

Highlights

Head and neck cancer is common in many areas across the world and is mainly linked to tobacco smoking, alcohol consumption and Human Papilloma Virus (HPV) infections
To further investigate the role of platelets in Head and neck squamous cell carcinoma (HNSCC), we studied the association of medications known to interfere with platelet function; anti-platelet medications and nonsteroidal anti-inflammatory drugs (NSAIDs) [27], with survival of HNSCC patients
We evaluated the association between the 5 platelet categories and survival by fitting univariate Cox Proportional Hazards (CPH) regression models

Summary

Introduction

Head and neck cancer is common in many areas across the world and is mainly linked to tobacco smoking, alcohol consumption and Human Papilloma Virus (HPV) infections. Recent work has shown hematological parameters including neutrophils, lymphocytes and monocytes to predict outcome in head and neck cancers [3,4,5]. Platelets secrete cytokines and growth factors such as TGF-β [16], VEGF [17], MMP-2, PF4 [18] and PDGF [19], which in turn induce hallmarks of cancer progression such as epithelial-mesenchymal transition (EMT) [20], angiogenesis, cell migration and/or proliferation. Platelet-derived TGF-β acts on cancer cells to activate the Smad and NF-κB pathways, promoting cancer metastasis [22]. Head and neck squamous cell carcinoma (HNSCC) mortality rates have not shown significant reduction in decades. We comprehensively investigate the predictive value of platelet counts at diagnosis and post-diagnosis antiplatelet treatment in the overall survival of HNSCC patients

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