Sex Differences in Using Systemic Inflammatory Markers to Prognosticate Patients with Head and Neck Squamous Cell Carcinoma

Background: Remarkable discrepancy exists in outcomes between men and women for multiple malignancies. We sought to expose sex differences in using platelet count and neutrophil-to-lymphocyte ratio (NLR) to predict overall survival for select cancer types with focus on head and neck squamous cell carcinoma (HNSCC). Methods: Peripheral blood samples from 9,365 patients seen in a tertiary teaching hospital with nine different primary tumors were retrospectively examined. HNSCC RNA-sequencing data from The Cancer Genome Atlas were analyzed by two computational means [Cell-type Identification By Estimating Relative Subsets Of RNA Transcripts (CIBERSORT) and Estimation of Stromal and Immune cells in Malignant Tumor tissues using Expression data (ESTIMATE)] to extend our observations to the tumor microenvironment. Results: For HNSCC, platelet count was more predictive of overall survival for males [log-rank test: HR = 1.809; 95% confidence interval (CI), 1.461–2.239 vs. HR = 1.287; 95% CI, 0.8901–1.861], whereas NLR was more predictive for females (HR = 2.627; 95% CI, 1.716–4.02 vs. HR = 1.261; 95% CI, 0.998–1.593). For females, lymphocyte count was more associated with survival than neutrophil count (multivariate Cox regression: P = 0.0015 vs. P = 0.7476). Both CIBERSORT (P = 0.0061) and ESTIMATE (P = 0.022) revealed greater immune infiltration in females. High tumor infiltration by T lymphocytes was more strikingly associated with survival in females (HR = 0.20, P = 0.0281) than in males (HR = 0.49, P = 0.0147). Conclusions: This is the first study to comprehensively demonstrate sex bias in the clinical utility of platelet, granulocyte, and lymphocyte counts as biomarkers to prognosticate HNSCC patients. Impact: This work emphasizes the necessity to consider sex in appraising inflammatory markers for cancer risk stratification. Cancer Epidemiol Biomarkers Prev; 27(10); 1176–85. ©2018 AACR.