Potential Non-Invasive Biomarkers for Early Diagnosis of Oral Squamous Cell Carcinoma

Abstract

This study aimed to investigate the role of a panel of salivary cytokines as biomarkers for early detection oral squamous cell carcinoma (OSCC), comparing their levels among healthy individuals, patients with oral leukoplakia (OL), and malignant lesions. Cytokine profiling analysis performed in a minimally invasive sample was correlated with clinicopathological variables in our patient cohorts. Unstimulated saliva was obtained from subjects with OSCC at early (n = 33) and advanced (n = 33) disease, OL with homogeneous (n = 33) and proliferative verrucous (n = 33) clinical presentations, and healthy controls (n = 25). Salivary IL-1α, IL-6, IL-8, IP-10, MCP-1, TNF-α, HCC-1, and PF-4 levels were analyzed by a sensitive bead-based multiplex immunoassay. Mean levels of IL-6, IL-8, TNF-α, HCC-1, MCP-1, and PF-4 differed significantly between OSCC, OL, and control saliva (p < 0.05). We found notably higher IL-6 and TNF-α in advanced compared to early OSCC stages. The area under the curve (AUC) for OSCC vs. control was greater than 0.8 for IL-6, IL-8, TNF-α, and HCC-1, and greater than 0.7 for PF-4. The presence of neck metastases (NM) was associated with increased IL-6 and TNF-α levels. Our findings suggest that salivary IL-6, IL-8, TNF-α, HCC-1, and PF-4 may discriminate between OSCC, OL, and healthy controls. IL-6 and TNF-α may indicate OSCC progression, being distinctive in the presence of NM.