Background: Epithelial integrity in head and neck squamous cell carcinoma (HNSCC) is often disrupted, and microbial products and inflammation are potentially important in HNSCC pathogenesis. “Pro-inflammatory” CD16-positive monocytes expand in various malignancies, but their role in HNSCC is not known. Monocyte-lineage cells (MCs) are associated with HNSCC progression, potentially in part because MCs produce interleukin 6 (IL-6) in response to endotoxin (lipopolysaccharide, LPS), and IL-6 stimulates activation of STAT3, important in carcinogenesis. However, MC phenotypes and functions in HNSCC have not been characterized.