| Summary: | <i>Background and Objectives</i>: Increased osteopontin (OPN) concentrations in the plasma of patients with head and neck squamous cancer (HNSCC) have diagnostic significance, and it can indicate more aggressive biological behavior of cancer. The aim of this study was to determine OPN levels in patients with HNSCC of different primary locations and to assess its prognostic significance in metastasis development. <i>Materials and Methods</i>: This cohort study included 45 patients (41 male and 4 female patients) with HNSCC with different primary localization of head and neck. All patients underwent surgery—neck dissection. All patients were categorized according to the histological findings of the resected material and tumor–node–metastasis (TNM) classification system. After surgery, N categories were determined on the basis of histological features of resected material. <i>Results</i>: The histological findings of our patients showed: N0 in 11 patients, N1 in 8 patients, N2a in 4 patients, N2b in 14 patients and N2c in 8 patients. Plasma OPN values in all study participants ranged from 2.24 to 109.10 ng/mL. OPN levels in plasma of patients with negative nodes compared to the group of patients with positive nodes in the neck differed significantly (16.89 ng/mL to 34.08 ng/mL, respectively; <i>p</i> = 0.03). There were significantly lower OPN plasma levels in the group of subjects with histologically positive one lymph node in the neck (N1) compared to the group of patients with N2b histologically positive findings of resected neck material (10.4 ng/mL to 43.9 ng/mL, respectively; <i>p</i> = 0.02). <i>Conclusions</i>: The results have shown that growing N degrees of positive neck nodes classification were accompanied by growing values of plasma osteopontin. Osteopontin might be important for the development of neck metastases.
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