SPP1 and head and neck squamous cell carcinoma: In this exploratory, hypothesis-generating study, we investigated selected functional polymorphisms in <i>OPN</i> (<i>SPP1</i>) and <i>CD44</i> genes, together with pretreatment plasma OPN levels, in relation to overall survival (OS), locoregional recurrence-free survival (LRFS), and metastasis-free survival (MFS) in 242 HNSCC patients treated with curative-intent radiotherapy alone (RT) or combined with chemotherapy (RT + CT).