Head and neck cancers (HNCs) are often diagnosed late, leading to poor prognosis. Chronic inflammation, particularly periodontitis, has been linked to carcinogenesis, but systemic inflammatory markers remain underexplored. This study was the first to examine whether elevated C-reactive protein (CRP) can serve as a cost-effective adjunct in HNC risk assessment, alongside oral health indicators. A retrospective cohort study analysed 23,742 hospital records (4833 patients, 2015-2022) from the University Hospital of Debrecen. HNC cases were identified using ICD-10 codes, with CRP and periodontitis as key predictors. Kaplan-Meier survival analysis, log-rank tests, and Weibull regression were used to assess risk, with model performance evaluated via AIC/BIC and ROC curves. Periodontitis was significantly associated with HNC (HR 5.99 [1.96-18.30]), while elevated CRP (>
15 mg/L) independently increased risk (HR 4.16 [1.45-12.00]). Females had a significantly lower risk than males (HR 0.06 [0.01-0.50]). CRP may serve as a cost-effective, easily accessible biomarker for early HNC detection when combined with oral health screening. Integrating systemic inflammation markers into HNC risk assessment models could potentially improve early diagnosis in high-risk populations.