Whether "periodontal disease" can be considered as an independent risk factor for head and neck cancer (HNC) remains controversial. The aim of the current meta-analysis was to quantitatively assess this relationship in order to determine whether this represents a true risk factor, with implications for cancer prevention and management. PubMed, Scopus, and Embase databases were systematically searched. Selective studies were reviewed, and meta-analysis was performed to estimate the pooled odds ratio (OR) with 95% confidence intervals (CIs) on eligible studies using a random effects model. In total, 21 eligible observational studies (4 cohorts and 17 case-controls) were identified for qualitative synthesis after a review of 1051 articles. Significant heterogeneity could be identified in measures utilized for reporting of periodontal disease. Meta-analysis performed on nine studies that employed objective measures for reporting periodontal disease demonstrated a significant association between periodontal disease and HNC [OR 3.17, 95% CI, 1.78-5.64]. A diseased periodontium represents an independent risk marker, and a putative risk factor, for HNC. Prospective studies with standardized measures of periodontal disease severity and extent, integrated with microbiological and host susceptibility facets, are needed to elucidate the mechanisms of this positive association and whether treatment of the former influences the incidence and outcomes for HNC.