This study was to determine the sociodemographic and clinicopathological factors that were associated with mortality of OSCC patients managed at Hospital USM. The prevalence of high-risk human papillomavirus (HPV) in these patients and its association with epithelial proliferation rate were also determined. A retrospective study was conducted whereby medical records of patients diagnosed with OSCC and tissue specimens from 2005 to 2015 were studied. Formalin-fixed paraffin-embedded (FFPE) tissue specimens were evaluated for histological grading of OSCC, p16 overexpression and Ki-67 immunostaining. Descriptive statistics, simple and multiple logistics regressions were used for data analysis. Prognostic factors for mortality includes male gender (AOR=10.89; 95% CI: 1.99, 59.65; p = 0.006), alcohol consumption (AOR = 16.45; 95% CI: 1.36, 59.65; p = 0.028), not receiving treatment (AOR = 5.88; 95% CI: 1.03, 33.61; p = 0.046) and late stage (T3, T4) at presentation (AOR = 4.85; 95% CI: 1.12, 21.02; p = 0.035). Significant association was found between high-risk HPV positivity and higher epithelial proliferation rate expression (p < 0.003) in the OSCC tissue specimens.