Objectives: Oral squamous cell carcinoma (OSCC) is a multifactorial disease. The individual effect of each risk factor for OSCC may be conditioned by the frequency of other factors. The objective of this study was to identify the association between chronic mechanical irritation (CMI) and OSCC and to analyse the influence of CMI on other important risk factors for OSCC. Materials and methods: A prospective and age/sex-matched case-control study was performed in two institutions from Argentina between 2009 and 2019, with consecutive and newly diagnosed OSCC. The frequencies of tobacco, alcohol, and CMI were analysed using conditional logistic regression. Cumulative tobacco consumption and the presence of CMI were analysed using the Mann-Whitney test. Results: CMI and OSCC were associated with an OR of 7.02 (95% CI 3.57–13.78, p < 0.001). The combination of CMI and alcohol demonstrated the highest risk of OSCC (OR 53.83, CI 95% 8.04–360, p < 0.0001), followed by the combination of CMI, tobacco, and alcohol (OR 48.06, CI 95% 8.47–272, p < 0.0001). The combination of CMI and tobacco was also significant (OR 5.61, CI 95% 1.07–29.54, p = 0.042). Patients with CMI developed OSCC with less cumulative tobacco use compared with those without CMI. Conclusion: CMI is an independent risk factor for OSCC, and it could act as a risk modifier among tobacco and alcohol users having an enhancing effect. Clinical relevance: Elimination of CMI could decrease the risk of OSCC.
