Prognosis Impact of Betel Nut on Oral Squamous Cell Carcinoma: A Population-Based Study

Purpose: The prognostic impact of betel nut on oral squamous cell carcinoma (OSCC) remains controversial. This study aimed to determine whether betel nut chewing is an independent prognostic factor in patients treated with standardized surgery. Methods: This retrospective population-based cohort study enrolled 1113 patients with primary OSCC, including 922 betel nut chewers and 191 non-chewers. All patients underwent standardized surgical treatment. The prognostic impact of betel nut chewing was evaluated by returning to all patients and comparing the disease-free survival times between the two groups. The Chi-square test was used to explore the clinical characteristics associated with betel nut chewing. Kaplan-Meier survival analysis, univariable Cox regression, and multivariable Cox regression analyses were used to investigate the prognostic impact of betel nut. Results: No significant difference was observed in the disease-free survival time between chewers and non-chewers in either the overall group or subgroup analyses. Univariable Cox regression analysis indicated that betel nut use was not a prognostic factor. After adjusting for potential confounders, multivariable Cox regression confirmed that cervical lymph node metastasis, clinical stage, and pathological grade were independent risk factors for prognosis, whereas betel nut use had no significant impact on prognosis. Conclusion: These findings suggest that the prognosis of OSCC is dictated by the biological stage of the tumor rather than betel nut use. This allows clinicians to develop more objective, precise treatment plans for OSCC patients. Plain Language Summary: Betel nut chewing is a major cause of oral cancer; however, its prognostic impact of betel nut on oral cancer remains unclear. This study aimed to verify whether betel nut chewing is an independent prognostic factor in patients undergoing standardized surgery. Our study included 1113 patients diagnosed with oral cancer between 2018 and 2022. All patients received standard surgical treatment and regular follow-up visits. We then compared the disease-free survival times of those who chewed betel nut with those who did not. We found that betel nut has no impact on prognosis of oral cancer. Instead, the most important prognostic factors remain cervical lymph node metastasis, clinical stage, and pathological grade. These results suggest a “dual role” of betel nut: it is a dangerous trigger of oral cancer, but it has no impact on the prognosis of oral cancer. Rather than focusing on a history of betel nut use, clinicians should pay more attention to the specific stage of the tumor to create more objective and precise treatment plans. Keywords: oral squamous cell carcinoma, betel nut, prognosis