The impact of tobacco smoking on survival of patients with oral squamous cell carcinoma: a population-based retrospective study

This article aims to evaluate the impact of smoking status, accumulated tobacco exposure (ATE), and smoking cessation on overall- and disease-free survival (OS and DFS) of patients with oral squamous cell carcinoma (OSCC). Patients with primary OSCC treated with curative intent between 2000 and 2019 in Copenhagen were included (<i>n</i> = 1808). Kaplan–Meier curves and multivariable Cox regression analyses were performed to compare the survival of patients with different smoking history. Interactions between ATE and (A) tumor subsite and (B) excessive alcohol consumption (EAC) on the survival were evaluated using multivariable Cox regression analyses with interaction terms. We included 1717 patients with known smoking status (62.8% males, median age: 64 years (IQR: 57–71 years)), who had a 5-year OS of 53.7% (95%CI: 49.8%–57.9%). Based on fully adjusted multivariable Cox regression analyses, significantly elevated hazard ratios (HRs) for OS and DFS were identified for current, but not former smokers, compared to never-smokers. An approximately linear relationship between continuous ATE and survival estimates was identified. ATE analyzed as a categorical variable showed significantly elevated HRs for OS of patients with all categories (0&lt;<i>x</i> ≤ 30, 30&lt;<i>x</i> ≤ 60, and &gt;60 PYs), however only for DFS of patients with &gt;60 PYs, compared to 0 PYs. Furthermore, an unfavorable long-term prognosis was evident after &gt;3.5 (OS) and &gt;2.5 (DFS) years from diagnosis for patients who continued smoking compared to patients with smoking cessation at diagnosis. The survival estimates of patients with different tumor subsite and alcohol consumption differed with increasing ATE. Tobacco smoking (assessed as smoking status and ATE) was associated with inferior survival (OS and DFS) among patients with OSCC. Unfavorable long-term prognosis was significant for patients who continued smoking compared to patients with smoking cessation at diagnosis. The impact of ATE on survival of patients with OSCC may depend on the tumor subsite and/or alcohol consumption.

本研究旨在评估吸烟状态、累计烟草暴露量（accumulated tobacco exposure, ATE）以及戒烟行为对口腔鳞状细胞癌（oral squamous cell carcinoma, OSCC）患者总生存期（overall survival, OS）与无病生存期（disease-free survival, DFS）的影响。本研究纳入2000年至2019年间于哥本哈根接受根治性治疗的原发性口腔鳞状细胞癌患者（n=1808）。采用卡普兰-迈耶（Kaplan–Meier）曲线及多变量考克斯回归分析，对比不同吸烟史患者的生存情况。通过引入交互项的多变量考克斯回归分析，评估了累计烟草暴露量分别与（A）肿瘤亚位点、（B）过量饮酒（excessive alcohol consumption, EAC）之间对患者生存期的交互效应。
最终纳入1717例明确吸烟状态的患者（男性占比62.8%，中位年龄64岁，四分位间距57~71岁），该队列患者的5年总生存率为53.7%（95%置信区间：49.8%~57.9%）。经完全校正的多变量考克斯回归分析显示，与从未吸烟者相比，当前吸烟者的总生存期与无病生存期风险比（hazard ratios, HRs）显著升高，而已戒烟者则无此差异。研究发现连续型累计烟草暴露量与患者生存期估计值之间呈近似线性相关关系。将累计烟草暴露量作为分类变量分析时，所有暴露层级（0<x≤30、30<x≤60及>60包年，pack-years, PYs）患者的总生存期风险比均显著升高；但仅>60包年层级患者的无病生存期风险比相较于0包年层级显著升高。此外，与确诊时即戒烟的患者相比，确诊后仍持续吸烟的患者在确诊后超过3.5年（总生存期）及超过2.5年（无病生存期）时，预后不良风险更为显著。不同肿瘤亚位点及饮酒状态的患者，其生存期估计值随累计烟草暴露量升高呈现差异化变化。
烟草吸烟（以吸烟状态及累计烟草暴露量评估）与口腔鳞状细胞癌患者较差的总生存期及无病生存期显著相关。与确诊时戒烟的患者相比，持续吸烟患者的长期预后不良风险更为显著。累计烟草暴露量对口腔鳞状细胞癌患者生存期的影响，可能依赖于肿瘤亚位点及/或饮酒状态。