BACKGROUND The optimal clinical management of oral precancer remains uncertain. We investigated the natural-history of oral leukoplakia, the most common oral precancerous lesion, to estimate the relative and absolute risks of progression to cancer, the predictive accuracy of a clinician's decision to biopsy a leukoplakia vis-à-vis progression, and histopathologic predictors of progression. METHODS We conducted a retrospective cohort study (1996-2012) of patients with oral leukoplakia (N = 4,886), identified using electronic medical records within Kaiser Permanente Northern California (KPNC). Among patients with leukoplakia who received a biopsy (n = 1,888), we conducted a case-cohort study to investigate histopathologic predictors of progression. Analyses included indirect standardization and unweighted/weighted Cox regression. RESULTS Compared with the overall KPNC population, oral cancer incidence was substantially elevated in oral leukoplakia patients (standardized incidence ratio [SIR]=40.8; 95%CI=34.8-47.6; n = 161 cancers over 22,582 person-years). Biopsied leukoplakias had a higher oral cancer risk compared to those that were not biopsied (adjusted-hazard ratio [HR]=2.38; 95%CI=1.73-3.28). However, to identify a prevalent/incident oral cancer, the biopsy-decision had low sensitivity (59.6%), low specificity (62.1%), and moderate positive-predictive-value (PPV=5.1%). Risk of progression to oral cancer statistically significantly increased with the grade of dysplasia; 5-year competing-risk-adjusted absolute risks: leukoplakia overall=3.3% (95%CI=2.7%-3.9%); no-dysplasia=2.2% (95%CI=1.5%-3.1%); mild-dysplasia=11.9% (95%CI=7.1%-18.1%); moderate-dysplasia=8.7% (3.2%-17.9%); and severe-dysplasia=32.2% (8.1%-60.0%). Yet, 39.6% of cancers arose from biopsied-leukoplakias without dysplasia. CONCLUSIONS The modest accuracy of the decision to biopsy a leukoplakia vis-à-vis presence/eventual development of oral cancer highlights the need for routine biopsy of all leukoplakias, regardless of visual/clinical impression. Leukoplakia patients, particularly those with dysplasia, need to be closely-monitored for signs of early cancer.

中文翻译：

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口腔白斑和发展为口腔癌的风险：一项基于人群的队列研究。

背景技术口腔癌的最佳临床管理仍不确定。我们调查了口腔白斑的自然病史（最常见的口腔癌前病变），以评估癌症进展的相对和绝对风险，临床医师决定白斑相对于进展的活检的预测准确性以及组织病理学预测因子进展。方法我们进行了一项回顾性队列研究（1996-2012年），对口腔白斑患者（N = 4,886）进行了回顾性研究，这些患者是通过北加州凯撒永久医疗（KPNC）内的电子病历确定的。在接受活检的白斑患者中（n = 1,888），我们进行了一项病例队列研究，以研究进展的组织病理学预测因子。分析包括间接标准化和未加权/加权Cox回归。结果与整个KPNC人群相比，口腔白斑患者的口腔癌发病率显着升高（标准发病率[SIR] = 40.8； 95％CI = 34.8-47.6； n = 161例超过22582人年的癌症）。与未进行活检的患者相比，活检的白斑患者的口腔癌风险更高（调整风险比[HR] = 2.38； 95％CI = 1.73-3.28）。然而，为了确定流行/意外口腔癌，活检决定具有低敏感性（59.6％），低特异性（62.1％）和中等阳性预测值（PPV = 5.1％）。随着发育不良的程度，发展为口腔癌的风险在统计学上显着增加；经过5年竞争风险调整后的绝对风险：白斑总数= 3.3％（95％CI = 2.7％-3.9％）；无发育异常= 2.2％（95％CI = 1.5％-3.1％）; 轻度发育不良= 11.9％（95％CI = 7.1％-18.1％）; 中度发育不良= 8.7％（3。2％-17.9％）；严重不典型增生= 32.2％（8.1％-60.0％）。然而，有39.6％的癌症是由活检的白斑无增生引起的。结论相对于口腔癌的存在/最终发展，对白斑进行活检的决定的准确性不高，这凸显了对所有白斑进行常规活检的需要，无论其视觉/临床印象如何。白斑患者，尤其是发育不良的患者，需要密切监测早期癌症的征兆。