Abstract：
BACKGROUND: Despite the oral cavity being readily accessible, oral cancer (OC) remains a significant burden. The objective of this study is to develop a DNA ploidy-based cytology test for early detection of high-risk oral lesions.
METHODS: This retrospective study was conducted using 569 oral brushing samples collected from 95 normal and 474 clinically abnormal mucosa with biopsy diagnosis of reactive, low-grade or high-grade precancer or cancers. Brushing cells were processed to characterize DNA ploidy. A two-step DNA ploidy-based algorithm, the DNA ploidy oral cytology (DOC) test, was developed using a training set, and verified in test and validation sets to differentiate high-grade lesions (HGLs) from normal. The prognostic value of the test was evaluated by an independent outcome cohort, including progressed and non-progressing normal, reactive and low-grade lesions. Classification performance was assessed by accuracy, sensitivity, and specificity, while the prognostic value was evaluated by using the Cox proportional hazards analysis on 3-year progression-free survival (PFS).
RESULTS: The developed DOC test exhibited high accuracy for detecting HGLs in the test and validation sets, with a sensitivity of 0.97 and 0.96, respectively. Its application to the Outcome cohort demonstrated significant prognostic value for 3-year PFS (log rank, p < 0.001). Multivariate analysis showed that high-grade pathology was the only variable explaining positive DOC test, not age, smoking, or lesional site.
CONCLUSIONS: Clinical implementation of the DOC test could provide an effective screening method for detecting HGLs for biopsy and lesions at risk of progression.
METHODS: This retrospective study was conducted using 569 oral brushing samples collected from 95 normal and 474 clinically abnormal mucosa with biopsy diagnosis of reactive, low-grade or high-grade precancer or cancers. Brushing cells were processed to characterize DNA ploidy. A two-step DNA ploidy-based algorithm, the DNA ploidy oral cytology (DOC) test, was developed using a training set, and verified in test and validation sets to differentiate high-grade lesions (HGLs) from normal. The prognostic value of the test was evaluated by an independent outcome cohort, including progressed and non-progressing normal, reactive and low-grade lesions. Classification performance was assessed by accuracy, sensitivity, and specificity, while the prognostic value was evaluated by using the Cox proportional hazards analysis on 3-year progression-free survival (PFS).
RESULTS: The developed DOC test exhibited high accuracy for detecting HGLs in the test and validation sets, with a sensitivity of 0.97 and 0.96, respectively. Its application to the Outcome cohort demonstrated significant prognostic value for 3-year PFS (log rank, p < 0.001). Multivariate analysis showed that high-grade pathology was the only variable explaining positive DOC test, not age, smoking, or lesional site.
CONCLUSIONS: Clinical implementation of the DOC test could provide an effective screening method for detecting HGLs for biopsy and lesions at risk of progression.
摘要：
背景：尽管口腔易于接近，口腔癌（OC）仍然是一个巨大的负担。这项研究的目的是开发一种基于DNA倍性的细胞学检查，以早期发现高危口腔病变。
方法：这项回顾性研究是使用从95个正常粘膜和474个临床异常粘膜收集的569个口腔刷牙样本进行的，活检诊断为反应性，低级或高级癌前病变或癌症。处理刷细胞以表征DNA倍性。基于DNA倍性的两步算法，DNA倍性口腔细胞学（DOC）测试，是使用训练集开发的，并在测试和验证集中验证，以区分高级别病变（HGL）与正常。通过独立的结局队列评估测试的预后价值，包括进展和非进展正常，反应性和低度病变。分类性能是通过准确性来评估的，灵敏度,和特异性，而预后价值通过Cox比例风险分析对3年无进展生存期(PFS)进行评估.
结果：开发的DOC测试在测试和验证集中检测HGL时表现出很高的准确性，灵敏度分别为0.97和0.96。其在结果队列中的应用证明了3年PFS的显着预后价值（logrank，p<0.001)。多因素分析显示，高级别病理是解释DOC检验阳性的唯一变量，不是年龄,吸烟,或病变部位。
结论：临床实施DOC检测可以为检测活检和有进展风险的病变的HGL提供一种有效的筛查方法。
方法：这项回顾性研究是使用从95个正常粘膜和474个临床异常粘膜收集的569个口腔刷牙样本进行的，活检诊断为反应性，低级或高级癌前病变或癌症。处理刷细胞以表征DNA倍性。基于DNA倍性的两步算法，DNA倍性口腔细胞学（DOC）测试，是使用训练集开发的，并在测试和验证集中验证，以区分高级别病变（HGL）与正常。通过独立的结局队列评估测试的预后价值，包括进展和非进展正常，反应性和低度病变。分类性能是通过准确性来评估的，灵敏度,和特异性，而预后价值通过Cox比例风险分析对3年无进展生存期(PFS)进行评估.
结果：开发的DOC测试在测试和验证集中检测HGL时表现出很高的准确性，灵敏度分别为0.97和0.96。其在结果队列中的应用证明了3年PFS的显着预后价值（logrank，p<0.001)。多因素分析显示，高级别病理是解释DOC检验阳性的唯一变量，不是年龄,吸烟,或病变部位。
结论：临床实施DOC检测可以为检测活检和有进展风险的病变的HGL提供一种有效的筛查方法。
