Novel adjunctive screening aids are needed to reduce the morbidity and mortality related to cancer, and every effort should be made for early diagnosis. This systematic review aimed to evaluate salivary metabolites and their diagnostic value in patients with cancer.

The systematic review was performed in two phases and included studies that focused on the diagnostic value of salivary metabolites in humans with solid malignant neoplasms. Five electronic databases were searched, and the risk of bias in individual studies was evaluated using the revised Quality Assessment of Diagnostic Accuracy Studies criteria (QUADAS-2). All procedures were performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.

Of the 1151 studies retrieved, 25 were included; 13 studies used targeted and 12 untargeted metabolomics approaches. Most studies included patients with breast and oral cancer. Except for one, all studies had case–control designs, and none fulfilled all quality assessments. Overall, 140 salivary metabolites were described. The most frequently reported metabolites were alanine, valine, and leucine. Among the 11 studies that reported diagnostic test accuracy (DTA) values, proline, threonine, and histidine in combination and monoacylglycerol alone demonstrated the highest DTA for breast cancer. Combined choline, betaine, pipecolinic acid, and l-carnitine showed better discriminatory performance for early oral cancer.

This systematic review highlights the current evidence on salivary metabolites that may be used as a future strategy to diagnose cancer. Further studies including larger sample sizes with confirmation of the results by untargeted analysis are warranted.

需要新型辅助筛查手段来降低与癌症相关的发病率和死亡率，并应尽一切努力进行早期诊断。本系统评价旨在评估唾液代谢物及其对癌症患者的诊断价值。

系统评价分两个阶段进行，包括侧重于唾液代谢物对患有实体恶性肿瘤的人类的诊断价值的研究。检索了五个电子数据库，并使用修订后的诊断准确性研究质量评估标准 (QUADAS-2) 评估了个别研究的偏倚风险。所有程序均根据系统评价和元分析的首选报告项目 (PRISMA) 指南进行。

在检索到的 1151 项研究中，纳入了 25 项；13 项研究使用了靶向和 12 种非靶向代谢组学方法。大多数研究包括乳腺癌和口腔癌患者。除一项研究外，所有研究均采用病例对照设计，没有一项研究满足所有质量评估要求。总共描述了 140 种唾液代谢物。最常报告的代谢物是丙氨酸、缬氨酸和亮氨酸。在报告诊断测试准确度 (DTA) 值的 11 项研究中，脯氨酸、苏氨酸和组氨酸的组合以及单酰甘油显示出乳腺癌的最高 DTA。结合胆碱，甜菜碱，哌啶酸，和升肉碱表现出对早期口腔癌的更好的歧视性表现。

这篇系统综述强调了唾液代谢物的当前证据，这些证据可用作未来诊断癌症的策略。进一步的研究包括更大的样本量并通过非靶向分析确认结果是有必要的。