Oral cancer is one of the most prevalent forms of cancer worldwide. Carcinogenesis is a complex process, in which heterogeneity plays an important role in the development and progression of the disease. This review provides an overview of the current biological and clinical significance of circulating tumour cells (CTCs), circulating tumour DNA (ctDNA), and exosomes for diagnosis and prognosis of oral cancer. We highlight the importance of liquid biopsy—using blood and saliva—which represents a potential alternative to solid biopsy for diagnosis and prognosis. Moreover, liquid biomarkers allow for the real-time monitoring of tumour evolution and therapeutic responses, initiating the era of personalized medicine. However, in oral cancer, the impact of liquid biopsies in clinical settings is still limited, requiring further studies to discover the best scenario for its clinical use.

Circulating microRNAs (miRNAs) have emerged as excellent candidates for cancer biomarkers. Several recent studies have highlighted the potential use of saliva for the identification of miRNAs as novel biomarkers, which represents a great opportunity to improve diagnosis and monitor general health and disease. This review summarises the mechanisms of miRNAs deregulation in cancer, the value of targeting them with a therapeutic intention and the evidence of the potential clinical use of miRNAs expressed in saliva for the detection of different cancer types. We also provide a comprehensive review of the different methods for normalising the levels of specific miRNAs present in saliva, as this is a critical step in their analysis, and the challenge to validate salivary miRNAs as a reality to manage cancer patients.

Colorectal cancer (CRC) is one of the most common cancers and a leading cause of cancer-related deaths worldwide. Despite numerous advances in therapeutic approaches, this cancer has a poor prognosis when it is diagnosed at late stages. Therefore, the scientific effort is nowadays directed towards the development of new non-invasive and dynamic biomarkers to improve the survival expectancy of CRC patients. In this sense, deregulated expression of many miRNAs has been shown to play an important role for CRC carcinogenesis and dissemination. Noticeably, an increasing number of studies highlight that circulating miRNAs, including those traveling inside exosomes or those released by tumor cells into circulation, constitute a promising tool for early detection, prognosis and therapy selection of CRC. Therefore, in this review we focus on the clinical potential of blood circulating miRNAs as emerging biomarkers with high value to improve the clinical management of CRC patients, providing a deep and complete perspective of the realities and challenges to translate these biomarkers to the clinical context.

Salivary microRNAs (miRNAs) are of high interest as diagnostic biomarkers for non-oral cancer. However, little is known about their value for colorectal cancer (CRC) detection. Our study aims to characterize salivary miRNAs in order to identify non-invasive markers for CRC diagnosis. The screening of 754 miRNAs was performed in saliva samples from 14 CRC and 10 healthy controls. The differential expressed miRNAs were validated by RT-qPCR in 51 CRC, 19 adenomas and 37 healthy controls. Receiver operating characteristic (ROC) curves and logistic regression models were performed to analyze the clinical value of these miRNAs. Twenty-two salivary miRNAs were significantly deregulated in CRC patients vs. healthy individuals (p < 0.05) in the discovery phase. From those, five upregulated miRNAs (miR-186-5p, miR-29a-3p, miR-29c-3p, miR-766-3p, and miR-491-5p) were confirmed to be significantly higher in the CRC vs. healthy group (p < 0.05). This five-miRNA signature showed diagnostic value (72% sensitivity, 66.67% specificity, AUC = 0.754) to detect CRC, which was even higher in combination with carcinoembryonic antigen (CEA) levels. Overall, after the first global characterization of salivary miRNAs in CRC, a five-miRNA panel was identified as a promising tool to diagnose this malignancy, representing a novel approach to detect cancer-associated epigenetic alterations using a non-invasive strategy.

Background: Saliva represents a promising non-invasive source of novel biomarkers for diagnosis and prognosis cancer. This meta-analysis evaluates the diagnostic value of salivary biomarkers for detection of malignant non-oral tumors to better define the value of saliva as an alternative liquid biopsy. Materials and Methods: We performed a systematic review and meta-analysis. PubMed, Embase, LILACS and the Cochrane Library were searched to identify articles that examined the potential of salivary biomarkers for the diagnosis of malignant non-oral tumors. To assess the overall accuracy, we calculated the diagnostic odds ratio (DOR), area under hierarchical summary receiver operating characteristic (AUC) curve, sensitivity, specificity, positive likelihood ratio (PLR) and negative likelihood ratio (NLR) using a random- or fixed-effects model. Heterogeneity and publication bias were assessed. Statistical tests were two-sided. Results: One hundred fifty-five study units from twenty-nine articles with 11,153 subjects were included. The pooled sensitivity, specificity, PLR, NLR, DOR and AUC were 0.76 (95% confidence intervals (CI), 0.74 to 0.77), 0.76 (95% CI, 0.75 to 0.77), 3.22 (95% CI, 2.92 to 3.55), 0.31 (95% CI, 0.28 to 0.34), 13.42 (95% CI, 12.28 to 15.96) and 0.85 (95% CI, 0.84 to 0.87), respectively. Conclusions: Salivary biomarkers may be potentially used for non-invasive diagnosis of malignant non-oral tumors.