• The effect of salivary biomarkers in the diagnosis of oral cancer
  • amin hajhosseini,1,* pouya mokari amjad,2 poorya hosseinabadi,3 simin bina,4 fatemeh ghasemi,5
    1. Student Research Committee, Bushehr University of Medical Sciences, Bushehr, Iran
    2. department of human science, hemadan branch, islamic azad university, hamedna, iran
    3. university of birjand, birjand, iran
    4. university of tehran, tehran, iran
    5. islamic azad university, qom branch, qom, iran


  • Introduction: Cancer as a disease is associated with changes in gene expression and function due to genetic and epigenetic changes and is associated with strong genomic instability. Oral cancer is a malignancy that affects both the lips and the oral cavity and ranks as the 16th most common cancer. Oral squamous cell carcinoma (OSCC) accounts for about 90% of these tumors. Some patients develop OSCC from a clinically detectable precancerous stage. These conditions are collectively known as oral potentially malignant disorders (OPMD). A biomarker (DNA, RNA, proteins, and metabolites) is defined as a characteristic measured as an indicator of normal biological processes, pathogenic processes, or responses to exposure or intervention. The resulting disease is the treatment of advanced disease and the reduction of the economic burden of disease management. However, the current approach to OSCC diagnosis, which involves visual examination of the oral cavity followed by biopsy, is sometimes ineffective. Biomarkers for the diagnosis of OSCC can greatly improve the early detection of OSCC. For this purpose, the salivary proteome of OSCC patients was quantitatively investigated in this study.
  • Methods: In the following article, data were collected by using keywords and searching in valid databases such as Google Scholar, Scopus, ProQuest and PubMed. The statistical population of this study includes all articles published until 2022. In this research, after checking the findings and data quality, we analyzed a total of 11 articles.
  • Results: The biomarkers reported in the studies were classified according to the molecular type. 52% of studies reported protein biomarkers, followed by DNA (12%), RNA (8%), metabolites (3%) and microbial (2%) biomarkers. Early detection of OPMD lesions allows the application of secondary preventive measures, thereby reducing the incidence of malignant transformation. Accumulating evidence shows that the measurement of oral-specific miRNAs and cytokines in saliva is a very promising technique for the diagnosis and prognosis of OSCC. The analysis of these salivary biomarkers together with the study of other histopathological markers such as the presence of eosinophils and the immune phenotype can be a key factor in the development of new strategies in the treatment of OSCC. The main limitation of this review is that the included studies show a high heterogeneity with regard to the methods and protocols used for the analysis of miRNA and cytokines. Saliva also has disadvantages, including rapid biofouling on the surface of biosensors, the effect of interferents present in saliva at different concentrations, and the presence of a highly dynamic oral environment.
  • Conclusion: The importance of saliva as an available and continuously regenerated biological fluid for further stimulation has been emphasized. However, the origin of these molecules needs to be confirmed before classifying them as candidate biomarkers. The abundance of salivary biomarkers that have been proposed for cancer screening or early detection in the last decade shows the intense interest of the medical community. However, validation of findings obtained in pilot studies among larger population groups is essential in order to establish meaningful correlations between outcomes. Rapid advances in electronics and nanotechnology now allow the fabrication of advanced biosensor systems at a fraction of the cost of complex laboratory equipment. Given that the concentration of salivary biomarkers is usually lower than that of other biofluids, typically in the ppb-ppt range, highly sensitive biosensors are required for reliable detection of the analyte of interest. As a non-invasive specimen for liquid biopsy, human WMS is expected to play an important role in uncovering the mysteries of the diagnosis and pathogenesis of oral cancers. It will have additional advantages such as non-invasive, painless, simple and easier to administer. The emergence of new technologies with higher sensitivity for detection purposes can be expected in the near future. Access to these highly sensitive techniques (next-generation sequencing, mass spectrometry, microarray technologies) makes even smaller amounts of salivary analytes possible for accurate detection.
  • Keywords: Biomarkers, Oral, saliva, Neoplasms