The objective of this article was to provide an account of some of the developments related to saliva over the first 100 years of the Journal of Dental Research and to outline some of the many biomarkers identified in saliva in the last few years. The first section covers findings in salivary physiology, biochemistry, calcium phosphate chemistry related to saliva, microbiology, and the role of saliva in maintaining oral health. The second section highlights salivary diagnostics, salivaomics, and saliva exosomics in the context of the emerging theme of personalized and precision medicine.

Head and neck cancer is the sixth most common cancer worldwide. It remains one of the leading causes of death, and its early detection is crucial. Liquid biopsy has emerged as a promising tool for detecting and monitoring the disease status of patients with early and advanced cancers. Circulating tumor DNA (ctDNA), circulating tumor cells (CTCs), and exosomal miRNAs have received enormous attention because of their apparent clinical implications. Analyses of these circulating biomarkers have paved the way for novel therapeutic approaches and precision medicine. A growing number of reports have implicated the use of circulating biomarkers for detection, treatment planning, response monitoring, and prognosis assessment. Although these new biomarkers can provide a wide range of possible clinical applications, no validated circulating biomarkers have yet been integrated into clinical practice for head and neck cancer. In this review, we summarize the current knowledge of circulating biomarkers in this field, focusing on their feasibility, limitations, and key areas of clinical applications. We also highlight recent advances in salivary diagnostics and their potential application in head and neck cancer.

Coevolution of the human host and its associated microbiota has led to sophisticated interactions to maintain a delicate homeostasis. Emerging evidence suggests that in addition to small molecules, peptides, and proteins, small regulatory noncoding RNAs (sRNAs) might play an important role in cross-domain interactions. In this study, we revealed the presence of diverse host transfer RNA-derived small RNAs (tsRNAs) among human salivary sRNAs. We selected 2 tsRNAs (tsRNA-000794 and tsRNA-020498) for further study based on their high sequence similarity to specific tRNAs from a group of Gram-negative oral bacteria, including Fusobacterium nucleatum, a key oral commensal and opportunistic pathogen. We showed that the presence of F. nucleatum triggers exosome-mediated release of tsRNA-000794 and tsRNA-020498 by human normal oral keratinocyte cells. Furthermore, both tsRNA candidates exerted a growth inhibition effect on F. nucleatum, likely through interference with bacterial protein biosynthesis, but did not affect the growth of Streptococcus mitis, a health-associated oral Gram-positive bacterium whose genome does not carry sequences bearing high similarity to either tsRNA. Our data provide the first line of evidence for the modulatory role of host-derived tsRNAs in the microbial-host interaction.

Background: Salivary biomarkers for systemic diseases have been undermined due to lack of mechanistic and biological rationale. Results: Suppression of exosome biogenesis leads to ablation of salivary biomarkers. Conclusion: Tumor-derived exosomes provide a mechanism for discriminatory biomarkers in saliva. Significance: Tumor-derived exosomes provide the scientific rationale that connects pancreatic tumors and the oral cavity leading to salivary biomarkers. © 2013 by The American Society for Biochemistry and Molecular Biology, Inc.