Saliva, which contains molecular information that may reflect an individual’s health status, has become a valuable tool for discovering biomarkers of oral and general diseases. Due to the high vascularization of the salivary glands, there is a molecular exchange between blood and saliva. However, the composition of saliva is complex and influenced by multiple factors. This study aimed to investigate the possible relationships between the salivary and serum metabolomes to gain a comprehensive view of the metabolic phenotype under physiological conditions. Using ¹H-NMR spectroscopy, we obtained the serum metabolite profiles of 20 healthy young individuals and compared them with the metabolomes of parotid, submandibular/sublingual, and whole-saliva samples collected concurrently from the same individuals using multivariate and univariate statistical analysis. Our results show that serum is more concentrated and less variable for most of the shared metabolites than the three saliva types. While we found moderate to strong correlations between serum and saliva concentrations of specific metabolites, saliva is not simply an ultrafiltrate of blood. The intense oral metabolism prevents very strong correlations between serum and salivary concentrations. This study contributes to a better understanding of salivary metabolic composition, which is crucial for utilizing saliva in laboratory diagnostics.

The activity of dental caries, combined with its multifactorial etiology, alters salivary molecule composition. The present systematic review was developed to answer the following question: “Are salivary biomarkers reliable for diagnosis of dental caries?”. Following the “Preferred Reporting Item for Systematic Reviews and Meta-analysis” (PRISMA) guidelines, the review was conducted using multiple database research (Medline, Web of Science, and Scopus). Studies performed on healthy subjects with and without dental caries and providing detailed information concerning the clinical diagnosis of caries (Decayed, Missing, Filled Teeth-DMFT and International Caries Detection and Assessment System-ICDAS criteria) were included. The quality assessment was performed following a modified version of the Joanna Briggs Institute Prevalence Critical Appraisal Checklist. The protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO, ID: CRD42022304505). Sixteen papers were included in the review. All studies reported statistically significant differences in the concentration of salivary molecules between subjects with and without caries (p < 0.05). Proteins were the most investigated molecules, in particular alpha-amylase and mucins. Some studies present a risk of bias, such as identifying confounding factors and clearly defining the source population. Nevertheless, the 16 papers were judged to be of moderate to high quality. There is evidence that some salivary compounds studied in this review could play an important diagnostic role for dental caries, such as salivary mucins, glycoproteins (sCD14), interleukins (IL-2RA, 4,-13), urease, carbonic anhydrase VI, and urea.

Background. Sialadenoma papilliferum (SP) is a rare benign epithelial tumor of salivary gland origin, its diagnosis being potentially challenging. It was first described by Abrams and Finck in 1969 as an analog of the cutaneous syringocystadenoma papilliferum. The aim of this comprehensive review is to highlight the clinical and histopathological diagnostic aspects of intraoral SP, analyzing cases previously described and reporting new cases. Methods. Medline, Scopus, and Web of Science were searched up to February 2022, using as entry term “sialadenoma papilliferum”. No time limits were applied and only studies in English were taken into account. Only cases involving the mouth were included. Conference proceedings, personal communications, and letters to the editor were excluded. Results. In total, 42 out of 234 articles fulfilled the inclusion criteria, with 64 cases reported. Mean age of patients with SP was 57.2 years, with a higher prevalence among males. The most affected site was the palate, particularly the hard palate. Four cases with uncertain malignant features have been reported. While clinical manifestations of SP are rather unspecific (e.g., submucosal swelling with ulceration), histopathological and immunohistochemical features are quite peculiar, SP have a limited growth potential, leading to conservative excision as treatment of choice. Conclusions. SP, though rare, should be taken into consideration in the differential diagnosis of intraoral swellings, particularly those located on the palate.

Leukoplakia is a condition marked by white patches on the inner surfaces of the oral cavity. Its potential to progress to oral squamous cell carcinoma underscores the need for effective screening and early diagnosis procedures. We employed NMR-based salivary and tissue metabolomics to identify potential biomarkers for leukoplakia and dysplastic leukoplakia. Univariate and multivariate methods were used to evaluate the NMR-derived metabolite concentrations. The salivary metabolite profile of leukoplakia exhibited specific alterations compared to healthy controls. These metabolic changes were more pronounced in cases of dysplastic lesions. Multivariate ROC curve analysis, based on a selection of salivary metabolites, ascribed high diagnostic accuracy to the models that discriminate between dysplastic and healthy cases. However, NMR analysis of tissue biopsies was ineffective in extracting metabolic signatures to differentiate between lesional, peri-lesional, and healthy tissues. Our pilot study employing a metabolomics-based approach led to the development of salivary models that represent a complementary strategy for clinically detecting leukoplakia. However, larger-scale validation is required to fully evaluate their diagnostic potential and to effectively stratify leukoplakia patients according to dysplasia status.