Salivary diagnosis of dental caries

The systematic review "Salivary Diagnosis of Dental Caries" investigates whether salivary biomarkers can be considered reliable for diagnosing dental caries. The multifactorial nature of dental caries, combined with its impact on salivary molecular composition, forms the basis for exploring saliva as a diagnostic medium. Dental caries remains one of the most prevalent chronic diseases worldwide, despite advances in prevention, with millions of people affected, both children and adults.

The study adhered to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) guidelines and involved an extensive literature search across databases like Medline, Web of Science, and Scopus. The inclusion criteria targeted studies focusing on healthy individuals with or without dental caries, while also providing clinical data based on the DMFT (Decayed, Missing, Filled Teeth) and ICDAS (International Caries Detection and Assessment System) indices. These indices are established methods for assessing the prevalence and severity of dental caries, with ICDAS allowing for a more detailed classification of carious lesions.

To assess the quality of the included studies, a modified Joanna Briggs Institute Prevalence Critical Appraisal Checklist was employed. Ultimately, 16 papers met the criteria for inclusion in this review. All selected studies showed statistically significant differences in the concentrations of salivary molecules between participants with dental caries and those without (p < 0.05). Among the most frequently investigated biomarkers were salivary proteins, particularly alpha-amylase and mucins, although several other molecules also showed promise for caries diagnosis.

The review highlights potential challenges and risks of bias in some of the studies, including issues like confounding factors and clearly defining the population. However, the overall quality of the papers was judged as moderate to high. Despite some limitations, the evidence suggests that specific salivary biomarkers, including mucins, glycoproteins like sCD14, and several interleukins (IL-2RA, 4, and 13), alongside enzymes like urease and carbonic anhydrase VI, could serve as reliable diagnostic tools for dental caries.

Introduction to Dental Caries

Dental caries, also known as tooth decay, is a process of demineralization of the tooth’s hard tissues, eventually leading to cavity formation. It is considered a multifactorial disease, influenced by the interaction of diet, oral bacteria, saliva, and individual behaviors such as oral hygiene practices. The incidence of caries has decreased in certain age groups in Western countries due to improved prevention strategies, but it remains a significant public health issue globally. According to global health estimates, untreated cavities affect approximately 2.4 billion people, and 621 million children experience caries in deciduous teeth.

The primary causative agents of caries are acid-producing bacteria, such as Streptococcus mutans, which metabolize dietary sugars, leading to acid production that demineralizes tooth enamel. Saliva plays a critical role in maintaining oral health by neutralizing acids and aiding in the remineralization of enamel, but alterations in salivary flow or composition can contribute to the progression of caries.

Current Diagnostic Methods for Dental Caries

Caries diagnosis typically relies on clinical and radiographic examination. The World Health Organization recommends using the DMFT index, which quantifies the number of decayed, missing, or filled teeth to assess caries prevalence. The ICDAS system is also widely used to classify caries according to severity, ranging from early enamel lesions to advanced dentin involvement. While these methods are effective, there is growing interest in non-invasive diagnostic technologies that use saliva as a diagnostic medium due to its easy collection, rich molecular composition, and potential to reflect systemic and oral health status.

The Role of Saliva in Caries Diagnosis

Saliva, produced by the major and minor salivary glands, contains various components, including proteins, enzymes, antibodies, and cytokines, that can serve as biomarkers for disease. It is increasingly viewed as a valuable biological fluid for disease diagnosis due to its non-invasive collection and complex composition. Salivary flow and composition can be influenced by multiple factors, including gland function, diet, age, and health conditions. Biomarkers found in saliva include proteins, metabolites, and other molecules that can help monitor health, diagnose disease, and assess treatment responses.

Key Findings on Salivary Biomarkers for Caries

The systematic review analyzed 16 studies that investigated the association between salivary biomarkers and dental caries. Most of these studies focused on protein biomarkers, particularly mucins, glycoproteins, and enzymes, while some explored metabolite or genetic markers. Significant findings include:

1. Mucins: Several studies reported increased levels of salivary mucins, specifically mucin-1 (MUC1), in subjects with active dental caries, suggesting their role in caries pathogenesis. However, not all mucin types (MUC5B, MUC7) showed significant associations with caries, pointing to the complexity of salivary components in caries development.
2. Glycoproteins and Immunoglobulins: Soluble CD14 (sCD14) and secretory IgA (sIgA) were among the glycoproteins and immunoglobulins analyzed. Elevated sCD14 levels were found in subjects with active caries, while the relationship between sIgA levels and caries activity was inconsistent across studies.
3. Enzymes and Other Proteins: Enzymes like alpha-amylase and urease, alongside proteins such as carbonic anhydrase VI, were also investigated. While alpha-amylase showed inconsistent results, lower levels of carbonic anhydrase VI and higher urease activity were associated with a reduced risk of caries, indicating their potential protective roles in caries prevention.
4. Metabolites and Genetic Markers: Although less frequently studied, certain metabolites and genetic markers, such as interleukins, also demonstrated potential as caries biomarkers. Interleukins like IL-2RA, 4, and 13 were elevated in subjects with dental caries, suggesting that inflammatory responses in saliva may reflect caries activity.

Conclusion and Future Directions

The review concludes that saliva contains a wealth of potential biomarkers that could aid in the non-invasive diagnosis of dental caries. While proteins, particularly mucins and glycoproteins, were the most studied biomarkers, metabolites and genetic markers also hold promise. However, the variability in study methodologies and the presence of confounding factors in some studies highlight the need for further research to standardize diagnostic approaches and validate these biomarkers across diverse populations.

Future studies should focus on improving the reliability and specificity of salivary biomarkers for caries diagnosis, possibly through the development of multiplex assays that combine multiple biomarkers for a more comprehensive assessment of caries risk and activity.

From:

Antonelli R, Massei V, Ferrari E, Gallo M, Pertinhez TA, Vescovi P, Pizzi S, Meleti M. Salivary Diagnosis of Dental Caries: A Systematic Review. Curr Issues Mol Biol. 2024 May 2;46(5):4234-4250. doi: 10.3390/cimb46050258. PMID: 38785526; PMCID: PMC11120503.