Cytokines in saliva as biomarkers of oral and systemic oncological or infectious diseases: A systematic review

Recent evidence suggests that salivary cytokines provide information about both oral conditions and systemic diseases. This review summarizes evidence for the use of salivary cytokines as biomarkers for oral and systemic diseases. We included studies in adults and children with a focus on the latter, due to the importance of noninvasive diagnostic methods in the paediatric age group. A systematic review was performed using Medline and Web of Science covering the period of January 1996 to December 2019 according to the preferred reporting items for systematic reviews. Thirty-four studies were included in the final analysis, for a total of 2407 patients and healthy controls. Pro-inflammatory cytokines including interleukin (IL)-10, IL-2, IL-6 and tumor necrosis factor (TNF)-alpha were associated with the severity of oral mucosal tissue damage in patients with cancer, and IL-10 may be an early marker of graft-versus-host disease. Salivary interferon-gamma levels were correlated with oral complications and the presence of the underlying disease in HIV-infected individuals, and salivary cytokine patterns may be useful for diagnosing tuberculosis. In summary, current data illustrate that salivary cytokines are associated with oral inflammation, making them potential biomarkers for disease diagnosis and treatment efficacy. Because of the simplicity of saliva collection, this method may be useful in pediatric studies and in resource-limited settings.