Abstract
BackgroundOral cancer (OC) is usually diagnosed at advanced clinical stages due to its asymptomatic nature and absence of pathognomonic signs in its early development phase. Delayed diagnosis is one of the major causes of OC treatment failure and poor prognosis. Development of alternative diagnostic approaches are imperative for improving early detection and therapeutic success rates. Salivary cytokines (SC) have been studied as potential diagnostic biomarkers for OC and may represent a potential tool for improvement of its early detection.MethodsIn this systematic review and meta-analysis we identified SC studied as OC biomarkers by systematically reviewing the PubMed and Cochrane Library databases using the terms: “oral cancer”, “cytokine”, and “saliva”, and also combined with “interleukin” or “interferon”. Only case-control studies that measured SC by ELISA from treatment naïve patients were included in the qualitative review. For the meta-analysis were included all comparable studies that provided enough data (sample size, mean and standard deviation or standard error of the mean) for SC levels in OC patients, non-cancer controls and patients with oral potentially malignant disorders (OPMD), including leukoplakia. Comparisons with patients with oral lichen planus (OLP) and gingivitis were included in the qualitative analysis.ResultsA total of 28 articles (from 2004 to 2018) were included in the systematic review, describing 10 different SC, being IL-8 and IL-6 the most studied ones. SC levels were consistently higher among OC patients when compared to healthy controls and to patients with OPMD, OLP and gingivitis. Meta-analysis including 23 eligible studies showed that IL-8, IL-6, TNF-α, IL-1β and IL-10 salivary levels were significantly higher in OC patients compared to controls; and that IL-8, IL-6, TNF-α and IL-1β salivary levels were also higher in OC patients compared to individuals with OPMD. When compared to healthy controls, OPMD patients showed significantly higher IL-6 and TNF-α salivary levels.ConclusionsOur analyses showed that the salivary levels of some cytokines are consistently different among OC, OPMD and healthy patients, indicating that these SC may represent potential diagnostic biomarkers for OC and OPMD. Despite of that, SC levels were highly variable among studies, suggesting that further technical improvement and standardization for SC measurement by ELISA is needed in order to successfully translate these biomarkers to the clinical practice.
Highlights
Oral cancer (OC) is usually diagnosed at advanced clinical stages due to its asymptomatic nature and absence of pathognomonic signs in its early development phase
Our analyses showed that the salivary levels of some cytokines are consistently different among OC, oral potentially malignant disorders (OPMD) and healthy patients, indicating that these Salivary cytokines (SC) may represent potential diagnostic biomarkers for OC and OPMD
SC levels were highly variable among studies, suggesting that further technical improvement and standardization for SC measurement by enzymelinked immunosorbent assay (ELISA) is needed in order to successfully translate these biomarkers to the clinical practice
Summary
Oral cancer (OC) is usually diagnosed at advanced clinical stages due to its asymptomatic nature and absence of pathognomonic signs in its early development phase. Development of alternative diagnostic approaches are imperative for improving early detection and therapeutic success rates. Salivary cytokines (SC) have been studied as potential diagnostic biomarkers for OC and may represent a potential tool for improvement of its early detection. Detection of early lesions is usually incidental, since they are usually asymptomatic and rarely perceived by patients. Early OC lesions may resemble other benign oral mucosal conditions, which can lead to delayed diagnosis. Only 2% of the OPMD will eventually turn into cancer, determination of its malignant transformation risk and distinction from early stage OC are quite challenging [4,5,6,7]. Histopathological assessment is imperative for definitive diagnosis which can contribute to further delay in OC detection [8, 9]
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