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      Clinical and diagnostic utility of saliva as a non-invasive diagnostic fluid:
a systematic review

      review-article

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          Abstract

          This systematic review presents the latest trends in salivary research and its applications in health and disease. Among the large number of analytes present in saliva, many are affected by diverse physiological and pathological conditions. Further, the non-invasive, easy and cost-effective collection methods prompt an interest in evaluating its diagnostic or prognostic utility. Accumulating data over the past two decades indicates towards the possible utility of saliva to monitor overall health, diagnose and treat various oral or systemic disorders and drug monitoring. Advances in saliva based systems biology has also contributed towards identification of several biomarkers, development of diverse salivary diagnostic kits and other sensitive analytical techniques. However, its utilization should be carefully evaluated in relation to standardization of pre-analytical and analytical variables, such as collection and storage methods, analyte circadian variation, sample recovery, prevention of sample contamination and analytical procedures. In spite of all these challenges, there is an escalating evolution of knowledge with the use of this biological matrix.

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          Most cited references81

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          Saliva specimen: a new laboratory tool for diagnostic and basic investigation.

          The assay of saliva is an increasing area of research with implications for basic and clinical purposes. Although this biological fluid is easy to manipulate and collect, careful attention must be directed to limit variation in specimen integrity. Recently, the use of saliva has provided a substantial addition to the diagnostic armamentarium as an investigative tool for disease processes and disorders. In addition to its oral indications, the analysis of saliva provides important information about the functioning of various organs within the body. In this respect, endocrine research certainly occupies a central role. The present review considers the laboratory aspects of salivary assays with respect to the different analytes including ions, drugs and various non-protein/protein compounds such as hormones and immunoglobulins. This review also examines the consequences of preanalytical variation with respect to collection strategy and subsequent storage conditions. It is likely that the use of saliva in assays will continue to expand thus providing a new instrument of investigation for physiologic as well as pathophysiologic states.
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            Is Open Access

            The salivary microbiota as a diagnostic indicator of oral cancer: A descriptive, non-randomized study of cancer-free and oral squamous cell carcinoma subjects

            Background The purpose of the present investigation was to determine if the salivary counts of 40 common oral bacteria in subjects with an oral squamous cell carcinoma (OSCC) lesion would differ from those found in cancer-free (OSCC-free) controls. Methods Unstimulated saliva samples were collected from 229 OSCC-free and 45 OSCC subjects and evaluated for their content of 40 common oral bacteria using checkerboard DNA-DNA hybridization. DNA counts per ml saliva were determined for each species, averaged across subjects in the 2 subject groups, and significance of differences between groups determined using the Mann-Whitney test and adjusted for multiple comparisons. Diagnostic sensitivity and specificity in detection of OSCC by levels of salivary organisms were computed and comparisons made separately between a non-matched group of 45 OSCC subjects and 229 controls and a group of 45 OSCC subjects and 45 controls matched by age, gender and smoking history. Results Counts of 3 of the 40 species tested, Capnocytophaga gingivalis, Prevotella melaninogenica and Streptococcus mitis, were elevated in the saliva of individuals with OSCC (p < 0.001). When tested as diagnostic markers the 3 species were found to predict 80% of cancer cases (sensitivity) while excluding 83% of controls (specificity) in the non-matched group. Diagnostic sensitivity and specificity in the matched group were 80% and 82% respectively. Conclusion High salivary counts of C. gingivalis, P. melaninogenica and S. mitis may be diagnostic indicators of OSCC.
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              Salivary proteomics for oral cancer biomarker discovery.

              This study aims to explore the presence of informative protein biomarkers in the human saliva proteome and to evaluate their potential for detection of oral squamous cell carcinoma (OSCC). Whole saliva samples were collected from patients (n = 64) with OSCC and matched healthy subjects (n = 64). The proteins in pooled whole saliva samples of patients with OSCC (n = 16) and matched healthy subjects (n = 16) were profiled using shotgun proteomics based on C4 reversed-phase liquid chromatography for prefractionation, capillary reversed-phase liquid chromatography with quadruple time-of-flight mass spectrometry, and Mascot sequence database searching. Immunoassays were used for validation of the candidate biomarkers on a new group of OSCC (n = 48) and matched healthy subjects (n = 48). Receiver operating characteristic analysis was exploited to evaluate the diagnostic value of discovered candidate biomarkers for OSCC. Subtractive proteomics revealed several salivary proteins at differential levels between the OSCC patients and matched control subjects. Five candidate biomarkers were successfully validated using immunoassays on an independent set of OSCC patients and matched healthy subjects. The combination of these candidate biomarkers yielded a receiver operating characteristic value of 93%, sensitivity of 90%, and specificity of 83% in detecting OSCC. Patient-based saliva proteomics is a promising approach to searching for OSCC biomarkers. The discovery of these new targets may lead to a simple clinical tool for the noninvasive diagnosis of oral cancer. Long-term longitudinal studies with large populations of individuals with oral cancer and those who are at high risk of developing oral cancer are needed to validate these potential biomarkers.
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                Author and article information

                Journal
                Biochem Med (Zagreb)
                Biochem Med (Zagreb)
                BM
                Biochemia Medica
                Croatian Society of Medical Biochemistry and Laboratory Medicine
                1330-0962
                1846-7482
                05 June 2015
                June 2015
                : 25
                : 2
                : 177-192
                Affiliations
                [1 ]Faculty of Biomedical Sciences, Metrocamp College – IBMEC Group, Campinas, SP, Brazil
                [2 ]Department of Biochemistry, Centre for Post Graduate Studies, Jain University, Bangalore, India
                Author notes
                Corresponding author: Omana Sukumaran Bindhu, bindhupradip@ 123456yahoo.co.in , os.bindhu@ 123456jainuniversity.ac.in
                Article
                bm-25-177
                10.11613/BM.2015.018
                4470107
                26110030
                dd83553d-fb4b-4796-9b66-758c9394011f
                Copyright @ 2015
                History
                : 09 December 2014
                : 14 May 2015
                Categories
                Review Article

                saliva,non-invasive,biological markers,drug monitoring,oral health

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