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 Table of Contents  
Year : 2021  |  Volume : 2  |  Issue : 1  |  Page : 8-10

Biomarkers in saliva as diagnostic tool in early diagnosis of oral submucous fibrosis

Department of Public Health Dentistry, Kalinga Institute of Dental Sciences, KIIT Deemed to be University, Bhubaneswar, Odisha, India

Date of Submission16-Dec-2020
Date of Acceptance05-Feb-2021
Date of Web Publication9-Mar-2021

Correspondence Address:
Yagnaseni Mandal
Department of Public Health Dentistry, Kalinga Institute of Dental Sciences, KIIT University, Campus - 5, Patia, Bhubaneswar - 751 024, Odisha
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/jpcdoh.jpcdoh_9_20

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The potentially malignant lesions of oral cavity pose a sensitive challenge to the public health status. The risk is considerably high of malignant transformation of oral submucous fibrosis (OSMF) into oral cancer. The more rapidly they get diagnosed early, the better it is for public oral health. The need of the hour is to put into general practice the minimally invasive and noninvasive procedures of diagnostics for these lesions. Salivary biomarkers are recently advanced diagnostic tools fit for the requirement. With more researches and developments in technology, they are becoming a fast and with ease both patient and clinician-friendly choice and also medically appropriate. High expectations are that salivary biomarkers become sole noninvasive and exact method of diagnosing premalignant disorders such as OSMF.

Keywords: Biomarkers, diagnosis, malignancies, oral health, oral submucous fibrosis

How to cite this article:
Mandal Y, Jha K, Jnaneswar A. Biomarkers in saliva as diagnostic tool in early diagnosis of oral submucous fibrosis. J Prim Care Dent Oral Health 2021;2:8-10

How to cite this URL:
Mandal Y, Jha K, Jnaneswar A. Biomarkers in saliva as diagnostic tool in early diagnosis of oral submucous fibrosis. J Prim Care Dent Oral Health [serial online] 2021 [cited 2021 Oct 24];2:8-10. Available from: http://www.jpcdoh.org/text.asp?2021/2/1/8/310947

  Introduction Top

The oral submucous fibrosis (OSMF) is a clinocopathologically graded potentially malignant disorder of oral cavity which clinically characterizes as chronic inflammation with exaggerated collagen deposition in oral mucosa leading to burning sensation and inability to open mouth[1] and is mostly prevalent in betel chewing population of Southeast Asian countries, particularly India. The continuous stimulation to fibrosis is due to long term exposure to areca quid alkaloids and other ingredients. This disease has a high-risk predisposition of malignant transformation despite having less dysplastic changes clinically or histologically.[2] The reason for it being a premalignant disorder is that fibrosis and hyalinization occur in lamina propria, resulting in a loss of vascularity, mucosal pallor, and subsequent atrophy of the overlying epithelium.[3] Due to its progressively scarring nature, noninvasive or minimum invasive procedures are highly preferred for both diagnosis and treatment procedures. In India, the malignant transformation rate is of 7.6%[4] whereas in china it is 1.19%.[5]

A study conducted in the rural area of Sindh, Pakistan, recorded a higher (99%) incidence of OSF among consumers of areca nut and related products.[6] [Table 1][7],[8] shows the degree at which Oral submucous fibrosis is prevalent in India
Table 1: Recent scenario of OSMF in India

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A biomarker is “a characteristic objectively measured and evaluated as an indicator of normal biological process, pathogenic process or pharmacological responses to a therapeutic intervention” as per biomarkers definitions working group of the national institutes of health.[9] Most clinical chemistry tests available today rely on old technologies, and these tests are neither sensitive nor specific for any particular disease and traditional markers only increase significantly after substantial disease injury and thus more sensitive markers of diseases are eagerly needed, particularly, for the early detection of disease; highly sensitive and specific biomarkers as primary indicators are relatively more useful.[3] The recent advancements in diagnostics have appropriately exploited saliva and its expression of biomarkers property as a biofluid tool for noninvasive diagnostic method in a variety of oral diseases and even general diseases and thus oral submucos fibrosis is no different.[10],[11],[12] The use of saliva as a tool has been mostly from the standpoint of measuring markers derived from any tissue in direct contact with oral cavity including genetic components, microbes, trace elements, cellular sheddings, expectorations, and drugs metabolites. Thus any molecular marker derived from these glands through secretion or passive diffusion or simply being suspended through contact with salivary fluid could be found in saliva.[13] More than 100 biomarkers have been found in accordance with various studies regarding the diagnosis of oral malignancies and pre malignancies.[14]

Regarding OSMF a variety of salivary biomarkers of different types have been investigated and claimed to warn clinically about the precancerous lesion by various studies[14],[15] [Table 2]. Some of them are generally present in oral precancerous and cancerous lesions while some have been specifically found in OSMF.[15],[16],[17],[18],[19],[20],[21],[22] These have been under a lot of thorough scrutinizes and still are under subjective research.
Table 2: Shows some salivary biomarkers and their categories found in cancerous and premalignant disorders

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[Table 2] shows some salivary biomarkers and their categories found in cancerous and premalignant disorders.[14]

[Table 3] shows some of the salivary biomarkers found in OSMF patients.[15],[16],[17],[18],[19],[20],[21],[22]
Table 3: Some of the salivary biomarkers found in oral submucous fibrosis patients

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  Methods To Detect Salivary Biomarkers Top

The procedure of detection of salivary biomarkers is easy, patient compliant, painless, and better than other kinds of biochemical test sample collection procedures and thus can be performed in and for a wide range of patients of all conscious levels.

There are various techniques namely Gel electrophoresis, Mass spectrometry, Microarray analysis, Spectrophotometer, Flame photometry, reverse transcriptase-polymerase chain reaction, enzyme-linked immunosorbent assay, few which are used for salivary biomarkers' level detection and analyses. The technique of sample collection mostly involves spit method. Salimetrics oral swab for adults and infants, Oragene-RNA and DNA, DNAgard are a few of the saliva collection aids.[9],[10]

Although variations in individual salivary flow and characteristics can affect the analyses, variations may be least.

Recent advancements in salivary biomarkers in OSMF include the advancements in field of salivary genomics given improved polymerase chain reaction and other gene amplification techniques that would considerably aid in analysis within microscale ranges and providing near-exact diagnostic results.[11],[12]

  Role in Public Health Top

The salivary biomarkers are to a high extent responsible for early detection of oral potentially malignant disorders and thus contribute to proper therapeutic intervention and prevention of the masses. It is a necessary diagnostic tool in countries like India where there is a wide prevalence of acquaintances with carcinogenic habits and deaths and disabilities due to oral carcinoma thus vital in relaxing deleterious effects of the malignancies and pre malignancies on public health.[8] Diagnosticians can use salivary biomarkers as aids as and in combination to other health education and clinical diagnostic methods and so would help a great deal in patient motivation for relieving of causative habits and ease of treatment along with high rate of therapeutic success.

  Conclusion Top

Not too many specific biomarkers are found out regarding OSMF but researchers are motivated to discover more specific and novel biomarkers for specific oral diseases like OSMF and standardize them for clinical efficacy. Ready to use equipment and kits which could be biomarker-specific and show rapid results when used chairside along with being cost-effective keeping in mind the socioeconomic statuses of the South Asian and South-East Asian countries should be focussed on for future invention and development.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

  References Top

Shafer, William G, Maynard K. Hine, and Barnet M. Levy. 'A Textbook of Oral Pathology.': B Sivapathasundharam (ed.) 8th edition, 2016. Elsevier, Netherlands. p. 147-50.  Back to cited text no. 1
Thomson, Peter James. 'Oral Precancer Diagnosis and Management of Potentially Malignant Disorders'. Wiley-Blackwell, New York, 2012. p. 66-7.  Back to cited text no. 2
Prasad RS, Pai A, Shyamala K, Bhadranna A, Shenoy S, Yaji A. Assessment of epithelial-mesenchymal transition signatures in oral submucous fibrosis. J Oral Maxillofac Pathol 2019;23:308. doi: 10.4103/jomfp.JOMFP_177_18.  Back to cited text no. 3
Li N, Jian X, Hu Y, Xu C, Yao Z, Zhong X. Discovery of novel biomarkers in oral submucous fibrosis by microarray analysis. Cancer Epidemiol Biomarkers Prev 2008;17:2249-59. doi: 10.1158/1055-9965.EPI-07-2908.  Back to cited text no. 4
Shih YH, Wang TH, Shieh TM, Tseng YH. Oral Submucous Fibrosis: A Review on Etiopathogenesis, Diagnosis, and Therapy. Int J Mol Sci 2019;20:2940. doi: 10.3390/ijms20122940.   Back to cited text no. 5
Raffat MA, Hadi NI, Alghamdi O, Al-Aali KA, Al Deeb M, Abduljabbar T, Vohra F. Expression of Salivary S100A7 Levels in Stage I Oral Submucous Fibrosis: A Clinical and Laboratory Study. Asian Pac J Cancer Prev 2020;21:1115-9. doi: 10.31557/APJCP.2020.21.4.1115.  Back to cited text no. 6
Shaikh AH, Ahmed S, Siddique S, Iqbal N, Mohd S, Hasan U, Zaidi SJA, Ali A. “Oral Submucous Fibrosis; Study of Cases Reported at Dow International Medical College Hospital In Karachi, Pakistan.” Professional Med J 2019;26:275-81. doi: 10.29309/TPMJ/2019.26.02.3100.  Back to cited text no. 7
Rao NR, Villa A, More CB, Jayasinghe RD, Kerr AR, Johnson NW. Oral submucous fibrosis: A contemporary narrative review with a proposed inter-professional approach for an early diagnosis and clinical management. J Otolaryngol Head Neck Surg 2020;49:3. doi: 10.1186/s40463-020-0399-7.  Back to cited text no. 8
Kamath VV, Satelur K, Komali Y. Biochemical markers in oral submucous fibrosis: A review and update. Dent Res J (Isfahan). 2013;10:576-84.   Back to cited text no. 9
Yoshizawa JM, Schafer CA, Schafer JJ, Farrell JJ, Paster BJ, Wong DT. Salivary biomarkers: toward future clinical and diagnostic utilities. Clin Microbiol Rev 2013;26:781-91. doi: 10.1128/CMR.00021-13.   Back to cited text no. 10
David T.Wong. “Salivary Diagnostics”.2nd Edition.Willey Blackwell, New York, 2008. p. 98-101.  Back to cited text no. 11
Charles F. Streckfus (ed). “Advances in Salivary Diagnostics”. Springer, Midtown Manhattan; 2015. p. 134.  Back to cited text no. 12
Zhang A, Sun H, Wang X. Saliva metabolomics opens door to biomarker discovery, disease diagnosis, and treatment. Appl Biochem Biotechnol 2012;168:1718-27. doi: 10.1007/s12010-012-9891-5.   Back to cited text no. 13
Kaur J, Jacobs R, Huang Y, Salvo N, Politis C. Salivary biomarkers for oral cancer and pre-cancer screening: A review. Clin Oral Investig 2018;22:633-40. doi: 10.1007/s00784-018-2337-x.  Back to cited text no. 14
Kaur J, Politis C, Jacobs R. Salivary 8-hydroxy-2-deoxyguanosine, malondialdehyde, vitamin C, and vitamin E in oral pre-cancer and cancer: diagnostic value and free radical mechanism of action. Clin Oral Investig 2016;20:315-9. doi: 10.1007/s00784-015-1506-4.   Back to cited text no. 15
Prageet K, Freeland-Graves, Jeanne FG & Beretvas, S. & Sanjeevi, Namrata. (2018). “Zinc, Copper, and Iron in Oral Submucous Fibrosis: A Meta-Analysis. International Journal of Dentistry.” 2018. 1-14. 10.1155/2018/3472087.   Back to cited text no. 16
Shetty, Shishir & Gogineni, Subhas & Kumari, Suchetha & Shetty, Pushparaja & Hegde, Shruthi & Castelino, Renita. Status of salivary iron in oral cancer and oral potentially malignant disorders. Journal of Cranio-Maxillary Diseases 2014;3:17-20. DOI 10.4103/2278-9588.130432.   Back to cited text no. 17
Kallalli BN, Rawson K, Muzammil, Singh A, Awati MA, Shivhare P. Lactate dehydrogenase as a biomarker in oral cancer and oral submucous fibrosis. J Oral Pathol Med 2016;45:687-90. doi: 10.1111/jop.12451.   Back to cited text no. 18
Ankita K, Shwetha V, Vanitha S, Reddy Sujatha S, Nagaraju R, Tupakula Pavan K. Assessment of salivary endothelin-1 in patients with leukoplakia, submucous fibrosis, oral cancer and healthy individuals - A comparative study. J Stomatol Oral Maxillofac Surg 2019;120:326-31. doi: 10.1016/j.jormas.2019.02.024.   Back to cited text no. 19
Kode MA, Karjodkar FR. Estimation of the Serum and the Salivary Trace Elements in OSMF Patients. J Clin Diagn Res 2013;7:1215-8. doi: 10.7860/JCDR/2013/5207.3023.   Back to cited text no. 20
Punyani SR, Sathawane RS. Salivary level of interleukin-8 in oral precancer and oral squamous cell carcinoma. Clin Oral Investig 2013;17:517-24. doi: 10.1007/s00784-012-0723-3.   Back to cited text no. 21
Shetty SR, Babu S, Kumari S, Shetty P, Hegde S, Karikal A. Status of trace elements in saliva of oral precancer and oral cancer patients. J Cancer Res Ther 2015;11:146-9. doi: 10.4103/0973-1482.137973.  Back to cited text no. 22


  [Table 1], [Table 2], [Table 3]


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