Salivary Biomarkers in Oral Squamous Cell Carcinoma: Current Perspectives and Challenges in their Clinical Application
DOI:
https://doi.org/10.70749/ijbr.v2i02.171Keywords:
Salivary Biomarkers, Oral Squamous Cell Carcinoma, Clinical Application Challenges, Early Diagnosis, Cancer Biomarker DetectionAbstract
Oral cancer is a life-threatening disease that predominantly affects the oral cavity, with approximately 90% of cases being oral squamous cell carcinomas (OSCC). Rapid metastasis and late detection are key factors contributing to the poor prognosis of OSCC. The alarming rise in OSCC-related mortality underscores the urgent need for clinical diagnostic methods that enable early detection. In recent years, salivaomics has gained popularity in molecular diagnostics due to the accessibility and non-invasive nature of saliva. Researchers have identified over 100 salivary biomarkers with potential roles in OSCC screening, categorized into proteomic, genomic, transcriptomic, and metabolic biomarkers. Although these biomarkers show high specificity and sensitivity, challenges such as variability and the need for standardized protocols must be addressed to improve diagnostic accuracy and treatment outcomes. This review explores significant salivary biomarkers in OSCC management and highlights the challenges that hinder their clinical application, emphasizing the need for optimized protocols to enhance test validity
References
Ali, J., Sabiha, B., Jan, H. U., Haider, S. A., Khan, A. A., & Ali, S. S. (2017). Genetic etiology of oral cancer. Oral oncology, 70, 23-28. https://linkinghub.elsevier.com/retrieve/pii/S1368837517301136
Kumar, M., Nanavati, R., Modi, T., & Dobariya, C. (2018). Oral cancer: Etiology and risk factors: A review. Journal of Cancer Research and Therapeutics, 12(2). https://doi.org/10.4103/0973-1482.147708
Rivera, C. (2015). Essentials of oral cancer. International Journal of Clinical and Experimental Pathology, 8(9), 11884–11894. http://www.ncbi.nlm.nih.gov/pubmed/26617944
Ram, H., Sarkar, J., Kumar, H., Konwar, R., Bhatt, M. L. B., & Mohammad, S. (2011). Oral Cancer: Risk Factors and Molecular Pathogenesis. Journal of Maxillofacial and Oral Surgery, 10(2), 132–137. https://doi.org/10.1007/s12663-011-0195-z
Ram, H., Sarkar, J., Kumar, H., Konwar, R., Bhatt, M. L. B., & Mohammad, S. (2011). Oral Cancer: Risk Factors and Molecular Pathogenesis. Journal of Maxillofacial and Oral Surgery, 10(2), 132–137. https://doi.org/10.1007/s12663-011-0195-z
Bagan, J., Sarrion, G., & Jimenez, Y. (2010). Oral cancer: clinical features. Oral oncology, 46(6), 414-417. https://linkinghub.elsevier.com/retrieve/pii/S1368837510000989
Messadi, D. V. (2013). Diagnostic aids for detection of oral precancerous conditions. International Journal of Oral Science, 5(2), 59–65. https://doi.org/10.1038/ijos.2013.24
Khurshid, Z., Zafar, M. S., Khan, R. S., Najeeb, S., Slowey, P. D., & Rehman, I. U. (2018). Role of salivary biomarkers in oral cancer detection. Advances in clinical chemistry, 86, 23-70. https://linkinghub.elsevier.com/retrieve/pii/S0065242318300313
Zhang, C.-Z., Cheng, X.-Q., Li, J.-Y., Zhang, P., Yi, P., Xu, X., & Zhou, X.-D. (2016). Saliva in the diagnosis of diseases. International Journal of Oral Science, 8(3), 133–137. https://doi.org/10.1038/ijos.2016.38
Kaur, J., Jacobs, R., Huang, Y., Salvo, N., & Politis, C. (2018). Salivary biomarkers for oral cancer and pre-cancer screening: a review. Clinical Oral Investigations, 22(2), 633–640. https://doi.org/10.1007/s00784-018-2337-x
Lousada-Fernandez, F., Rapado-Gonzalez, O., Lopez-Cedrun, J.-L., Lopez-Lopez, R., Muinelo-Romay, L., & Suarez-Cunqueiro, M. (2018). Liquid Biopsy in Oral Cancer. International Journal of Molecular Sciences, 19(6), 1704. https://doi.org/10.3390/ijms19061704
Roblegg, E., Coughran, A., & Sirjani, D. (2019). Saliva: An all-rounder of our body. European Journal of Pharmaceutics and Biopharmaceutics, 142, 133–141. https://doi.org/10.1016/j.ejpb.2019.06.016
Ngamchuea, K., Chaisiwamongkhol, K., Batchelor-McAuley, C., & G. Compton, R. (2018). Chemical analysis in saliva and the search for salivary biomarkers – a tutorial review. Analyst, 143(1), 81–99. https://doi.org/10.1039/C7AN01571B
Dawes, C., & Wong, D. T. W. (2019). Role of Saliva and Salivary Diagnostics in the Advancement of Oral Health. Journal of Dental Research, 98(2), 133–141. https://doi.org/10.1177/0022034518816961
Wang, X., Kaczor-Urbanowicz, K. E., & Wong, D. T. (2017). Salivary biomarkers in cancer detection. Medical Oncology, 34, 1-8. https://linkinghub.elsevier.com/retrieve/pii/S189611261730072X
Wang, X., Kaczor-Urbanowicz, K. E., & Wong, D. T. W. (2016). Salivary biomarkers in cancer detection. Medical Oncology, 34(1). https://doi.org/10.1007/s12032-016-0863-4
Roi, A., Roi, C. I., Negruțiu, M. L., Riviș, M., Sinescu, C., & Rusu, L.-C. (2020). The Challenges of OSCC Diagnosis: Salivary Cytokines as Potential Biomarkers. Journal of Clinical Medicine, 9(9), 2866. https://doi.org/10.3390/jcm9092866
Sannam Khan, R., Khurshid, Z., Akhbar, S., & Faraz Moin, S. (2016). Advances of Salivary Proteomics in Oral Squamous Cell Carcinoma (OSCC) Detection: An Update. Proteomes, 4(4), 41. https://doi.org/10.3390/proteomes4040041
Malik, U. U., Zarina, S., & Pennington, S. R. (2016). Oral squamous cell carcinoma: Key clinical questions, biomarker discovery, and the role of proteomics. Archives of oral biology, 63, 53-65. https://linkinghub.elsevier.com/retrieve/pii/S0003996915300893
Katakura, A., Yamamoto, N., Sakuma, T., Sugahara, K., Onda, T., Noguchi, S., & Shibahara, T. (2015). A screening test for oral cancer using saliva samples: Proteomic analysis of biomarkers in whole saliva. Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology, 27(1), 1-5. https://linkinghub.elsevier.com/retrieve/pii/S2212555813000823
Yakob, M., Fuentes, L., Wang, M. B., Abemayor, E., & Wong, D. T. W. (2014). Salivary Biomarkers for Detection of Oral Squamous Cell Carcinoma: Current State and Recent Advances. Current Oral Health Reports, 1(2), 133–141. https://doi.org/10.1007/s40496-014-0014-y
Franzmann, E. J., Reategui, E. P., Pedroso, F. E., Javier, F., Baris Karakullukcu, Carraway, K. L., Hamilton, K., Singal, R., & W. Jarrard Goodwin. (2007). Soluble CD44 Is a Potential Marker for the Early Detection of Head and Neck Cancer. Cancer Epidemiology, Biomarkers & Prevention, 16(7), 1348–1355. https://doi.org/10.1158/1055-9965.epi-06-0011
St. John MAR, Li Y, Zhou X, Denny P, Ho C-M, Montemagno C, et al. Interleukin 6 and Interleukin 8 as St. John, M. A. R., Li, Y., Zhou, X., Denny, P., Ho, C.-M., Montemagno, C., Shi, W., Qi, F., Wu, B., Sinha, U., Jordan, R., Wolinsky, L., Park, N.-H., Liu, H., Abemayor, E., & Wong, D. T. W. (2004). Interleukin 6 and Interleukin 8 as Potential Biomarkers for Oral Cavity and Oropharyngeal Squamous Cell Carcinoma. Archives of Otolaryngology–Head & Neck Surgery, 130(8), 929. https://doi.org/10.1001/archotol.130.8.929
Márton, I. J., Horváth, J., Lábiscsák, P., Márkus, B., Dezső, B., Szabó, A., Tar, I., Piffkó, J., Jakus, P., Barabás, J., Barabás, P., Olasz, L., Kövér, Z., Tőzsér, J., Sándor, J., Csősz, É., Scholtz, B., & Kiss, C. (2019). Salivary IL-6 mRNA is a Robust Biomarker in Oral Squamous Cell Carcinoma. Journal of Clinical Medicine, 8(11), 1958. https://doi.org/10.3390/jcm8111958
Lee, L. T., Wong, Y. K., Hsiao, H. Y., Wang, Y. W., Chan, M. Y., & Chang, K. W. (2018). Evaluation of saliva and plasma cytokine biomarkers in patients with oral squamous cell carcinoma. International Journal of Oral and Maxillofacial Surgery, 47(6), 699-707. https://linkinghub.elsevier.com/retrieve/pii/S0901502717316752
Radhika, T., Jeddy, N., Nithya, S., & Muthumeenakshi, R. M. (2016). Salivary biomarkers in oral squamous cell carcinoma–An insight. Journal of oral biology and craniofacial research, 6, S51-S54. https://linkinghub.elsevier.com/retrieve/pii/S2212426816300641
Yen, C.-Y., Huang, C.-Y., Hou, M.-F., Yang, Y.-H., Chang, C.-H., Huang, H.-W., Chen, C.-H., & Chang, H.-W. (2012). Evaluating the performance of fibronectin 1 (FN1), integrin α4β1 (ITGA4), syndecan-2 (SDC2), and glycoprotein CD44 as the potential biomarkers of oral squamous cell carcinoma (OSCC). Biomarkers, 18(1), 63–72. https://doi.org/10.3109/1354750x.2012.737025
Honarmand, M., Saravani, R., Farhad-Mollashahi, L., & Smailpoor, A. (2021). Salivary Lactate Dehydrogenase, C-Reactive Protein, and Cancer Antigen 125 Levels in Patients with Oral Lichen Planus and Oral Squamous Cell Carcinoma. International Journal of Cancer Management, 14(3). https://sites.kowsarpub.com/ijcm/articles/108344.html
Malhotra, R., Urs, A. B., Chakravarti, A., Kumar, S., Gupta, V. K., & Mahajan, B. (2016). Correlation of Cyfra 21-1 levels in saliva and serum with CK19 mRNA expression in oral squamous cell carcinoma. Tumor Biology, 37(7), 9263–9271. https://doi.org/10.1007/s13277-016-4809-4
Geng, X., Du, M., Han, J., Zhang, M., Tang, X., & Xing, R. (2013). Saliva CA125 and TPS Levels in Patients with Oral Squamous Cell Carcinoma. The International Journal of Biological Markers, 28(2), 216–220. https://doi.org/10.5301/jbm.5000001
Panta, P., & Wong, D. T. W. (2019). Salivary Biomarkers in Oral Cancer. Oral Cancer Detection, 265–295. https://doi.org/10.1007/978-3-319-61255-3_14
Wang, H., Deng, X., Zhang, J., Ou, Z., Mai, J., Ding, S., & Huo, S. (2017). Elevated Expression of Zinc Finger Protein 703 Promotes Cell Proliferation and Metastasis through PI3K/AKT/GSK-3β Signalling in Oral Squamous Cell Carcinoma. Cellular Physiology and Biochemistry, 44(3), 920–934. https://doi.org/10.1159/000485360
Ren, Z.-H., Wu, K., Yang, R., Liu, Z.-Q., & Cao, W. (2020). Differential expression of matrix metalloproteinases and miRNAs in the metastasis of oral squamous cell carcinoma. BMC Oral Health, 20(1). https://doi.org/10.1186/s12903-020-1013-0
Alaseem, A., Alhazzani, K., Dondapati, P., Alobid, S., Bishayee, A., & Rathinavelu, A. (2019, June). Matrix Metalloproteinases: A challenging paradigm of cancer management. In Seminars in cancer biology (Vol. 56, pp. 100-115). Academic Press. https://linkinghub.elsevier.com/retrieve/pii/S1044579X17301840
Ajila, V., Babu, S., Shetty, V., Hegde, S., & Shenoy, S. (2019). Secretory Leukocyte Protease Inhibitor in Oral Potentially Malignant Disorders and Oral Squamous Cell Carcinoma. Indian Journal of Medical and Paediatric Oncology, 40(04), 491–495. https://doi.org/10.4103/ijmpo.ijmpo_75_18
Sahibzada, H. A., Khurshid, Z., Khan, R. S., Naseem, M., Siddique, K. M., Mali, M., & Zafar, M. S. (2017). Salivary IL-8, IL-6 and TNF-α as Potential Diagnostic Biomarkers for Oral Cancer. Diagnostics (Basel, Switzerland), 7(2). https://doi.org/10.3390/diagnostics7020021
Xu, H. J., Ma, Y., Deng, F., Ju, W. B., Sun, X. Y., & Wang, H. (2017). The prognostic value of C-reactive protein/albumin ratio in human malignancies: an updated meta-analysis. OncoTargets and therapy, 3059-3070. https://www.dovepress.com/the-prognostic-value-of-c-reactive-proteinalbumin-ratio-in-human-malig-peer-reviewed-article-OTT
Wang, Q., Song, X., Zhao, Y., He, Q., Shi, M., Xu, P., Ni, S., Chen, Y., Lin, J., & Zhang, L. (2019). Preoperative high c-reactive protein/albumin ratio is a poor prognostic factor of oral squamous cell carcinoma. Future Oncology, 15(19), 2277–2286. https://doi.org/10.2217/fon-2019-0063
Lee, J. R., Roh, J.-L., Lee, S. M., Park, Y., Cho, K.-J., Choi, S.-H., Nam, S. Y., & Kim, S. Y. (2017). Overexpression of glutathione peroxidase 1 predicts poor prognosis in oral squamous cell carcinoma. Journal of Cancer Research and Clinical Oncology, 143(11), 2257–2265. https://doi.org/10.1007/s00432-017-2466-7
Madki, P., Tejasvi, M. L. A., Paramkusam, G., Khan, R., & J., S. (2021). Evaluation of Serum Immunoglobulins (IgG, IgA, IgM) and Circulating Immune Complexes in Oral Precancer and Cancer Patients. Global Medical Genetics, 08(03), 095–099. https://doi.org/10.1055/s-0041-1725157
Chu, H. W., Chang, K. P., Hsu, C. W., Chang, I. Y. F., Liu, H. P., Chen, Y. T., & Wu, C. C. (2019). Identification of salivary biomarkers for oral cancer detection with untargeted and targeted quantitative proteomics approaches*[S]. Molecular & Cellular Proteomics, 18(9), 1796-1806. https://linkinghub.elsevier.com/retrieve/pii/S1535947620317795
Cristaldi, M., Mauceri, R., Di Fede, O., Giuliana, G., Campisi, G., & Panzarella, V. (2019). Salivary biomarkers for oral squamous cell carcinoma diagnosis and follow-up: current status and perspectives. Frontiers in physiology, 10, 1476. https://www.frontiersin.org/article/10.3389/fphys.2019.01476/full
Rai, V., Mukherjee, R., Ghosh, A. K., Routray, A., & Chakraborty, C. (2018). “Omics” in oral cancer: New approaches for biomarker discovery. Archives of Oral Biology, 87, 15-34. https://linkinghub.elsevier.com/retrieve/pii/S0003996917303801
Shah, F. D., Begum, R., Vajaria, B. N., Patel, K. R., Patel, J. B., Shukla, S. N., & Patel, P. S. (2011). A Review on Salivary Genomics and Proteomics Biomarkers in Oral Cancer. Indian Journal of Clinical Biochemistry, 26(4), 326–334. https://doi.org/10.1007/s12291-011-0149-8
Galot, R., & Machiels, J. P. H. (2020). Current applications and challenges of circulating tumor DNA (ctDNA) in squamous cell carcinoma of the head and neck (SCCHN). Cancer treatment reviews, 85, 101992. https://linkinghub.elsevier.com/retrieve/pii/S030573722030030X
Fendt, L., Fazzini, F., Weissensteiner, H., Bruckmoser, E., Schönherr, S., Schäfer, G., ... & Laimer, J. (2020). Profiling of mitochondrial DNA heteroplasmy in a prospective oral squamous cell carcinoma study. Cancers, 12(7), 1933. https://www.mdpi.com/2072-6694/12/7/1933
Cao, Y., Green, K., Quattlebaum, S., Milam, B., Lu, L., Gao, D., He, H., Li, N., Gao, L., Hall, F., Whinery, M., Handley, E., Ma, Y., Xu, T., Jin, F., Xiao, J., Wei, M., Smith, D., Bornstein, S., & Gross, N. (2018). Methylated genomic loci encoding microRNA as a biomarker panel in tissue and saliva for head and neck squamous cell carcinoma. Clinical Epigenetics, 10(1). https://doi.org/10.1186/s13148-018-0470-7
Deuerling, L., Gaida, K., Neumann, H., & Remmerbach, T. W. (2019). Evaluation of the Accuracy of Liquid-Based Oral Brush Cytology in Screening for Oral Squamous Cell Carcinoma. Cancers, 11(11), 1813. https://doi.org/10.3390/cancers11111813
Kim, S. Y., Han, Y. K., Song, J. M., Lee, C. H., Kang, K., Yi, J. M., & Park, H. R. (2019). Aberrantly hypermethylated tumor suppressor genes were identified in oral squamous cell carcinoma (OSCC). Clinical Epigenetics, 11(1). https://doi.org/10.1186/s13148-019-0715-0
Kaczor-Urbanowicz, K. E., Wei, F., Rao, S. L., Kim, J., Shin, H., Cheng, J., ... & Kim, Y. (2019). Clinical validity of saliva and novel technology for cancer detection. Biochimica et Biophysica Acta (BBA)-Reviews on Cancer, 1872(1), 49-59. https://linkinghub.elsevier.com/retrieve/pii/S0304419X18302208
Webber, L. P., Wagner, V. P., Curra, M., Vargas, P. A., Meurer, L., Carrard, V. C., Squarize, C. H., & Castilho, R. M. (2017). Hypoacetylation of acetyl‐histone H3 (H3K9ac) as marker of poor prognosis in oral cancer. Histopathology, 71(2), 278–286. https://doi.org/10.1111/his.13218
Cheng, Y.-S. L., Jordan, L., Rees, T., Chen, H.-S., Oxford, L., Brinkmann, O., & Wong, D. (2013). Levels of potential oral cancer salivary mRNA biomarkers in oral cancer patients in remission and oral lichen planus patients. Clinical Oral Investigations, 18(3), 985–993. https://doi.org/10.1007/s00784-013-1041-0
Ogden, G. R., Kiddie, R. A., Lunny, D. P., & Lane, D. P. (1992). Assessment of p53 protein expression in normal, benign, and malignant oral mucosa. The Journal of Pathology, 166(4), 389–394. https://doi.org/10.1002/path.1711660411
Zhang, L., Poh, C. F., Williams, M., Laronde, D. M., Berean, K., Gardner, P. J., Jiang, H., Wu, L., Lee, J. J., & Rosin, M. P. (2012). Loss of Heterozygosity (LOH) Profiles--Validated Risk Predictors for Progression to Oral Cancer. Cancer Prevention Research, 5(9), 1081–1089. https://doi.org/10.1158/1940-6207.capr-12-0173
Hernando-Rodriguez, M., Rey-Barja, N., Marichalar-Mendia, X., Rodriguez-Tojo, M. J., Acha-Sagredo, A., & Aguirre-Urizar, J. M. (2011). Role of cytochrome P-450 genetic polymorphisms in oral carcinogenesis. Journal of Oral Pathology & Medicine, 41(1), 1–8. https://doi.org/10.1111/j.1600-0714.2011.01067.x
Nayak, C. S., Carvalho, A. L., Jeronimo, C., Henrique, R., Kim, M. M., Hoque, M. O., Chang, S., Jiang, W.-W., Koch, W., Westra, W., Sidransky, D., & Califano, J. (2007). Positive Correlation of Tissue Inhibitor of Metalloproteinase-3 and Death-Associated Protein Kinase Hypermethylation in Head and Neck Squamous Cell Carcinoma. The Laryngoscope, 117(8), 1376–1380. https://doi.org/10.1097/mlg.0b013e31806865a8
Li, Y., Elashoff, D., Oh, M., Sinha, U. K., John, Zhou, X., Abemayor, E., & Wong, D. (2006). Serum Circulating Human mRNA Profiling and Its Utility for Oral Cancer Detection. J Clin Oncol , 24(11), 1754–1760. https://doi.org/10.1200/jco.2005.03.7598
Li, Y. (2004). Salivary Transcriptome Diagnostics for Oral Cancer Detection. Clinical Cancer Research, 10(24), 8442–8450. https://doi.org/10.1158/1078-0432.ccr-04-1167
Park, N. J., Zhou, H., Elashoff, D., Henson, B. S., Kastratovic, D. A., Abemayor, E., & Wong, D. T. (2009). Salivary microRNA: Discovery, Characterization, and Clinical Utility for Oral Cancer Detection. Clinical Cancer Research, 15(17), 5473–5477. https://doi.org/10.1158/1078-0432.ccr-09-0736
Liu, C. T., Kao, S. C., Hsi Feng Tu, Tsai, M. M., Chang, K.-J., & Lin, S. (2010). Increase of microRNAmiR-31level in plasma could be a potential marker of oral cancer. Oral Dis , 16(4), 360–364. https://doi.org/10.1111/j.1601-0825.2009.01646.x
Zeljic, K., Jovanovic, I., Jovanovic, J., Magic, Z., Stankovic, A., & Supic, G. (2018). MicroRNA meta-signature of oral cancer: evidence from a meta-analysis. Upsala Journal of Medical Sciences, 123(1), 43–49. https://doi.org/10.1080/03009734.2018.1439551
Elashoff, D., Zhou, H., Reiss, J., Wang, J., Xiao, H., Henson, B., Hu, S., Arellano, M., Sinha, U., Le, A., Messadi, D., Wang, M., Nabili, V., Lingen, M., Morris, D., Randolph, T., Feng, Z., Akin, D., Kastratovic, D. A., & Chia, D. (2012). Prevalidation of Salivary Biomarkers for Oral Cancer Detection. Cancer Epidemiology Biomarkers & Prevention, 21(4), 664–672. https://doi.org/10.1158/1055-9965.epi-11-1093
Khor, G. H., Froemming, G. R. A., Zain, R. B., Abraham, M. T., Omar, E., Tan, S. K., Tan, A. C., Vincent-Chong, V. K., & Thong, K. L. (2013). DNA Methylation Profiling Revealed Promoter Hypermethylation-induced Silencing of p16, DDAH2 and DUSP1 in Primary Oral Squamous Cell Carcinoma. International Journal of Medical Sciences, 10(12), 1727–1739. https://doi.org/10.7150/ijms.6884
Yue, Q., Zhang, L., Zhang, L., Wang, Y., Li, H., Ren, X., Wei, F., Yu, W., Liu, T., Wang, X., Zhou, X., Yu, J., & Hao, X. (2015). Long non-coding RNA HOTAIR promotes tumor cell invasion and metastasis by recruiting EZH2 and repressing E-cadherin in oral squamous cell carcinoma. Int J Oncol, 46(6), 2586–2594. https://doi.org/10.3892/ijo.2015.2976
Ishikawa, S., Sugimoto, M., Kitabatake, K., Sugano, A., Nakamura, M., Kaneko, M., Ota, S., Hiwatari, K., Enomoto, A., Soga, T., Tomita, M., & Iino, M. (2016). Identification of salivary metabolomic biomarkers for oral cancer screening. Scientific Reports, 6(1), 31520. https://doi.org/10.1038/srep31520
Chen, X., & Yu, D. (2019). Metabolomics study of oral cancers. Metabolomics, 15(2). https://doi.org/10.1007/s11306-019-1483-8
Cheng, Y.-S., Rees, T., & Wright, J. (2014). A review of research on salivary biomarkers for oral cancer detection. Clinical and Translational Medicine, 3(1), 3. https://doi.org/10.1186/2001-1326-3-3
Lee, A. J., Walsh, T. F., Hodges, S. J., & Rawlinson, A. (1999). Gingival crevicular fluid osteocalcin in adult periodontitis. Journal of Clinical Periodontology, 26(4), 252–256. https://doi.org/10.1034/j.1600-051x.1999.260409.x
Wong, D. T. (2006). Salivary diagnostics powered by nanotechnologies, proteomics and genomics. The Journal of the American Dental Association, 137(3), 313–321. https://doi.org/10.14219/jada.archive.2006.0180
Yoshizawa, J. M., Schafer, C. A., Schafer, J. J., Farrell, J. J., Paster, B. J., & Wong, D. T. W. (2013). Salivary Biomarkers: Toward Future Clinical and Diagnostic Utilities. Clinical Microbiology Reviews, 26(4), 781–791. https://doi.org/10.1128/cmr.00021-13
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