Document Type : Literature Review

Authors

1 Violet Vines Marshman Centre for Rural Health Research, La Trobe Rural Health School, La Trobe University, Bendigo, VIC, 3552, Australia.

2 Shiraz Institute for Cancer Research, Shiraz University of Medical Sciences, Shiraz, Iran.

3 Shiraz Neuroscience Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.

4 Faculty of Science, School of Human Science, University of Western Australia, WA.

10.30476/dentjods.2023.96159.1924

Abstract

Oral cancer is a malignant neoplasia that can originate in the oral cavity or lips. It is a serious global health problem and one of the ten most common cancers worldwide. Over the years, changes in the trends of the oral cavity and oropharyngeal cancers have been observed. The management of oral cancer is complicated due to the functional and cosmetic consequences of treating malignancies at these anatomical locations. The tumor and its treatment can affect a variety of functional activities, including smell, sight, speaking, respiration, taste, jaw function, and mastication, either temporarily or permanently. Based on the importance of this tumor, screening oral cancer for early detection and finding the best biomarkers for diagnosis is a crucial concern. In this review of literature, the etiology, risk factors, treatment, and diagnosis of oral cancer will be reviewed with a focus on the most important biomarkers.

Highlights

Estie Kruger (Google Scholar)

Keywords

  • Rivera C. Essentials of oral cancer. Int J Clin Ex Patho. 2015; 8: 11884.
  • Kim YJ, Kim JH. Increasing incidence and improving survival of oral tongue squamous cell carcinoma. Sci Rep. 2020; 10: 1-11.
  • Di Spirito F, Amato A, Romano A, Dipalma G, Xhajanka E, Baroni A, et al. Analysis of risk factors of oral cancer and periodontitis from a sex-and gender-related perspective: gender dentistry. Appl Sci. 2022; 12: 9135.
  • Sarode G, Maniyar N, Sarode SC, Jafer M, Patil S, Awan Kh. Epidemiologic aspects of oral cancer. Dis Mon. 2020; 66: 100988.
  • Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Can J Clin. 2021; 71: 209-249.
  • Alramadhan SA, Fitzpatrick SG, Cohen DM, Bhattacharyya I, Islam MN. Incidence of oral squamous cell carcinoma in patients aged 30 years and under: a single institution retrospective analysis. Saudi J Oral Dent Res. 2022; 7: 351-358.
  • Capote-Moreno A, Brabyn P, Muñoz-Guerra M, Sastre-Pérez J, Escorial-Hernandez V, Rodríguez-Campo F, et al. Oral squamous cell carcinoma: epidemiological study and risk factor assessment based on a 39-year series. Int J Oral Maxillofac Surg. 2020; ‌49: 1525-1534.
  • Siegel RL, Miller KD, Fuchs HE, Jemal A. Cancer statistics, 2022. CA A Can J Clin. 2022; 72: 7-33.
  • Siegel RL, Miller KD, Wagle NS, Jemal A. Cancer statistics, 2023. CA A Can J Clin. 2023; 73: 17-48.
  • Abati S, Bramati C, Bondi S, Lissoni A, Trimarchi M. Oral cancer and precancer: a narrative review on the relevance of early diagnosis. Int J Environ Res Public Health. 2020; 17: 9160.
  • Dhanuthai K, Rojanawatsirivej S, Thosaporn W, Kintarak S, Subarnbhesaj A, Darling M, et al. Oral cancer: A multicenter study. Med Oral Oral Cir Bucal. 2018; 23: e23.
  • Howard A, Agrawal N, Gooi Z. Lip and Oral Cavity Squamous Cell Carcinoma. Hematol Oncol Clin. 2021; 35: 895-911.
  • McCord C, Kiss A, Magalhaes MA, Leong IT, Jorden T, Bradley G. Oral Squamous Cell Carcinoma Associated with Precursor LesionsOral Cancer Associated with Precursor Lesions. Cancer Prev Res. 2021; 14: 873-884.
  • Phookan J, Saikia K. A clinicopathological study of the pre-malignant conditions of oral cavity. Indian J Otolaryngol Head Neck Surg. 1998; 50: 246-249.
  • Yardimci G, Kutlubay Z, Engin B, Tuzun Y. Precancerous lesions of oral mucosa. World J Clin Case (WJCC). 2014; 2: 866.
  • Wong T, Wiesenfeld D. Oral Cancer. Australian Dent J. 2018; 63: S91-S9.
  • Mercadante S, Aielli F, Adile C, Ferrera P, Valle A, Fusco F, et al. Prevalence of oral mucositis, dry mouth, and dysphagia in advanced cancer patients. Support Care Cancer. 2015; 23: 3249-3255.
  • Hanchanale S, Adkinson L, Daniel S, Fleming M, Oxberry SG. Systematic literature review: xerostomia in advanced cancer patients. Support Care Cancer. 2015; 23: 881-888.
  • Plemons JM, Al-Hashimi I, Marek CL. Managing xerostomia and salivary gland hypofunction: executive summary of a report from the American Dental Association Council on Scientific Affairs. J Am Dent Assoc. 2014; 145: 867-873.
  • Johnson DE, Burtness B, Leemans CR, Lui VWY, Bauman JE, Grandis JR. Head and neck squamous cell carcinoma. Nat Rew Dis Primers. 2020; 6: 1-22.
  • Edirisinghe ST, Weerasekera M, De*Silva DK, Liyanage I, Niluka M, Madushika K, et al. The risk of oral cancer among different categories of exposure to tobacco smoking in Sri Lanka. Asian Pac J Cancer Prev. 2022; 23: 2929-2935.
  • Lee YCA, Marron M, Benhamou S, Bouchardy C, Ahrens W, Pohlabeln H, et al. Active and involuntary tobacco smoking and upper aerodigestive tract cancer risks in a multicenter case-control study. Cancer Epidemiol Biomarkers Prev. 2009; 18: 3353-3561.
  • Hussain A, Dulay P, Rivera MN, Aramouni C, Saxena V. Neoplastic pathogenesis associated with cigarette carcinogens. Cureus. 2019; 11: e3955.
  • Lee J, Taneja V, Vassallo R. Cigarette smoking and inflammation: cellular and molecular mechanisms. J Dent Res. 2012; 91: 142-149.
  • Qian Y, Wang W, Chen D, Zhu Y, Wang Y, Wang X. Cigarette smoking induces the activation of RIP2/ caspase-12/NF-κB axis in oral squamous cell carcinoma. Peer J. 2022; 10: e14330.
  • Sarkar R, Das A, Paul RR, Barui A. Cigarette smoking promotes cancer-related transformation of oral epithelial cells through activation of Wnt and MAPK pathway. Future Oncology. 2019; 15: 3619-3631.
  • De*Oliveira SRL, Da*Silva ICB, Mariz BALA, Pereira AMBC, De*Oliveira NFP. DNA methylation analysis of cancer-related genes in oral epithelial cells of healthy smokers. Arch Oral Biol. 2015; 60: 825-833.
  • Valinluck V, Sowers LC. Inflammation-mediated cytosine damage: a mechanistic link between inflammation and the epigenetic alterations in human cancers. Cancer Res. 2007; 67: 5583-5586.
  • Schuch LF, De*Arruda JAA, Viana KSS, Caldeira PC, Abreu MHNG, Bernardes VF, et al. DNA damage-related proteins in smokers and non-smokers with oral cancer. Brazilian Oral Res. 2022; 36: e027.
  • Kashyap B, Mikkonen JJW, Bhardwaj T, Dekker H, Schulten EAJM, Bloemena E, et al. Effect of smoking on MUC1 expression in oral epithelial dysplasia, oral cancer, and irradiated oral epithelium. Arch Oral Biol. 2022; 142: 105525.
  • Chien CY, Chen YC, Lee CH, Wu JR, Huang TW, Huang RY, et al. Dysregulation of the miR-30a/BiP axis by cigarette smoking accelerates oral cancer progression. Cancer Cell Int. 2021; 21: 1-14.
  • Liu Y, Chen H, Sun Z, Chen X. Molecular mechanisms of ethanol-associated oro-esophageal squamous cell carcinoma. Cancer Lett. 2015; 361: 164-173.
  • Reidy J, McHugh E, Stassen L. A review of the relations hip between alcohol and oral cancer. The Surgeon. 2011; 9: 278-283.
  • Bolesina NJ, Gatti G, López*de*Blanc S, Dhooge S, Rocha D, Fernández E, et al. Oral Squamous Cell Carcinoma (OSCC) tumors from heavy alcohol consumers are associated with higher levels of TLR9 and a particular immunophenotype: impact on patient overall survival. Front Immunol. 2022: 13: 941667.
  • Nguyen A, Kim AH, Kang MK, Park NH, Kim RH, Kim Y, et al. Chronic alcohol exposure promotes cancer stemness and glycolysis in oral/oropharyngeal squamous cell carcinoma cell lines by activating NFAT signaling. Int J Mol Sci. 2022; 23: 9779.
  • Chamoli A, Gosavi AS, Shirwadkar UP, Wangdale KV, Behera SK, Kurrey NK, et al. Overview of oral cavity squamous cell carcinoma: Risk factors, mechanisms, and diagnostics. Oral Oncol. 2021; 121: 105451.
  • Ali J, Sabiha B, Jan HU, Haider SA, Khan AA, Ali SS. Genetic etiology of oral cancer. Oral Oncol. 2017; 70: 23-28.
  • Nigam K, Srivastav RK. Notch signaling in oral pre-cancer and oral cancer. Med Oncol. 2021; 38: 1-13.
  • Wu F, Shi X, Zhang R, Tian Y, Wang X, Wei C, et al. Regulation of proliferation and cell cycle by protein regulator of cytokinesis 1 in oral squamous cell carcinoma. Cell Death Dis. 2018; 9: 1-12.
  • Maturana-Ramírez A, Aitken-Saavedra J, de Guevara-Benítez AL, Espinoza-Santander I. Hypovitaminosis D, oral potentially malignant disorders, and oral squamous cell carcinoma: a systematic review. Med Oral Patol Oral Cir Bucal. 2022; 27: e135.
  • Van*der*Waal I. Are we able to reduce the mortality and morbidity of oral cancer; some considerations. Med Oral Patol Oral Cir Bucal. 2013; 18: e33.
  • Colevas AD, Yom SS, Pfister DG, Spencer S, Adelstein D, Adkins D, et al. NCCN guidelines insights: head and neck cancers, version 1.2018. J Natl Compr Canc Netw. 2018; 16: 479-490.
  • Shah JP, Gil Z. Current concepts in management of oral cancer–surgery. Oral Oncol. 2009; 45: 394-401.
  • Hartner L. Chemotherapy for oral cancer. Dent Clin North Am. 2018; 62: 87-97.
  • D’Cruz AK, Vaish R. Risk-based oral cancer screening-lessons to be learnt. Nat Rev Clin Oncol. 2021; 18: 471- 472.
  • Wang S, Yang M, Li R, Bai J. Current advances in non invasive methods for the diagnosis of oral squamous cell carcinoma: a review. Eur J Med Res. 2023; 28: 1-12.
  • Jitender S, Sarika G, Varada HR, Omprakash Y, Mohsin K. Screening for oral cancer. J Exp Ther Oncol. 2016; 11: 303–307.
  • Badvi J, Kulsoom J, Ujjan I. Recent techniques for diagnosis of oral squamous cell carcinoma. EC Microbiol. 2017; 5: 165-168.
  • Rao RS, Chatura KR, Sowmya S, Prasad K, Lakshminarayana S, Ali FM, et al. Procedures and pitfalls in incisional biopsies of oral squamous cell carcinoma with respect to histopathological diagnosis. Dis Mon. 2020; 66: 101035.
  • Sciubba JJ. Oral cancer and its detection: history-taking and the diagnostic phase of management. J Am Dent Assoc. 2001; 132: 12S-18S.
  • Carreras-Torras C, Gay-Escoda C. Techniques for early diagnosis of oral squamous cell carcinoma: Systematic review. Med Oral Patol Oral Cir Bucal. 2015; 20: e305.
  • Epstein JB, Güneri P, Boyacioglu H, Abt E. The limitations of the clinical oral examination in detecting dysplastic oral lesions and oral squamous cell carcinoma. J Am Dent Assoc. 2012; 143: 1332-1342.
  • Epstein JB, Oakley C, Millner A, Emerton S, Van*Der*Meij E, Le N. The utility of toluidine blue application as a diagnostic aid in patients previously treated for upper oropharyngeal carcinoma. Oral Surg Oral Med Oral Patho Oral Radio Endo. 1997; 83: 537-547.
  • Parakh MK, Reddy RJ, Subramani P. Toluidine blue staining in identification of a biopsy site in potentially malignant lesions: A case–control study. Asia Pac J Oncol Nurs. 2017; 4: 356-360.
  • Epstein JB, Feldman R, Dolor RJ, Porter SR. The utility of tolonium chloride rinse in the diagnosis of recurrent or second primary cancers in patients with prior upper aerodigestive tract cancer. Head Neck. 2003; 25: 911-921.
  • Pavlova I, Williams M, El-Naggar A, Richards-Kortum R, Gillenwater A. Understanding the biological basis of autofluorescence imaging for oral cancer detection: high-resolution fluorescence microscopy in viable tissue. Clin Can Res. 2008; 14: 2396-2404.
  • Rashid A, Warnakulasuriya S. The use of light‐based (optical) detection systems as adjuncts in the detection of oral cancer and oral potentially malignant disorders: a systematic review. J Oral Patho Med. 2015; 44: 307-328.
  • Morikawa T, Shibahara T, Nomura T, Katakura A, Takano M. Non-invasive early detection of oral cancers using fluorescence visualization with optical instruments. Cancers. 2020; 12: 2771.
  • Bhatia N, Lalla Y, Vu AN, Farah CS. Advances in optical adjunctive AIDS for visualisation and detection of oral malignant and potentially malignant lesions. Int J Dent. 2013; 2013: 194029
  • Mehrotra R, Gupta A, Singh M, Ibrahim R. Application of cytology and molecular biology in diagnosing premalignant or malignant oral lesions. Mol Cancer. 2006; 6: 1-9.
  • Smith JH. Cytology, liquid-based cytology and automation. Best Pract Res Clin Obstet Gynaecol. 2011; 25: 585-596.
  • Rosin MP, Epstein JB, Berean K, Durham S, Hay J, Cheng X, et al. The use of exfoliative cell samples to map clonal genetic alterations in the oral epithelium of high-risk patients. Can Res. 1997; 57: 5258-5260.
  • Kujan O, Desai M, Sargent A, Bailey A, Turner A, Sloan P. Potential applications of oral brush cytology with liquid-based technology: results from a cohort of normal oral mucosa. Oral Oncol. 2006; 42: 810-818.
  • Remmerbach T, Pomjanski N, Bauer U, Neumann H. Liquid-based versus conventional cytology of oral brush biopsies: a split-sample pilot study. Clin Oral Invest. 2017; 21: 2493-2498.
  • Hayama FH, Motta A, Migliari D. Liquid-based preparations versus conventional cytology: specimen adequacy and diagnostic agreement in oral lesions. Med Oral Patol Oral Cir Bucal. 2005; 10: 115-122.
  • Navone R, Burlo P, Pich A, Pentenero M, Broccoletti R, Marsico A, et al. The impact of liquid‐based oral cytology on the diagnosis of oral squamous dysplasia and carcinoma. Cytopathology. 2007; 18: 356-360.
  • Sarhadi VK, Armengol G. Molecular Biomarkers in Cancer. Biomolecules. 2022; 12: 1021.
  • Santosh ABR, Jones T, Harvey J. A review on oral cancer biomarkers: Understanding the past and learning from the present. J Can Res Ther. 2016; 12: 486.
  • Nguyen TTH, SodnomIsh B, Choi SW, Jung HI, Cho J, Hwang I, et al. Salivary biomarkers in oral squamous cell carcinoma. J Korean Assoc Oral Maxillofac Surg. 2020; 46: 301-312.
  • Riccardi G, Bellizzi MG, Fatuzzo I, Zoccali F, Cavalcanti L, Greco A, et al. Salivary biomarkers in oral squamous cell carcinoma: a proteomic overview. Proteomes. 2022; 10: 37.
  • Shaw AK, Garcha V, Shetty V, Vinay V, Bhor K, Ambildhok K, et al. Diagnostic accuracy of salivary biomarkers in detecting early oral squamous cell carcinoma: a systematic review and meta-analysis. Asian Pac J Cancer Prev. 2022; 23: 1483-1495.
  • Gaba FI, Sheth CC, Veses V. Salivary biomarkers and their efficacies as diagnostic tools for oral squamous cell carcinoma: systematic review and meta‐ J Oral Patho Med. 2021; 50: 299-307.
  • Enomoto Y, Kimoto A, Suzuki H, Nishiumi S, Yoshida M, Komori T. Exploring a novel screening method for patients with oral squamous cell carcinoma: A plasma metabolomics analysis. Kobe J Med Sci. 2018; 64: E26.
  • Monteiro LS, Delgado ML, Ricardo S, Garcez F, do*Amaral B, Warnakulasuriya S, et al. Phosphorylated mammalian target of rapamycin is associated with an adverse outcome in oral squamous cell carcinoma. Oral Surg Oral Med Oral Patho Oral Radio. 2013; 115: 638-645.
  • Yang C, Ma J, Zhu D, Liu Y, Montgomery B, Wang L, et al. GDF15 is a potential predictive biomarker for TPF induction chemotherapy and promotes tumorigenesis and progression in oral squamous cell carcinoma. Ann Oncol. 2014; 25: 1215-1222.
  • Bag A, Jyala N, Bag N. Indian studies on genetic polymorphisms and cancer risk. Indian J Can. 2012; 49: 144.
  • Sulzyc-Bielicka V, Bielicki D, Binczak-Kuleta A, Kaczmarczyk M, Pioch W, Machoy-Mokrzynska A, et al. Thymidylate synthase gene polymorphism and survival of colorectal cancer patients receiving adjuvant 5-fluorouracil. Genet Test Mol Biomarkers. 2013; 17: 799-806.
  • Huang WC, Chan SH, Jang TH, Chang JW, Ko YC, Yen TC, et al. miRNA-491-5p and GIT1 serve as modulators and biomarkers for oral squamous cell arcinoma invasion and metastasis. Can Res. 2014; 74: 751-764.
  • Scholtz B, Horváth J, Tar I, Kiss C, Márton IJ. Salivary miR-31-5p, miR-345-3p, and miR-424-3p are reliable biomarkers in patients with oral squamous cell carcinoma. Pathogens. 2022; 11: 229.
  • Cai M, Zheng Z, Bai Z, Ouyang K, Wu Q, Xu S, et al. Overexpression of angiogenic factors and matrix metalloproteinases in the saliva of oral squamous cell carcinoma patients: Potential non-invasive diagnostic and therapeutic biomarkers. BMC Cancer. 2022; 22: 1-15.
  • Rapado‐González Ó, López‐Cedrún JL, Lago‐Lestón RM, Abalo A, Rubin‐Roger G, Salgado‐Barreira Á, et al. Integrity and quantity of salivary cell‐free DNA as a potential molecular biomarker in oral cancer: A preliminary study. J Oral Patho Med. 2022; 51: 429-435.
  • Ueda S, Goto M, Hashimoto K, Hasegawa S, Imazawa M, Takahashi M, et al. Salivary CCL20 level as a biomarker for oral squamous cell carcinoma. Cancer Genomics Proteomics. 2021; 18: 103-112.
  • Koopaie M, Manifar S, Lahiji SS. Assessment of micro-RNA-15a and microRNA-16-1 salivary level in oral squamous cell carcinoma patients. Microrna. 2021; 10: 74-79.
  • Ueda S, Goto M, Hashimoto K, Imazawa M, Takahashi M, OhIwa I, et al. Salivary CPLANE1 levels as a biomarker of oral squamous cell carcinoma. Anticancer Res. 2021; 41: 765-772.
  • Romani C, Salviato E, Paderno A, Zanotti L, Ravaggi A, Deganello A, et al. Genome-wide study of salivary miRNAs identifies miR-423-5p as promising diagnostic and prognostic biomarker in oral squamous cell carcinoma. Theranostics. 2021; 11: 2987.
  • Mehterov N, Vladimirov B, Sacconi A, Pulito C, Rucinski M, Blandino G, et al. Salivary miR-30c-5p as potential biomarker for detection of oral squamous cell carcinoma. Biomedicines. 2021; 9: 1079.
  • Farag AF, Sabry D, Hassabou NF, Alaa EL-Din Y. MicroRNA-134/microRNA-200a derived salivary exosomes are novel diagnostic biomarkers of oral squamous cell carcinoma. Egypt Dent J. 2021; 67: 367-377.
  • Ueda S, Hashimoto K, Miyabe S, Hasegawa S, Goto M, Shimizu D, et al. Salivary NUS1 and RCN1 levels as biomarkers for oral squamous cell carcinoma diagnosis. In vivo. 2020; 34: 2353-2561.
  • He L, Ping F, Fan Z, Zhang C, Deng M, Cheng B, et al. Salivary exosomal miR-24-3p serves as a potential detective biomarker for oral squamous cell carcinoma screening. Biomed Pharmacother. 2020; 121: 109553.
  • Liu CJ, Chen JH, Hsia SM, Liao CC, Chang HW, Shieh TM, et al. Salivary LDOC1 is a gender-difference biomarker of oral squamous cell carcinoma. Peer J. 2019; 7: e6732.
  • Márton IJ, Horváth J, Lábiscsák P, Márkus B, Dezső B, Szabó A, et al. Salivary IL-6 mRNA is a robust biomarker in oral squamous cell carcinoma. J Clin Med. 2019; 8: 1958.
  • Yap T, Koo K, Cheng L, Vella LJ, Hill AF, Reynolds E, et al. Predicting the Presence of Oral Squamous Cell Carcinoma Using Commonly Dysregulated MicroRNA in Oral SwirlsOSCC Prediction from MicroRNA in Oral Swirls. Can Prev Res. 2018; 11: 491-502.
  • Gai C, Camussi F, Broccoletti R, Gambino A, Cabras M, Molinaro L, et al. Salivary extracellular vesicle-associated miRNAs as potential biomarkers in oral squamous cell carcinoma. BMC Cancer. 2018; 18: 1-11.
  • Piyarathne NS, Weerasekera MM, Fonseka PFD, Karunatilleke AHTS, Liyanage RLPR, Jayasinghe RD, et al. Salivary interleukin levels in oral squamous cell carcinoma and oral epithelial dysplasia: findings from a sri Lankan study. Cancers. 2023; 15: 1510.
  • Chu HW, Chang KP, Yen WC, Liu HP, Chan XY, Liu CR, et al. Identification of salivary autoantibodies as biomarkers of oral cancer with immunoglobulin A enrichment combined with affinity mass spectrometry. Proteomics. 2023: 23: 2200321.
  • Shabbir A, Waheed H, Ahmed S, Shaikh SS, Farooqui WA. Association of salivary Cathepsin B in different histological grades among patients presenting with oral squamous cell carcinoma. BMC Oral Health. 2022; 22: 63.
  • Man QW, Li RF, Bu LL, Zhao Y, Liu B. Salivary non‐apoptotic tumoral microvesicles: A potential progressive marker in oral cancer patients. J Cell Mol Med. 2022; 26: 5955-5965.
  • Shin YJ, Vu H, Lee JH, Kim HD. Diagnostic and prognostic ability of salivary MMP-9 for oral squamous cell carcinoma: A pre-/post-surgery case and matched control study. PLoS One. 2021; 16: e0248167.
  • Saleem Z, Shaikh AH, Zaman U, Ahmed S, Majeed MM, Kazmi A, et al. Estimation of salivary matrix metalloproteinases-12 (MMP-12) levels among patients presenting with oral submucous fibrosis and oral squamous cell carcinoma. BMC Oral Health. 2021; 21: 205.
  • Jain A, Kotimoole CN, Ghoshal S, Bakshi J, Chatterjee A, Prasad TSK, et al. Identification of potential salivary biomarker panels for oral squamous cell carcinoma. Scientific Reports. 2021; 11: 3365.
  • Salarić I, Karmelić I, Lovrić J, Baždarić K, Rožman M, Čvrljević I, et al. Salivary melatonin in oral squamous cell carcinoma patients. Scientific Reports. 2021; 11: 13201.
  • Sivadasan P, Gupta MK, Sathe G, Sudheendra H, Sunny SP, Renu D, et al. Salivary proteins from dysplastic leukoplakia and oral squamous cell carcinoma and their potential for early detection. J Proteomics. 2020; 212: 103574.
  • Singh P, Verma JK, Singh JK. Validation of Salivary markers, IL-1β, IL-8 and Lgals3bp for detection of oral squamous cell carcinoma in an Indian population. Sci Rep. 2020; 10: 1-9.
  • Smriti K, Ray M, Chatterjee T, Shenoy RP, Gadicherla S, Pentapati KC, et al. Salivary MMP-9 as a biomarker for the diagnosis of oral potentially malignant disorders and oral squamous cell carcinoma. Asian Pacific J Can Prevention (APJCP). 2020; 21: 233.
  • Chi LM, Hsiao YC, Chien KY, Chen SF, Chuang YN, Lin SY, et al. Assessment of candidate biomarkers in paired saliva and plasma samples from oral cancer patients by targeted mass spectrometry. J Proteomics. 2020; 211: 103571.
  • Scholtz B, Vo Minh D, Kiss C, Tar I, Kumar A, Tőzsér J, et al. Examination of oral squamous cell carcinoma and precancerous lesions using proximity extension assay and salivary RNA quantification. Biomedicines. 2020; 8: 610.
  • Feng Y, Li Q, Chen J, Yi P, Xu X, Fan Y, et al. Salivary protease spectrum biomarkers of oral cancer. Int J Oral Sci. 2019; 11: 1-11.
  • Wang K, Shen Y, Xu J, Li Z, Liu Y, Yu C, et al. Evaluation of synucleinγ levels by novel monoclonal antibody in saliva and cancer tissues from oral squamous cell carcinoma patients. Neoplasma. 2020; 67: 707-713.
  • Hsu CW, Chang KP, Huang Y, Liu HP, Hsueh PC, Gu PW, et al. Proteomic profiling of paired interstitial fluids reveals dysregulated pathways and salivary NID1 as a biomarker of oral cavity squamous cell carcinoma. Mol Cell Proteomics. 2019; 18: 1939-1949. 
  • Abbas MJ, Al-Rawi NA, Al-Duboni GI. Assessment of interleukin-10 and interferon-gamma with oral squamous cell carcinoma patients compared with healthy subjects as a prediction for early detection and monitor treatment response. Mustansiria Dent J. 2019; 16: 48-52.
  • Ankita K, Shwetha V, Vanitha S, Sujatha SR, Nagaraju R, Pavan KT. Assessment of salivary endothelin-1 in patients with leukoplakia, submucous fibrosis, oral cancer and healthy individuals–a comparative study. J Stomato, Oral Maxillofac Surg. 2019; 120: 326-331.
  • Chu HW, Chang KP, Hsu CW, Chang IYF, Liu HP, Chen YT, et al. Identification of salivary biomarkers for oral cancer detection with untargeted and targeted quantitative proteomics approaches. Mol Cell Proteomics. 2019; 18: 1796-1806.
  • Gupta A, Tripathi A, Patil R, Kumar V, Khanna V, Singh V. Estimation of salivary and serum basic fibroblast growth factor in treated and untreated patients with oral squamous cell carcinoma. J Oral Biol Craniofac Res. 2019; 9: 19-23.
  • Heawchaiyaphum C, Pientong C, Phusingha P, Vatanasapt P, Promthet S, Daduang J, et al. Peroxiredoxin-2 and zinc-alpha-2-glycoprotein as potentially combined novel salivary biomarkers for early detection of oral squamous cell carcinoma using proteomic approaches. J Proteomics. 2018; 173: 52-61.
  • Zheng J, Sun L, Yuan W, Xu J, Yu X, Wang F, et al. Clinical value of Naa10p and CEA levels in saliva and serum for diagnosis of oral squamous cell carcinoma. J Oral Patho Med. 2018; 47: 830-835.
  • Lee L, Wong Y, Hsiao H, Wang Y, Chan M, Chang K. Evaluation of saliva and plasma cytokine biomarkers in patients with oral squamous cell carcinoma. Int J Oral Maxillofac Surg. 2018; 47: 699-707.
  • Singh HP. Estimation of salivary biomarkers in patients with squamous cell carcinoma. Int J Clin Diagnos Patho. 2018; 1: 29-31.
  • Shan J, Sun Z, Yang J, Xu J, Shi W, Wu Y, et al. Discovery and preclinical validation of proteomic biomarkers in saliva for early detection of oral squamous cell carcinomas. Oral Dis. 2019; 25: 97-107.
  • Ameena M, Rathy R. Evaluation of tumor necrosis factor: Alpha in the saliva of oral cancer, leukoplakia, and healthy controls: A comparative study. J Int Oral Health. 2019; 11: 92.
  • Ishikawa S, Sugimoto M, Konta T, Kitabatake K, Ueda S, Edamatsu K, et al. Salivary metabolomics for prognosis of oral squamous cell carcinoma. Front Oncol. 2022; 11: 5633.
  • Tantray S, Sharma S, Prabhat K, Nasrullah N, Gupta M. Salivary metabolite signatures of oral cancer and leukoplakia through gas chromatography-mass spectrometry. J Oral Maxillofac Patho (JOMFP). 2022; 26: 31.
  • De*Sá*Alves M, de*Sá*Rodrigues N, Bandeira CM, Chagas JFS, Pascoal MBN, Nepomuceno GLJT, et al. Identification of possible salivary metabolic biomarkers and altered metabolic pathways in South American patients diagnosed with oral squamous cell carcinoma. Metabolites. 2021; 11: 650.
  • Sridharan G, Ramani P, Patankar S, Vijayaraghavan R. Evaluation of salivary metabolomics in oral leukoplakia and oral squamous cell carcinoma. J Oral Patho Med. 2019; 48: 299-306.
  • Mujawar SJ, Suchitra G, Kosandal KA, Choudhari S, Inamdar NA, Ahmed KB. Evaluation of salivary gamma-glutamyl transpeptidase as a biomarker in oral squamous cell carcinoma and precancerous lesions. J Oral Maxillofac Patho (JOMFP). 2020; 24: 584.
  • Abdelkawy M, El*Refai S, Shaker OG, Elbattawy W. Malondialdehyde and nitrous oxide as salivary biomarkers for malignant and premalignant oral lesions. Adv Dent J. 2020; 2: 117-128.
  • Tiwari P, Khajuria N, Metgud R. Estimation of serum and salivary albumin and uric acid levels in oral submucous fibrosis and oral squamous cell carcinoma: a biochemical study. Int J Res Health Allied Sci. 2019; 5: 5-9.
  • Piao Y, Jung SN, Lim MA, Oh C, Jin YL, Kim HJ, et al. A circulating microRNA panel as a novel dynamic monitor for oral squamous cell carcinoma. Sci Rep. 2023; 13: 2000.
  • He T, Guo X, Li X, Liao C, Wang X, He K. Plasma-derived exosomal microRNA-130a serves as a noninvasive biomarker for diagnosis and prognosis of oral squamous cell carcinoma. J Oncol. 2021; 2021: 5547911.
  • Bolandparva F, Nasab MSH, Mohamadnia A, Garajei A, Nasab AF, Bahrami N. Early diagnosis of oral squamous cell carcinoma (OSCC) by miR-138 and miR-424 -5p expression as a cancer marker. Asian Pac J Cancer Prev. 2021; 22: 2185.
  • Shao T, Huang J, Zheng Z, Wu Q, Liu T, Lv X. SCCA, TSGF, and the long non-coding RNA AC007271. 3 are effective biomarkers for diagnosing oral squamous cell carcinoma. Cell Physiol Biochem. 2018; 47: 26-38.
  • Schneider A, Victoria B, Lopez YN, Suchorska W, Barczak W, Sobecka A, et al. Tissue and serum microRNA profile of oral squamous cell carcinoma patients. Sci Rep. 2018; 8: 675.
  • Chang YA, Weng SL, Yang SF, Chou CH, Huang WC, Tu SJ, et al. A three–microRNA signature as a potential biomarker for the early detection of oral cancer. Int J Mol Sci. 2018; 19: 758.
  • Gautam SS, Singh RP, Karsauliya K, Sonker AK, Reddy PJ, Mehrotra D, et al. Label-free plasma proteomics for the identification of the putative biomarkers of oral squamous cell carcinoma. J Proteomics. 2022; 259: 104541.
  • Usman M, Ilyas A, Syed B, Hashim Z, Ahmed A, Zarina S. Serum HSP90-alpha and oral squamous cell carcinoma: a prospective biomarker. Protein Pept Lett. 2021; 28: 1157-1163.
  • Zhang M, Chen X, Chen H, Zhou M, Liu Y, Hou Y, et al. Identification and validation of potential novel biomarkers for oral squamous cell carcinoma. Bioengineered. 2021; 12: 8845-8862.
  • Li X, Liu L, Li N, Jia Q, Wang X, Zuo L, et al. Metabolomics based plasma biomarkers for diagnosis of oral squamous cell carcinoma and oral erosive lichen planus. J Cancer. 2022; 13: 76.
  • Faedo RR, da*Silva G, da*Silva RM, Ushida TR, da*Silva RR, Lacchini R, et al. Sphingolipids signature in plasma and tissue as diagnostic and prognostic tools in oral squamous cell carcinoma. Biochim Biophys Acta Mol Cell Biol Lipids. 2022; 1867: 159057.
  • Abulaiti Z, Chen L, Xiao Q, Aimaier A, Ma Y, He S, et al. PLCE1 as a diagnostic and prognostic biomarker by promoting the growth and progression of oral squamous cell carcinoma. J Oral Patho Med. 2022; 51: 771-779.
  • Sun Y, Zhou Q, Sun J, Bi W, Li R, Wu X, et al. DDX59-AS1 is a prognostic biomarker and correlated with immune infiltrates in OSCC. Front Genet. 2022: 13: 892727.
  • Hu X, Xiong H, Wang W, Huang L, Mao T, Yang L, et al. Study on the expression and function of smad family member 7 in oral submucous fibrosis and oral squamous cell carcinoma. Arch Oral Biol. 2020; 112: 104687.
  • Li L, Zhang ZT. Hsa_circ_0086414 Might Be a Diagnostic Biomarker of Oral Squamous Cell Carcinoma. Med Sci Monit. 2020; 26: e919383. 
  • Ries J, Baran C, Wehrhan F, Weber M, Motel C, Kesting M, et al. The altered expression levels of miR-186, miR-494 and miR-3651 in OSCC tissue vary from those of the whole blood of OSCC patients. Cancer Biomarkers. 2019; 24: 19-30.
  • Yanagiya M, Dawood RI, Maishi N, Hida Y, Torii C, Annan DA, et al. Correlation between endothelial CXCR7 expression and clinicopathological factors in oral squamous cell carcinoma. Patho Int. 2021; 71: 383-391.
  • Li Y, Cao X, Li H. Identification and validation of novel long non-coding RNA biomarkers for early diagnosis of oral squamous cell carcinoma. Front Bioeng and Biotechnol. 2020; 8: 256.