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Potentially Malignant Disorders of the Oral Cavity

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Early Detection and Treatment of Head & Neck Cancers

Abstract

Head and neck cancers, including varieties of oral cancers, can adversely impact the patients’ quality of life. Oral cancers could be preceded by visible intermediate clinical changes in the oral mucosa. With a progressive understanding of the premalignancy process, a terminology is specified and updated by WHO (2005) as to “Oral Potentially Malignant Disorders (OPMDs).” This includes varieties of precancerous lesions (i.e., oral leukoplakia and oral erythroplakia) and conditions (i.e., oral submucous fibrosis and lichen planus). Successful screening of OPMDs is very critical in the early detection, management, and prevention of malignant transformation. Conventional clinical examination has been supported with different vital staining, light-based detection systems, optical diagnostic technologies, and more recently potential molecular biomarkers. Future studies should focus on predicting the malignant potential of OPMDs with improved specificity and sensitivity. This would minimize the associated morbidities and mortalities of late detection of malignant changes that may progress to involve the head and neck region with metastasis.

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References

  1. Dhanuthai K, Rojanawatsirivej S, Thosaporn W, Kintarak S, Subarnbhesaj A, Darling M, Kryshtalskyj E, Chiang C-P, Shin H-I, Choi S-Y, Lee S-S, Aminishakib P. Oral cancer: a multicenter study. Med Oral Patol Oral Cir Bucal. 2018;23:e23–9. https://doi.org/10.4317/medoral.21999.

    Article  CAS  PubMed  Google Scholar 

  2. Warnakulasuriya S, Johnson NW, van der Waal I. Nomenclature and classification of potentially malignant disorders of the oral mucosa. J Oral Pathol Med. 2007;36:575–80. https://doi.org/10.1111/j.1600-0714.2007.00582.x.

    Article  CAS  PubMed  Google Scholar 

  3. Müller S. Update from the 4th edition of the World Health Organization of head and neck tumours: tumours of the oral cavity and mobile tongue. Head Neck Pathol. 2017;11:33–40. https://doi.org/10.1007/s12105-017-0792-3.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Mello FW, Miguel AFP, Dutra KL, Porporatti AL, Warnakulasuriya S, Guerra ENS, Rivero ERC. Prevalence of oral potentially malignant disorders: a systematic review and meta-analysis. J Oral Pathol Med. 2018;47:633–40. https://doi.org/10.1111/jop.12726.

    Article  PubMed  Google Scholar 

  5. Iocca O, Sollecito TP, Alawi F, Weinstein GS, Newman JG, De Virgilio A, Di Maio P, Spriano G, Pardiñas López S, Shanti RM. Potentially malignant disorders of the oral cavity and oral dysplasia: a systematic review and meta-analysis of malignant transformation rate by subtype. Head Neck. 2020;42:539–55. https://doi.org/10.1002/hed.26006.

    Article  PubMed  Google Scholar 

  6. Mortazavi H, Baharvand M, Mehdipour M. Oral potentially malignant disorders: an overview of more than 20 entities. J Dent Res Dent Clin Dent Prospects. 2014;8:6–14. https://doi.org/10.5681/joddd.2014.002.

    Article  PubMed  PubMed Central  Google Scholar 

  7. van der Waal I. Potentially malignant disorders of the oral and oropharyngeal mucosa; terminology, classification and present concepts of management. Oral Oncol. 2009;45:317–23. https://doi.org/10.1016/j.oraloncology.2008.05.016.

    Article  PubMed  Google Scholar 

  8. Petti S. Pooled estimate of world leukoplakia prevalence: a systematic review. Oral Oncol. 2003;39:770–80. https://doi.org/10.1016/S1368-8375(03)00102-7.

    Article  PubMed  Google Scholar 

  9. Kumar Srivastava V. To study the prevalence of premalignancies in teenagers having betel, gutkha, khaini, tobacco chewing, beedi and ganja smoking habit and their association with social class and education status. Int J Clin Pediatr Dent. 2014;7:86–92. https://doi.org/10.5005/jp-journals-10005-1243.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Vazquez-Alvarez R, Fernandez-Gonzalez F, Gandara-Vila P, Reboiras-Lopez D, Garcia-Garcia A, Gandara-Rey J. Correlation between clinical and pathologic diagnosis in oral leukoplakia in 54 patients. Med Oral Patol Oral Cir Bucal. 2010;15:e832–8. https://doi.org/10.4317/medoral.15.e832.

    Article  PubMed  Google Scholar 

  11. Warnakulasuriya S. Clinical features and presentation of oral potentially malignant disorders. Oral Surg Oral Med Oral Pathol Oral Radiol. 2018;125:582–90. https://doi.org/10.1016/j.oooo.2018.03.011.

    Article  PubMed  Google Scholar 

  12. Haya-Fernández MC, Bagán JV, Murillo-Cortés J, Poveda-Roda R, Calabuig C. The prevalence of oral leukoplakia in 138 patients with oral squamous cell carcinoma. Oral Dis. 2004;10:346–8. https://doi.org/10.1111/j.1601-0825.2004.01031.x.

    Article  PubMed  Google Scholar 

  13. Cerero-Lapiedra R, Baladé-Martínez D, Moreno-López L-A, Esparza-Gómez G, Bagán JV. Proliferative verrucous leukoplakia: a proposal for diagnostic criteria. Med Oral Patol Oral Cir Bucal. 2010;15:e839–45. http://www.ncbi.nlm.nih.gov/pubmed/20173704.

    Article  Google Scholar 

  14. Carrard VC, Brouns EREA, van der Waal I. Proliferative verrucous leukoplakia; a critical appraisal of the diagnostic criteria. Med Oral Patol Oral Cir Bucal. 2013;18:e411–3. https://doi.org/10.4317/medoral.18912.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Warnakulasuriya S, Ariyawardana A. Malignant transformation of oral leukoplakia: a systematic review of observational studies. J Oral Pathol Med. 2016;45:155–66. https://doi.org/10.1111/jop.12339.

    Article  CAS  PubMed  Google Scholar 

  16. Farah CS, Fox SA. Dysplastic oral leukoplakia is molecularly distinct from leukoplakia without dysplasia. Oral Dis. 2019;25:1715–23. https://doi.org/10.1111/odi.13156.

    Article  PubMed  Google Scholar 

  17. Nieto MA, Huang RY-J, Jackson RA, Thiery JP. EMT: 2016. Cell. 2016;166:21–45. https://doi.org/10.1016/j.cell.2016.06.028.

    Article  CAS  Google Scholar 

  18. Liu P-F, Kang B-H, Wu Y-M, Sun J-H, Yen L-M, Fu T-Y, Lin Y-C, Liou H-H, Lin Y-S, Sie H-C, Hsieh I-C, Tseng Y-K, Shu C-W, Hsieh Y-D, Ger L-P. Vimentin is a potential prognostic factor for tongue squamous cell carcinoma among five epithelial–mesenchymal transition-related proteins. PLoS One. 2017;12:e0178581. https://doi.org/10.1371/journal.pone.0178581.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Holmstrup P. Oral erythroplakia-what is it? Oral Dis. 2018;24:138–43. https://doi.org/10.1111/odi.12709.

    Article  CAS  PubMed  Google Scholar 

  20. Reichart PA, Philipsen HP. Oral erythroplakia – a review. Oral Oncol. 2005;41:551–61. https://doi.org/10.1016/j.oraloncology.2004.12.003.

    Article  PubMed  Google Scholar 

  21. Lapthanasupkul P, Poomsawat S, Punyasingh J. A clinicopathologic study of oral leukoplakia and erythroplakia in a Thai population. Quintessence Int. 2007;38:e448–55. http://www.ncbi.nlm.nih.gov/pubmed/17823667.

    PubMed  Google Scholar 

  22. Villa A, Villa C, Abati S. Oral cancer and oral erythroplakia: an update and implication for clinicians. Aust Dent J. 2011;56:253–6. https://doi.org/10.1111/j.1834-7819.2011.01337.x.

    Article  CAS  PubMed  Google Scholar 

  23. van der Waal I. Potentially malignant disorders of the oral and oropharyngeal mucosa; present concepts of management. Oral Oncol. 2010;46:423–5. https://doi.org/10.1016/j.oraloncology.2010.02.016.

    Article  PubMed  Google Scholar 

  24. Warnakulasuriya S, Reibel J, Bouquot J, Dabelsteen E. Oral epithelial dysplasia classification systems: predictive value, utility, weaknesses and scope for improvement. J Oral Pathol Med. 2008;37:127–33. https://doi.org/10.1111/j.1600-0714.2007.00584.x.

    Article  CAS  PubMed  Google Scholar 

  25. Yang SW, Lee YS, Chang LC, Hsieh TY, Chen TA. Outcome of excision of oral erythroplakia. Br J Oral Maxillofac Surg. 2015;53:142–7. https://doi.org/10.1016/j.bjoms.2014.10.016.

    Article  CAS  PubMed  Google Scholar 

  26. Mignogna MD, Fedele S. Oral cancer screening: 5 minutes to save a life. Lancet. 2005;365:1905–6. https://doi.org/10.1016/S0140-6736(05)66635-4.

    Article  PubMed  Google Scholar 

  27. Zain RB, Ikeda N, Gupta PC, Warnakulasuriya S, van Wyk CW, Shrestha P, Axéll T. Oral mucosal lesions associated with betel quid, areca nut and tobacco chewing habits: consensus from a workshop held in Kuala Lumpur, Malaysia, November 25–27, 1996. J Oral Pathol Med. 1999;28:1–4. https://doi.org/10.1111/j.1600-0714.1999.tb01985.x.

    Article  CAS  PubMed  Google Scholar 

  28. Cox SC, Walker DM. Oral submucous fibrosis. A review. Aust Dent J. 1996;41:294–9. https://doi.org/10.1111/j.1834-7819.1996.tb03136.x.

    Article  CAS  PubMed  Google Scholar 

  29. Paissat DK. Oral submucous fibrosis. Int J Oral Surg. 1981;10:307–12. https://doi.org/10.1016/s0300-9785(81)80026-9.

    Article  CAS  PubMed  Google Scholar 

  30. Chattopadhyay A, Ray JG. Molecular pathology of malignant transformation of oral submucous fibrosis. J Environ Pathol Toxicol Oncol. 2016;35:193–205. https://doi.org/10.1615/JEnvironPatholToxicolOncol.2016014024.

    Article  PubMed  Google Scholar 

  31. Pant I, Rao SG, Kondaiah P. Role of areca nut induced JNK/ATF2/Jun axis in the activation of TGF-β pathway in precancerous Oral Submucous Fibrosis. Sci Rep. 2016;6:34314. https://doi.org/10.1038/srep34314.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Hernandez BY, Zhu X, Goodman MT, Gatewood R, Mendiola P, Quinata K, Paulino YC. Betel nut chewing, oral premalignant lesions, and the oral microbiome. PLoS One. 2017;12:e0172196. https://doi.org/10.1371/journal.pone.0172196.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Lian I-B, Tseng Y-T, Su C-C, Tsai K-Y. Progression of precancerous lesions to oral cancer: results based on the Taiwan National Health Insurance Database. Oral Oncol. 2013;49:427–30. https://doi.org/10.1016/j.oraloncology.2012.12.004.

    Article  PubMed  Google Scholar 

  34. Haque MF, Harris M, Meghji S, Barrett AW. Immunolocalization of cytokines and growth factors in oral submucous fibrosis. Cytokine. 1998;10:713–9. https://doi.org/10.1006/cyto.1997.0342.

    Article  CAS  PubMed  Google Scholar 

  35. Chang M-C, Wu H-L, Lee J-J, Lee P-H, Chang H-H, Hahn L-J, Lin B-R, Chen Y-J, Jeng J-H. The induction of prostaglandin E2 production, interleukin-6 production, cell cycle arrest, and cytotoxicity in primary oral keratinocytes and KB cancer cells by areca nut ingredients is differentially regulated by MEK/ERK activation. J Biol Chem. 2004;279:50676–83. https://doi.org/10.1074/jbc.M404465200.

    Article  CAS  PubMed  Google Scholar 

  36. Khan I, Agarwal P, Thangjam GS, Radhesh R, Rao SG, Kondaiah P. Role of TGF-β and BMP7 in the pathogenesis of oral submucous fibrosis. Growth Factors. 2011;29:119–27. https://doi.org/10.3109/08977194.2011.582839.

    Article  CAS  PubMed  Google Scholar 

  37. Agarwal RK, Hebbale M, Mhapuskar A, Tepan M. Correlation of ultrasonographic measurements, histopathological grading, and clinical staging in oral submucous fibrosis. Indian J Dent Res. 2017;28:476–81. https://doi.org/10.4103/ijdr.IJDR_517_16.

    Article  PubMed  Google Scholar 

  38. Canniff JP, Harvey W, Harris M. Oral submucous fibrosis: its pathogenesis and management. Br Dent J. 1986;160:429–34. https://doi.org/10.1038/sj.bdj.4805876.

    Article  CAS  PubMed  Google Scholar 

  39. Kadani M, Satish BNVS, Maharudrappa B, Prashant KM, Hugar D, Allad U, Prabhu PS. Evaluation of plasma fibrinogen degradation products and total serum protein concentration in oral submucous fibrosis. J Clin Diagn Res. 2014;8:ZC54–7. https://doi.org/10.7860/JCDR/2014/9061.4385.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Sur TK, Biswas TK, Ali L, Mukherjee B. Anti-inflammatory and anti-platelet aggregation activity of human placental extract. Acta Pharmacol Sin. 2003;24:187–92. http://www.ncbi.nlm.nih.gov/pubmed/12546729.

    CAS  PubMed  Google Scholar 

  41. Kakar PK, Puri RK, Venkatachalam VP. Oral submucous fibrosis – treatment with hyalase. J Laryngol Otol. 1985;99:57–9. https://doi.org/10.1017/s0022215100096286.

    Article  CAS  PubMed  Google Scholar 

  42. Haque MF, Meghji S, Nazir R, Harris M. Interferon gamma (IFN-gamma) may reverse oral submucous fibrosis. J Oral Pathol Med. 2001;30:12–21. https://doi.org/10.1034/j.1600-0714.2001.300103.x.

    Article  CAS  PubMed  Google Scholar 

  43. Kumar A, Bagewadi A, Keluskar V, Singh M. Efficacy of lycopene in the management of oral submucous fibrosis. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2007;103:207–13. https://doi.org/10.1016/j.tripleo.2006.07.011.

    Article  PubMed  Google Scholar 

  44. Liu J, Chen F, Wei Z, Qiu M, Li Z, Dan H, Chen Q, Jiang L. Evaluating the efficacy of pentoxifylline in the treatment of oral submucous fibrosis: a meta-analysis. Oral Dis. 2018;24:706–16. https://doi.org/10.1111/odi.12715.

    Article  CAS  PubMed  Google Scholar 

  45. Nayak DR, Mahesh SG, Aggarwal D, Pavithran P, Pujary K, Pillai S. Role of KTP-532 laser in management of oral submucous fibrosis. J Laryngol Otol. 2009;123:418–21. https://doi.org/10.1017/S0022215108003642.

    Article  CAS  PubMed  Google Scholar 

  46. Chaudhry Z, Gupta SR, Oberoi SS. The efficacy of ErCr:YSGG laser fibrotomy in management of moderate oral submucous fibrosis: a preliminary study. J Maxillofac Oral Surg. 2014;13:286–94. https://doi.org/10.1007/s12663-013-0511-x.

    Article  PubMed  Google Scholar 

  47. Alsarraf AH, Kujan O, Farah CS. The utility of oral brush cytology in the early detection of oral cancer and oral potentially malignant disorders: a systematic review. J Oral Pathol Med. 2018;47:104–16. https://doi.org/10.1111/jop.12660.

    Article  Google Scholar 

  48. Fitzpatrick SG, Hirsch SA, Gordon SC. The malignant transformation of oral lichen planus and oral lichenoid lesions. J Am Dent Assoc. 2014;145:45–56. https://doi.org/10.14219/jada.2013.10.

    Article  PubMed  Google Scholar 

  49. Gómez I, Seoane J, Varela-Centelles P, Diz P, Takkouche B. Is diagnostic delay related to advanced-stage oral cancer? A meta-analysis. Eur J Oral Sci. 2009;117:541–6. https://doi.org/10.1111/j.1600-0722.2009.00672.x.

    Article  PubMed  Google Scholar 

  50. Silverman S, Gorsky M, Lozada F. Oral leukoplakia and malignant transformation. A follow-up study of 257 patients. Cancer. 1984;53:563–8. https://doi.org/10.1002/1097-0142(19840201)53:3<563::aid-cncr2820530332>3.0.co;2-f.

    Article  PubMed  Google Scholar 

  51. Warnakulasuriya S, Kovacevic T, Madden P, Coupland VH, Sperandio M, Odell E, Møller H. Factors predicting malignant transformation in oral potentially malignant disorders among patients accrued over a 10-year period in South East England. J Oral Pathol Med. 2011;40:677–83. https://doi.org/10.1111/j.1600-0714.2011.01054.x.

    Article  CAS  PubMed  Google Scholar 

  52. Torezan LAR, Festa-Neto C. Cutaneous field cancerization: clinical, histopathological and therapeutic aspects. An Bras Dermatol. 2013;88:775–86. https://doi.org/10.1590/abd1806-4841.20132300.

    Article  PubMed  PubMed Central  Google Scholar 

  53. Warnakulasuriya S. Oral potentially malignant disorders: a comprehensive review on clinical aspects and management. Oral Oncol. 2020;102:104550. https://doi.org/10.1016/j.oraloncology.2019.104550.

    Article  PubMed  Google Scholar 

  54. Downer MC, Moles DR, Palmer S, Speight PM. A systematic review of test performance in screening for oral cancer and precancer. Oral Oncol. 2004;40:264–73. https://doi.org/10.1016/j.oraloncology.2003.08.013.

    Article  PubMed  Google Scholar 

  55. Awan KH, Morgan PR, Warnakulasuriya S. Assessing the accuracy of autofluorescence, chemiluminescence and toluidine blue as diagnostic tools for oral potentially malignant disorders – a clinicopathological evaluation. Clin Oral Investig. 2015;19:2267–72. https://doi.org/10.1007/s00784-015-1457-9.

    Article  CAS  PubMed  Google Scholar 

  56. Speight PM, Khurram SA, Kujan O. Oral potentially malignant disorders: risk of progression to malignancy. Oral Surg Oral Med Oral Pathol Oral Radiol. 2018;125:612–27. https://doi.org/10.1016/j.oooo.2017.12.011.

    Article  PubMed  Google Scholar 

  57. Seoane Lestón J, Diz Dios P. Diagnostic clinical aids in oral cancer. Oral Oncol. 2010;46:418–22. https://doi.org/10.1016/j.oraloncology.2010.03.006.

    Article  PubMed  Google Scholar 

  58. Lingen MW, Kalmar JR, Karrison T, Speight PM. Critical evaluation of diagnostic aids for the detection of oral cancer. Oral Oncol. 2008;44:10–22. https://doi.org/10.1016/j.oraloncology.2007.06.011.

    Article  Google Scholar 

  59. Du G-F, Li C-Z, Chen H-Z, Chen X-M, Xiao Q, Cao Z-G, Shang S-H, Cai X. Rose Bengal staining in detection of oral precancerous and malignant lesions with colorimetric evaluation: a pilot study. Int J Cancer. 2007;120:1958–63. https://doi.org/10.1002/ijc.22467.

    Article  CAS  PubMed  Google Scholar 

  60. Mittal N, Palaskar S, Shankari M. Rose Bengal staining – diagnostic aid for potentially malignant and malignant disorders: a pilot study. Indian J Dent Res. 2012;23:561–4. https://doi.org/10.4103/0970-9290.107326.

    Article  PubMed  Google Scholar 

  61. Chaudhari A, Hegde-Shetiya S, Shirahatti R, Agrawal D. Comparison of different screening methods in estimating the prevalence of precancer and cancer amongst male inmates of a jail in Maharashtra, India. Asian Pac J Cancer Prev. 2013;14:859–64. https://doi.org/10.7314/apjcp.2013.14.2.859.

    Article  PubMed  Google Scholar 

  62. Pallagatti S, Sheikh S, Aggarwal A, Gupta D, Singh R, Handa R, Kaur S, Mago J. Toluidine blue staining as an adjunctive tool for early diagnosis of dysplastic changes in the oral mucosa. J Clin Exp Dent. 2013;5:e187–91. https://doi.org/10.4317/jced.51121.

    Article  PubMed  PubMed Central  Google Scholar 

  63. Riaz A, Shreedhar B, Kamboj M, Natarajan S. Methylene blue as an early diagnostic marker for oral precancer and cancer. Springerplus. 2013;2:95. https://doi.org/10.1186/2193-1801-2-95.

    Article  PubMed  PubMed Central  Google Scholar 

  64. Gandolfo S, Pentenero M, Broccoletti R, Pagano M, Carrozzo M, Scully C. Toluidine blue uptake in potentially malignant oral lesions in vivo: clinical and histological assessment. Oral Oncol. 2006;42:89–95. https://doi.org/10.1016/j.oraloncology.2005.06.016.

    Article  CAS  PubMed  Google Scholar 

  65. Driemel O, Kunkel M, Hullmann M, von Eggeling F, Müller-Richter U, Kosmehl H, Reichert TE. Diagnosis of oral squamous cell carcinoma and its precursor lesions. J Dtsch Dermatol Ges. 2007;5:1095–100. https://doi.org/10.1111/j.1610-0387.2007.06397.x.

    Article  PubMed  Google Scholar 

  66. Macey R, Walsh T, Brocklehurst P, Kerr AR, Liu JLY, Lingen MW, Ogden GR, Warnakulasuriya S, Scully C. Diagnostic tests for oral cancer and potentially malignant disorders in patients presenting with clinically evident lesions. Cochrane Database Syst Rev. 2015;2015(5):CD010276. https://doi.org/10.1002/14651858.CD010276.pub2.

    Article  PubMed Central  Google Scholar 

  67. Sambandham T, Masthan KMK, Kumar MS, Jha A. The application of vizilite in oral cancer. J Clin Diagn Res. 2013;7:185–6. https://doi.org/10.7860/JCDR/2012/5163.2704.

    Article  PubMed  PubMed Central  Google Scholar 

  68. Rajmohan M, Rao UK, Joshua E, Rajasekaran ST, Kannan R. Assessment of oral mucosa in normal, precancer and cancer using chemiluminescent illumination, toluidine blue supravital staining and oral exfoliative cytology. J Oral Maxillofac Pathol. 2012;16:325–9. https://doi.org/10.4103/0973-029X.102476.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. McIntosh L, McCullough MJ, Farah CS. The assessment of diffused light illumination and acetic acid rinse (Microlux/DL) in the visualisation of oral mucosal lesions. Oral Oncol. 2009;45:e227–31. https://doi.org/10.1016/j.oraloncology.2009.08.001.

    Article  CAS  PubMed  Google Scholar 

  70. Awan KH, Morgan PR, Warnakulasuriya S. Utility of chemiluminescence (ViziLite™) in the detection of oral potentially malignant disorders and benign keratoses. J Oral Pathol Med. 2011;40:541–4. https://doi.org/10.1111/j.1600-0714.2011.01048.x.

    Article  CAS  PubMed  Google Scholar 

  71. 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 Pathol Med. 2015;44:307–28. https://doi.org/10.1111/jop.12218.

    Article  CAS  PubMed  Google Scholar 

  72. Farah CS, McIntosh L, Georgiou A, McCullough MJ. Efficacy of tissue autofluorescence imaging (VELscope) in the visualization of oral mucosal lesions. Head Neck. 2012;34:856–62. https://doi.org/10.1002/hed.21834.

    Article  PubMed  Google Scholar 

  73. 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. https://doi.org/10.1155/2013/194029.

    Article  PubMed  PubMed Central  Google Scholar 

  74. Balevi B. Evidence-based decision making: should the general dentist adopt the use of the VELscope for routine screening for oral cancer? J Can Dent Assoc. 2007;73:603–6. http://www.ncbi.nlm.nih.gov/pubmed/17868507.

    PubMed  Google Scholar 

  75. Moro A, Di Nardo F, Boniello R, Marianetti TM, Cervelli D, Gasparini G, Pelo S. Autofluorescence and early detection of mucosal lesions in patients at risk for oral cancer. J Craniofac Surg. 2010;21:1899–903. https://doi.org/10.1097/SCS.0b013e3181f4afb4.

    Article  PubMed  Google Scholar 

  76. Mercadante V, Paderni C, Campisi G. Novel non-invasive adjunctive techniques for early oral cancer diagnosis and oral lesions examination. Curr Pharm Des. 2012;18:5442–51. https://doi.org/10.2174/138161212803307626.

    Article  CAS  PubMed  Google Scholar 

  77. Figueira JA, Veltrini VC. Photodynamic therapy in oral potentially malignant disorders-critical literature review of existing protocols. Photodiagn Photodyn Ther. 2017;20:125–9. https://doi.org/10.1016/j.pdpdt.2017.09.007.

    Article  CAS  Google Scholar 

  78. Hopper C. Photodynamic therapy: a clinical reality in the treatment of cancer. Lancet Oncol. 2000;1:212–9. https://doi.org/10.1016/s1470-2045(00)00166-2.

    Article  CAS  PubMed  Google Scholar 

  79. Zhu TC, Finlay JC. The role of photodynamic therapy (PDT) physics. Med Phys. 2008;35:3127–36. https://doi.org/10.1118/1.2937440.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Li Y, Wang B, Zheng S, He Y. Photodynamic therapy in the treatment of oral leukoplakia: a systematic review. Photodiagn Photodyn Ther. 2019;25:17–22. https://doi.org/10.1016/j.pdpdt.2018.10.023.

    Article  CAS  Google Scholar 

  81. Jin X, Xu H, Deng J, Dan H, Ji P, Chen Q, Zeng X. Photodynamic therapy for oral potentially malignant disorders. Photodiagn Photodyn Ther. 2019;28:146–52. https://doi.org/10.1016/j.pdpdt.2019.08.005.

    Article  CAS  Google Scholar 

  82. Gondivkar SM, Gadbail AR, Choudhary MG, Vedpathak PR, Likhitkar MS. Photodynamic treatment outcomes of potentially-malignant lesions and malignancies of the head and neck region: a systematic review. J Investig Clin Dent. 2018;9:e12270. https://doi.org/10.1111/jicd.12270.

    Article  Google Scholar 

  83. Wu C, Gleysteen J, Teraphongphom NT, Li Y, Rosenthal E. In-vivo optical imaging in head and neck oncology: basic principles, clinical applications and future directions. Int J Oral Sci. 2018;10:10. https://doi.org/10.1038/s41368-018-0011-4.

    Article  PubMed  PubMed Central  Google Scholar 

  84. Stephen MM, Jayanthi JL, Unni NG, Kolady PE, Beena VT, Jeemon P, Subhash N. Diagnostic accuracy of diffuse reflectance imaging for early detection of pre-malignant and malignant changes in the oral cavity: a feasibility study. BMC Cancer. 2013;13:278. https://doi.org/10.1186/1471-2407-13-278.

    Article  PubMed  PubMed Central  Google Scholar 

  85. Green B, Tsiroyannis C, Brennan PA. Optical diagnostic systems for assessing head and neck lesions. Oral Dis. 2016;22:180–4. https://doi.org/10.1111/odi.12398.

    Article  CAS  PubMed  Google Scholar 

  86. Krishna H, Majumder SK, Chaturvedi P, Sidramesh M, Gupta PK. In vivo Raman spectroscopy for detection of oral neoplasia: a pilot clinical study. J Biophotonics. 2014;7:690–702. https://doi.org/10.1002/jbio.201300030.

    Article  CAS  PubMed  Google Scholar 

  87. Green B, Cobb ARM, Brennan PA, Hopper C. Optical diagnostic techniques for use in lesions of the head and neck: review of the latest developments. Br J Oral Maxillofac Surg. 2014;52:675–80. https://doi.org/10.1016/j.bjoms.2014.06.010.

    Article  PubMed  Google Scholar 

  88. Chen X-J, Zhang X-Q, Liu Q, Zhang J, Zhou G. Nanotechnology: a promising method for oral cancer detection and diagnosis. J Nanobiotechnology. 2018;16:52. https://doi.org/10.1186/s12951-018-0378-6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Wetzel SL, Wollenberg J. Oral potentially malignant disorders. Dent Clin N Am. 2020;64:25–37. https://doi.org/10.1016/j.cden.2019.08.004.

    Article  PubMed  Google Scholar 

  90. Dancyger A, Heard V, Huang B, Suley C, Tang D, Ariyawardana A. Malignant transformation of actinic cheilitis: a systematic review of observational studies. J Investig Clin Dent. 2018;9:e12343. https://doi.org/10.1111/jicd.12343.

    Article  PubMed  Google Scholar 

  91. Miller KD, Siegel RL, Lin CC, Mariotto AB, Kramer JL, Rowland JH, Stein KD, Alteri R, Jemal A. Cancer treatment and survivorship statistics, 2016. CA Cancer J Clin. 2016;66:271–89. https://doi.org/10.3322/caac.21349.

    Article  PubMed  Google Scholar 

  92. Foy J-P, Bertolus C, Saintigny P. Oral cancer prevention worldwide: challenges and perspectives. Oral Oncol. 2019;88:91–4. https://doi.org/10.1016/j.oraloncology.2018.11.008.

    Article  PubMed  Google Scholar 

  93. Warnakulasuriya S. Potentially malignant disorders of the oral cavity. In: Textbook of oral cancer. Cham: Springer; 2020. p. 141–58. https://doi.org/10.1007/978-3-030-32316-5_12.

    Chapter  Google Scholar 

  94. Vogelstein B, Lane D, Levine AJ. Surfing the p53 network. Nature. 2000;408:307–10. https://doi.org/10.1038/35042675.

    Article  CAS  PubMed  Google Scholar 

  95. Goldstein I, Marcel V, Olivier M, Oren M, Rotter V, Hainaut P. Understanding wild-type and mutant p53 activities in human cancer: new landmarks on the way to targeted therapies. Cancer Gene Ther. 2011;18:2–11. https://doi.org/10.1038/cgt.2010.63.

    Article  CAS  PubMed  Google Scholar 

  96. Scholzen T, Gerdes J. The Ki-67 protein: from the known and the unknown. J Cell Physiol. 2000;182:311–22. https://doi.org/10.1002/(SICI)1097-4652(200003)182:3<311::AID-JCP1>3.0.CO;2-9.

    Article  CAS  PubMed  Google Scholar 

  97. Pelosi G, Massa F, Gatti G, Righi L, Volante M, Birocco N, Maisonneuve P, Sonzogni A, Harari S, Albini A, Papotti M. Ki-67 evaluation for clinical decision in metastatic lung carcinoids: a proof of concept. Clin Pathol. 2019;12:2632010X19829259. https://doi.org/10.1177/2632010X19829259.

    Article  PubMed  PubMed Central  Google Scholar 

  98. Niotis A, Tsiambas E, Fotiades PP, Ragos V, Polymeneas G. Ki-67 and topoisomerase IIa proliferation markers in colon adenocarcinoma. J BUON. 2018;23:24–7. http://www.ncbi.nlm.nih.gov/pubmed/30722108.

    PubMed  Google Scholar 

  99. Mello FW, Melo G, Guerra ENS, Warnakulasuriya S, Garnis C, Rivero ERC. Oral potentially malignant disorders: a scoping review of prognostic biomarkers. Crit Rev Oncol Hematol. 2020;153:102986. https://doi.org/10.1016/j.critrevonc.2020.102986.

    Article  PubMed  Google Scholar 

  100. Mei Y, Zhang P, Zuo H, Clark D, Xia R, Li J, Liu Z, Mao L. Ebp1 activates podoplanin expression and contributes to oral tumorigenesis. Oncogene. 2014;33:3839–50. https://doi.org/10.1038/onc.2013.354.

    Article  CAS  PubMed  Google Scholar 

  101. Martin-Villar E, Megias D, Castel S, Yurrita MM, Vilaro S, Quintanilla M. Podoplanin binds ERM proteins to activate RhoA and promote epithelial-mesenchymal transition. J Cell Sci. 2006;119:4541–53. https://doi.org/10.1242/jcs.03218.

    Article  CAS  PubMed  Google Scholar 

  102. Suzuki-Inoue K, Osada M, Ozaki Y. Physiologic and pathophysiologic roles of interaction between C-type lectin-like receptor 2 and podoplanin: partners from in utero to adulthood. J Thromb Haemost. 2017;15:219–29. https://doi.org/10.1111/jth.13590.

    Article  CAS  PubMed  Google Scholar 

  103. Danielsen HE, Pradhan M, Novelli M. Revisiting tumour aneuploidy – the place of ploidy assessment in the molecular era. Nat Rev Clin Oncol. 2016;13:291–304. https://doi.org/10.1038/nrclinonc.2015.208.

    Article  CAS  PubMed  Google Scholar 

  104. Zaini ZM, McParland H, Møller H, Husband K, Odell EW. Predicting malignant progression in clinically high-risk lesions by DNA ploidy analysis and dysplasia grading. Sci Rep. 2018;8:15874. https://doi.org/10.1038/s41598-018-34165-5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  105. Siebers TJH, Bergshoeff VE, Otte-Höller I, Kremer B, Speel EJM, van der Laak JAWM, Merkx MAW, Slootweg PJ. Chromosome instability predicts the progression of premalignant oral lesions. Oral Oncol. 2013;49:1121–8. https://doi.org/10.1016/j.oraloncology.2013.09.006.

    Article  CAS  PubMed  Google Scholar 

  106. Bradley G, Odell EW, Raphael S, Ho J, Le LW, Benchimol S, Kamel-Reid S. Abnormal DNA content in oral epithelial dysplasia is associated with increased risk of progression to carcinoma. Br J Cancer. 2010;103:1432–42. https://doi.org/10.1038/sj.bjc.6605905.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  107. Nayak S, Goel MM, Makker A, Bhatia V, Chandra S, Kumar S, Agarwal SP. Fibroblast growth factor (FGF-2) and its receptors FGFR-2 and FGFR-3 may be putative biomarkers of malignant transformation of potentially malignant oral lesions into oral squamous cell carcinoma. PLoS One. 2015;10:e0138801. https://doi.org/10.1371/journal.pone.0138801.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  108. Poh CF, Zhu Y, Chen E, Berean KW, Wu L, Zhang L, Rosin MP. Unique FISH patterns associated with cancer progression of oral dysplasia. J Dent Res. 2012;91:52–7. https://doi.org/10.1177/0022034511425676.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  109. Taoudi Benchekroun M, Saintigny P, Thomas SM, El-Naggar AK, Papadimitrakopoulou V, Ren H, Lang W, Fan Y-H, Huang J, Feng L, Lee JJ, Kim ES, Hong WK, Johnson FM, Grandis JR, Mao L. Epidermal growth factor receptor expression and gene copy number in the risk of oral cancer. Cancer Prev Res (Phila). 2010;3:800–9. https://doi.org/10.1158/1940-6207.CAPR-09-0163.

    Article  CAS  Google Scholar 

  110. Foy J-P, Bertolus C, Ortiz-Cuaran S, Albaret M-A, Williams WN, Lang W, Destandau S, De Souza G, Sohier E, Kielbassa J, Thomas E, Deneuve S, Goudot P, Puisieux A, Viari A, Mao L, Caux C, Lippman S, Saintigny P. Immunological and classical subtypes of oral premalignant lesions. Onco Targets Ther. 2018;7:e1496880. https://doi.org/10.1080/2162402X.2018.1496880.

    Article  Google Scholar 

  111. William WN, Papadimitrakopoulou V, Lee JJ, Mao L, Cohen EEW, Lin HY, Gillenwater AM, Martin JW, Lingen MW, Boyle JO, Shin DM, Vigneswaran N, Shinn N, Heymach JV, Wistuba II, Tang X, Kim ES, Saintigny P, Blair EA, Meiller T, Gutkind JS, Myers J, El-Naggar A, Lippman SM. Erlotinib and the risk of oral cancer. JAMA Oncol. 2016;2:209. https://doi.org/10.1001/jamaoncol.2015.4364.

    Article  PubMed  PubMed Central  Google Scholar 

  112. Sarode GS, Sarode SC, Maniyar N, Sharma N, Yerwadekar S, Patil S. Recent trends in predictive biomarkers for determining malignant potential of oral potentially malignant disorders. Oncol Rev. 2019;13:424. https://doi.org/10.4081/oncol.2019.424.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  113. El-Sakka H, Kujan O, Farah CS. Assessing miRNAs profile expression as a risk stratification biomarker in oral potentially malignant disorders: a systematic review. Oral Oncol. 2018;77:57–82. https://doi.org/10.1016/j.oraloncology.2017.11.021.

    Article  CAS  PubMed  Google Scholar 

  114. von Elm E, Altman DG, Egger M, Pocock SJ, Gøtzsche PC, Vandenbroucke JP. The strengthening the reporting of observational studies in epidemiology (STROBE) statement: guidelines for reporting observational studies. Int J Surg. 2014;12:1495–9. https://doi.org/10.1016/j.ijsu.2014.07.013.

    Article  Google Scholar 

  115. Moher D, Hopewell S, Schulz KF, Montori V, Gøtzsche PC, Devereaux PJ, Elbourne D, Egger M, Altman DG. CONSORT 2010 explanation and elaboration: updated guidelines for reporting parallel group randomised trials. Int J Surg. 2012;10:28–55. https://doi.org/10.1016/j.ijsu.2011.10.001.

    Article  PubMed  Google Scholar 

  116. McCullough MJ, Prasad G, Farah CS. Oral mucosal malignancy and potentially malignant lesions: an update on the epidemiology, risk factors, diagnosis and management. Aust Dent J. 2010;55(Suppl 1):61–5. https://doi.org/10.1111/j.1834-7819.2010.01200.x.

    Article  PubMed  Google Scholar 

  117. Kujan O, Oliver RJ, Khattab A, Roberts SA, Thakker N, Sloan P. Evaluation of a new binary system of grading oral epithelial dysplasia for prediction of malignant transformation. Oral Oncol. 2006;42:987–93. https://doi.org/10.1016/j.oraloncology.2005.12.014.

    Article  PubMed  Google Scholar 

  118. Ranganathan K, Kavitha L. Oral epithelial dysplasia: classifications and clinical relevance in risk assessment of oral potentially malignant disorders. J Oral Maxillofac Pathol. 2019;23:19–27. https://doi.org/10.4103/jomfp.JOMFP_13_19.

    Article  PubMed  PubMed Central  Google Scholar 

  119. Mehrotra R, Gupta A, Singh M, Ibrahim R. Retraction: application of cytology and molecular biology in diagnosing premalignant or malignant oral lesions. Mol Cancer. 2012;11:57. https://doi.org/10.1186/1476-4598-11-57.

    Article  PubMed Central  Google Scholar 

  120. Casparis S, Borm JM, Tomic MA, Burkhardt A, Locher MC. Transepithelial brush biopsy – oral CDx® – a noninvasive method for the early detection of precancerous and cancerous lesions. J Clin Diagn Res. 2014;8:222–6. https://doi.org/10.7860/JCDR/2014/7659.4065.

    Article  Google Scholar 

  121. Lingen MW, Tampi MP, Urquhart O, Abt E, Agrawal N, Chaturvedi AK, Cohen E, D’Souza G, Gurenlian J, Kalmar JR, Kerr AR, Lambert PM, Patton LL, Sollecito TP, Truelove E, Banfield L, Carrasco-Labra A. Adjuncts for the evaluation of potentially malignant disorders in the oral cavity: diagnostic test accuracy systematic review and meta-analysis-a report of the American Dental Association. J Am Dent Assoc. 2017;148:797–813.e52. https://doi.org/10.1016/j.adaj.2017.08.045.

    Article  PubMed  PubMed Central  Google Scholar 

  122. Liu D, Zhao X, Zeng X, Dan H, Chen Q. Non-invasive techniques for detection and diagnosis of oral potentially malignant disorders. Tohoku J Exp Med. 2016;238:165–77. https://doi.org/10.1620/tjem.238.165.

    Article  CAS  PubMed  Google Scholar 

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Alkofahi, H., Ebrahimi, M. (2021). Potentially Malignant Disorders of the Oral Cavity. In: El Assal, R., Gaudilliere, D., Connelly, S.T. (eds) Early Detection and Treatment of Head & Neck Cancers. Springer, Cham. https://doi.org/10.1007/978-3-030-69852-2_2

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