Introduction to Oral Cancer

  • Prashanth PantaEmail author
  • Dimitrios Andreadis


Oral cancer is the 6th most common type of human cancer with a 5-year survival rate approximately 50%, and its formation occurs in multiple steps. In the majority of cases, a well-established, preventable risk factor is involved. Several potentially malignant disorders precede oral cancer, each of them showing a well-defined clinical presentation. Spotting such precursor lesions should be no challenge to experienced clinicians. The 2017 World Health Organization (WHO) classification system on “oral potentially malignant disorders” is also presented here. Potentially malignant disorders encompass habit associated conditions, immune-mediated and inflammatory disorders, and also conditions that may arise due to solar radiation like actinic cheilitis and also genetic disorders like dyskeratosis congenita. Like in other cancer models, studies have focused on oral cancer stem cell population as the cancer-initiating cells and hidden culprits. Besides tobacco and alcohol, viruses (HPV), nutritional deficiencies, mechanical trauma and galvanic phenomenon, candidal infection, and inherited mutations are now established etiological or synergistic factors that cannot be underestimated in the genesis and progress of oral cancer. This chapter deals with common risk factors and oral potentially malignant disorders.


Oral cancer Oral squamous cell carcinoma Oral potentially malignant disorders Oral dysplasia Oral cancer stem cells 


  1. 1.
    India Project Team of the International Cancer Genome Consortium. Mutational landscape of gingivo-buccal oral squamous cell carcinoma reveals new recurrently-mutated genes and molecular subgroups. Nat Commun. 2013;4:2873.CrossRefGoogle Scholar
  2. 2.
    Stadler ME, Patel MR, Couch ME, Hayes DN. Molecular biology of head neck Cancer: risks and pathways. Hematol Oncol Clin North Am. 2008;22:1099–124.CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Chen R-J, Chang LW, Lin P, Wang Y-J. Epigenetic effects and molecular mechanisms of tumorigenesis induced by cigarette smoke: an overview. J Oncol. 2011;2011:654931.CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Farsalinos KE, Polosa R. Safety evaluation and risk assessment of electronic cigarettes as tobacco cigarette substitutes: a systematic review. Ther Adv Drug Saf. 2014;5:67–86.CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Rosenquist K. Risk factors in oral and oropharyngeal squamous cell carcinoma: a population-based case-control study in southern Sweden. Swed Dent J Suppl. 2005;179:1–66.Google Scholar
  6. 6.
    Boyle JO, Gümüs ZH, Kacker A, Choksi VL, Bocker JM, Zhou XK, et al. Effects of cigarette smoke on the human oral mucosal transcriptome. Cancer Prev Res (Phila). 2010;3:266–78.CrossRefGoogle Scholar
  7. 7.
    Amaral-Silva GK, Martins MD, Pontes HA, Fregnani ER, Lopes MA, Fonseca FP et al. Mismatch repair system proteins in oral benign and malignant lesions. J Oral Pathol Med. 2017;46:241–5.Google Scholar
  8. 8.
    Gupta B, Johnson NW. Systematic review and meta-analysis of association of smokeless tobacco and of betel quid without tobacco with incidence of oral cancer in South Asia and the Pacific. PLoS One. 2014;9:e113385.CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Liu Y, Chen H, Sun Z, Chen X. Molecular mechanisms of ethanol-associated Oro-esophageal squamous cell carcinoma. Cancer Lett. 2015;361:164–73.CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Urvalek AM, Osei-Sarfo K, Tang X-H, Zhang T, Scognamiglio T, Gudas LJ. Identification of ethanol and 4-Nitroquinoline-1-oxide induced epigenetic and oxidative stress markers during oral cavity carcinogenesis. Alcohol Clin Exp Res. 2015;39:1360–72.CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Khan I, Kumar N, Pant I, Narra S, Kondaiah P. Activation of TGF-β pathway by Areca nut constituents: a possible cause of oral Submucous fibrosis. PLoS One. 2012;7:e51806.CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Mohammed F, Manohar V, Jose M, Thapasum AF, Mohamed S, Shamaz BH, et al. Estimation of copper in saliva and areca nut products and its correlation with histological grades of oral submucous fibrosis. J Oral Pathol Med. 2015;44:208–13.CrossRefPubMedGoogle Scholar
  13. 13.
    Bodner L, Manor E, Friger MD, van der Waal I. Oral squamous cell carcinoma in patients twenty years of age or younger—review and analysis of 186 reported cases. Oral Oncol. 2014;50:84–9.CrossRefPubMedGoogle Scholar
  14. 14.
    Soudry E, Preis M, Hod R, Hamzany Y, Hader T, Bahar G, et al. Squamous cell carcinoma of the oral tongue in patients younger than 30 years: clinicopathologic features and outcome. Clin Otolaryngol. 2010;35:307–12.Google Scholar
  15. 15.
    Ames BN, Wakimoto P. Are vitamin and mineral deficiencies a major cancer risk? Nat Rev Cancer. 2002;2:694–704.CrossRefPubMedGoogle Scholar
  16. 16.
    Lawal AO, Kolude B, Adeyemi BF, Lawoyin JO, Akang EE. Serum antioxidant vitamins and the risk of oral cancer in patients seen at a tertiary institution in Nigeria. Niger J Clin Pract. 2012;15:30–3.CrossRefPubMedGoogle Scholar
  17. 17.
    Athirajan V, Razak IA, Thurairajah N, Ghani WM, Ching HN, Yang YH. High serum level of retinol and α-tocopherol affords protection against oral cancer in a multiethnic population. Asian Pac J Cancer Prev. 2014;15:8183–9.CrossRefPubMedGoogle Scholar
  18. 18.
    de Munter L, Maasland DH, van den Brandt PA, Kremer B, Schouten LJ. Vitamin and carotenoid intake and risk of head-neck cancer subtypes in the Netherlands cohort study. Am J Clin Nutr. 2015;102:420–32.CrossRefPubMedGoogle Scholar
  19. 19.
    Edefonti V, Hashibe M, Parpinel M, Turati F, Serraino D, Matsuo K, et al. Natural vitamin C intake and the risk of head and neck cancer: a pooled analysis in the international head and neck Cancer epidemiology consortium. Int J Cancer. 2015;137:448–62.CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Li Q, Chuang SC, Eluf-Neto J, Menezes A, Matos E, Koifman S, et al. Vitamin or mineral supplement intake and the risk of head and neck cancer: pooled analysis in the INHANCE consortium. Int J Cancer. 2012;131:1686–99.CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Jayaprakash V, Reid M, Hatton E, Merzianu M, Rigual N, Marshall J, Gill S, Frustino J, Wilding G, Loree T, Popat S, Sullivan M. Human papillomavirus types 16 and 18 in epithelial dysplasia of oral cavity and oropharynx: a meta-analysis, 1985–2010. Oral Oncol. 2011;47:1048–54.CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Gupta K, Metgud R. Evidences suggesting involvement of viruses in oral squamous cell carcinoma. Patholog Res Int. 2013;2013:642496.PubMedPubMedCentralGoogle Scholar
  23. 23.
    Miller CS, Johnstone BM. Human papillomavirus as a risk factor for oral squamous cell carcinoma: a meta-analysis, 1982-1997. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2001;91:622–35.CrossRefPubMedGoogle Scholar
  24. 24.
    Fornatora M, Jones AC, Kerpel S, Freedman P. Human papillomavirus-associated oral epithelial dysplasia (koilocytic dysplasia) an entity of unknown biologic potential. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 1996;82:47–56.CrossRefPubMedGoogle Scholar
  25. 25.
    D'Souza G, Kreimer AR, Viscidi R, Pawlita M, Fakhry C, Koch WM, Westra WH, Gillison ML. Case-control study of human papillomavirus and oropharyngeal cancer. N Engl J Med. 2007;356:1944–56.CrossRefPubMedGoogle Scholar
  26. 26.
    Holtzman AL, Medicine HKIC. Human papillomavirus-associated oropharyngeal squamous-cell carcinoma. N Engl J Med. 2016;375:1269.CrossRefPubMedGoogle Scholar
  27. 27.
    Boscolo-Rizzo P, Del Mistro A, Bussu F, Lupato V, Baboci I, Almadori G, et al. New insights into human papillomavirus-associated head and neck squamous cell carcinoma. Acta Otorhinolaryngol Ital. 2013;33:77–87.PubMedPubMedCentralGoogle Scholar
  28. 28.
    Kian Ang K, Harris J, Wheeler R, Weber R, Rosenthal DI, Nguyen-Tân PF, et al. Human papillomavirus and survival of patients with oropharyngeal cancer. N Engl J Med. 2010;363:24–35.CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    Kashyap RR, Kashyap RS. Self-inflicted injury as a potential trigger for carcinoma of lip—a case report. Gerodontology. 2013;30:236–8.CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    Fan H, Yoon K-Y, Kim S-M, Myoung H, Lee J-H, Kim M-J. Relationship between squamous cell carcinoma of the tongue and the position of dental prosthesis. J Adv Prosthodont. 2015;7:129–37.CrossRefPubMedPubMedCentralGoogle Scholar
  31. 31.
    Piemonte ED, Lazos JP, Brunotto M. Relationship between chronic trauma of the oral mucosa, oral potentially malignant disorders and oral cancer. J Oral Pathol Med. 2010;39:513–7.PubMedPubMedCentralGoogle Scholar
  32. 32.
    Albuquerque RP, Richards A. Images in clinical medicine. Squamous-cell carcinoma of the tongue. N Engl J Med. 2016;374:e32.CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    Panta P, Sarode SC, Sarode GS, Patil S. ‘Chronic traumatic ulcer of lateral tongue’- An underestimated ‘oral potentially malignant disorder’? Oral Oncol. 2018;85:101–2.Google Scholar
  34. 34.
    Winn DM, Blot WJ, McLaughlin JK, Austin DF, Greenberg RS, Preston-Martin S, et al. Mouthwash use and oral conditions in the risk of oral and pharyngeal cancer. Cancer Res. 1991;51:3044–7.PubMedPubMedCentralGoogle Scholar
  35. 35.
    Damm DD, Curran A, White DK, Drummond JF. Leukoplakia of the maxillary vestibule—an association with Viadent? Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 1999;87:61–6.CrossRefPubMedPubMedCentralGoogle Scholar
  36. 36.
    Mascarenhas AK, Allen CM, Moeschberger ML. The association between Viadent use and oral leukoplakia—results of a matched case-control study. J Public Health Dent. 2002;62:158–62.CrossRefPubMedPubMedCentralGoogle Scholar
  37. 37.
    Shephard MK, Schifter M, Palme CE. Multiple oral squamous cell carcinomas associated with autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy. Oral Surg Oral Med Oral Pathol Oral Radiol. 2012;114:e36–42.CrossRefGoogle Scholar
  38. 38.
    Rosa DD, Pasqualotto AC, Denning DW. Chronic mucocutaneous candidiasis and oesophageal cancer. Med Mycol. 2008;46:85–91.CrossRefGoogle Scholar
  39. 39.
    Rautemaa R, Hietanen J, Niissalo S, Pirinen S, Perheentupa J. Oral and oesophageal squamous cell carcinoma—a complication or component of autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED, APS-I). Oral Oncol. 2007;43:607–13.CrossRefGoogle Scholar
  40. 40.
    McCullough M, Jaber M, Barrett AW, Bain L, Speight PM, Porter SR. Oral yeast carriage correlates with presence of oral epithelial dysplasia. Oral Oncol. 2002;38:391–3.CrossRefPubMedPubMedCentralGoogle Scholar
  41. 41.
    Bakri MM, Hussaini HM, Holmes AR, Cannon RD, Rich AM. Revisiting the association between candidal infection and carcinoma, particularly oral squamous cell carcinoma. J Oral Microbiol. 2010;2.Google Scholar
  42. 42.
    Van der Waal I. Potentially malignant disorders of the oral and oropharyngeal mucosa; present concepts of management. Oral Oncol. 2010;46:423–5.CrossRefPubMedPubMedCentralGoogle Scholar
  43. 43.
    WHO classification of head and neck tumours/edited by Adel K. El-Naggar, John K.C. Chan, Jennifer R. Grandis, Takashi Takata, Pieter J. Slootweg. 4th edition; Ninth; Lyon: International Agency for Research on Cancer, 2017.Google Scholar
  44. 44.
    Prime SS, Thakker NS, Pring M, Guest PG, Paterson ICA. Review of inherited cancer syndromes and their relevance to oral squamous cell carcinoma. Oral Oncol. 2001;37:1–16.CrossRefPubMedPubMedCentralGoogle Scholar
  45. 45.
    Sarode SC, Sarode GS, Karmarkar S, Tupkari JV. A new classification for potentially malignantdisorders of the oral cavity. Oral Oncol. 2011;47:920–1.CrossRefPubMedPubMedCentralGoogle Scholar
  46. 46.
    Warnakulasuriya S, Ariyawardana A. Malignant transformation of oral leukoplakia: a systematic review of observational studies. J Oral Pathol Med. 2016;45:155–66.CrossRefPubMedPubMedCentralGoogle Scholar
  47. 47.
    Anderson A, Ishak N. Marked variation in malignant transformation rates of oral leukoplakia. Evid Based Dent. 2015;16:102–3.CrossRefGoogle Scholar
  48. 48.
    Islam MN, Kornberg L, Veenker E, Cohen DM, Bhattacharyya I. Anatomic site based ploidy analysis of oral premalignant lesions. Head Neck Pathol. 2010;4:10–4.CrossRefGoogle Scholar
  49. 49.
    Pagin O, Santos PS d S, Del Neri NB, de Lima HG, Lara VS. The importance of a proper selection area to be biopsied in nodular leukoplakia: a case report. Acta Stomatol Croat. 2014;48:42–7.CrossRefPubMedPubMedCentralGoogle Scholar
  50. 50.
    Cerero-Lapiedra R, Baladé-Martínez D, Moreno-López LA, Esparza-Gómez G, Bagán JV. Proliferative verrucous leukoplakia: a proposal for diagnostic criteria. Med Oral Patol Oral Cir Bucal. 2010;15:e839–45.CrossRefGoogle Scholar
  51. 51.
    Bagán JV, Murillo J, Poveda R, Gavaldá C, Jiménez Y, Scully C. Proliferative verrucous leukoplakia: unusual locations of oral squamous cell carcinomas, and field cancerization as shown by the appearance of multiple OSCCs. Oral Oncol. 2004;40:440–3.CrossRefGoogle Scholar
  52. 52.
    Thomson PJ, Hamadah O. Cancerisation within the oral cavity: the use of 'field mapping biopsies' in clinical management. Oral Oncol. 2007;43:20–6.CrossRefGoogle Scholar
  53. 53.
    Bari S, Metgud R, Vyas Z, Tak A. An update on studies on etiological factors, disease progression, and malignant transformation in oral submucous fibrosis. J Cancer Res Ther. 2017;13:399–405.PubMedGoogle Scholar
  54. 54.
    Bathi RJ, Parveen S, Burde K. The role of gutka chewing in oral submucous fibrosis: a case-control study. Quintessence Int. 2009;40:e19–25.PubMedGoogle Scholar
  55. 55.
    Sharma A, Sahni P, Nayak MT, Singhvi A, Kumar R. Identification of the pattern of copper as an etiological factor in oral submucous fibrosis: a cytological study. J Exp Ther Oncol. 2014;10:317–23.PubMedGoogle Scholar
  56. 56.
    Ray JG, Ghosh R, Mallick D, Swain N, Gandhi P, Ram SS, et al. Correlation of trace elemental profiles in blood samples of Indian patients with leukoplakia and oral submucous fibrosis. Biol Trace Elem Res. 2011;144:295–305.CrossRefGoogle Scholar
  57. 57.
    Chiu CJ, Chang ML, Chiang CP, Hahn LJ, Hsieh LL, Chen CJ. Interaction of collagen-related genes and susceptibility to betel quid-induced oral submucous fibrosis. Cancer Epidemiol Biomark Prev. 2002;11:646–53.Google Scholar
  58. 58.
    Agrawal D, Gupta S, Agarwal D, Gupta OP, Agarwal M. Role of GSTM1 and GSTT1 polymorphism: susceptibility to oral submucous fibrosis in the north Indian population. Oncology. 2010;79:181–6.CrossRefPubMedGoogle Scholar
  59. 59.
    Chaudhuri SR, Mukherjee S, Paul RR, Haldar A, Chaudhuri K. CYP1AI and CYP2E1 gene polymorphisms may increase susceptibility to oral submucous fibrosis among betel quid chewers of eastern India. Gene. 2013;513:268–71.CrossRefPubMedGoogle Scholar
  60. 60.
    Ray JG, Ranganathan K, Chattopadhyay A. Malignant transformation of oral submucous fibrosis: overview of histopathological aspects. Oral Surg Oral Med Oral Pathol Oral Radiol. 2016;122:200–9.CrossRefPubMedGoogle Scholar
  61. 61.
    Ekanayaka RP, Tilakaratne WM. Oral submucous fibrosis: review on mechanisms of malignant transformation. Oral Surg Oral Med Oral Pathol Oral Radiol. 2016;122:192–9.CrossRefPubMedPubMedCentralGoogle Scholar
  62. 62.
    Jayasooriya PR, Nadeeka Jayasinghe KA, Mudiyanselage Tilakaratne W. Relationship between thickness of fibrosis and epithelial dysplasia in oral submucous fibrosis. J Investig Clin Dent. 2011;2:171–5.CrossRefPubMedPubMedCentralGoogle Scholar
  63. 63.
    Tilakaratne WM, Iqbal Z, Teh MT, Ariyawardana A, Pitiyage G, Cruchley A, et al. Upregulation of HIF-1alpha in malignant transformation of oral submucous fibrosis. J Oral Pathol Med. 2008;37:372–7.CrossRefPubMedPubMedCentralGoogle Scholar
  64. 64.
    Chaturvedi P, Vaishampayan SS, Nair S, Nair D, Agarwal JP, Kane SV, et al. Oral squamous cell carcinoma arising in background of oral submucous fibrosis: a clinicopathologically distinct disease. Head Neck. 2013;35:1404–9.PubMedPubMedCentralGoogle Scholar
  65. 65.
    Shirani S, Kargahi N, Razavi SM, Homayoni S. Epithelial dysplasia in oral cavity. Iran J Med Sci. 2014;39:406–17.PubMedPubMedCentralGoogle Scholar
  66. 66.
    Reichart PA, Philipsen HP. Oral erythroplakia—a review. Oral Oncol. 2005;41:551–61.CrossRefPubMedPubMedCentralGoogle Scholar
  67. 67.
    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.PubMedPubMedCentralGoogle Scholar
  68. 68.
    Villa A, Villa C, Abati S. Oral cancer and oral erythroplakia: an update and implication for clinicians. Aust Dent J. 2011;56:253–6.CrossRefPubMedGoogle Scholar
  69. 69.
    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.CrossRefPubMedGoogle Scholar
  70. 70.
    Pindborg JJ, Mehta FS, Gupta PC, Daftary DK, Smith CJ. Reverse smoking in Andhra Pradesh, India: a study of palatal lesions among 10,169 villagers. Br J Cancer. 1971;25:10–20.CrossRefPubMedPubMedCentralGoogle Scholar
  71. 71.
    Kim DS, Park SH, Kwon SB, Joo YH, Youn SW, Sohn UD, et al. Temperature regulates melanin synthesis in melanocytes. Arch Pharm Res. 2003;26:840–5.CrossRefPubMedGoogle Scholar
  72. 72.
    Sreenivasa Bharath T, Govind Raj N, Kumar AN, Saraswathi TR, Suresh Babu G, Ramanjaneya Raju P. Palatal changes of reverse smokers in a rural coastal Andhra population with review of literature. J Oral Maxillofac Pathol. 2015;19:182–7.CrossRefPubMedPubMedCentralGoogle Scholar
  73. 73.
    Reddy CR, Venkatarathnam G, Kameswari VR. Distribution of glands in the mucosa of the hard palate and its relation to carcinoma. J Oral Surg. 1976;34:232–6.PubMedGoogle Scholar
  74. 74.
    van der Eb MM, Leyten EM, Gavarasana S, Vandenbroucke JP, Kahn PM, Cleton FJ. Reverse smoking as a risk factor for palatal cancer: a cross-sectional study in rural Andhra Pradesh, India. Int J Cancer. 1993;54:754–8.CrossRefPubMedGoogle Scholar
  75. 75.
    Gupta S, Jawanda MK. Oral lichen planus: an update on etiology, pathogenesis, clinical presentation, diagnosis and management. Indian J Dermatol. 2015;60:222–9.CrossRefPubMedPubMedCentralGoogle Scholar
  76. 76.
    Lauritano D, Arrica M, Lucchese A, Valente M, Pannone G, Lajolo C, et al. Oral lichen planus clinical characteristics in Italian patients: a retrospective analysis. Head Face Med. 2016;12:18.CrossRefPubMedPubMedCentralGoogle Scholar
  77. 77.
    Ingafou M, Leao JC, Porter SR, Scully C. Oral lichen planus: a retrospective study of 690 British patients. Oral Dis. 2006;12:463–8.CrossRefPubMedGoogle Scholar
  78. 78.
    Alaizari NA, Al-Maweri SA, Al-Shamiri HM, Tarakji B, Shugaa-Addin B. Hepatitis C virus infections in oral lichen planus: a systematic review and meta-analysis. Aust Dent J. 2016;61:282–7.CrossRefPubMedGoogle Scholar
  79. 79.
    Roitberg-Tambur A, Friedmann A, Korn S, Markitziu A, Pisanti S, Safirman C, et al. Serologic and molecular analysis of the HLA system in Israeli Jewish patients with oral erosive lichen planus. Tissue Antigens. 1994;43:219–23.CrossRefPubMedGoogle Scholar
  80. 80.
    Rode M, Kogoj-Rode M. Malignant potential of the reticular form of oral lichen planus over a 25-year observation period in 55 patients from Slovenia. J Oral Sci. 2002;44:109–11.PubMedGoogle Scholar
  81. 81.
    Brant JM, Aguiar MC, Grandinetti HA, Rodrigues LV, Vasconcelos AC. A comparative study of apoptosis in reticular and erosive oral lichen planus. Braz Dent J. 2012;23:564–9.CrossRefPubMedGoogle Scholar
  82. 82.
    Lavanya N, Jayanthi P, Rao UK, Ranganathan K. Oral lichen planus: an update on pathogenesis and treatment. J Oral Maxillofac Pathol. 2011;15:127–32.CrossRefPubMedPubMedCentralGoogle Scholar
  83. 83.
    Zhang J, Zhou G. Green tea consumption: an alternative approach to managing oral lichen planus. Inflamm Res. 2012;61:535–9.CrossRefPubMedGoogle Scholar
  84. 84.
    Madhusudhan KS, Sharma R. Esophageal lichen planus: a case report and review of literature. Indian J Dermatol. 2008;53:26–7.CrossRefPubMedPubMedCentralGoogle Scholar
  85. 85.
    Chryssostalis A, Gaudric M, Terris B, Coriat R, Prat F, Chaussade S. Esophageal lichen planus: a series of eight cases including a patient with esophageal verrucous carcinoma. A case series. Endoscopy. 2008;40:764–8.CrossRefPubMedGoogle Scholar
  86. 86.
    Eisen D. The vulvovaginal-gingival syndrome of lichen planus. The clinical characteristics of 22 patients. Arch Dermatol. 1994;130:1379–82.CrossRefPubMedGoogle Scholar
  87. 87.
    Rogers RS 3rd, Eisen D. Erosive oral lichen planus with genital lesions: the vulvovaginal-gingival syndrome and the peno-gingival syndrome. Dermatol Clin. 2003;21:91–8. vi-viiCrossRefPubMedGoogle Scholar
  88. 88.
    Fang M, Zhang W, Chen Y, He Z. Malignant transformation of oral lichen planus: a retrospective study of 23 cases. Quintessence Int. 2009;40:235–42.PubMedGoogle Scholar
  89. 89.
    Markopoulos AK, Antoniades D, Papanayotou P, Trigonidis G. Malignant potential of oral lichen planus; a follow-up study of 326 patients. Oral Oncol. 1997;33:263–9.CrossRefPubMedGoogle Scholar
  90. 90.
    Eisen D. The clinical features, malignant potential, and systemic associations of oral lichen planus: a study of 723 patients. J Am Acad Dermatol. 2002;46:207–14.CrossRefPubMedGoogle Scholar
  91. 91.
    Gandolfo S, Richiardi L, Carrozzo M, Broccoletti R, Carbone M, Pagano M, et al. Risk of oral squamous cell carcinoma in 402 patients with oral lichen planus: a follow-up study in an Italian population. Oral Oncol. 2004;40:77–83.CrossRefPubMedGoogle Scholar
  92. 92.
    Fitzpatrick SG, Hirsch SA, Gordon SC. The malignant transformation of oral lichen planus and oral lichenoid lesions: a systematic review. J Am Dent Assoc. 2014;145:45–56.CrossRefPubMedGoogle Scholar
  93. 93.
    Van der Meij EH, Schepman KP, van der Waal I. The possible premalignant character of oral lichen planus and oral lichenoid lesions: a prospective study. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2003;96:164–71.CrossRefPubMedGoogle Scholar
  94. 94.
    Patil S, Rao RS, Sanketh DS, Warnakulasuriya S. Lichenoid dysplasia revisited—evidence from a review of Indian archives. J Oral Pathol Med. 2015;44:507–14.CrossRefPubMedGoogle Scholar
  95. 95.
    Ranginwala AM, Chalishazar MM, Panja P, Buddhdev KP, Kale HM. Oral discoid lupus erythematosus: a study of twenty-one cases. J Oral Maxillofac Pathol. 2012;16:368–73.CrossRefPubMedPubMedCentralGoogle Scholar
  96. 96.
    Schiödt M, Halberg P, Hentzer B. A clinical study of 32 patients with oral discoid lupus erythematosus. Int J Oral Surg. 1978;7:85–94.CrossRefPubMedGoogle Scholar
  97. 97.
    Schiødt M, Andersen L, Shear M, Smith CJ. Leukoplakia-like lesions developing in patients with oral discoid lupus erythematosus. Acta Odontol Scand. 1981;39:209–16.CrossRefPubMedGoogle Scholar
  98. 98.
    Jeffrey David Unsworth, Andrew Baldwin, and Louise Byrd. Systemic lupus erythematosus, pregnancy and carcinoma of the tongue. BMJ Case Rep. 2013; 2013: bcr2013008864.Google Scholar
  99. 99.
    Grimaldo-Carjevschi M, López-Labady J, Villarroel-Dorrego M. Squamous cell carcinoma on the palate in a patient with systemic lupus erythematosus: case report and review of literature. Lupus. 2011;20:519–22.CrossRefPubMedGoogle Scholar
  100. 100.
    Bernatsky S, Ramsey-Goldman R, Clarke AE. Malignancy in systemic lupus erythematosus: what have we learned? Best Pract Res Clin Rheumatol. 2009;23:539–47.CrossRefPubMedPubMedCentralGoogle Scholar
  101. 101.
    Bernatsky S, Boivin JF, Joseph L, Rajan R, Zoma A, Manzi S, et al. An international cohort study of cancer in systemic lupus erythematosus. Arthritis Rheum. 2005;52:1481–90.CrossRefPubMedGoogle Scholar
  102. 102.
    Wood NH, Khammissa R, Meyerov R, Lemmer J, Cheilitis LFA. A case report and a review of the literature. Eur J Dent. 2011;5:101–6.PubMedPubMedCentralGoogle Scholar
  103. 103.
    Lopes MLD d S, Júnior FL d S, Lima KC, de Oliveira PT, da Silveira ÉJD. Clinicopathological profile and management of 161 cases of actinic cheilitis. An Bras Dermatol. 2015;90:505–12.CrossRefPubMedPubMedCentralGoogle Scholar
  104. 104.
    Markopoulos A, Albanidou-Farmaki E, Kayavis I. Actinic cheilitis: clinical and pathologic characteristics in 65 cases. Oral Dis. 2004;10:212–6.CrossRefPubMedGoogle Scholar
  105. 105.
    Rossi R, Assad GB, Buggiani G, Lotti T. Photodynamic therapy: treatment of choice for actinic cheilitis? Dermatol Ther. 2008;21(5):412.CrossRefPubMedGoogle Scholar
  106. 106.
    Leuci S, Martina S, Adamo D, Ruoppo E, Santarelli A, Sorrentino R. Oral syphilis: a retrospective analysis of 12 cases and a review of the literature. Oral Dis. 2013;19:738–46.CrossRefPubMedGoogle Scholar
  107. 107.
    Cherniak W, Silverman M. Images in clinical medicine: syphilitic Gumma. N Engl J Med. 2014;371:667.CrossRefPubMedGoogle Scholar
  108. 108.
    Pires FR, da Silva PJ, Natal RF, Alves FA, Pinto CA, Rumayor A, et al. Clinicopathologic features, microvessel density, and immunohistochemical expression of ICAM-1 and VEGF in 15 cases of secondary syphilis with oral manifestations. Oral Surg Oral Med Oral Pathol Oral Radiol. 2016;121:274–81.Google Scholar
  109. 109.
    Dickenson AJ, Currie WJ, Avery BS. Screening for syphilis in patients with carcinoma of the tongue. Br J Oral Maxillofac Surg. 1995;33:319–20.CrossRefPubMedGoogle Scholar
  110. 110.
    Rahima S, Riyaz N, Latheef EN, Shyni PM.  Squamous cell carcinoma on a syphilitic gumma: a unique presentation. Indian J Sex Transm Dis. 2015;36:89–91.CrossRefGoogle Scholar
  111. 111.
    Atkinson JC, Harvey KE, Domingo DL, Trujillo MI, Guadagnini J-P, Gollins S, et al. Oral and dental phenotype of Dyskeratosis Congenita. Oral Dis. 2008;14:419–27.CrossRefPubMedPubMedCentralGoogle Scholar
  112. 112.
    Alter BP, Giri N, Savage SA, Rosenberg PS. Cancer in dyskeratosis congenita. Blood. 2009;113:6549–57.CrossRefPubMedPubMedCentralGoogle Scholar
  113. 113.
    Batista LF, Pech MF, Zhong FL, Nguyen HN, Xie KT, Zaug AJ, et al. Telomere shortening and loss of self-renewal in dyskeratosis congenita induced pluripotent stem cells. Nature. 2011;474:399–402.CrossRefPubMedPubMedCentralGoogle Scholar
  114. 114.
    Walne AJ, Vulliamy T, Beswick R, Kirwan M, Dokal I. TINF2 mutations result in very short telomeres: analysis of a large cohort of patients with dyskeratosis congenita and related bone marrow failure syndromes. Blood. 2008;112:3594–600.CrossRefPubMedPubMedCentralGoogle Scholar
  115. 115.
    Brandizzi D, Gandolfo M, Velazco ML, Cabrini RL, Lanfranchi HE. Clinical features and evolution of oral cancer: a study of 274cases in Buenos Aires, Argentina. Med Oral Patol Oral Cir Bucal. 2008;13:E544–8.PubMedGoogle Scholar
  116. 116.
    Macfarlane TV, Wirth T, Ranasinghe S, Ah-See KW, Renny N, Hurman D, et al. Head and neck Cancer pain: systematic review of prevalence and associated factors. J Oral Maxillofac Res. 2012;e1:3.Google Scholar
  117. 117.
    Gorsky M, Epstein JB, Oakley C, Le ND, Hay J, Stevenson-Moore P. Carcinoma of the tongue: a case series analysis of clinical presentation, risk factors, staging, and outcome. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2004;98:546–52.CrossRefPubMedGoogle Scholar
  118. 118.
    Pathak J, Swain N, Patel S, Poonja LS. Histopathological variants of oral squamous cell carcinoma-institutional case reports. J Oral Maxillofac Pathol. 2014;18:143–5.PubMedPubMedCentralGoogle Scholar
  119. 119.
    Pereira MC, Oliveira DT, Landman G, Kowalski LP. Histologic subtypes of oral squamous cell carcinoma: prognostic relevance. J Can Dent Assoc. 2007;73:339–44.PubMedGoogle Scholar
  120. 120.
    Peng Q, Wang Y, Quan H, Li Y, Tang Z. Oral verrucous carcinoma: from multifactorial etiology to diverse treatment regimens (review). Int J Oncol. 2016;49:59–73.CrossRefPubMedGoogle Scholar
  121. 121.
    Sonalika WG, Anand T. Oral verrucous carcinoma: a retrospective analysis for clinicopathologic features. J Cancer Res Ther. 2016;12:142–5.CrossRefPubMedGoogle Scholar
  122. 122.
    Terada T. Multiple verrucous carcinomas of the oral cavity. J Maxillofac Oral Surg. 2015;14:393–6.CrossRefPubMedGoogle Scholar
  123. 123.
    Samman M, Wood HM, Conway C, Stead L, Daly C, Chalkey R, et al. A novel genomic signature reclassifies an oral cancer subtype. Int J Cancer. 2015;137:2364–73.CrossRefPubMedGoogle Scholar
  124. 124.
    Hosseinpour S, Mashhadiabbas F, Ahsaie MG. Diagnostic biomarkers in oral verrucous carcinoma: a systematic review. Pathol Oncol Res. 2017;23:19–32.CrossRefPubMedGoogle Scholar
  125. 125.
    Fu TY, Tsai MH, Wang JS, Ger LP. Antioxidant enzymes in oral verrucous carcinoma. J Oral Pathol Med. 2017;46:46–9.Google Scholar
  126. 126.
    Pereira T, Shetty S, Dodal S, Tamgadge A. Verruciform xanthoma of the lip: a rarity. Indian Dermatol Online J. 2016;7:180–2.CrossRefPubMedPubMedCentralGoogle Scholar
  127. 127.
    Patil S, Warnakulasuriya S, Raj T, Sanketh DS, Rao RS. Exophytic oral verrucous hyperplasia: a new entity. J Investig Clin Dent. 2016;7:417–23.Google Scholar
  128. 128.
    Wang YP, Chen HM, Kuo RC, Yu CH, Sun A, Liu BY, et al. Oral verrucous hyperplasia: histologic classification, prognosis, and clinical implications. J Oral Pathol Med. 2009;38:651–6.CrossRefPubMedPubMedCentralGoogle Scholar
  129. 129.
    Sharma P, Wadhwan V, Aggarwal P, Sharma A. Oral verrucous hyperplasia versus oral verrucous carcinoma: a clinicopathologic dilemma revisited using p53 as immunohistochemical marker. J Oral Maxillofac Pathol. 2016;20:362–8.CrossRefPubMedPubMedCentralGoogle Scholar
  130. 130.
    Woo SB, Cashman EC, Lerman MA. Human papillomavirus-associated oral intraepithelial neoplasia. Mod Pathol. 2013;26:1288–97.CrossRefGoogle Scholar
  131. 131.
    Kobayashi T, Maruyama S, Cheng J, Ida-Yonemochi H, Yagi M, Takagi R, et al. Histopathological varieties of oral carcinoma in situ: diagnosis aided by immunohistochemistry dealing with the second basal cell layer as the proliferating center of oral mucosal epithelia. Pathol Int. 2010;60:156–66.CrossRefGoogle Scholar
  132. 132.
    Waldron CA, Shafer WG. Oral carcinoma in situ. Oral Surg Oral Med Oral Pathol. 1975;39:227–38.CrossRefGoogle Scholar
  133. 133.
    Matsumoto N, Kitano T, Oki H, Omagari D, Matsue Y, Okudera M, et al. Pigmented oral carcinoma in situ: a case report and literature review. Oral Surg Oral Med Oral Pathol Oral Radiol. 2014;118:e79–83.CrossRefGoogle Scholar
  134. 134.
    Arvanitidis E, Andreadis P, Andreadis D, Belazi M, Epivatianos A. Reviewing the oral carcinogenic process: key genetic events, growth factors and molecular signaling pathways. J Biol Res—Thessaloniki. 2011;16:313–36.Google Scholar
  135. 135.
    Akhter M, Hossain S, Rahman QB, Molla MR. A study on histological grading of oral squamous cell carcinoma and its co-relationship with regional metastasis. J Oral Maxillofac Pathol. 2011;15:168–76.CrossRefPubMedPubMedCentralGoogle Scholar
  136. 136.
    van Oijen MG. Slootweg PJ oral field cancerization: carcinogen-induced independent events or micrometastatic deposits? Cancer Epidemiol Biomark Prev. 2000;9:249–56.Google Scholar
  137. 137.
    Mohan M, Jagannathan N. Oral field cancerization: an update on current concepts. Oncol Rev. 2014;8:244.CrossRefPubMedPubMedCentralGoogle Scholar
  138. 138.
    Martin CL, Reshmi SC, Ried T, Gottberg W, Wilson JW, Reddy JK, et al. Chromosomal imbalances in oral squamous cell carcinoma. Examination of 31 cell lines and review of the literature. Oral Oncol. 2008;44:369–82.CrossRefPubMedGoogle Scholar
  139. 139.
    Thomson PJ. Field change and oral cancer: new evidence for widespread carcinogenesis? Int J Oral Maxillofac Surg. 2002;31:262–6.CrossRefPubMedGoogle Scholar
  140. 140.
    Major AG, Pitty LP, Farah CS. Cancer stem cell markers in head and neck squamous cell carcinoma. Stem Cells Int. 2013;2013:319489.CrossRefPubMedPubMedCentralGoogle Scholar
  141. 141.
    Prince ME, Sivanandan R, Kaczorowski A, Wolf GT, Kaplan MJ, Dalerba P, et al. Identification of a subpopulation of cells with cancer stem cell properties in head and neck squamous cell carcinoma. Proc Natl Acad Sci U S A. 2007;104:973–8.CrossRefPubMedPubMedCentralGoogle Scholar
  142. 142.
    Han J, Fujisawa T, Husain SR, Puri RK. Identification and characterization of cancer stem cells in human head and neck squamous cell carcinoma. BMC Cancer. 2014;14:173.CrossRefPubMedPubMedCentralGoogle Scholar
  143. 143.
    Okamoto A, Chikamatsu K, Sakakura K, Hatsushika K, Takahashi G, Masuyama K. Expansion and characterization of cancer stem-like cells in squamous cell carcinoma of the head and neck. Oral Oncol. 2009;45:633–9.CrossRefPubMedGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Oral Medicine and RadiologyMNR Dental College and HospitalSangareddyIndia
  2. 2.Department of Oral Medicine/PathologySchool of Dentistry, Aristotle University of ThessalonikiThessalonikiGreece

Personalised recommendations