Systemic Diseases with an Increased Risk of Oral Squamous Cell Carcinoma

  • Martina K. ShephardEmail author
  • Esther A. Hullah
Part of the Head and Neck Cancer Clinics book series (HNCC)


There is a growing awareness of the important relationships between systemic inflammatory diseases, infections, genetic disorders, medical therapies and cancer risk. A number of systemic disorders have been associated with an increased risk of head and neck squamous cell carcinoma. These include autoimmune conditions, genetic syndromes, infections, iatrogenic causes such as haematopoietic stem cell transplantation and graft-versus-host disease and rare associations including novel drugs. This chapter will discuss conditions which confer an increased risk of head and neck squamous cell carcinoma, as well as review the evidence for diseases which have been historically associated with oral cancer.


  1. 1.
    Eisenbarth GS, Gottlieb PA. Autoimmune polyendocrine syndromes. N Engl J Med. 2004;350(20):2068–79.PubMedCrossRefPubMedCentralGoogle Scholar
  2. 2.
    Perheentupa J. Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy. J Clin Endocrinol Metab. 2006;91(8):2843–50.PubMedCrossRefPubMedCentralGoogle Scholar
  3. 3.
    Husebye ES, Perheentupa J, Rautemaa R, Kämpe O. Clinical manifestations and management of patients with autoimmune polyendocrine syndrome type I. J Intern Med. 2009;265(5):514–29.PubMedCrossRefPubMedCentralGoogle Scholar
  4. 4.
    Betterle C, Greggio NA. Autoimmune polyglandular syndrome type 1. J Clin Endocrinol Metab. 1998;83(4):1049.PubMedCrossRefPubMedCentralGoogle Scholar
  5. 5.
    Shikama N, Nusspaumer G, Holländer GA. Clearing the AIRE: on the pathophysiological basis of the autoimmune polyendocrinopathy syndrometype-1. Endocrinol Metabol Clin N A. 2009;38(2):273–88.CrossRefGoogle Scholar
  6. 6.
    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(6):607–13.PubMedCrossRefPubMedCentralGoogle Scholar
  7. 7.
    Kisand K, Bøe Wolff AS, Podkrajšek KT, Tserel L, Link M, Kisand KV, et al. Chronic mucocutaneous candidiasis in APECED or thymoma patients correlates with autoimmunity to Th17-associated cytokines. J Exp Med. 2010;207(2):299–308.PubMedPubMedCentralCrossRefGoogle Scholar
  8. 8.
    Puel A, Döffinger R, Natividad A, Chrabieh M, Barcenas-Morales G, Picard C, et al. Autoantibodies against IL-17A, IL-17F, and IL-22 in patients with chronic mucocutaneous candidiasis and autoimmune polyendocrine syndrome type I. J Exp Med. 2010;207(2):291–7.PubMedPubMedCentralCrossRefGoogle Scholar
  9. 9.
    Perheentupa J. APS-I/APECED: the clinical disease and therapy. Endocrinol Metabol Clin N A. 2002;31(2):295–320. vi.CrossRefGoogle Scholar
  10. 10.
    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(6):e36–42.PubMedCrossRefPubMedCentralGoogle Scholar
  11. 11.
    Bockle BC, Wilhelm M, Muller H, Gotsch C, Sepp NT. Oral mucous squamous cell carcinoma—an anticipated consequence of autoimmune polyendocrinopathy- candidiasis-ectodermal dystrophy (APECED). J Am Dermatol. 2010;62(5):864–8.CrossRefGoogle Scholar
  12. 12.
    O’Grady JF, Reade PC. Candida albicans as a promoter of oral mucosal neoplasia. Carcinogenesis. 1992;13(5):783–6.PubMedCrossRefPubMedCentralGoogle Scholar
  13. 13.
    Uittamo J, Siikala E, Kaihovaara P, Salaspuro M, Rautemaa R. Chronic candidosis and oral cancer in APECED-patients: production of carcinogenic acetaldehyde from glucose and ethanol by Candida albicans. Int J Cancer. 2009;124(3):754–6.PubMedCrossRefPubMedCentralGoogle Scholar
  14. 14.
    Rautemaa R, Richardson M, Pfaller M, Koukila-Kahkola P, Perheentupa J, Saxen H. Decreased susceptibility of Candida albicans to azole antifungals: a complication of long-term treatment in autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) patients. J Antimicrob Chemother. 2007;60(4):889–92.PubMedCrossRefPubMedCentralGoogle Scholar
  15. 15.
    Schiødt M. Oral discoid lupus erythematosus. II. Skin lesions and systemic lupus erythematosus in sixty-six patients with 6-year follow-up. Oral Surg Oral Med Oral Pathol. 1984;57(2):177–80.PubMedCrossRefPubMedCentralGoogle Scholar
  16. 16.
    Tebbe B. Clinical course and prognosis of cutaneous lupus erythematosus. Clin Dermatol. 2004;22(2):121–4.PubMedCrossRefPubMedCentralGoogle Scholar
  17. 17.
    Siegel M, Lee SL. The epidemiology of systemic lupus erythematosus. Semin Arthritis Rheum. 1973;3(1):1–54.PubMedCrossRefPubMedCentralGoogle Scholar
  18. 18.
    Santiago-Casas Y, Vila LM, McGwin GJ, Cantor RS, Petri M, Ramsey-Goldman R, et al. Association of discoid lupus erythematosus with clinical manifestations and damage accrual in a multiethnic lupus cohort. Arthritis Care Res. 2012;64(5):704–12.CrossRefGoogle Scholar
  19. 19.
    Miot HA, Bartoli Miot LD, Haddad GR. Association between discoid lupus erythematosus and cigarette smoking. Dermatology. 2005;211(2):118–22.PubMedCrossRefPubMedCentralGoogle Scholar
  20. 20.
    Menzies S, O’Shea F, Galvin S, Wynne B. Oral manifestations of lupus. Ir J Med Sci. 2018;187:91.PubMedCrossRefPubMedCentralGoogle Scholar
  21. 21.
    Savage NW, Boras VV, Zaini ZM. Oral squamous cell carcinoma with discoid lupus erythematosus. Oral Oncol Extra. 2006;42(1):32–5.CrossRefGoogle Scholar
  22. 22.
    Achtman JC, Werth VP. Pathophysiology of cutaneous lupus erythematosus. Arthritis Res Ther. 2015;17:182.PubMedPubMedCentralCrossRefGoogle Scholar
  23. 23.
    Liu W, Shen Z-Y, Wang L-J, Hu Y-H, Shen X-M, Zhou Z-T, et al. Malignant potential of oral and labial chronic discoid lupus erythematosus: a clinicopathological study of 87 cases. Histopathology. 2011;59(2):292–8.PubMedCrossRefPubMedCentralGoogle Scholar
  24. 24.
    Frohnmayer D, Frohnmayer L, Guinan E, et al., editors. Fanconi anemia: guidelines for diagnosis and management. 4th ed. Eugene, OR: Fanconi Anemia Research Fund, Inc; 2014. Accessed 8 Mar 2017.Google Scholar
  25. 25.
    Mamrak NE, Shimamura A, Howlett NG. Recent discoveries in the molecular pathogenesis of the inherited bone marrow failure syndrome Fanconi anemia. Blood Rev. 2017;31:93.PubMedCrossRefPubMedCentralGoogle Scholar
  26. 26.
    Joenje H, Patel KJ. The emerging genetic and molecular basis of Fanconi anaemia. Nat Rev Genet. 2001;2(6):446–57.PubMedCrossRefPubMedCentralGoogle Scholar
  27. 27.
    Kutler DI, Singh B, Satagopan J, Batish SD, Berwick M. A 20-year perspective on the International Fanconi Anemia Registry (IFAR). Blood. 2003;101:1249.PubMedCrossRefPubMedCentralGoogle Scholar
  28. 28.
    Kutler DI, Patel KR, Auerbach AD, Kennedy J, Lach FP, Sanborn E, et al. Natural history and management of Fanconi anemia patients with head and neck cancer: a 10-year follow-up. Laryngoscope. 2015;126(4):870–9.PubMedPubMedCentralCrossRefGoogle Scholar
  29. 29.
    Romick-Rosendale LE, Lui VWY, Grandis JR, Wells SI. The Fanconi anemia pathway: Repairing the link between DNA damage and squamous cell carcinoma. Mutat Res. 2013;743-744:78–88.PubMedCrossRefPubMedCentralGoogle Scholar
  30. 30.
    Smith AR, Wagner JE. Current clinical management of Fanconi anemia. Expert Rev Hematol. 2014;5(5):513–22.CrossRefGoogle Scholar
  31. 31.
    Rosenberg PS. Risk of head and neck squamous cell cancer and death in patients with Fanconi anemia who did and did not receive transplants. Blood. 2005;105(1):67–73.PubMedCrossRefPubMedCentralGoogle Scholar
  32. 32.
    Schneider M, Chandler K, Tischkowitz M, Meyer S. Fanconi anaemia: genetics, molecular biology, and cancer - implications for clinical management in children and adults. Clin Genet. 2014;88(1):13–24.PubMedCrossRefPubMedCentralGoogle Scholar
  33. 33.
    Auerbach AD. Fanconi anemia and its diagnosis. Mutat Res. 2009;668(1-2):4–10.PubMedPubMedCentralCrossRefGoogle Scholar
  34. 34.
    Scheckenbach K, Wagenmann M, Freund M, Schipper J, Hanenberg H. Squamous cell carcinomas of the head and neck in fanconi anemia: risk, prevention, therapy, and the need for guidelines. Klin Padiatr. 2012;224(03):132–8.PubMedCrossRefPubMedCentralGoogle Scholar
  35. 35.
    Kutler DI, Auerbach AD, Satagopan J, Giampietro PF, Batish SD, Huvos AG, et al. High incidence of head and neck squamous cell carcinoma in patients with Fanconi anemia. Arch Otolaryngol Head Neck Surg. 2003;129(1):106–12.PubMedCrossRefGoogle Scholar
  36. 36.
    Rosenberg PS. Cancer incidence in persons with Fanconi anemia. Blood. 2002;101(3):822–6.PubMedCrossRefPubMedCentralGoogle Scholar
  37. 37.
    Alter BP. Cancer in Fanconi anemia, 1927-2001. Cancer. 2003;97(2):425–40.PubMedCrossRefGoogle Scholar
  38. 38.
    Reinhard H, Peters I, Gottschling S, Ebell W, Graf N. Squamous cell carcinoma of the tongue in a 13-year-old girl with Fanconi anemia. J Pediatr Hematol Oncol. 2007;29(7):488–91.PubMedCrossRefGoogle Scholar
  39. 39.
    Hashibe M, Brennan P, Benhamou S, Castellsague X, Chen C, Curado MP, et al. Alcohol drinking in never users of tobacco, cigarette smoking in never drinkers, and the risk of head and neck cancer: pooled analysis in the International Head and Neck Cancer Epidemiology Consortium. J Natl Cancer Inst. 2007;99(10):777–89.PubMedCrossRefGoogle Scholar
  40. 40.
    Iype EM, Pandey M, Mathew A, Thomas G, Sebastian P, Nair MK. Oral cancer among patients under the age of 35 years. J Postgrad Med. 2001;47(3):171–6.PubMedPubMedCentralGoogle Scholar
  41. 41.
    Amsterdam JT, Strawitz JG. Squamous cell carcinoma of the oral cavity in young adults. J Surg Oncol. 1982;19(2):65–8.PubMedCrossRefPubMedCentralGoogle Scholar
  42. 42.
    Birkeland AC. Postoperative clinical radiosensitivity in patients with fanconi anemia and head and neck squamous cell carcinoma. Arch Otolaryngol Head Neck Surg. 2011;137(9):930.PubMedPubMedCentralCrossRefGoogle Scholar
  43. 43.
    Alter BP, Joenje H, Oostra AB. Fanconi anemia: adult head and neck cancer and hematopoietic mosaicism. Arch Otolaryngol Head Neck Surg. 2005;131:635.PubMedCrossRefPubMedCentralGoogle Scholar
  44. 44.
    Masserot C, Peffault de Latour R, Rocha V, Leblanc T, Rigolet A, Pascal F, et al. Head and neck squamous cell carcinoma in 13 patients with Fanconi anemia after hematopoietic stem cell transplantation. Cancer. 2008;113(12):3315–22.PubMedCrossRefPubMedCentralGoogle Scholar
  45. 45.
    Marur S, D’Souza G, Westra WH, Forastiere AA. HPV-associated head and neck cancer: a virus-related cancer epidemic. Lancet Oncol. 2010;11(8):781–9. Available from: Scholar
  46. 46.
    Park JW, Pitot HC, Strati K, Spardy N, Duensing S, Grompe M, et al. Deficiencies in the fanconi anemia DNA damage response pathway increase sensitivity to HPV-associated head and neck cancer. Cancer Res. 2010;70(23):9959–68.PubMedPubMedCentralCrossRefGoogle Scholar
  47. 47.
    Liu GB, Chen J, Wu ZH, Zhao K-N. Association of human papillomavirus with Fanconi anemia promotes carcinogenesis in Fanconi anemia patients. Rev Med Virol. 2015;25(6):345–53.PubMedCrossRefPubMedCentralGoogle Scholar
  48. 48.
    Kutler DI, Wreesmann VB, Goberdhan A, Ben-Porat L, Satagopan J, Ngai I, et al. Human papillomavirus DNA and p53 polymorphisms in squamous cell carcinomas from Fanconi anemia patients. J Natl Cancer Inst. 2003;95(22):1718–21.PubMedCrossRefPubMedCentralGoogle Scholar
  49. 49.
    van Zeeburg HJT, Snijders PJF, Wu T, Gluckman E, Soulier J, Surralles J, et al. Clinical and molecular characteristics of squamous cell carcinomas from Fanconi anemia patients. J Natl Cancer Inst. 2008;100(22):1649–53.PubMedPubMedCentralCrossRefGoogle Scholar
  50. 50.
    Curtis RE, Rowlings PA, Deeg HJ, Shriner DA, Socie G, Travis LB, et al. Solid cancers after bone marrow transplantation. N Engl J Med. 1997;336(13):897–904.PubMedCrossRefPubMedCentralGoogle Scholar
  51. 51.
    Savage SA, Alter BP. Dyskeratosis congenita. Hematol Oncol Clin North Am. 2009;23(2):215–31.PubMedPubMedCentralCrossRefGoogle Scholar
  52. 52.
    Savage SA. Dyskeratosis congenita. In: Pagon RA, Adam MP, Ardinger HH, Wallace SE, Amemiya A, Bean L, et al., editors. GeneReviews®. Seattle, WA: University of Washington; 1993.Google Scholar
  53. 53.
    Bessler M, Wilson DB, Mason PJ. Dyskeratosis congenita. FEBS Lett. 2010;584(17):3831–8.PubMedPubMedCentralCrossRefGoogle Scholar
  54. 54.
    Alter BP, Giri N, Savage SA, Rosenberg PS. Cancer in dyskeratosis congenita. Blood. 2009;113(26):6549–57.PubMedPubMedCentralCrossRefGoogle Scholar
  55. 55.
    Kumar K, Shilpasree AS, Chaudhary M. Oral manifestations and molecular basis of oral genodermatoses: a review. J Clin Diagn Res. 2016;10(5):ZE08–12.PubMedPubMedCentralGoogle Scholar
  56. 56.
    Vulliamy T, Dokal I. Dyskeratosis congenita. Semin Hematol. 2006;43(3):157–66.PubMedCrossRefPubMedCentralGoogle Scholar
  57. 57.
    Sakiyama T, Kubo A. Hereditary palmoplantar keratoderma clinical and genetic differential diagnosis. J Dermatol. 2016;43(3):264–74.PubMedCrossRefPubMedCentralGoogle Scholar
  58. 58.
    Hennies HC, Hagedorn M, Reis A. Palmoplantar keratoderma in association with carcinoma of the esophagus maps to chromosome 17q distal to the keratin gene cluster. Genomics. 1995;29(2):537–40.PubMedCrossRefPubMedCentralGoogle Scholar
  59. 59.
    Fred HL, Gieser RG, Berry WR, Eiband JM. Keratosis palmaris et plantaris. Arch Intern Med. 1964;113:866–71.PubMedCrossRefPubMedCentralGoogle Scholar
  60. 60.
    Lucker GP, Van de Kerkhof PC, Steijlen PM. The hereditary palmoplantar keratoses: an updated review and classification. Br J Dermatol. 1994;131(1):1–14.PubMedCrossRefPubMedCentralGoogle Scholar
  61. 61.
    Ellis A, Risk JM, Maruthappu T, Kelsell DP. Tylosis with oesophageal cancer: diagnosis, management and molecular mechanisms. Orphanet J Rare Dis. 2015;10:126.PubMedPubMedCentralCrossRefGoogle Scholar
  62. 62.
    Ilhan M, Erbaydar T, Akdeniz N, Arslan S. Palmoplantar keratoderma is associated with esophagus squamous cell cancer in Van region of Turkey: a case control study. BMC Cancer. 2005;5:90.PubMedPubMedCentralCrossRefGoogle Scholar
  63. 63.
    Stevens HP, Kelsell DP, Bryant SP, Bishop DT, Spurr NK, Weissenbach J, et al. Linkage of an American pedigree with palmoplantar keratoderma and malignancy (palmoplantar ectodermal dysplasia type III) to 17q24. Literature survey and proposed updated classification of the keratodermas. Arch Dermatol. 1996;132(6):640–51.PubMedCrossRefPubMedCentralGoogle Scholar
  64. 64.
    Kraemer KH, DiGiovanna JJ. Xeroderma pigmentosum. In: Pagon RA, Adam K, Ardinger HH, Wallace SE, Amemiya A, Bean L, et al., editors. GeneReviews®. Seattle, WA: University of Washington; 1993.Google Scholar
  65. 65.
    Lengauer C, Kinzler KW, Vogelstein B. Genetic instabilities in human cancers. Nature. 1998;396(6712):643–9.CrossRefGoogle Scholar
  66. 66.
    Butt FMA, Moshi JR, Owibingire S, Chindia ML. Xeroderma pigmentosum: a review and case series. J Craniomaxillofac Surg. 2010;38(7):534–7.PubMedCrossRefPubMedCentralGoogle Scholar
  67. 67.
    Fassihi H, Sethi M, Fawcett H, Wing J, Chandler N, Mohammed S, et al. Deep phenotyping of 89 xeroderma pigmentosum patients reveals unexpected heterogeneity dependent on the precise molecular defect. Proc Natl Acad Sci U S A. 2016;113(9):E1236–45.PubMedPubMedCentralCrossRefGoogle Scholar
  68. 68.
    Black JO. Xeroderma pigmentosum. Head Neck Pathol. 2016;10(2):139–44.PubMedPubMedCentralCrossRefGoogle Scholar
  69. 69.
    Dignan FL, Clark A, Amrolia P, Cornish J, Jackson G, Mahendra P, et al. Diagnosis and management of acute graft-versus-host disease. Br J Haematol. 2012;158(1):30–45.PubMedCrossRefPubMedCentralGoogle Scholar
  70. 70.
    Flowers MED, Inamoto Y, Carpenter PA, Lee SJ, Kiem H-P, Petersdorf EW, et al. Comparative analysis of risk factors for acute graft-versus-host disease and for chronic graft-versus-host disease according to National Institutes of Health consensus criteria. Blood. 2011;117(11):3214–9.PubMedPubMedCentralCrossRefGoogle Scholar
  71. 71.
    Dignan FL, Amrolia P, Clark A, Cornish J, Jackson G, Mahendra P, et al. Diagnosis and management of chronic graft-versus-host disease. Br J Haematol. 2012;158(1):46–61.PubMedCrossRefPubMedCentralGoogle Scholar
  72. 72.
    Zecca M. Chronic graft-versus-host disease in children: incidence, risk factors, and impact on outcome. Blood. 2002;100(4):1192–200.PubMedCrossRefPubMedCentralGoogle Scholar
  73. 73.
    Rizzo JD, Curtis RE, Socie G, Sobocinski KA, Gilbert E. Solid cancers after allogeneic hematopoietic cell transplantation. Blood. 2009;113:1175.PubMedPubMedCentralCrossRefGoogle Scholar
  74. 74.
    Dhir S, Slatter M, Skinner R. Recent advances in the management of graft-versus-host disease. Arch Dis Child. 2014;99(12):1150–7.PubMedCrossRefPubMedCentralGoogle Scholar
  75. 75.
    Mays JW, Fassil H, Edwards DA, Pavletic SZ, Bassim CW. Oral chronic graft-versus-host disease: current pathogenesis, therapy, and research. Oral Dis. 2012;19(4):327–46.PubMedPubMedCentralCrossRefGoogle Scholar
  76. 76.
    Sandmaier BM, Mackinnon S, Childs RW. Reduced intensity conditioning for allogeneic hematopoietic cell transplantation: current perspectives. Biol Blood Marrow Transplant. 2007;13(1 Suppl 1):87–97.PubMedPubMedCentralCrossRefGoogle Scholar
  77. 77.
    Mawardi H, Elad S, Correa ME, Stevenson K, Woo S-B, Almazrooa S, et al. Oral epithelial dysplasia and squamous cell carcinoma following allogeneic hematopoietic stem cell transplantation: clinical presentation and treatment outcomes. Bone Marrow Transplant. 2011;46(6):884–91.PubMedPubMedCentralCrossRefGoogle Scholar
  78. 78.
    Khan FM, Sy S, Louie P, Ugarte-Torres A, Berka N, Sinclair GD, et al. Genomic instability after allogeneic hematopoietic cell transplantation is frequent in oral mucosa, particularly in patients with a history of chronic graft-versus-host disease, and rare in nasal mucosa. Blood. 2010;116(10):1803–6.PubMedCrossRefPubMedCentralGoogle Scholar
  79. 79.
    Janin A, Murata H, Leboeuf C, Cayuela J-M, Gluckman E, Legrès L, et al. Donor-derived oral squamous cell carcinoma after allogeneic bone marrow transplantation. Blood. 2009;113(8):1834–40.PubMedCrossRefPubMedCentralGoogle Scholar
  80. 80.
    Jagasia MH, Greinix HT, Arora M, Williams KM, Wolff D, Cowen EW, et al. National Institutes of Health consensus development project on criteria for clinical trials in chronic graft-versus-host disease: I. The 2014 diagnosis and staging working group report. Biol Blood Marrow Transplant. 2015;21(3):389–401.e1.PubMedCrossRefPubMedCentralGoogle Scholar
  81. 81.
    Treister N, Duncan C, Cutler C, Lehmann L. How we treat oral chronic graft-versus-host disease. Blood. 2012;120(17):3407–18.PubMedCrossRefPubMedCentralGoogle Scholar
  82. 82.
    Filipovich AH, Weisdorf D, Pavletic S, Socie G, Wingard JR, Lee SJ, et al. National Institutes of Health consensus development project on criteria for clinical trials in chronic graft-versus-host disease: I. Diagnosis and staging working group report. Biol Blood Marrow Transplant. 2005;11(12):945–56.PubMedCrossRefPubMedCentralGoogle Scholar
  83. 83.
    Filipovich AH. Diagnosis and manifestations of chronic graft-versus-host disease. Best Pract Res Clin Haematol. 2008;21(2):251–7.PubMedCrossRefPubMedCentralGoogle Scholar
  84. 84.
    Choi SW, Reddy P. Current and emerging strategies for the prevention of graft-versus-host disease. Nat Rev Clin Oncol. 2014;11(9):536–47.PubMedPubMedCentralCrossRefGoogle Scholar
  85. 85.
    Lee SJ, Vogelsang G, Flowers MED. Chronic graft-versus-host disease. Biol Blood Marrow Transplant. 2003;9(4):215–33.PubMedCrossRefPubMedCentralGoogle Scholar
  86. 86.
    Ho VT, Soiffer RJ. The history and future of T-cell depletion as graft-versus-host disease prophylaxis for allogeneic hematopoietic stem cell transplantation. Blood. 2001;98(12):3192–204.PubMedCrossRefPubMedCentralGoogle Scholar
  87. 87.
    Dignan FL, Scarisbrick JJ, Cornish J, Clark A, Amrolia P, Jackson G, et al. Organ-specific management and supportive care in chronic graft-versus-host disease. Br J Haematol. 2012;158(1):62–78.PubMedCrossRefPubMedCentralGoogle Scholar
  88. 88.
    Greinix HT, van Besien K, Elmaagacli AH, Hillen U, Grigg A, Knobler R, et al. Progressive improvement in cutaneous and extracutaneous chronic graft-versus-host disease after a 24-week course of extracorporeal photopheresis—results of a crossover randomized study. Biol Blood Marrow Transplant. 2011;17(12):1775–82.PubMedCrossRefPubMedCentralGoogle Scholar
  89. 89.
    Curtis RE. Impact of chronic GVHD therapy on the development of squamous-cell cancers after hematopoietic stem-cell transplantation: an international case-control study. Blood. 2005;105(10):3802–11.PubMedPubMedCentralCrossRefGoogle Scholar
  90. 90.
    Leisenring W, Friedman DL, Flowers MED, Schwartz JL, Deeg HJ. Nonmelanoma skin and mucosal cancers after hematopoietic cell transplantation. J Clin Oncol. 2006;24(7):1119–26.PubMedCrossRefPubMedCentralGoogle Scholar
  91. 91.
    Bhatia S, Louie AD, Bhatia R, O’Donnell MR, Fung H, Kashyap A, et al. Solid cancers after bone marrow transplantation. J Clin Oncol. 2001;19(2):464–71.PubMedCrossRefPubMedCentralGoogle Scholar
  92. 92.
    Majhail NS, Rizzo JD, Lee SJ, Aljurf M, Atsuta Y, Bonfim C, et al. Recommended screening and preventive practices for long-term survivors after hematopoietic cell transplantation. Bone Marrow Transplant. 2012;47(3):337–41.PubMedPubMedCentralCrossRefGoogle Scholar
  93. 93.
    Grulich AE, van Leeuwen MT, Falster MO, Vajdic CM. Incidence of cancers in people with HIV/AIDS compared with immunosuppressed transplant recipients: a meta-analysis. Lancet. 2007;370:59.PubMedCrossRefPubMedCentralGoogle Scholar
  94. 94.
    Flaitz CM, Nichols CM, Adler-Storthz K, Hicks MJ. Intraoral squamous cell carcinoma in human immunodeficiency virus infection. A clinicopathologic study. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 1995;80(1):55–62.PubMedCrossRefPubMedCentralGoogle Scholar
  95. 95.
    Singh B. Alterations in head and neck cancer occurring in HIV-infected patients: results of a pilot, longitudinal, prospective study. Acta Oncol. 1999;38(8):1047–50.PubMedCrossRefPubMedCentralGoogle Scholar
  96. 96.
    Roland JT, Rothstein SG, Mittal KR, Perksy MS. Squamous cell carcinoma in HIV-positive patients under age 45. Laryngoscope. 2006;103(5):509–11.Google Scholar
  97. 97.
    Butt FMA, Chindia ML, Rana F. Oral squamous cell carcinoma in human immunodeficiency virus positive patients: clinicopathological audit. J Laryngol Otol. 2011;126(03):276–8.PubMedCrossRefPubMedCentralGoogle Scholar
  98. 98.
    UNAIDS Core Epidemiology [Internet]. Accessed 29 Mar 2017. Available from:
  99. 99.
    England PH. HIV diagnoses, late diagnoses and numbers accessing treatment and care. London: Public Health England; 2016.Google Scholar
  100. 100.
    Adler MW, Edwards SG, Miller RF, Sethi G, Williams I. ABC of HIV and AIDS. London: BMJ Books; 2012.Google Scholar
  101. 101.
    Centers for Disease Control and Prevention. Revised surveillance case definition for HIV infection--United States, 2014. MMWR Recommend Rep. 2014;63(RR-03):1–10.Google Scholar
  102. 102.
    Frisch M, Biggar RJ, Engels EA, Goedert JJ. AIDS-Cancer Match Registry Study Group. Association of cancer with AIDS-related immunosuppression in adults. JAMA. 2001;285(13):1736–45.PubMedCrossRefPubMedCentralGoogle Scholar
  103. 103.
    Engels EA, Biggar RJ, Hall HI, Cross H, Crutchfield A, Finch JL, et al. Cancer risk in people infected with human immunodeficiency virus in the United States. Int J Cancer. 2008;123(1):187–94.PubMedCrossRefPubMedCentralGoogle Scholar
  104. 104.
    Clifford GM, Polesel J, Rickenbach M, on behalf of the Swiss HIV Cohort Study, Dal Maso L, Keiser O, et al. Cancer risk in the Swiss HIV cohort study: associations with immunodeficiency, smoking, and highly active antiretroviral therapy. J Natl Cancer Inst. 2005;97(6):425–32.PubMedCrossRefPubMedCentralGoogle Scholar
  105. 105.
    Hessol NA, Pipkin S, Schwarcz S, Cress RD, Bacchetti P, Scheer S. The impact of highly active antiretroviral therapy on non-AIDS-defining cancers among adults with AIDS. Am J Epidemiol. 2007;165(10):1143–53.PubMedCrossRefPubMedCentralGoogle Scholar
  106. 106.
    Singh B, Balwally AN, Shaha AR, Rosenfeld RM, Har-El G, Lucente FE. Upper aerodigestive tract squamous cell carcinoma. The human immunodeficiency virus connection. Arch Otolaryngol Head Neck Surg. 1996;122(6):639–43.PubMedCrossRefPubMedCentralGoogle Scholar
  107. 107.
    Butt FMA, Chindia ML, Rana F, Machigo FG. Pattern of head and neck malignant neoplasms in HIV-infected patients in Kenya. Int J Oral Maxillofac Surg. 2008;37(10):907–11.PubMedCrossRefPubMedCentralGoogle Scholar
  108. 108.
    Winstone TA, Man SFP, Hull M, Montaner JS, Sin DD. Epidemic of lung cancer in patients with HIV infection. Chest. 2013;143(2):305–14.PubMedPubMedCentralCrossRefGoogle Scholar
  109. 109.
    Deeken JF, Tjen-A-Looi A, Rudek MA, Okuliar C, Young M, Little RF, et al. The rising challenge of non-AIDS-defining cancers in HIV-infected patients. Clin Infect Dis. 2012;55(9):1228–35.PubMedPubMedCentralCrossRefGoogle Scholar
  110. 110.
    Beachler DC, DʼSouza G. Oral human papillomavirus infection and head and neck cancers in HIV-infected individuals. Curr Opin Oncol. 2013;25(5):503–10.PubMedPubMedCentralCrossRefGoogle Scholar
  111. 111.
    Beachler DC, Weber KM, Margolick JB, Strickler HD, Cranston RD, Burk RD, et al. Risk factors for oral HPV infection among a high prevalence population of HIV-positive and at-risk HIV-negative adults. Cancer Epidemiol Biomarkers Prev. 2012;21(1):122–33.PubMedCrossRefPubMedCentralGoogle Scholar
  112. 112.
    Chaturvedi AK. Epidemiology and clinical aspects of HPV in head and neck cancers. Head Neck Pathol. 2012;6(S1):16–24.PubMedCentralCrossRefGoogle Scholar
  113. 113.
    Gillison ML. Oropharyngeal cancer: a potential consequence of concomitant HPV and HIV infection. Curr Opin Oncol. 2009;21(5):439–44.PubMedCrossRefPubMedCentralGoogle Scholar
  114. 114.
    Chikumaru H, Okubo M, Ueda A. HIV-infected persons are at high risk of developing precancerous lesions of the oral cavity. Open Forum Infect Dis. 2016;3(Suppl 1):2131.Google Scholar
  115. 115.
    Baughn RE, Musher DM. Secondary syphilitic lesions. Clin Microbiol Rev. 2005;18(1):205–16.PubMedPubMedCentralCrossRefGoogle Scholar
  116. 116.
    Public Health England: Syphilis epidemiology in London [Internet]. Accessed 11 Jun 2017. Available from:
  117. 117.
    Little JW. Syphilis: an update. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2005;100(1):3–9.PubMedCrossRefPubMedCentralGoogle Scholar
  118. 118.
    Kingston M, French P, Higgins S, McQuillan O, Sukthankar A, Stott C, et al. UK national guidelines on the management of syphilis 2015. Int J STD AIDS. 2016;27(6):421–46.PubMedCrossRefPubMedCentralGoogle Scholar
  119. 119.
    Meyer I, Shklar G. The oral manifestations of acquired syphilis. A study of eighty-one cases. Oral Surg Oral Med Oral Pathol. 1967;23(1):45–57.PubMedCrossRefPubMedCentralGoogle Scholar
  120. 120.
    Wynder EL, Bross IJ. Aetiological factors in mouth cancer. An approach to its prevention. Br Med J. 1957;1(5028):1137–43.PubMedPubMedCentralCrossRefGoogle Scholar
  121. 121.
    Dickenson AJ, Currie WJ, Avery BS. Screening for syphilis in patients with carcinoma of the tongue. Br J Oral Maxillofac Surg. 1995;33(5):319–20.PubMedCrossRefPubMedCentralGoogle Scholar
  122. 122.
    Walker DM, Boey G, McDonald LA. The pathology of oral cancer. Pathology. 2003;35(5):376–83.PubMedCrossRefPubMedCentralGoogle Scholar
  123. 123.
    Samad A, Mohan N, Balaji RVS, Augustine D, Patil SG. Oral manifestations of plummer-vinson syndrome: a classic report with literature review. J Int Oral Health. 2015;7(3):68–71.PubMedPubMedCentralGoogle Scholar
  124. 124.
    Dinler G, Tander B, Kalayci AG, Rizalar R. Plummer-Vinson syndrome in a 15-year-old boy. Turk J Pediatr. 2009;51(4):384–6.PubMedPubMedCentralGoogle Scholar
  125. 125.
    Messmann H. Squamous cell cancer of the oesophagus. Best Pract Res Clin Gastroenterol. 2001;15(2):249–65.PubMedCrossRefPubMedCentralGoogle Scholar
  126. 126.
    Jessner W, Vogelsang H, Puspok A, Ferenci P, Gangl A, Novacek G, et al. Plummer-Vinson syndrome associated with celiac disease and complicated by postcricoid carcinoma and carcinoma of the tongue. Am J Gastroenterol. 2003;98(5):1208–9.PubMedCrossRefPubMedCentralGoogle Scholar
  127. 127.
    Puzanov I, Amaravadi RK, McArthur GA, Flaherty KT, Chapman PB, Sosman JA, et al. Long-term outcome in BRAF(V600E) melanoma patients treated with vemurafenib: patterns of disease progression and clinical management of limited progression. Eur J Cancer. 2015;51(11):1435–43.PubMedPubMedCentralCrossRefGoogle Scholar
  128. 128.
    Larkin J, Del Vecchio M, Ascierto PA, Krajsova I. Vemurafenib in patients with BRAF V600 mutated metastatic melanoma: an open-label, multicentre, safety study. Lancet Oncol. 2014;15:436.PubMedCrossRefPubMedCentralGoogle Scholar
  129. 129.
    Owosho AA, Randazzo J, Rosen EB, Estilo CL, Huryn JM, Chi P, et al. Squamous cell carcinoma associated with chronic graft versus host disease-like/lichen planus-like lesion of the oral cavity in a patient managed for metastatic melanoma with a PD-1 inhibitor pembrolizumab. Oral Oncol. 2016;63:e1–3.PubMedPubMedCentralCrossRefGoogle Scholar
  130. 130.
    Lloyd-Lavery A, Hodgson T, Coupe N, Bond S, Shah K, Espinosa O, et al. Delayed oral toxicity from long-term vemurafenib therapy. Br J Dermatol. 2016;174(5):1159–60.PubMedCrossRefPubMedCentralGoogle Scholar
  131. 131.
    Vigarios E, Lamant L, Delord JP, Fricain JC, Chevreau C, Barrés B, et al. Oral squamous cell carcinoma and hyperkeratotic lesions with BRAF inhibitors. Br J Dermatol. 2015;172(6):1680–2.PubMedCrossRefPubMedCentralGoogle Scholar
  132. 132.
    Cipriani NA, Blair E, Taxy JB. WHIM syndrome and oral squamous cell carcinoma. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2010;109(1):105–8.PubMedCrossRefPubMedCentralGoogle Scholar
  133. 133.
    Vinarsky V, Fine RL, Assaad A, Qian Y, Chabot JA, Su GH, et al. Head and neck squamous cell carcinoma in FAMMM syndrome. Head Neck. 2009;31(11):1524–7.PubMedCrossRefPubMedCentralGoogle Scholar
  134. 134.
    Muzio Lo L. Nevoid basal cell carcinoma syndrome (Gorlin syndrome). Orphanet J Rare Dis. 2008;3(1):32.CrossRefGoogle Scholar
  135. 135.
    Nicot R, Denglehem C, Qassemyar A, Raoul G, Ferri J. Squamous cell carcinoma of the maxilla in a patient with basal cell nevus syndrome. J Craniofac Surg. 2014;25(2):662–4.PubMedCrossRefPubMedCentralGoogle Scholar
  136. 136.
    Hasegawa K, Amagasa T, Shioda S, Kayano T. Basal cell nevus syndrome with squamous cell carcinoma of the maxilla: report of a case. J Oral Maxillofac Surg. 1989;47(6):629–33.PubMedCrossRefPubMedCentralGoogle Scholar
  137. 137.
    Moos KF, Rennie JS. Squamous cell carcinoma arising in a mandibular keratocyst in a patient with Gorlin’s syndrome. Br J Oral Maxillofac Surg. 1987;25(4):280–4.PubMedCrossRefPubMedCentralGoogle Scholar
  138. 138.
    Coggshall K, Farsani T, Ruben B. Keratitis, ichthyosis, and deafness (KID) syndrome: a review of infectious and neoplastic complications. J Am Acad Dermatol. 2013;69:127.PubMedCrossRefPubMedCentralGoogle Scholar
  139. 139.
    Homeida L, Wiley RT, Fatahzadeh M. Oral squamous cell carcinoma in a patient with keratitis-ichthyosis-deafness syndrome: a rare case. Oral Surg Oral Med Oral Pathol Oral Radiol. 2015;119(4):e226–32.PubMedCrossRefPubMedCentralGoogle Scholar
  140. 140.
    Lancaster LJ, Fournet LF. Carcinoma of the tongue in a child: report of case. J Oral Surg. 1969;27(4):269–70.PubMedPubMedCentralGoogle Scholar
  141. 141.
    Baden HP, Alper JC. Ichthyosiform dermatosis, keratitis, and deafness. Arch Dermatol. 1977;113(12):1701–4.PubMedCrossRefPubMedCentralGoogle Scholar
  142. 142.
    Mazereeuw-Hautier J, Bitoun E, Chevrant-Breton J, Man SYK, Bodemer C, Prins C, et al. Keratitis-ichthyosis-deafness syndrome: disease expression and spectrum of connexin 26 (GJB2) mutations in 14 patients. Br J Dermatol. 2007;156(5):1015–9.PubMedCrossRefPubMedCentralGoogle Scholar
  143. 143.
    Cunniff C, Bassetti JA, Ellis NA. Bloom’s syndrome: clinical spectrum, molecular pathogenesis, and cancer predisposition. Mol Syndromol. 2017;8(1):4–23.PubMedCrossRefPubMedCentralGoogle Scholar
  144. 144.
    Berkower AS, Biller HF. Head and neck cancer associated with Bloom’s syndrome. Laryngoscope. 1988;98(7):746–8.PubMedCrossRefPubMedCentralGoogle Scholar
  145. 145.
    Wong BJ, Hashisaki GT. Treatment of Bloom syndrome patients: guidelines and report of a case. Otolaryngol Head Neck Surg. 1996;114(2):295–8.PubMedCrossRefPubMedCentralGoogle Scholar
  146. 146.
    Ma B, Corry J, Rischin D, Leong T, Peters LJ. Combined modality treatment for locally advanced squamous-cell carcinoma of the oropharynx in a woman with Bloom’s syndrome: a case report and review of the literature. Ann Oncol. 2001;12(7):1015–7.PubMedCrossRefPubMedCentralGoogle Scholar
  147. 147.
    Mallipeddi R. Epidermolysis bullosa and cancer. Clin Exp Dermatol. 2002;27(8):616–23.PubMedCrossRefPubMedCentralGoogle Scholar
  148. 148.
    Pfendner EG, Lucky AW. Dystrophic epidermolysis bullosa. In: Pagon RA, Adam MP, Ardinger HH, Wallace SE, Amemiya A, Bean L, et al., editors. GeneReviews®. Seattle, WA: University of Washington; 1993.Google Scholar
  149. 149.
    Fine J-D, Mellerio JE. Extracutaneous manifestations and complications of inherited epidermolysis bullosa: part II. Other organs. J Am Acad Dermatol. 2009;61(3):387–402. quiz 403–4.PubMedCrossRefPubMedCentralGoogle Scholar
  150. 150.
    Martinez L, Goodman P, Crow WN. Squamous cell carcinoma of the maxillary sinus and palate in epidermolysis bullosa: CT demonstration: J Comput Assist Tomogr 1992;16(2):317–319.PubMedCrossRefPubMedCentralGoogle Scholar

Copyright information

© Peter A. Brennan, Tom Aldridge, Raghav C. Dwivedi, Rehan Kazi 2019

Authors and Affiliations

  1. 1.Oral Medicine, Eastman Dental HospitalUniversity College London Hospitals NHS TrustLondonUK
  2. 2.Oral MedicineGuy’s and St Thomas’ NHS Foundation TrustLondonUK

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