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. 1994;72(6):985–996.

Oral submucous fibrosis: etiology, pathogenesis, and future research.

R Rajendran 1
PMCID: PMC2486725  PMID: 7867145

Abstract

Oral submucous fibrosis (OSMF), a precancerous condition of the oral cavity, has been studied by a number of workers in the field. The available epidemiological data showed a clear-cut geographical and ethnic predisposition, which suggested that certain customs/habits prevalent among the population groups in south-east Asia might be possible etiological factors. However, none of these customs was shown to be causally linked and the association in many cases was 'casual'. This led some workers to consider the importance of systemic predisposition, in addition to the effects of local factors on the oral mucosa. More research is needed to elucidate this problem.

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Selected References

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  1. Bhonsle R. B., Murti P. R., Daftary D. K., Gupta P. C., Mehta F. S., Sinor P. N., Irani R. R., Pindborg J. J. Regional variations in oral submucous fibrosis in India. Community Dent Oral Epidemiol. 1987 Aug;15(4):225–229. doi: 10.1111/j.1600-0528.1987.tb00526.x. [DOI] [PubMed] [Google Scholar]
  2. Bhonsle R. B., Murti P. R., Pindborg J. J., Daftary D. K., Mehta F. S. Focal vascular dilatations and petechiae in oral submucous fibrosis. Scand J Dent Res. 1981 Jun;89(3):270–274. doi: 10.1111/j.1600-0722.1981.tb01682.x. [DOI] [PubMed] [Google Scholar]
  3. Binnie W. H., Cawson R. A. A new ultrastructural finding in oral submucous fibrosis. Br J Dermatol. 1972 Mar;86(3):286–290. doi: 10.1111/j.1365-2133.1972.tb02230.x. [DOI] [PubMed] [Google Scholar]
  4. Boyd N. M., Reade P. C. Mechanisms of carcinogenesis with particular reference to the oral mucosa. J Oral Pathol. 1988 May;17(5):193–201. doi: 10.1111/j.1600-0714.1988.tb01524.x. [DOI] [PubMed] [Google Scholar]
  5. Brandtzaeg P., Tolo K. Mucosal penetrability enhanced by serum-derived antibodies. Nature. 1977 Mar 17;266(5599):262–263. doi: 10.1038/266262a0. [DOI] [PubMed] [Google Scholar]
  6. Canniff J. P., Harvey W., Harris M. Oral submucous fibrosis: its pathogenesis and management. Br Dent J. 1986 Jun 21;160(12):429–434. doi: 10.1038/sj.bdj.4805876. [DOI] [PubMed] [Google Scholar]
  7. Canniff J. P., Harvey W. The aetiology of oral submucous fibrosis: the stimulation of collagen synthesis by extracts of areca nut. Int J Oral Surg. 1981;10(Suppl 1):163–167. [PubMed] [Google Scholar]
  8. Chang S. E., Bhatia P., Johnson N. W., Morgan P. R., McCormick F., Young B., Hiorns L. Ras mutations in United Kingdom examples of oral malignancies are infrequent. Int J Cancer. 1991 May 30;48(3):409–412. doi: 10.1002/ijc.2910480318. [DOI] [PubMed] [Google Scholar]
  9. Chen H. R., Lin H. J. Clinicopathological study on submucosal injection of collagenase in the treatment of submucous fibrosis in the oral cavity. Gaoxiong Yi Xue Ke Xue Za Zhi. 1986 Mar;2(3):212–219. [PubMed] [Google Scholar]
  10. DESA J. V. Submucous fibrosis of the palate and cheek. Ann Otol Rhinol Laryngol. 1957 Dec;66(4):1143–1159. doi: 10.1177/000348945706600420. [DOI] [PubMed] [Google Scholar]
  11. Dayal P. K., Joshi H. N., Dayal J. P. Concomitant occurrence of oral submucous fibrosis, pemphigus and squamous cell carcinoma. Indian J Pathol Microbiol. 1988 Oct;31(4):334–337. [PubMed] [Google Scholar]
  12. Ghosh P. K., Madhavi R., Guntur M., Ghosh R. Sister chromatid exchanges in patients with oral submucous fibrosis. Cancer Genet Cytogenet. 1990 Feb;44(2):197–201. doi: 10.1016/0165-4608(90)90047-e. [DOI] [PubMed] [Google Scholar]
  13. Gupta D. S., Gupta M., Oswal R. H. Estimation of major immunoglobulin profile in oral submucous fibrosis by radial immunodiffusion. Int J Oral Surg. 1985 Dec;14(6):533–537. doi: 10.1016/s0300-9785(85)80060-0. [DOI] [PubMed] [Google Scholar]
  14. Gupta D., Sharma S. C. Oral submucous fibrosis--a new treatment regimen. J Oral Maxillofac Surg. 1988 Oct;46(10):830–833. doi: 10.1016/0278-2391(88)90043-2. [DOI] [PubMed] [Google Scholar]
  15. Hakomori S. Glycosphingolipids in cellular interaction, differentiation, and oncogenesis. Annu Rev Biochem. 1981;50:733–764. doi: 10.1146/annurev.bi.50.070181.003505. [DOI] [PubMed] [Google Scholar]
  16. Hamner J. E., 3rd, Mehta F. S., Pindborg J. J., Daftary D. K. Altered staining reaction of connective tissues in 53 submucous fibrosis patients. J Dent Res. 1971 Mar-Apr;50(2):388–392. doi: 10.1177/00220345710500024601. [DOI] [PubMed] [Google Scholar]
  17. Hardie J. Oral submucous fibrosis. A review with case reports. J Can Dent Assoc. 1987 May;53(5):389–393. [PubMed] [Google Scholar]
  18. Howell R. E., Wong F. S., Fenwick R. G. A transforming Kirsten ras oncogene in an oral squamous carcinoma. J Oral Pathol Med. 1990 Aug;19(7):301–305. doi: 10.1111/j.1600-0714.1990.tb00849.x. [DOI] [PubMed] [Google Scholar]
  19. Johnson R. L., Ziff M. Lymphokine stimulation of collagen accumulation. J Clin Invest. 1976 Jul;58(1):240–252. doi: 10.1172/JCI108455. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Langvad E., Zachariah J., Pindborg J. J. Lactate dehydrogenase isoenzyme patterns in leukoplakia, submucous fibrosis and carcinoma of the oral mucosa in south Indians. Acta Pathol Microbiol Scand A. 1970;78(5):509–515. doi: 10.1111/j.1699-0463.1970.tb02533.x. [DOI] [PubMed] [Google Scholar]
  21. Laskaris G., Bovopoulou O., Nicolis G. Oral submucous fibrosis in a Greek female. Br J Oral Surg. 1981 Sep;19(3):197–201. doi: 10.1016/0007-117x(81)90004-4. [DOI] [PubMed] [Google Scholar]
  22. Lay K. M., Sein K., Myint A., Ko S. K., Pindborg J. J. Epidemiologic study of 600 villagers of oral precancerous lesions in Bilugyun: preliminary report. Community Dent Oral Epidemiol. 1982 Jun;10(3):152–155. doi: 10.1111/j.1600-0528.1982.tb01341.x. [DOI] [PubMed] [Google Scholar]
  23. Lemmer J., Shear M. Oral submucous fibrosis. A possible case in a person of Caucasian descent. Br Dent J. 1967 Apr 18;122(8):343–346. [PubMed] [Google Scholar]
  24. Mani N. J. Studies on oral submucous fibrosis. IV. Connective tissue changes. J Oral Med. 1977 Jul-Sep;32(3):70-4, 83. [PubMed] [Google Scholar]
  25. Meghji S., Scutt A., Harvey W., Canniff J. P. An in-vitro comparison of human fibroblasts from normal and oral submucous fibrosis tissue. Arch Oral Biol. 1987;32(3):213–215. doi: 10.1016/0003-9969(87)90138-5. [DOI] [PubMed] [Google Scholar]
  26. Mehta F. S., Gupta P. C., Daftary D. K., Pindborg J. J., Choksi S. K. An epidemiologic study of oral cancer and precancerous conditions among 101,761 villagers in Maharashtra, India. Int J Cancer. 1972 Jul 15;10(1):134–141. doi: 10.1002/ijc.2910100118. [DOI] [PubMed] [Google Scholar]
  27. Murti P. R., Bhonsle R. B., Pindborg J. J., Daftary D. K., Gupta P. C., Mehta F. S. Malignant transformation rate in oral submucous fibrosis over a 17-year period. Community Dent Oral Epidemiol. 1985 Dec;13(6):340–341. doi: 10.1111/j.1600-0528.1985.tb00468.x. [DOI] [PubMed] [Google Scholar]
  28. Nair M. K., Sankaranarayanan R., Padmanabhan T. K., Padmakumari G. Clinical profile of 2007 oral cancers in Kerala, India. Ann Dent. 1988 Summer;47(1):23–26. [PubMed] [Google Scholar]
  29. PAYMASTER J. C. Cancer of the buccal mucosa; a clinical study of 650 cases in Indian patients. Cancer. 1956 May-Jun;9(3):431–435. doi: 10.1002/1097-0142(195605/06)9:3<431::aid-cncr2820090302>3.0.co;2-t. [DOI] [PubMed] [Google Scholar]
  30. PINDBORG J. J., CHAWLA T. N., SRIVASTAVA A. N., GUPTA D., MEHROTRA M. L. CLINICAL ASPECTS OF ORAL SUBMUCOUS FIBROSIS. Acta Odontol Scand. 1964 Dec;22:679–691. doi: 10.3109/00016356409058581. [DOI] [PubMed] [Google Scholar]
  31. PINDBORG J. J., SINGH B. FORMATION OF VESICLES IN ORAL SUBMUCOUS FIBROSIS. Acta Pathol Microbiol Scand. 1964;62:562–566. doi: 10.1111/apm.1964.62.4.562. [DOI] [PubMed] [Google Scholar]
  32. Paissat D. K. Oral submucous fibrosis. Int J Oral Surg. 1981 Oct;10(5):307–312. doi: 10.1016/s0300-9785(81)80026-9. [DOI] [PubMed] [Google Scholar]
  33. Pindborg J. J., Bhonsle R. B., Murti P. R., Gupta P. C., Daftary D. K., Mehta F. S. Incidence and early forms of oral submucous fibrosis. Oral Surg Oral Med Oral Pathol. 1980 Jul;50(1):40–44. doi: 10.1016/0030-4220(80)90329-1. [DOI] [PubMed] [Google Scholar]
  34. Pindborg J. J. Is submucous fibrosis a precancerous condition in the oral cavity? Int Dent J. 1972 Dec;22(4):474–480. [PubMed] [Google Scholar]
  35. Pindborg J. J., Murti P. R., Bhonsle R. B., Gupta P. C., Daftary D. K., Mehta F. S. Oral submucous fibrosis as a precancerous condition. Scand J Dent Res. 1984 Jun;92(3):224–229. doi: 10.1111/j.1600-0722.1984.tb00883.x. [DOI] [PubMed] [Google Scholar]
  36. Pindborg J. J. Oral submucous fibrosis: a review. Ann Acad Med Singapore. 1989 Sep;18(5):603–607. [PubMed] [Google Scholar]
  37. Pindborg J. J., Sirsat S. M. Oral submucous fibrosis. Oral Surg Oral Med Oral Pathol. 1966 Dec;22(6):764–779. doi: 10.1016/0030-4220(66)90367-7. [DOI] [PubMed] [Google Scholar]
  38. Pindborg J. J., Zheng K. H., Kong C. R., Lin F. X. Pilot survey of oral mucosa in areca (betel) nut chewers on Hainan Island of the People's Republic of China. Community Dent Oral Epidemiol. 1984 Jun;12(3):195–196. doi: 10.1111/j.1600-0528.1984.tb01438.x. [DOI] [PubMed] [Google Scholar]
  39. Rajendran R., Nair S. M. Silver-binding nucleolar organizer region proteins as a possible prognostic indicator in oral submucous fibrosis. Oral Surg Oral Med Oral Pathol. 1992 Oct;74(4):481–486. doi: 10.1016/0030-4220(92)90300-f. [DOI] [PubMed] [Google Scholar]
  40. Rajendran R., Remani P., Vijayakumar T., Vasudevan D. M. Total hemolytic complement (CH50) and its fractions (C3 and C4) in the sera of patients with premalignant and malignant lesions of the oral cavity. Ann Dent. 1990 Summer;49(1):36-8, 51. [PubMed] [Google Scholar]
  41. Rajendran R., Sugathan C. K., Remani P., Ankathil R., Vijayakumar T. Cell mediated and humoral immune responses in oral submucous fibrosis. Cancer. 1986 Dec 15;58(12):2628–2631. doi: 10.1002/1097-0142(19861215)58:12<2628::aid-cncr2820581214>3.0.co;2-z. [DOI] [PubMed] [Google Scholar]
  42. Rajendran R., Vasudevan D. M., Vijayakumar T. Serum levels of iron and proteins in oral submucous fibrosis (OSMF). Ann Dent. 1990 Winter;49(2):23-5, 45. [PubMed] [Google Scholar]
  43. Rajendran R., Vijayakumar T., Vasudevan D. M. An alternative pathogenetic pathway for oral submucous fibrosis (OSMF). Med Hypotheses. 1989 Sep;30(1):35–37. doi: 10.1016/0306-9877(89)90122-9. [DOI] [PubMed] [Google Scholar]
  44. Ramanathan K. Oral submucous fibrosis--an alternative hypothesis as to its causes. Med J Malaysia. 1981 Dec;36(4):243–245. [PubMed] [Google Scholar]
  45. Reichart P. A., Lenz H., König H., Becker J., Mohr U. The black layer on the teeth of betel chewers: a light microscopic, microradiographic and electronmicroscopic study. J Oral Pathol. 1985 Jul;14(6):466–475. doi: 10.1111/j.1600-0714.1985.tb00518.x. [DOI] [PubMed] [Google Scholar]
  46. Reichart P., Böning W., Srisuwan S., Theetranont C., Mohr U. Ultrastructural findings in the oral mucosa of betel chewers. J Oral Pathol. 1984 Apr;13(2):166–177. doi: 10.1111/j.1600-0714.1984.tb01413.x. [DOI] [PubMed] [Google Scholar]
  47. Remani P., Ankathil R., Vijayan K. K., Haseena Beevi V. M., Rajendran R., Vijayakumar T. Circulating immune complexes as an immunological marker in premalignant and malignant lesions of the oral cavity. Cancer Lett. 1988 Jun 15;40(2):185–191. doi: 10.1016/0304-3835(88)90009-2. [DOI] [PubMed] [Google Scholar]
  48. SIRSAT S. M., KHANOLKAR V. R. Submucous fibrosis of the palate and pillars of the fauces. Indian J Med Sci. 1962 Mar;16:189–197. [PubMed] [Google Scholar]
  49. SIRSAT S. M., KHANOLKAR V. R. Submucous fibrosis of the palate in diet-preconditioned Wistar rats. Induction by local painting of capsaicin--an optical and electron microscopic study. Arch Pathol. 1960 Aug;70:171–179. [PubMed] [Google Scholar]
  50. Saranath D., Panchal R. G., Nair R., Mehta A. R., Sanghavi V., Sumegi J., Klein G., Deo M. G. Oncogene amplification in squamous cell carcinoma of the oral cavity. Jpn J Cancer Res. 1989 May;80(5):430–437. doi: 10.1111/j.1349-7006.1989.tb02332.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  51. Seedat H. A., van Wyk C. W. Betel-nut chewing and submucous fibrosis in Durban. S Afr Med J. 1988 Dec 3;74(11):568–571. [PubMed] [Google Scholar]
  52. Sharma J. K., Gupta A. K., Mukhija R. D., Nigam P. Clinical experience with the use of peripheral vasodilator in oral disorders. Int J Oral Maxillofac Surg. 1987 Dec;16(6):695–699. doi: 10.1016/s0901-5027(87)80055-3. [DOI] [PubMed] [Google Scholar]
  53. Shiau Y. Y., Kwan H. W. Submucous fibrosis in Taiwan. Oral Surg Oral Med Oral Pathol. 1979 May;47(5):453–457. doi: 10.1016/0030-4220(79)90128-2. [DOI] [PubMed] [Google Scholar]
  54. Sinor P. N., Gupta P. C., Murti P. R., Bhonsle R. B., Daftary D. K., Mehta F. S., Pindborg J. J. A case-control study of oral submucous fibrosis with special reference to the etiologic role of areca nut. J Oral Pathol Med. 1990 Feb;19(2):94–98. doi: 10.1111/j.1600-0714.1990.tb00804.x. [DOI] [PubMed] [Google Scholar]
  55. Sirsat S. M., Pindborg J. J. Subepithelial changes in oral submucous fibrosis. Acta Pathol Microbiol Scand. 1967;70(2):161–173. doi: 10.1111/j.1699-0463.1967.tb01278.x. [DOI] [PubMed] [Google Scholar]
  56. Sirsat S. M., Pindborg J. J. The vascular response in early and advanced oral submucous fibrosis. Acta Pathol Microbiol Scand. 1967;70(2):179–184. doi: 10.1111/j.1699-0463.1967.tb01280.x. [DOI] [PubMed] [Google Scholar]
  57. Squier C. A., Hall B. K. The permeability of hyperplastic oral epithelium. J Oral Pathol. 1985 May;14(5):357–362. doi: 10.1111/j.1600-0714.1985.tb00505.x. [DOI] [PubMed] [Google Scholar]
  58. Steel C. M. Tracing disease genes through family studies. J Pathol. 1990 Sep;162(1):7–13. doi: 10.1002/path.1711620104. [DOI] [PubMed] [Google Scholar]
  59. Varghese I., Sugathan C. K., Balasubramoniyan G., Vijayakumar T. Serum copper and zinc levels in premalignant and malignant lesions of the oral cavity. Oncology. 1987;44(4):224–227. doi: 10.1159/000226482. [DOI] [PubMed] [Google Scholar]
  60. Vigneswaran N., Peters K. P., Hornstein O. P., Diepgen T. L. Alteration of cell surface carbohydrates associated with ordered and disordered proliferation of oral epithelia: a lectin histochemical study in oral leukoplakias, papillomas and carcinomas. Cell Tissue Kinet. 1990 Jan;23(1):41–55. doi: 10.1111/j.1365-2184.1990.tb01108.x. [DOI] [PubMed] [Google Scholar]
  61. Vilmer C., Civatte J. Fibrose orale sous-muqueuse. Revue de la littérature à propos d'un cas. Ann Dermatol Venereol. 1986;113(2):107–112. [PubMed] [Google Scholar]
  62. Wahi P. N., Luthra U. K., Kapur V. L. Submucous fibrosis of the oral cavity. Histomorphological studies. Br J Cancer. 1966 Dec;20(4):676–687. doi: 10.1038/bjc.1966.79. [DOI] [PMC free article] [PubMed] [Google Scholar]
  63. el-Labban N. G., Canniff J. P. Ultrastructural findings of muscle degeneration in oral submucous fibrosis. J Oral Pathol. 1985 Oct;14(9):709–717. doi: 10.1111/j.1600-0714.1985.tb00550.x. [DOI] [PubMed] [Google Scholar]
  64. van Wyk C. W., Seedat H. A., Phillips V. M. Collagen in submucous fibrosis: an electron-microscopic study. J Oral Pathol Med. 1990 Apr;19(4):182–187. doi: 10.1111/j.1600-0714.1990.tb00821.x. [DOI] [PubMed] [Google Scholar]

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