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Review Article

Oral submucous fibrosis: Newer proposed classification

with critical updates in pathogenesis and management
strategies
ABSTRACT
Oral submucous fibrosis (OSMF) is an oral precancerous condition characterized by inflammation and progressive fibrosis of the submucosal
tissues resulting in marked rigidity and trismus. OSMF still remains a dilemma to the clinicians due to elusive pathogenesis and less well‑defined
classification systems. Over the years, many classification systems have been documented in medical literature based on clinical, histopathological,
or functional aspects. However, none of these classifications have achieved universal acceptance. Each classification has its own merits and
demerits. An attempt is made to provide and update the knowledge of classification system of OSMF so that it can assist the clinicians, beneficial
in researches and academics in categorizing this potentially malignant disease for early detection, prompt management, and reducing the
mortality. Along with this, pathogenesis and management have also been discussed.

Keywords: Areca nut, blanching, collagen, fibrosis, oral submucous fibrosis

INTRODUCTION It is commonly prevalent in Southeast Asia and Indian

subcontinent.[3] The prevalence rate of OSMF in India is about
Oral submucous fibrosis (OSMF) precancerous condition 0.2%–0.5%. This increased prevalence is due to increased
and is chronic, resistant disease characterized by use and popularity of commercially prepared areca nut and
juxta‑epithelial inflammatory reaction and progressive tobacco product ‑ gutkha, pan masala, flavored supari, etc.[4]
fibrosis of the submucosal tissues. In 1966, Pindborg[1] The malignant transformation rate of OSMF was found to
defined OSMF as “an insidious chronic disease affecting be 7.6%.
any part of the oral cavity and sometimes pharynx. It is
associated with juxta‑epithelial inflammatory reaction Deepak Passi, Prateek Bhanot1, Dhruv Kacker2,
followed by fibroelastic changes in the lamina propria layer, Deepak Chahal3, Mansi Atri4, Yoshi Panwar5
Department of Oral and Maxillofacial Surgery, Inderprastha
along with epithelial atrophy which leads to rigidity of the
Dental College and Hospital, Sahibabad, Ghaziabad,
oral mucosa proceeding to trismus and difficulty in mouth 1
Department of Anaesthesiology, Fortis Hospital, Noida,
opening.” Other terms used to describe this condition Uttar Pradesh, Departments of 2Prosthodontics, 3Oral and
are juxta‑epithelial fibrosis, idiopathic scleroderma of the Maxillofacial Surgery and 4Public Health Dentistry, ESIC
mouth, idiopathic palatal fibrosis, submucous fibrosis of Dental College and Hospital, Rohini, 5Department of Oral
the palate and pillars, sclerosing stomatitis, and diffuse and Maxillofacial Surgery, Maulana Azad Institute of Dental
OSMF.[2] Sciences, New Delhi, India

Address for correspondence: Dr. Deepak Passi,

It occurs at any age but most commonly seen in young and Department of Oral and Maxillofacial Surgery, Inderprastha Dental
adults between 25 and 35 years (2nd–4th decade). Onset of College and Hospital, Sahibabad, Ghaziabad, Uttar Pradesh, India.
E‑mail: drdeepakpassi@gmail.com
this disease is insidious and is often 2–5 years of duration.

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How to cite this article: Passi D, Bhanot P, Kacker D, Chahal D, Atri M,

DOI:
Panwar Y. Oral submucous fibrosis: Newer proposed classification with
10.4103/njms.NJMS_32_17 critical updates in pathogenesis and management strategies. Natl J
Maxillofac Surg 2017;8:89-94.

© 2017 National Journal of Maxillofacial Surgery | Published by Wolters Kluwer - Medknow 89

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Passi, et al.: Newer proposed OSMF classification

ETIOPATHOGENESIS an autoimmune response.[9] The major histocompatibility

complex Class I chain‑related gene A (MICA), which is
OSMF was first described by Schwartz in 1952, where it was expressed by keratinocytes and epithelial cells, interacts
classified as an idiopathic disorder by the term atrophia with gamma/delta T cells localized in the submucosa.
idiopathica (tropica) mucosae oris.[5] Since then, many MICA has got a triplet repeat (guanine, thymine, cytosine)
hypotheses are being suggested that OSMF is multifactorial polymorphism in the transmembrane domain, which results
in origin with etiological factors are areca nut, capsaicin in five different allelic patterns. The phenotype frequency
in chilies, micronutrient deficiencies of iron, zinc, and of allele A6 of MICA is higher in OSMF.[10] Increased levels
essential vitamins. Autoimmune etiological basis of disease of pro‑inflammatory cytokines and reduced antifibrotic
with demonstration of various autoantibodies with a strong interferon gamma (IFN‑gamma) also contribute to the
association with specific human leukocyte antigen (HLA) pathogenesis of OSMF.[11]
antigens has also been suggested.[6]
Various staging/grading classification systems have been
Areca nut (betel nut) chewing is one of the most common documented in medical literature by various authors in the
causes of OMSF which contains tannins (11%–12%) and past. Some of the staging system is routinely used in the
alkaloids such as arecoline, arecaidine, guvacine, and clinical practice and help in early diagnosis and treatment
guvacoline (0.15%–0.67%). Out of all arecoline is the main [Table 1].
agent. Arecaidine is an active metabolite in fibroblast
stimulation and proliferation, thereby inducing collagen This classification system is based on clinical presentation
synthesis. With the addition of slaked lime (Ca[OH] 2) to areca and progression of the disease only.[12] It has not pointed
nut, it causes hydrolysis of arecoline to arecaidine making any functional component (mouth opening), histological
this agent available in the oral environment. Tannin present component treatment, and prognosis [Table 2].
in areca nut reduces collagen degradation by inhibiting
collagenases. OSMF is induced as a combined effect of tannin This classification system is based on the functional
and arecoline by the mechanism of reducing degradation and component.[12] Although commonly used, this classification
increased production of collagen, respectively.[5] has not highlighted clinical features, histological features,
treatment, and prognosis [Table 3].
Nutritional deficiencies
Deficiency of iron (anemia), Vitamin B complex, minerals, and This classification system is based on the histological features
malnutrition are promoting factors that disturbs the repair of the disease only.[12] No clinical part, functional component,
process of the inflamed oral mucosa, thus leads to deranged treatment, and prognosis are discussed [Table 4].
healing and resultant scarring and fibrosis. The resulting
atrophic oral mucosa is more susceptible to the effects of This classification system includes all the parameters/
chilies, betel nuts, and other irritants.[7] component of OSMF such as clinical features, histopathological
features, functional component, treatment part, and
Genetics and immunology prognosis [Table 5]. None of the previous classifications have
A genetic component is believed to be involvement in OSMF included all these features in one classification. The main
because there are cases reported in medical literature in drawback of this classification is that it is bit complex and
people without any history of betel nut chewing or chili lengthy to read.
ingestion. Patients with OSMF have increased frequency of
HLA‑A10, HLA‑B7, and HLA‑DR3.[8] Treatment of oral submucous fibrosis
The treatment of OSMF depends on the degree of disease
An immunologic phenomenon is thought to play a role in progression and clinical involvement. At early stages,
the etiopathogenesis of OSMF. The increase in CD4 cells and stopping habit and nutritional supplements are done. At
cells with HLA‑DR in these diseased tissues shows activation moderate stages, conservative treatment such as intralesional
of most lymphocytes and increased number of Langerhans injections along with medical treatment is provided. At
cells. These immunocompetent cells and high of CD4:CD8 advanced stages, surgical interventions are needed.
ratio in OSMF tissues show the activation of cellular immune
response which results in deranged immunoregulation and an Cessation of habit
altered local tissue morphology. These changes may be due The stoppage of habit such as betel quid, areca nut and other
to direct stimulation from exogenous antigens such as areca local irritants, spicy and hot food, alcohol, and smoking
alkaloids or due to changes in tissue antigenicity leading through education and patient motivation. All affected

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Passi, et al.: Newer proposed OSMF classification

Table 1: Different classification, staging, and grading systems

Clinical classification Histopathological classification Clinical and histopathological
Desa J.V (1957) Pindborg J.J. and Sirsat S.M. (1966) Khanna J.N. and Andrade N.N. (1995)
Wahi P.N. and Kapur V.L. et al. (1966) Utsonumiya H. et al. (2005)
Ahuja S.S. and Agarwal G.D. (1971) Kumar K. (2007)
Bhatt A.P. and Dholakia H.M. (1977)
Gupta D.S. and Golhar B.L. (1980)
Pindborg J.J (1989)
Katharia S.K. et al. (1992)
Bailoor D.N. (1993)
Racher S.K. (1993)
Lai D.R. et al. (1995)
Maher R. et al. (1996)
Haider S.M. et al. (2000)
Ranganathan K. et al. (2001)
Rajendran R. (2003)
Bose T. and Balan A. (2007)
Kumar K. et al. (2007)
Mehrotra D. et al. (2009)
More C.B. et al. (2011)
Kerr A.R. et al. (2011)
Patil S. and Maheshwari S. (2014)
Prakash R. et al. (2014)

Table 2: Clinical staging/classification

Stage I/early OSMF Stage II/moderate OSMF Stage III/severe OSMF
Stomatitis and vesiculation: Stomatitis Fibrosis: Blanching of the oral mucosa, vertical Sequelae of OSMF: Leukoplakia and erythroplakia
includes erythematous mucosa, and circular palpable fibrous bands in the is present in about 25% of OSMF cases
vesicles, mucosal ulcers, melanotic buccal mucosa and lips, mottled, marble‑like Speech and hearing difficulties may occur
mucosal pigmentation and mucosal appearance of the mucosa. Reduction of mouth because of involvement of tongue and the
petechiae opening, stiff and small tongue, blanched eustachian tube
and leathery floor of the mouth, fibrotic and
de‑pigmented gingiva, rubbery soft palate
with reduced mobility, atrophic and blanched
tonsils, shrunken cheeks and bud‑like uvula,
not commensurate with age or nutritional
status
OSMF: Oral submucous fibrosis

patients should be educated and warned about the possible Table 3: Functional staging/classification: Based on mouth
malignant transformation. opening between upper and lower central incisors
Grading/ Maximium Interincisal mouth opening
Staging
Supplementary care
Stage I Maximum interincisal mouth opening up to or >35 mm
Diet rich in iron, vitamins, and minerals should be
Stage II Maximum interincisal mouth opening between 25 and 35 mm
advised to patients with OSMF. Deficiency of iron plays Stage III Maximum interincisal mouth opening between 15 and 25 mm
important role in both etiology and pathogenesis of OSMF. Stage IV Maximum interincisal mouth opening 5 and 15mm
Hence, routine hemoglobin level should be monitored Stage V Maximum interincisal mouth opening <5 or nil
along with iron supplements should be given in diet.[5] Steroid therapy, placental extracts, and chymotrypsin
Vitamin B deficiency plays an important role in the etiology Steroids  → reduction of proliferation of fibroblasts → a
of degenerative changes in oral mucosa before malignant number of collagen fibers decreases. Steroids release cellular
transformation. Vitamin B complex supplement may relieve proteases enzymes in extracellular compartment in connective
glossitis, inflammation of tongue, and cheilosis in OSMF tissues → activation of collagen and zymogens → ingestion
patients.[13] of insoluble collagen → collagen breakdown stimulation.

Antioxidants Steroids also act by reducing inflammatory response. Steroid

Carotenoids (lycopene) induce stimulation of immune system ointment and intralesional dexamethasone injection are
or direct action in tumor cells. Lycopene inhibits hepatic generally used. Placentrex is an aqueous extract of human
fibrosis genes in LEC rats and also exerts a similar inhibition placenta having nucleotides, enzymes, steroids, vitamins, and
on the abnormal fibroblasts in OSMF.[14] amino acids. It acts by biogenic stimulation. It is injected into
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Passi, et al.: Newer proposed OSMF classification

Table 4: Histopathological staging/classification Immune milk

Grading/ Histological features Immune milk consists anti‑inflammatory component which
Staging suppresses the inflammatory process and stimulates the
Early stage Fine collagen fibers dispersed with marked edema. Young cytokine production. Good symptomatic relief in OSMF
fibroblast contains abundant cytoplasm. Congested blood
vessels. Inflammatory cells, mostly polymorphonuclear patients is due to micronutrients in the immune milk
leukocytes and occasional eosinophils are found. Large powder.[19]
number of lymphocytes in subepithelial, connective tissue,
zone along with myxedematous changes
Turmeric
Intermediate Initial hyalinization seen in juxta‑epithelial area. Collagen
stage is in separate thick bundles. Moderate amount of young Turmeric powder provides benzopyrene‑induced stimulated
fibroblasts is seen. Dilated and congested blood vessels. production of micronuclei in circulating lymphocytes. It also
Inflammatory cells are primarily lymphocytes, eosinophils,
and occasional plasma cells. Collagen is moderately
acts as an excellent scavenger of free radical. Turmeric oil
hyalinized. Thickened collagen bundles are separated and turmeric resin both act synergistically to protect against
by slight residual edema. Fibroblastic activity is less. DNA damage.[20]
Inflammatory exudate composed of lymphocytes and
plasma cells. Granulation changes occur close to the muscle
layer, and hyalinization appears in subepithelial layer where Physiotherapy
compression of blood vessels by fibrous bundles takes place. Muscle stretching exercises for the mouth are helpful in
Inflammatory cells are reduced in subepithelial layer
preventing further reduction in mouth opening. Forceful jaw
Advanced Collagen is completely hyalinized. A smooth sheet
stage with no separate bundles of collagen is present. No opening exercise is with mouth gag or heisters jaw opener.
edema. Hyalinized area is deficient of fibroblasts. Blood
vessels are completely obliterated. Inflammatory cells Diathermy, ultrasound, lasers: Microwave diathermy
are lymphocytes, and plasma cells inflammatory cell
infiltrate hardly seen. A number of blood vessels much Microwave diathermy acts by physio‑fibrinolysis of fibrous
reduced in subepithelial zone. Marked fibrous areas bands through selective heating of juxta‑epithelial connective
are present with hyaline changes which extend from
tissue. Ultrasound has a role in deep heating modality. It’s
subepithelial to superficial muscle layers are seen.
Muscle undergo degenerative and atrophic changes selectivity raises the temperature in accumulated areas.
CO2 laser techniques involve multiple small incisions which
the body after resistance to pathogenic factors and stimulates provide surgical relief of restricted oral aperture because
the laser beam seals all the blood vessels, thus allowing
the metabolic or regenerative processes. Chymotrypsin
the surgeon a perfect visibility and accuracy in fibrous band
is an endopeptidase enzyme which causes hydrolysis of
excision.[21]
ester and peptide bonds and hence acts as proteolytic and
anti‑inflammatory agent.[15]
Cryosurgery
It is the method of locally destroying the abnormal tissue by
Hyaluronidase
freezing it in situ and applying liquid nitrogen or argon gas.[22]
It acts by breaking down hyaluronic acid, lowers the viscosity
of intracellular substances, and decreases collagen formation. Surgical treatment
It produces burning sensation and trismus. Combination of In patients with severe trismus, surgical intervention is
steroids and hyaluronidase shows better long‑term results done which includes simple excision of fibrotic bands with
than either used alone.[16] reconstruction using buccal fat pad and split thickness
graft along with temporalis myotomy and coronoidectomy.
Pentoxifylline The surgery is performed under general anesthesia. The
Pentoxifylline is a tri substituted methyl methylxanithine intubation is difficult due to restricted mouth opening.
derivative. It is a rheological modifier; it improves Endotracheal intubation under deep inhalational anesthesia
microcirculation and decreased platelet aggregation as well or using muscle relaxants with regional block is preferred.
as granulocyte adhesion and also has good improvement Fiber‑optic guided intubation techniques have also been
in radiation‑induced superficial fibrotic lesions of skin and used.
direct effect on inhibiting burn scar fibroblasts. It has also
been used to alleviate the symptoms in patients with OSMF.[17] CONCLUSION

Interferon‑gamma OSMF is a premalignant condition and is enigma to

It has immino‑regulatory effect. It is also known as antifibrotic maxillofacial surgeon for its chronic, progressive, recurrent,
cytokine, patients treated with an intralesional injection of and malignant transformation potential. An attempt
IFN‑gamma experienced improvement of symptoms.[18] is made by us to update the knowledge of the recent

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Passi, et al.: Newer proposed OSMF classification

Table 5: Classification of oral submucous fibrosis: Passi D et al. (2017)

Grading/ Clinical Functional Histopathological Treatment Prognosis
staging
Grade 1 Involvement of less Mouth opening up to Stage of inflammation: Cessation of habit, nutritional Excellent
than one‑third of the 35 mm Fine edematous collagen, supplement, antioxidants,
oral cavity congested blood vessels, topical steroid ointment
Mild blanching, abundant neutrophils along with
burning sensation, lymphocytes with myxomatous
recurrent ulceration, changes in subepithelial,
and stomatitis. connective tissue layer of
dryness of mouth epithelium
Grade 2 Involvement of Mouth opening 25-35 mm Stage of hyalinization: Habit cessation, nutritional Good
one‑third to two‑third Cheek flexibility reduced Juxta‑epithelial collagen supplement, intralesional Recurrence rate
of the oral cavity by 33% hyalinization with lymphocytes, injection of placental is low
Blanching of oral eosinophils. Dilated and extracts, hyaluronidase,
mucosa with mottled congested blood vessels. Less steroid therapy
and marble like fibroblastic activity. Granulation Physiotherapy
appearance, fibrotic changes in muscle layer with
bands palpable and reduced inflammatory cells in
involvement of soft subepithelial layer
palate and premolar
area
Grade 3 Involvement of greater Mouth opening 15-25 mm Stage of fibrosis: Complete Surgical treatment Fair
than two‑third of the Cheek flexibility reduced collagen hyalinization without including band excision and Recurrence rate
oral cavity. Severe by 66% fibroblast and edema. reconstruction with BFP or is high
blanching, Broad Obliterated blood vessels split thickness graft bilateral
thick fibrous palpable Plasma cells and lymphocytes temporalis myotomy and
bands at cheeks are present coronoidectomy
and lips and rigid Extensive fibrosis with
mucosa, depapillated hyalinization from subepithelial
tongue and restricted to superficial muscle layers
tongue movement with atrophic, degenerative
and shrunken bud like changes
uvula. Floor of the
mouth involvement
and lymphadenopathy
Grade 4 Leukoplakia changes, Mouth opening <15 Stages of malignant Surgical treatment and Poor,
erythroplakia mm or nil transformation: Erythroplakia biopsy of suspicious lesion malignant
Ulcerating and changes transformation
suspicious malignant into squamous cell carcinoma
lesion

developments that enhances the understanding of the Immunohistochemical evaluation of mast cells and vascular
endothelial proliferation in oral submucous fibrosis. Indian J Dent Res
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Furthermore, a newer classification is derived which Proposed clinical classification for oral submucous fibrosis. Oral Oncol
provides all the components of OSMF functional, clinical, 2012;48:200‑2.
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Oral submucous fibrosis: Review on aetiology and pathogenesis. Oral
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There are no conflicts of interest.
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