Betel Nut Chewing and Its Deleterious Effects On Oral Cavity
Betel Nut Chewing and Its Deleterious Effects On Oral Cavity
8]
Review Article
carcinogens, of which the betel nut is believed to of the betel, the frequency of chewing, and the Quick Response Code:
be the main culprit.[7] A growing body of evidence duration of the habit. Root fractures have also
over the last 40 years, mainly in the form of been demonstrated in chronic betel chewers and
large‑scale epidemiological and experimental this is likely to be a consequence of the increased
studies, has shown that even when consumed masticatory load that is placed upon the teeth and
in the absence of tobacco or lime betel may have is not direct effect of betel.[10]
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• Lesions that are localized to the site where quid is regularly process, by inducing mutation, or by making the mucosa
placed. These lesions are equivalent to snuff induced susceptible to BQ ingredients and environmental toxicants.
lesions or tobacco lime user’s lesions, which arise only on The production and release of ROS occurs under alkaline
the mucosa in contact with the quid.[22,23] conditions during the autoxidation of betel nut polyphenols,
in the BQ chewer’s saliva. The ROS can be directly involved
Betel chewer’s mucosa in the tumor initiation process, by inducing genotoxicity and
A condition of the oral mucosa where, because of either gene mutation, or by attacking the salivary proteins and
direct action of the quid or traumatic effect of chewing, or oral mucosa, leading to structural change in the oral mucosa
both, there is a tendency for the oral mucosa to desquamate that may facilitate the penetration by other BQ ingredients
or peel [Figure 2]. Loose and detached tags of tissue can and environmental toxins. The nitrosation of betel alkaloids
also be seen and felt. The underlying areas assume a to AN‑specific nitrosamines occurs in the saliva of BQ chewers.
pseudomembranous or wrinkled appearance. The area may These AN‑specific nitrosamines are mutagenic, genotoxic, and
also show evidence of incorporation of ingredients of the quid capable of inducing tumors in animal model.[33]
in the form of yellowish or reddish‑brown encrustations.[24]
The lesion is usually localized and is associated strongly with Furthermore, there is also evidence that the presence of
the habit of BQ chewing, particularly in elderly women who tobacco in the quid is not essential for the development of
have been chronic chewers for long durations.[25] Several betel chewers mucosa. At present betel chewers mucosa is not
epidemiological studies have shown that the prevalence of considered to be potentially malignant, although the condition
betel chewer’s mucosa may vary between 0.2 and 60.8% in often co‑exists with other mucosal lesions such as leukoplakia
different southeast Asian populations.[26‑29] and oral submucous fibrosis (OSF), which are well known for
their potential for malignant change.[34]
This lesion should be distinguished from morsicatio buccarum
and/or labiorum, cheek or lip biting, which are very similar to Quid‑Induced lesion
betel chewer’s mucosa in terms of clinical appearance (without A quid‑induced lesion is a localized lesion of the oral mucosa
stains) and histology. The differences are: Cheek biting is corresponding to the regular site of placement of quid. It is
unintentional; whereas, chewer’s mucosa results from an characterized by one or more of the following characteristics:
intentional habit and the average age of the individuals with change of normal color, wrinkled appearance, thickening of
chewer’s mucosa is usually higher, 50 years and older;[24] the mucosa, scrapable or non‑scrapable epithelial surface, and
whereas, in cheek biting it is generally younger, around presence of ulceration. Examples of such quid‑induced lesions
20-35 years.[30‑32] are: Tobacco and lime user’s lesion, snuff‑induced lesions, and
BQ lesions.[23,35]
Pathogenesis
Although the exact mechanisms underlying the development Betel nut‑related lesion
of this condition are not fully understood, it is thought that Betel nut chewers, as in chewers of other kinds of quids,
the chemical and traumatic effects of the BQ on the oral may have clinically healthy mucosa with no textural or color
mucosa may be significant factors. Betel chewing produces changes. However, buccal mucosa, either bi‑ or unilaterally,
reactive oxygen species (ROS) that is detrimental to oral may show an ill‑defined whitish gray discoloration that
mucosa and can be directly involved in tumor initiation cannot be rubbed off. The mucosa, in addition, may show a
rough linen‑like texture and histologically show ortho‑ and/
or para‑keratinized epithelium.[36]
BQ lichenoid lesion
A quid‑induced lichenoid oral lesion has been reported
exclusively among BQ users.[37] It resembles oral lichen planus
a
but there are specific differences. It is characterized by the
b
presence of fine, white, wavy, parallel lines that do not overlap
or criss‑cross, are non‑elevated, and in some instances radiate
from a central erythematous area [Figure 2]. The lesion generally
occurs at the site of placement of the quid. This lesion was
described as a lichen planus‑like lesion, but it is now termed
a “betel‑quid lichenoid lesion”. This lesion may regress with
decrease in frequency, duration, or change in site of placement of
c d the quid. There may be complete regression when the quid habit
is given up. This lesion has been found to demonstrate a different
Figure 2: (a) Betel chewers mucosa, (b) betel-quid lichenoid lesion, natural history from lichen planus in intervention studies, and
(c) oral leukoplakia, and (d) oral submucous fibrosis therefore it should be recognized as a specific entity.[21]
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Figure 3: Role of betel nut in oral submucous fibrosis
by type I.[55] Type I collagen is more resistant to degradation continuous chewing and use of heavy force to crush the hard
than type III. An important finding from these studies is the nut. This increased muscle activity along with diminished
identification of excess alpha‑1 chains relative to alpha‑2, blood supply, following connective tissue changes leads to
suggesting an alteration of collagen molecules during the muscle degeneration and fibrosis.[55]
progression of the disease. Although, the biological function
of this trimer is not known, it is regarded as more resistant to Oral squamous cell carcinoma
degradation than the normal collagen molecule.[56] There is historical evidence dating back nearly a century
that suggests that the betel nut may be involved in the
Another component of betel nut that aids this cross‑linking development of oral squamous cell carcinoma.[57‑59] Although
is copper. It is a constituent of enzyme lysyl oxidase. This it is widely accepted that the presence of tobacco in BQ plays
enzyme also causes cross‑linking and makes collagen resistant an important role in the pathogenesis of oral squamous cell
to degradation by collagenase. Due to action of tannin and carcinoma, the carcinogenic potential of betel in the absence of
copper, collagen that is produced in OSF is highly resistant to other ingredients is less clear.[60] There are epidemiological data
remodeling and phagocytosis [Figure 3].[56] from several studies that confirm that the habit of BQ chewing
increases the relative risk of developing oral squamous cell
It is fibroblast that brings about remodeling and phagocytosis carcinoma.[48,61‑64]
of collagen. As in OSF, these firoblasts are affected and
phenotypically changed, they cannot degrade collagen. CONCLUSION
Studies on the effects of arecoline on both normal and OSF
fibroblasts in culture revealed an elevated rate of collagen It is clear from the literature that betel nut use may have
synthesis by OSF fibroblasts as compared to normal fibroblasts. significant effects on dental hard and soft tissues. Thus, there
Although the reason for this elevation is not clear, some is an urgent need to curb this ongoing epidemic of betel nut
authors proposed that it could reflect the clonal selection habit. Legislation against open sale and use of such products
of a highly fibrogenic cell population in the altered tissue should be stricter and more states and countries should
under the influence of local factors such as interleukin‑1 from bring out such legislations sooner than later. Public health
inflammatory cells. This leads to decrease in phagocytosis and programs regarding the harmful effects of betel nuts, coupled
accumulation of collagen in oral mucosa [Figure 3]. Glycogen with increased awareness by healthcare professionals of the
consumption is physiologically related to cellular activity of signs and symptoms of this disease, can limit its prevalence
muscle fibers. Overactivity of muscles results in excessive significantly. In addition to educating consumers about the
glycogen consumption; leading to its depletion. In betel nut health risks of betel nut use, dental professionals need to
chewers there is overactivity of muscles due to repeated, educate paan shop vendors about the repercussions of betel
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nut consumption and persuade them not to sell betel nut 23. Bhonsle RB, Murti PR, Daftary DK, Mehta FS. An oral lesion in
products to minors. tobacco‑lime users in Maharashtra, India. J Oral Pathol 1979;8:47‑52.
24. Gupta PC, Mehta FS, Daftary DK, Pindborg JJ, Bhonsle RB,
Jalnawalla PN, et al. Incidence of oral cancer and natural history
REFERENCES of oral precancerous lesions in a 10‑year follow‑up study of Indian
villagers. Community Dent Oral Epidemiol 1980;8:283‑333.
1. Lan TY, Chang WC, Tsai YJ, Chuang YL, Lin HS, Tai TY. Areca nut 25. Reichart PA, Schmidtberg W, Scheifele CH. Betel chewer’s mucosa in
chewing and mortality in an elderly cohort study. Am J Epidemiol elderly Cambodian women. J Oral Pathol Med 1996;25:367‑70.
2006;165:677‑83. 26. Zain R, Ikeda N, Yaacob MB. Oral mucosal lesions survey of adults in
2. Auluck A, Hislop G, Poh C, Zhang L, Rosin MP. Areca nut and betel Malaysia. Kuala Lampur: Ministry of Health; 1995.
quid chewing among South Asian immigrants to Western countries 27. Ikeda N, Handa Y, Khim SP, Durward C, Axéll T, Mizuno T, et al.
and its implications for oral cancer screening. Rural Remote Health Prevalence study of oral mucosal lesions in a selected Cambodian
2009;9:1118. population. Community Dent Oral Epidemiol 1995;23:49‑54.
3. Pindborg JJ, Sirsat SM. Oral submucous fibrosis. Oral Surg Oral Med 28. Reichart PA, Mohr U, Srisuwan S, Gerlings H, Theetranont C,
Oral Pathol 1966;22:764‑79. Kangwanpong T. Precancerous and other oral mucosal lesions related
4. Aziz SR. Coming to America. Betel nut and oral submucous fibrosis. to chewing, smoking and drinking habits in Thailand. Community
J Am Dent Assoc 2010;141:423‑8. Dent Oral Epidemiol 1987;15:152‑60.
5. Trivedy C, Warnakulasuriya S, Peters TJ. Areca nuts can have 29. International Agency for Research on Cancer. IARC monograph on the
deleterious effects. Br Med J 1999;318:1287. evaluation of Carcinogenic risks to humans. Betel‑quid and Areca‑nut
6. Pankaj C. Areca nut or Betel Nut Control is Mandatory if India wants chewing and some Areca‑nut derived Nitrosamines. Vol 85. Lyon:
to reduce the burden of Cancer especially Cancer of the Oral Cavity. IARC; 2004.
Int J Head Neck Surg 2010;1:17‑20. 30. Reichart P, Böning W, Srisuwan S, Theetranont C, Mohr U.
7. Verma S. Areca nut (betel nut) chewing: A popular Indian cultural Ultrastructural findings in the oral mucosa of betel chewers. J Oral
practice and its mucosal implications. Int J Dermatol 2011;50:229‑32. Pathol 1984;13:166‑77.
8. Trivedy CR, Craig G, Warnakulasuriya S. The oral health consequences 31. Hjorting‑Hansen E, Holst E. An analysis of oral mucosal changes due
of chewing areca nut. Addict Biol 2002;7:115‑25. to biting and sucking habits. Scand J Dent Res 1970;78:492‑9.
9. Review of Areca (Betel) Nut and Tobacco Use in the Pacific‑ A Technical 32. Van Wyk CW, Staz J, Farman AG. The chewing lesion of the cheeks
Report. World Health Organization; 2012. and lips: Its features and prevalence among a selected group of
10. Yeh CJ. Fatigue root fracture: a spontaneous root fracture in adolescents. J Dent 1977;5:193‑9.
non‑endodontically treated teeth. Br Dent J 1997;182:261‑6. 33. Mehrotra S, Yadav S. Oral squamous cell carcinoma: Etiology,
11. Norton SA. Betel: Consumption and consequences. J Am Acad pathogenesis and prognostic value of genomic alterations. Indian J
Dermatol 1998;38:81‑8. Cancer 2006;43:60‑6.
12. Schamschula RG, Adkins BR, Barmes DR, Charlton G. Betel chewing 34. Reichart PA, Phillipsen HP. Betel chewer’s mucosa‑a review. J Oral
and caries experience in New Guinea. Community Dent Oral Pathol Med 1998;27:239‑42.
Epidemiol 1977;5:284‑6. 35. Andersson G, Axéll T, Larsson A. Clinical classification of Swedish
13. Nigam P, Srivastava AB. Betel chewing and dental decay. Fed Oper snuff dipper’s lesions supported by histology. J Oral Pathol Med
Dent 1990;1:36‑8. 1991;20:253‑7.
14. Howden GF. The cariostatic effects of betel chewing. P N G Med J 36. Seedat HA. Oral submucous fibrosis in Durban, Natal: A study of its
1984;27:123‑31. epidemiology, aetiology and morphological features. PhD Thesis.
15. de Miranda CM, van Wyk CW, van der Biji P, Basson NJ. The University of Stellenbosch; 1985.
effect of areca nut on salivary and selected organisms. Int Dent J 37. Daftary DK, Bhonsle RB, Murti RB, Pindborg JJ, Mehta FS. An oral
1996;46:350‑6. lichen planus‑like lesion in Indian betel‑tobacco chewers. Scand J
16. Williams SA, Summers RM, Ahmed IH, Prendergast MJ. Caries Dent Res 1980;88:244‑9.
experience, tooth loss and oral health related behaviours among 38. Axell T, Holmstrup P, Kramer IR, Pindborg JJ, Shear M. International
Bangladeshi women resident in West Yorkshire, UK. Community seminar on oral leukoplakia and associated lesions related to tobacco
Dent Health 1996;13:150‑6. habits. Community Dent Oral Epidemiol 1984;12:145‑54.
17. Jeng JH, Hahn LJ, Lin BR, Hsieh CC, Chan CP, Chang MC. Effects 39. Shiu MN, Chen TH, Chang SH, Hahn LJ. Risk factors for leukoplakia
of areca nut, inflorescence piper betle extracts and arecoline on and malignant transformation to oral carcinoma: A leukoplakia
cytotoxicity, total and unscheduled DNA synthesis in cultured cohort in Taiwan. Br J Cancer 2000;82:1871‑4.
gingival keratinocytes. J Oral Pathol Med 1999;28:64‑71. 40. Thomas SJ, Harris R, Ness AR, Taulo J, Maclennan R, Howes N, Bain CJ.
18. Chang MC, Kuo MY, Hahn LJ, Hsieh CC, Lin SK, Jeng JH. Areca Betel quid not containing tobacco and oral leukoplakia: A report on
nut extract inhibits the growth, attachment, and matrix protein a cross‑sectional study in Papua New Guinea and a meta‑analysis of
synthesis of cultured human gingival fibroblasts. J Periodontol current evidence. Int J Cancer 2008;123:1871‑6.
1998;69:1092‑7. 41. Lee CH, Ko YC, Huang HL, Chao YY, Tsai CC, Shieh TY, et al. The
19. Anerud A, Loe H, Boysen H. The natural history and clinical course precancer risk of betel quid chewing, tobacco use and alcohol
of calculus formation in man. J Clin Periodontol 1991;18:160‑70. consumption in oral leukoplakia and oral submucous fibrosis in
20. Parmar G, Sangwan P, Vashi P, Kulkarni P, Kumar S. Effect of chewing southern Taiwan. Br J Cancer 2003;88:366‑72.
a mixture of Areca nut and tobacco on periodontal tissues and oral 42. Yang YH, Lee HY, Tung S, Shieh TY. Epidemiological survey of oral
hygiene status. J Oral Sci 2008;50:57‑62. submucous fibrosis and leukoplakia in aborigines of Taiwan. J Oral
21. Zain RB, Ikeda N, Gupta PC, Warnakulasuriya S, van Wyk CW, Pathol Med 2001;30:213‑9.
Shrestha P, et al. Oral mucosal lesions associated with betel quid, 43. Chung CH, Yang YH, Wang TY, Shieh TY, Warnakulasuriya S. Oral
areca nut and tobacco chewing habits: Consensus from a workshop precancerous disorders associated with areca quid chewing,
held in Kuala Lumpur, Malaysia, November 25‑27, 1996. J Oral Pathol smoking, and alcohol drinking in southern Taiwan. J Oral Pathol Med
Med 1999;28:1‑4. 2005;34:460‑6.
22. Avon SL. Oral mucosal lesions associated with use of quid. J Can Dent 44. Pindborg JJ, Murti PR, Bhonsle RB, Gupta PC, Daftary DK, Mehta FS.
Assoc 2004;70:244‑8. Oral submucous fibrosis as a precancerous condition. Scand J Dent
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