Oral mucosal disorders associated with habitual gutka usage:a reviewFawad Javed, BDS, PhD,a Milisha Chotai, DDS,b Abid Mehmood, BDS, MCPS,c andKhalid Almas, BDS, MSc, FDSRCS, FRACDS, FICD,d Huddinge, Sweden; Cambridge,United Kingdom; Karachi, Pakistan; and Farmington, ConnecticutKAROLINSKA INSTITUTET, DENTAL CLINIC - CAMBRIDGE, JINNAH POSTGRADUATE MEDICALCENTRE, AND UNIVERSITY OF CONNECTICUT SCHOOL OF DENTAL MEDICINE

Objective. The aim of this study was to investigate the oral mucosal disorders associated with habitual gutkaconsumption.Methods. Databases were searched from 1956 to June 2009 using the following terms: “gutka,” “gutkha,” “ghutka,”“guttkha,” “smokeless tobacco,” “areca nut,” “betel nut,” “slaked lime,” “dental,” “oral,” “periodontal,”“inflammation,” “submucous fibrosis,” “carcinoma,” and “cancer.” The eligibility criteria included: human andexperimental studies, use of control subjects, and articles published in English. Unpublished data were not sought.Odds ratios (ORs) and 95% confidence intervals (CIs) were computed.Results. Twelve studies were included. Three studies associated gutka consumption with periodontal inflammation(ORs 1.64 [CI 1.2-2.1], 2.20 [CI 1.1-4.9], and 3.56 [CI 1.9-5.5]). Five studies showed a direct relationship betweengutka usage and oral submucous fibrosis (ORs 1.65 [CI 1.2-2.3], 2.33 [CI 1.9-4.5], 2.98 [CI 1.5-3.9], 3.56 [CI 1.3-4.7],and 5.08 [CI 3.7-6.4]). An increased frequency of gutka usage was associated with malignant transformations in oralsubmucous fibrosis by 2 studies (ORs 4.59 [CI 2-5.6] and 18 [CI 5.8-61.6]). Two studies showed an extension of oralsubmucous fibrosis into the hypopharynx and esophagus in gutka users (ORs 4.59 [CI 2-5.6] and 33 [CI 2.2-46.6]).Conclusions. Habitual gutka usage is associated with severe oral mucosal disorders, and the consequences may

extend beyond the oral cavity. (Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2010;109:857-864)

Gutka (a form of smokeless tobacco) is chiefly a mix-ture of powdered tobacco, areca nut (fruit of Arecacatechu), and slaked lime (aqueous calcium hydrox-ide).1 Other components of gutka include perfumerycompounds such as sandalwood and musk ketones. Theeasy availability, low cost, and extensive marketing ofgutka has resulted in an increase in its usage. Gutka iscommercially available in colorful and glittery tins andsachets. Unlike cigarettes, gutka is commercially soldwithout a health warning, and lack of awareness of itsnegative impact on health increases its consumption.1

Gutka is initially placed between the teeth and gentlychewed. It is then held against the buccal mucosa over along duration and continued to be lightly chewed andsucked occasionally. The constituents may either be swal-

aDivision of Research, Department of Dental Medicine, KarolinskaInstitutet, Huddinge, Sweden.bDental Clinic, Cambridge, United Kingdom.cDepartment of Dentistry, Jinnah Postgraduate Medical Centre, Kara-chi, Pakistan.dDivision of Periodontology, University of Connecticut School ofDental Medicine, Farmington, Connecticut, USA.Received for publication Oct 17, 2009; returned for revision Dec 21,2009; accepted for publication Dec 23, 2009.1079-2104/$ - see front matter© 2010 Mosby, Inc. All rights reserved.

doi:10.1016/j.tripleo.2009.12.038

lowed or spat out when desired.1 Other forms of smoke-less tobacco products commonly used in the Indian sub-continent include betel quid/paan (a blend of areca nut,slaked lime, artificial sweeteners, and sometimes tobaccowrapped in Piper betel leaf) and khaini and zarda (mix-tures of powdered tobacco and slaked lime).1-3

Gutka usage is not restricted to the Indian subconti-nent, but is also enjoyed by immigrant communitiessettled in Europe and the United States.2-5 The actualprevalence of gutka usage in southeast Asia and othercountries is yet to be documented; however, varyingresults have been reported from community surveys. Ina recent study, 46% of the residents of a local commu-nity in Karachi, Pakistan, reported using gutka habitu-ally.1 Similarly, another study reported 35% of thepatients visiting a health care center in Karachi to behabitual gutka users.2 In the Indian State of Wardha, theprevalence of gutka usage by men and women wasreported to be 46.4% and 20%, respectively.3 In Tan-zania, 6.9% of the native inhabitants have been reportedto use gutka on a daily basis.6

Habitual gutka use has been associated with theoccurrence of several oral mucosal disorders, includingoral submucous fibrosis (OSF), oral cancer, and peri-odontal disease.1,7 OSF is a chronic premalignant con-

dition, characterized by progressive accumulation of

857

OOOOE858 Javed et al. June 2010

collagen fibers in the oral submucosa, and its clinicalpresentation depends on the stage of the disease atdetection.8,9 Most patients with OSF present with anintolerance to spicy food, with rigidity of lips, tongue,and palate leading to varying degrees of limitation ofmouth opening and tongue movement.8,9 Habitualgutka users have also been shown to present with OSFat earlier ages compared with traditional betel quidusers.10-16 This may be explained by the average weightand moisture content in a gutka sachet/pouch.15,17 Agutka sachet weighs �3.5 g and contains 7% moisture,whereas the net weight of a betel quid is nearly 4 g(with �1.14 g of tobacco) and contains 70% mois-ture.15 Because gutka users tend to consume more dryweight of tobacco, areca nut, and slaked lime, they maybe exposed to oral mucosal disorders at earlier agescompared to betel quid users.

Oral cancer is the fifth most common cancer world-wide, and tobacco use has been thought to account for30% of the global cancer load.18 In Karachi, oral cancer(mainly squamous cell carcinoma) ranks second in allmalignancies among both men and women, with thehighest reported incidence in the world.19 Bhurgri et al.identified areca nut and tobacco (which are also chiefingredients of gutka) as significant risk factors for thehigh oral cancer incidence in Pakistan.19 In a longitu-dinal study performed in India, 66 individuals withOSF were followed-up for malignant transformationsover a period of 17 years.7 The results showed that oralcancer developed in 7.6% of the individuals, and themalignant transformation rate in the study group wasreported to be 4.5% over a 15-year observational period.7

Malignant transformation rates up to 19.1% have alsobeen reported in patients with OSF.20,21 Those resultsshowed that a high degree of malignancy can be ob-served in patients with OSF.7

Periodontal inflammatory parameters have also beenreported to be higher among gutka users compared tocontrol subjects (individuals not using tobacco in anyform). In a recent study, Javed et al.1 measured theplaque index (PI), bleeding on probing (BOP), andperiodontal probing depth (PPD) among habitual gutkausers and control subjects. The results showed a signif-icantly higher PI, BOP, and PPD (4-6 mm) in habitualgutka users compared with control subjects.1 In thatstudy, self-perceived gingival bleeding also was moreoften reported by the gutka users than the control sub-jects.1 Similar results were reported in the study byParmar et al., that showed an increased incidence ofBOP, PPD, gingival recession, and oral ulceration insubjects chewing a mixture of areca nut and tobacco.22

Slaked lime is a strong alkali and has been shown topromote hyperplasia and irritation in the oral mucosal

tissues.23 Chewing a mixture of slaked-lime, areca nut,

and powdered tobacco has also been shown to facilitatethe development of oral cancer.24,25

It may be postulated that gutka use intensifies theseverity of oral mucosal disorders and exposes theconsumers to severe oral health risks at earlier ages.Because gutka usage is increasing worldwide and itsingredients are hazardous to oral mucosal health, theaim of the present review was to evaluate the oralmucosal diseases associated with habitual gutka con-sumption.

MATERIALS AND METHODSRationale and focus question

Individuals who consumed �1 gutka sachet daily for�6 months were designated as “habitual gutka users/chewers.”15 The objective of the present review was toassess the negative effects of habitual gutka consump-tion on oral mucosal health. Therefore, our focus ques-tion was: What are the deleterious effects of habitualgutka consumption on oral mucosal health?

Eligibility criteriaThe following eligibility criteria were imposed: 1)

human studies; 2) test group: individuals consuming�1 gutka sachet/pouch daily for �6 months; 3) controlgroup: individuals not using tobacco in any form; and4) articles published in English.

The reference lists of potentially relevant original andreview articles were also searched to identify articles thatwere not located in the original search. Table I presentsthe list of pertinent studies that were retrieved duringthe data extraction process. Letters to the editor, his-torical reviews, and unpublished articles were ex-cluded. Table II shows the 13 studies that did notcomply with the eligibility criteria and were excluded.

Search strategiesAs a first step, the authors searched the National Li-

brary of Medicine, Washington, DC (Medline-Pubmed),for appropriate articles addressing the focus question. Da-tabases were searched from 1956 up to and including June2009 using the following terms in different combinations:“gutka,” “gutkha,” “ghutka,” “guttkha,” “smokeless to-bacco,” “areca nut,” “betel nut,” “slaked lime,” “dental,”“oral,” “periodontal,” “inflammation,” “submucous fibro-sis,” “carcinoma,” and “cancer.”

The second step was to hand search the referencelists of original and review studies that were found to berelevant in the first step. Titles containing words sug-gesting smokeless tobacco consumption as an adjunctto oral health disorders were also sought.

After final selection of the papers, those studies thatfulfilled the selection criteria were processed for data

extraction. Full texts of the selected articles were re-

OOOOEVolume 109, Number 6 Javed et al. 859

trieved. The following data were extracted from all theselected studies: investigators and year of publicationof the study, study design, age/age range of the partic-ipants, gender of the participants, total number of studyparticipants, number of male and female participants(male:female ratio), daily frequency of gutka usage(number of times gutka was consumed daily), duration

Table I. Investigators (year), study design, age, samplemain results of selected studiesInvestigator(s),

yearStudydesign

Agerange (yrs)

Samplesize

Male:femaleratio

Periodontal inflammationJaved et al.,

20081Case-control 45-64 1,000 1:1

Doifode et al.,200013

Case-control 14-59 110 1:1

Parmar et al.,200822

Case-control 31-33 365 4:1

Oral submucous fibrosisBathi et al.,

200910Case-control 10-64 220 26.5:1

Hazarey et al.,200711

Cross-sectional 9 to �50 1,000 4.9:1

Saraswathi etal., 200612

Cross-sectional 13-84 2,017 1.7:1

Doifode et al.,200013

Case-control 14-59 110 1:1

Misra et al.,199814

Case-control 20-42 110 5.8:1

Babu et al.,199615

Case-control 20-30 90 NA

Bansode,200216

Retrospective 31-40 336 2:1

Ahmad et al.,200617

Case-control 11-54 292 2.7:1

Oral cancerGangane et al.,

200726Cross-sectional 29-70 520 2.1:1

Sapkota et al.,200727

Case-control 34-75 1,742 14.3:1

OR, odds ratio; CI, confidence interval; OSF, oral submucous fibros*Each sachet/pouch contains �3.5-3.8 g dry weight gutka.1,15

of gutka usage (years), oral mucosal disorders associ-

ated with habitual gutka usage, and odds ratio (OR) and95% confidence interval (CI). The structure of thisreview was customized to mainly summarize the rele-vant information.

Statistical analysisThe statistical analysis was performed using a soft-

odds ratios, duration of gutka use and daily intake, and

95% CIDuration ofgutka use

Daily intakeof gutka* Main results

1.1-4.9) �8 years �8� Periodontal inflammation washigher in gutka chewersthan in nonchewers.

1.9-5.5) NA NA Gutka chewing wassignificantly associatedwith OSF* and periodontaldisease.

1.2-2.1) NA NA Periodontal inflammation andoral ulcers were higher ingutka-chewers comparedto nonchewers.

1.5-3.9) 3-4 yrs 1-15� Gutka is strongly associatedwith the development ofOSF.*

1.9-4.5) 2-�5 yrs �4� Gutka consumption was amajor pre-malignantlesions associated withOSF* and oral cancer.

3.7-6.4) NA NA OSF*was the most prevalentlesion among gutkachewers.

1.3-4.7) NA NA Gutka-chewing is associatedwith periodontal diseaseand OSF.*

2.2-46.6) �6 yrs NA Gutka usage was associatedwith oesophagealsubepithelial fibrosis.

1.2-2.3) �3 yrs �4� Gutka consumption wasassociated with thepresentation of OSF.*

2.5-5.3) NA 10-12� Gutka usage was associatedwith OSF,* oral ulcerationand stomatitis.

3.1-15.5) 2-4 yrs 2-10� Gutka chewing waspositively associated withOSF*

5.8-61.6) 20-49 yrs NA Gutka consumption wassignificantly associatedwith oral cancer cases.

2-5.6) �1 yr NA Gutka use was associatedwith an increased risk ofhypopharyngeal cancer.

not available.

size,

OR

2.20 (

3.56 (

1.64 (

2.98 (

2.33 (

5.08 (

3.56 (

33 (

1.65 (

3.33 (

9.25 (

18 (

4.59 (

is; NA,

ware program (statistica v. 6.0; Statsoft, Tulsa, OK).

OOOOE860 Javed et al. June 2010

The ORs were computed and 95% CIs were constructedusing logistic regression to assess the association be-tween oral mucosal diseases among gutka chewers andcontrol subjects.

RESULTSCharacteristics of the publications

The initial Medline-Pubmed search resulted in 25citations. Titles of all articles obtained were screenedby each author and all abstracts of related articles werescreened further. The full text of articles fulfilling theeligibility criteria was assessed. Eventually, 12 studies(which varied by population characteristics and re-search methodology) were included in the present re-view (Table I). Thirteen studies, which did not complywith the selection protocol, as shown in Table II, wereexcluded.

All of the 12 studies1,10-17,22,26,27 included in thepresent review were carried out at either universities orhealth care centers. The sample sizes ranged from 90 to

Table II. Excluded studies and main reasons for excluInvestigator(s), year

Chaturvedi, 2009a Gutka consumptionChaturvedi, 2009b Gutka or areca-nut chewer’Tilakaratne et al., 2006c Oral submucous fibrosis: reReichart and Philipsen, 2006d Oral submucous fibrosis in

case report from GermanAvti et al., 2006e Smokeless tobacco impairs

lung, and kidney of ratsChangrani and Gany, 2005f Paan and gutka in the UniteMishra et al., 2005g Indian youth speak about to

discussions with school sGupta and Ray, 2004h Epidemiology of betel quidNair et al., 2004i Alert for an epidemic of ora

quid substitutes gutkha aand causative mechanism

Gupta and Ray, 2003j Smokeless tobacco and heaTobacco Free Initiative, World

Health Organization, 2002kTobacco and youth in the s

Pai, 2002l Gutkha banned in Indian stWarke et al., 1999m Irradiation of chewable toba

microbiological quality

aBr Dent J 2009;206:397.bIndian J Cancer 2009;46:170-2.cOral Oncol 2006;42:561-8.dMund Kiefer Gesichtschir 2006;10:192-6.eToxicol Sci 2006;89:547-53.fJ Immigr Health 2005;7:103-8.gHealth Educ Behav 2005;32:363-79.hAnn Acad Med Singapore 2004;33:31-6.iMutagenesis 2004;19:251-62.jRespirology 2003;8:419-31.kIndian J Cancer 2002;39:1-33.lLancet Oncol 2002;3:521.mJ Food Prot 1999;62:678-81.

5,061 individuals. The ages of the participants varied

between �9 years to �75 years. In 2 studies,1,13 themale:female ratio was 1:1; and in the remaining 10studies10-12,14-17,22,26,27 there were at least twice asmany men than women in the study population.

The duration of gutka-chewing habit was reported in8 studies1,10,11,14,15,17,26,27 and ranged between �1 yearand 49 years. Daily gutka consumption by participantswas reported by 5 studies.1,10,11,15,17 In those studies,the daily consumption of gutka by its consumers rangedfrom 1 time to 15 times.

Eleven studies10-17,22,26,27 were performed in India and 11

was conducted in Pakistan. Eight studies1,10,13-15,17,22,27

were clinical and 411,12,16,26 were epidemiologic. Threestudies1,13,22 showed a significant association betweenhabitual gutka consumption and periodontal inflamma-tory conditions, including gingivitis, gingival recession,and formation of periodontal pockets (ORs 1.64 [CI1.2-2.1], 2.20 [CI 1.1-4.9], and 3.56 [CI 1.9-5.5]). Re-sults by Javed et al.1 also reported self-perceived gin-gival bleeding to be significantly higher in gutka chewers

Main reason for exclusion

Letter to the editorme Letter to the editoraetiology and pathogenesis Review article

ar-old Indian women: first Article in German

ioxidant defense in liver, Focus question not addressed

s: an emerging threat Review articleresults of focus group Focus question not addressed

Review articler due to use of the betelmasala: a review of agents

Review article

dia and south Asia Review articlest Asian region Review article

News deskxes for improvement in Focus question not addressed

sionTitle

s syndroview ona 31-yeythe ant

d Statebacco:tudentsusagel cance

nd panslth in Inouth ea

ates.cco mi

than in nonchewers (OR 2.20 [CI 1.1-4.9]). Seven stud-

OOOOEVolume 109, Number 6 Javed et al. 861

ies10-13,15-17 (4 clinical10,13,15,17 and 3 epidemiologic11,12,16)showed that OSF was more common in gutka chewersthan in nontobacco users (ORs 1.65 [CI 1.2-2.3], 2.33[CI 1.9-4.5], 2.98 [CI 1.5-3.9], 3.33 [CI 2.5-5.3], 3.56[CI 1.3-4.7], 5.08 [CI 3.7-6.4]s and 9.25 [CI 3.1-15.5]).Hazarey et al.11 (OR 2.33) and Gangane et al.26 (OR 18[CI 5.8-61.6]) reported oral cancer to be more prevalentin gutka users than in individuals not using tobaccoproducts. An increased frequency of gutka usage wasassociated with malignant transformations in OSF casesin 2 studies (ORs 2.33 [CI 1.9-4.5] and 1.65 [CI 1.2-2.3]).11,15 Studies by Misra et al.14 (OR 33 [CI 2.2-46.6]) and Sapkota et al.27 (OR 4.59 [CI 2-5.6]) dem-onstrated an extension of oral mucosal fibrosis into thehypopharynx and esophagus in gutka users. Two stud-ies demonstrated an association between gutka con-sumption and oral mucosal ulcerations (ORs 3.33 [CI2.5-5.3] and 1.64 [CI 1.2-2.1]).16,22

DISCUSSIONThe deleterious effects of areca nut, smokeless to-

bacco, and slaked lime on oral health have been welldocumented; however, a more severe and intensepathogenic response may be expected when these sub-stances are consumed as a mixture (gutka).28,29 A sum-mary of the oral pathophysiologic events induced byhabitual gutka chewing is presented in Fig. 1.

The duration of smokeless tobacco usage has beenassociated with the development of oral mucosal dis-orders. The Eipe study30 reported that habitual use ofbetel quid for �5 years predisposes the oral mucosa tooral premalignant disorders including OSF. Maher etal.31 also reported that individuals using smokelesstobacco products for up to a decade are more suscep-tible to develop OSF compared with subjects usingsuch products for a shorter duration. However, habitualgutka use has been shown to expose its consumers toOSF at a much faster pace compared to betel quidusage.15 Results by Babu et al.15 showed that gutkausers with OSF had consumed it for �3 years com-pared with betel quid users with OSF who had startedthe habit nearly 8 years before. Similarly, a recentcase-control study reported that gutka-chewing habitfor up to 4 years increases the relative risk of develop-ing OSF.10 A possible explanation for this may be thathabitual gutka users consume more dry weight of to-bacco, areca nut, and slaked lime, which causes nico-tine to act synergistically on the cytotoxicity induced byarecoline (a major areca nut alkaloid), thereby increasingthe vulnerability of buccal mucosal fibroblasts to damageand enhanced collagen production (up to 170%).15,32-37

To our knowledge from the indexed literature, thereis no consensus regarding the influence of daily fre-

quency of gutka consumption on the occurrence of oral

mucosal disorders. According to results by Javed etal.,1 the frequency of gutka consumption among indi-viduals with oral mucosal disorders ranged from once aday to 10 times daily (average frequency 8 times daily).On the other hand, Bathi et al.10 reported that the risk ofdeveloping OSF is significantly higher in individualsconsuming gutka at least 15 times daily.

A direct association between oral inflammatory con-ditions and age of the subject has been reported.38

However, it seems that gutka can expose its consumersto severe oral mucosal disorders at any age. In a studyby Javed et al.,1 gutka chewers presenting with peri-odontal inflammation had a mean age of �51 years(range 45-64 years). In the study by Bathi et al.,10 themean age of gutka users was �34 years and rangedfrom 10 to 64 years. OSF has also been reported inchildren as young as 4 and 11 years of age who rapidlydeveloped submucosal fibrosis within 3 years of start-ing the chewing abuse.17,37,39

Gutka contains fine grains of areca nut, which be-sides causing mechanical injury to oral tissues, alsoallow ground tobacco to adhere to the traumatizedmucosa, leading to morphologic changes and mem-

Fig. 1. Pathophysiologic events (mechanisms) of gutka’s ef-fect on oral soft tissues.

brane damage. Thus, areca nut in combination with

OOOOE862 Javed et al. June 2010

tobacco may cause cross-links and accelerate the onsetof OSF in habitual gutka chewers. This may be anexplanation for clinical reports that have shown habit-ual gutka users to present with OSF at earlier agescompared with traditional betel quid users.10-15 How-ever, there are several other factors that may influencethe induction of OSF at younger ages regardless of thefrequency and quantity of daily gutka usage. Rajend-ran40 reported that vitamin and iron deficiency togetherwith malnourished state of the host leads to derange-ment in the inflammatory reparative response of thelamina propria, resulting in impaired healing and scar-ification, which eventually leads to OSF. Nutritionaldeficiency, deprived socioeconomic status (SES), pooreducation, as well as the duration of placement of gutkain the oral cavity may play cumulative roles on theinduction and severity of oral mucosal disor-ders.13,17,38-41 In studies by Ahmad et al.17 and Shiauand Kwan,41 the majority of gutka users presentingwith OSF were malnourished and had a deprived SES.In the study by Javed et al.,1 gutka users cited thechewing habit to be “beneficial” because it helped themto control hunger. Simultaneously, the role of a pooreducation status, which may compel tobacco chewersto continue with the abuse despite being aware of theirimpaired oral mucosal health, can not be overlooked. Inthe Eipe study,30 individuals with OSF were aware oftheir oral mucosal disorder, but they continued thetobacco-chewing habit until the diagnosis of oral cancerwas made. Regarding duration of placement of gutka inthe oral cavity, Ahmad et al.17 reported that 74.5% ofthe individuals with OSF were placing gutka in theirbuccal vestibule for 2-10 minutes. In another study,individuals with oral inflammatory disorders were plac-ing gutka in their buccal vestibule for 5-30 minutes.1

Therefore, it seems that the duration of the insult (incombination with the factors mentioned above) mayalso influence the occurrence and progression of oralmucosal disorders among gutka users. Although OSF isirreversible and persists even after cessation of thechewing habit, it may be hypothesized that cessation ofthe gutka-chewing habit may help to reduce the severityof the condition and may also prevent its progression tomalignancy. However, gutka prevention and cessationresearch and interventions are not yet documented.

A relationship between oral inflammatory conditionsand gender has been reported.42 However, the influenceof gender in relation to oral mucosal disorders amonggutka chewers remains debatable. Anwar et al.43 con-ducted a pilot study which aimed to investigate theattitudes and practices concerning habitual gutka use ina town in India. That study reported gutka usage to bemore common among men than women.43 Similarly,

results by Saraswathi et al.,12 Ahmad et al.17 and Gan-

gane et al.26 have reported oral mucosal diseases (in-cluding OSF and oral cancer) to be more prominentamong male than female gutka chewers. However, it isnoteworthy that there were at least twice as many menthan women in those studies.12,17,26 It may therefore beargued that the reported gender might have been due tothe increased number of male compared with femaleparticipants. However, results by Hazarey et al.11

showed that the severity of OSF was more prevalent inwomen than men even though the male:female ratiowas 4.9:1. In that study, an underprivileged SES andpoor education was significantly higher in women thanmen.11 These factors may have contributed to the in-creased severity of OSF in women compared with menwith OSF participating in that study.11 From the liter-ature reviewed, we believe that the question “Doesgender have any influence on oral mucosal disordersamong gutka chewers?” is yet to be answered andfurther studies are warranted to investigate this rela-tionship.

A study that investigated the effect of smokelesstobacco on blood flow responses showed that smoke-less tobacco significantly increases the heart rate, arte-rial blood pressure, and gingival blood flow.44 Further-more, gutka chewers have been shown to have reducedsalivation and mucous formation, thereby reducing thenormal commensal oral microflora and exposing theiroral cavities to pathogens (Aspergillus species).45 Thus,a reduced salivary flow may allow the pathogenic bac-teria to stagnate in the supra- and subgingival areas,thereby inducing periodontal inflammation in gutkachewers compared with nonchewers. Areca nut extractshave also been associated with the expression of matrixmetalloproteinase 9 in gingival epithelial cells, whichmight help to promote periodontal pathosis in gutkausers compared with control subjects.46 These might bepossible explanations for the raised periodontal inflam-matory parameters (including PI, BOP, PPD, and self-perceived gingival bleeding) among gutka users com-pared with controls.1,22 Nevertheless, the role ofconfounding factors such as a low SES and poor edu-cation that may also trigger periodontal inflammationcan not be overlooked.40

In conclusion, it is apparent that habitual gutka con-sumption can rapidly devastate the oral mucosa, and theconsequences may extend beyond the oral cavity.

RECOMMENDATIONIt is highly recommended that the department of

health and consumer protection should restrict access togutka for adolescents and prohibit its sale to minors tocurtail gutka usage. There should also be a healthhazard label on gutka products. By raising public

awareness about the negative effects and health hazards

OOOOEVolume 109, Number 6 Javed et al. 863

of gutka, the prevalence of oral cancer and other mu-cosal disorders might decrease among gutka users. Thismay also assist in improving the quality of life in theseindividuals.

REFERENCES1. Javed F, Altamash M, Klinge B, Engström PE. Periodontal

conditions and oral symptoms in gutka-chewers with and withouttype 2 diabetes. Acta Odontol Scand 2008;66:268-73.

2. Ali NS, Khuwaja AK, Ali T, Hameed R. Smokeless tobacco useamong adult patients who visited family practice clinics in Kara-chi, Pakistan. J Oral Pathol Med 2009;38:416-21.

3. Dongre A, Deshmukh P, Murali N, Garg B. Tobacco consump-tion among adolescents in rural Wardha: where and how tobaccocontrol should focus its attention? Indian J Cancer 2008;45:100-6.

4. Mazahir S, Malik R, Maqsood M, Merchant KA, Malik F,Majeed A, et al. Socio-demographic correlates of betel, areca andsmokeless tobacco use as a high risk behavior for head and neckcancers in a squatter settlement of Karachi, Pakistan. SubstAbuse Treat Prev Policy 2006;1:10.

5. Changrani J, Gany FM, Cruz G, Kerr R, Katz R. Paan and gutkause in the United States: a pilot study in Bangladeshi and Indian-Gujarati immigrants in New York City. J Immigr Refug Stud2006;4:99-110.

6. Kaduri P, Kitua H, Mbatia J, Kitua AY, Mbwambo J. Smokelesstobacco use among adolescents in Ilala Municipality, Tanzania.Tanzan J Health Res 2008;10:28-33.

7. Murti PR, Bhonsle RB, Pindborg JJ. Malignant transformationrate in oral submucous fibrosis over a 17-year period. Commu-nity Dent Oral Epidemiol 1985;13:340-1.

8. Pindborg JJ, Murti PR, Bhonsle RB, Gupta PC, Daftary DK,Mehta FS. Oral submucous fibrosis as a precancerous condition.Scand J Dent Res 1984;92:224-9.

9. Pindborg JJ, Bhonsle RB, Murti PR, Gupta PC, Daftary DK,Mehta FS. Incidence and early forms of oral submucous fibrosis.Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1980;50:40-4.

10. Bathi RJ, Parveen S, Burde K. The role of gutka chewing in oralsubmucous fibrosis: a case-control study. Quintessence Int 2009;40:e19-25.

11. Hazarey VK, Erlewad DM, Mundhe KA, Ughade SN. Oralsubmucous fibrosis: study of 1000 cases from central India.J Oral Pathol Med 2007;36:12-17.

12. Saraswathi TR, Ranganathan K, Shanmugam S, Sowmya R,Narasimhan PD, Gunaseelan R. Prevalence of oral lesions inrelation to habits: cross-sectional study in South India. Indian JDent Res 2006;17:121-5.

13. Doifode VV, Ambadekar NN, Lanewar AG. Assessment of oralhealth status and its association with some epidemiological factorsin population of Nagpur, India. Indian J Med Sci 2000;54:261-9.

14. Misra SP, Misra V, Dwivedi M, Gupta SC. Oesophageal subep-ithelial fibrosis: an extension of oral submucosal fibrosis. Post-grad Med J 1998;74:733-6.

15. Babu S, Bhat RV, Kumar PU, Sesikaran B, Rao KV, Aruna P,Reddy PR. A comparative clinico-pathological study of oralsubmucous fibrosis in habitual chewers of pan masala andbetelquid. J Toxicol Clin Toxicol 1996;34:317-22.

16. Bansode NN. An exploratory study on gutkha and smokelesstobacco consumption. Nurs J India 2002;93:127-28.

17. Ahmad MS, Ali SA, Ali AS, Chaubey KK. Epidemiological andetiological study of oral submucous fibrosis among gutkha chew-ers of Patna, Bihar, India. J Indian Soc Pedod Prev Dent 2006;

24:84-9.

18. Parkin DM, Pisani P, Ferlay J. Estimates of the worldwideincidence of eighteen major cancers in 1985. Int J Cancer 1993;54:594-606.

19. Bhurgri Y, Bhurgri A, Hussainy AS, et al. Cancer of the oralcavity and pharynx in Karachi—identification of potential riskfactors. Asian Pac J Cancer Prev 2003;4:125-30.

20. Anil S, Beena VT. Oral submucous fibrosis in a 12-year-old girl:case report. Pediatric Dental 1993;15:120-22.

21. Lund TW, Cohen JI. Trismus appliances and indications for use.Quintessence Int 1993;24:275-79.

22. Parmar G, Sangwan P, Vashi P, Kulkarni P, Kumar S. Effect ofchewing a mixture of areca-nut and tobacco on periodontaltissues and oral hygiene status. J Oral Sci 2008;50:57-62.

23. Dunham LJ, Muir CS, Hamner JE III. Epithelial atypia in ham-ster cheek pouches treated repeatedly with calcium hydroxide.Br J Cancer 1996;20:588-93.

24. Thomas SJ, MacLennan R. Slaked lime and betel nut cancer inPapua New Guinea. Lancet 1992;340:577-8.

25. Van der Bijl, Van Eyk AD, Van Wyk CW, Stander IA. Diffusionof reduced arecoline and arecaidine through human vaginal andbuccal mucosa. J Oral Pathol Med 2001;30:200-5.

26. Gangane N, Chawla S, Anshu, Gupta SS, Sharma SM. Reassess-ment of risk factors for oral cancer. Asian Pac J Cancer Prev2007;8:243-8.

27. Sapkota A, Gajalakshmi V, Jetly DH, Roychowdhury S, DikshitRP, Brennan P, et al. Smokeless tobacco and increased risk ofhypopharyngeal and laryngeal cancers: a multicentric case-con-trol study from India. Int J Cancer 2007;121:1793-8.

28. Sundqvist K, Grafström RC. Effects of areca nut on growth,differentiation and formation of DNA damage in cultured humanbuccal epithelial cells. Int J Cancer 1992;52:305-10.

29. Jeng JH, Chang MC, Hahn LJ. Role of areca nut in betelquid-associated chemical carcinogenesis: current awareness andfuture perspectives. Oral Oncol 2001;37:477-92.

30. Eipe N. The chewing of betel quid and oral submucous fibrosisand anesthesia. Anesth Analg 2005;100:1210-3.

31. Maher R, Lee AJ, Warnakulasuriya KA, Lewis JA, Johnson NW.Role of areca nut in the causation of oral submucous fibrosis: acase-control study in Pakistan. J Oral Pathol Med 1994;23:65-9.

32. Chang YC, Lii CK, Tai KW, Chou MY. Adverse effects ofarecoline and nicotine on human periodontal ligament fibroblastsin vitro. J Clin Periodontol 2001;28:277-82.

33. Jeng JH, Lan WH, Hahn LJ, Hsieh CC, Kuo MY. Inhibition ofthe migration, attachment, spreading, growth and collagen syn-thesis of human gingival fibroblasts by arecoline, a major arecaalkaloid, in vitro. J Oral Pathol Med 1996;25:371-5.

34. Chang YC, Tai KW, Cheng MH, Chou LS, Chou MY. Cytotoxicand nongenotoxic effects of arecoline on human buccal fibro-blasts in vitro. J Oral Pathol Med 1998;27:68-71.

35. Chang YC, Hu CC, Tseng TH, Tai KW, Lii CK, Chou MY.Synergistic effects of nicotine on arecoline-induced cytotoxicityin human buccal mucosal fibroblasts. J Oral Pathol Med2001;30:458-64.

36. Bagchi M, Balmoori J, Bagchi D, Stohs SJ, Chakrabarti J, DasDK. Role of reactive oxygen species in the development ofcytotoxicity with various forms of chewing tobacco and panmasala. Toxicology 2002;179:247-55.

37. Hayes PA. Oral submucous fibrosis in a 4-year-old girl. OralSurg Oral Med Oral Pathol Oral Radiol Endod 1985;59:475-8.

38. Javed F, Näsström K, Benchimol D, Altamash M, Klinge B,Engström PE. Comparison of periodontal and socioeconomicstatus between subjects with type 2 diabetes mellitus and non-diabetic controls. J Periodontol 2007;78:2112-9.

39. Shah B, Lewis MA, Bedi R. Oral submucous fibrosis in a

OOOOE864 Javed et al. June 2010

11-year-old Bangladeshi girl living in the United Kingdom. BrDent J 2001;191:130-2.

40. Rajendran R. Oral submucous fibrosis: etiology, pathogenesisand future research. Bull WHO 1994;72:985-96.

41. Shiau YY, Kwan HW. Submucous fibrosis in Taiwan. Oral SurgOral Med Oral Pathol Oral Radiol Endod 1979;47:453-7.

42. Javed F, Klingspor L, Sundin U, Altamash M, Klinge B, Eng-ström PE. Periodontal conditions, oral Candida albicans andsalivary proteins in type 2 diabetic subjects with emphasis ongender. BMC Oral Health 2009;9:12.

43. Anwar S, Williams SA, Scott-Smith J, Sage H, Baweja S, SingalM, Sharma NK. A comparison of attitudes and practices of gutkausers and nonusers in Chitrakoot, India. A pilot. Prim Dent Care2005;12:5-10.

44. Mavropoulos A, Aars H, Brodin P. The acute effects of smoke-less tobacco (snuff) on gingival blood flow in man. J Periodontal

Res 2001;36:221-6.

45. Avasn Maruthit Y, Rao RS, Palivela H, Thakre S. Impact ofgutkha chewing and smoking on microbial environment of oralcavity: a case study on slum dwellers of selected areas in Visa-khapatnam. J Environ Sci Eng 2004;46:268-73.

46. Tseng YH, Chang KW, Liu CJ, Lin CY, Yang SC, Lin SC.Areca-nut extract represses migration and differentiation whileactivating matrix metalloproteinase-9 of normal gingival epithe-lial cells. J Periodontal Res 2008;43:490-9.

Reprint requests:

Dr. Fawad JavedDivision of ResearchDepartment of Dental MedicineKarolinska InstitutetHuddingeSweden

fawjav@gmail.com