Content uploaded by Kandasamy Ravichandran
Author content
All content in this area was uploaded by Kandasamy Ravichandran on Mar 02, 2023
Content may be subject to copyright.
ORALCANCERINSOUTHERNINDIA:THEINFLUENCEOFSMOKING,
DRINKING,PAAN-CHEWINGANDORALHYGIENE
PrabhaBALARAM
1
,HemaSRIDHAR
2
,ThangarajanRAJKUMAR
3
,SalvatoreVACCARELLA
4
,RolandoHERRERO
5
,
AmbakumarNANDAKUMAR
2
,KandaswamyRAVICHANDRAN
3
,KunnambathRAMDAS
1
,RengaswamySANKARANARAYANAN
4
,
VendhanGAJALAKSHMI
3
,NubiaMU˜NOZ
4
andSilviaFRANCESCHI
4
*
1
RegionalCancerCenter,Trivandrum,Kerala,India
2
KidwaiMemorialInstituteofOncology,Bangalore,Karnataka,India
3
CancerInstitute(WIA),Adyar,Chennai,India
4
InternationalAgencyforResearchonCancer,Lyon,France
5
CostaRicanCancerInstitute,SanJose´,CostaRica
Between1996and1999wecarriedoutacase-control
studyin3areasinSouthernIndia(Bangalore,Madrasand
Trivandrum)including591incidentcasesofcancerofthe
oralcavity(282women)and582hospitalcontrols(290wom-
en),frequency-matchedwithcasesbyageandgender.Odds
ratios(ORs)and95%confidenceintervals(CIs)wereob-
tainedfromunconditionalmultiplelogisticregressionsand
adjustedforage,gender,center,education,chewinghabit
and(menonly)smokinganddrinkinghabits.Loweducational
attainment,occupationasafarmerormanualworkerand
variousindicatorsofpoororalhygienewereassociatedwith
significantlyincreasedrisk.AnORof2.5(95%CI1.4–4.4)was
foundinmenforsmoking>20bidiorequivalentsversus
0/day.TheORforalcoholdrinkingwas2.2(95%CI1.4–3.3).
TheORforpaanchewingwasmoreelevatedamongwomen
(OR42;95%CI24–76)thanamongmen(OR5.1;95%CI
3.4–7.8).AsimilarORwasfoundamongchewersofpaan
with(OR6.1inmenand46inwomen)andwithouttobacco
(OR4.2inmenand16.4inwomen).Amongmen,35%oforal
cancerisattributabletothecombinationofsmokingand
alcoholdrinkingand49%topan-tobaccochewing.Among
women,chewingandpoororalhygieneexplained95%oforal
cancer.
©2002Wiley-Liss,Inc.
Keywords:oralcancer;tobacco;paanchewing;alcohol;oralhy-
giene
Canceroftheoralcavityandpharynxisthefirstandthird
commonestcancerinIndianmenandwomen,respectively.
1
Whereasinmostareasathighriskforcanceroftheoralcavity
otherthanIndia(e.g.,centralandEasternEurope,SouthAmerica),
theratiosbetweenmaleandfemaleincidenceratesrangebetween
3and10,inIndiathemale-to-femaleratioisapproximately1(e.g.,
Madras)orlowerthan0.5(Bangalore).
2
Suchveryhighincidence
ratesinIndianwomenreflectthepersistentimportanceinIndiaof
paanchewing,ahabitthatisequallycommoninthe2genders.
3
Paangenerallyincludescalciumhydroxide,arecanut(fromthe
Arecacatechutree)andbetelleaf(fromthePiperbetlevine).
Tobaccoand/orvariousspicesarecommonlyadded.
4
Paanrepre-
sentsacheappharmacologicallyaddictingstimulant,principally
usedbymembersoflowsocialclassesinSouthAsia.Fewerefforts
havebeenmadeinAsiatodiscouragepaanchewingthantobacco
smoking,
5
andonlyrecentlyhavelinksbeenestablishedbetween
paanandoralcancerthatcannotbeexplainedbythepresenceof
tobacco.
3,6
AnnualpercapitaconsumptionofcigarettesinIndiawasmax-
imalinthe1970sand1980sanddeclinedbyapproximately40%
intheearly1990s.
7
Twonation-widesurveys
8,9
showedasome-
whatlowerprevalenceoftobaccouseinanyformin1993–1994
(23%inurbanand34%inruralareasinmenand4%and9%,
respectively,inwomen)thanin1987–1988(26%and35%inmen
and6%and11%inwomen,respectively).Itisestimatedthat150
millionmalesand34millionfemalesusedtobaccoinIndiain
1996.
8,9
Relativelyfewcase-controlstudieshaverecentlyaddressedthe
impactofpaanchewingandsmokingonoralcancerinIndia,
10–12
andinformationonwomenandonriskfactorsotherthansmoking
orchewingisscanty.
12
Thepresentcase-controlstudywasconductedin3areasof
SouthernIndiainordertoevaluatetherelativeimportanceof
smoking,alcoholdrinkingandpaanchewing,withorwithout
tobacco,oncanceroftheoralcavityinmenandwomenandthe
modifyingeffect,ifany,ofvariousindicatorsoforalhygiene.Our
studyispartofaninternationalstudyonoralcancercoordinated
bytheInternationalAgencyforResearchonCancerandcarried
outalsoinItaly,
13
Cuba,
14
Spain,NorthernIreland,Poland,Can-
ada,SudanandAustralia,whosemajoraimistoevaluatetherole
ofhumanpapillomavirus(HPV).
15
Infact,manycase-seriesanda
fewcase-controlstudieshaveraisedthepossibilitythatHPVmay
becausallyassociatedwithasubsetofheadandneckcancer,most
notablytonsillarcarcinoma.
15
MATERIALANDMETHODS
BetweenJuly1996andMay1999theincidentcasesofcancer
oftheoralcavitywereidentifiedin3Indiancenters:Bangalore,
MadrasandTrivandrum,SouthernIndia.Amongidentifiedcases,
20weretoosicktobeinterviewed.Atotalof309malecases
(medianage56;range22–85years)and282femalecases(median
age58;range18–87years)werethusenrolled(TableI).Twenty-
ninecases(24males)oforopharynxcancerwerealsointerviewed
butwerenotincludedintheanalysis.Thedistributionbycancer
stageamongmenwasasfollows:stage1,16%;stage2,18%;
stage3,28%;andstage4,38%.Amongwomen,itwasasfollows:
stage1,8%;stage2,14%;stage3,38%;andstage4,40%.All
caseshadtheirinterviewandoralexaminationbeforeanycancer
treatment.
Controlsubjectswerefrequency-matchedwithcasesbycenter,
quinquenniumofageandgender.Theywereallidentifiedand
interviewedinthesamehospitalwherecaseswerefound.In
MadrasandBangalore,controlsubjectswereidentifiedamong
relativesandfriendswhowereattendingpatientsadmittedfor
cancerotherthanoralcancerto,respectively,theMadrasCancer
InstituteortheKidwaiMemorialInstituteofOncology.InTrivan-
drum,controlsubjectswerechosenamongoutpatientswhoat-
tendedtheclinicsoftheMedicalCollegeHospitalorofthe
*Correspondenceto:InternationalAgencyforResearchonCancer,150,
CoursAlbertThomas,F-69372Lyon,c´edex08,France.
Fax:⫹33-4-72-73-83-45.E-mail:franceschi@iarc.fr
Received14August2001;Revised29October2001;Accepted2No-
vember2001
Publishedonline4January2002
Int.J.Cancer:98,440–445(2002)
©2002Wiley-Liss,Inc.
DOI10.1002/ijc.10200
PublicationoftheInternationalUnionAgainstCancer
Regional Cancer Center but were found to be free from malignant
diseases. In all 3 centers, over 90% of eligible controls accepted
participation in the study. Overall, the control group included 292
men (median age 55; range 20 –76 years) and 290 women (median
age 52; range 18 –80 years) (Table I).
Cases and controls were interviewed by social workers. The
section of smoking habits included questions of smoking status
(never, ex-smoker or current smokers), daily number of cigarettes,
cigars or bidi smoked, age at starting and duration of the habit.
Bidi is a local cigarette made by wrapping less than 0.5 g of coarse
tobacco dust in a dry temburni (Diospyros melanoxylon) leaf.
When estimating risk associated with tobacco smoking, 1 bidi was
considered equivalent to 1 cigarette or
1
⁄
4
of a cigar. The consump-
tion of the commonest alcoholic beverages was also investigated.
The alcoholic beverages used are mainly a locally fermented and
distilled sap from palm trees called “toddy”(approximately 4%
ethanol) and another locally brewed liquor called “arrack”(ap-
proximately 40% ethanol). Taking into account the different eth-
anol concentration, 1 drink corresponded to approximately 40 ml
of hard liquor (arrack included), 450 ml of beer and toddy, and 150
ml of wine, equivalent to 15 g of ethanol. In Bangalore, a simpli-
fied questionnaire was used for drinking habits, and study subjects
could be classified as ever/never drinkers only.
The habit of paan chewing was investigated by considering the
chewing status (never, ex-chewer or current chewer) before cancer
onset, different kinds of products (i.e., paan with or without
tobacco), number of paan consumed per day, age at starting and
duration of the habit. Paan chewing involved the addition of
locally cured dried tobacco leaves and/or stem in most study
subjects. Never-smokers, never-drinkers and never-chewers were
individuals who had abstained respectively from smoking, alco-
holic beverages and chewing, lifelong. Former smokers, former
drinkers and former chewers had abstained respectively from any
type of smoking, chewing or drinking for at least 12 months before
cancer diagnosis or interview (for controls).
Indicators of oral hygiene were self-reported by means of 9
specific questions. The number of missing teeth that had not been
replaced and the general oral condition, on the basis of presence of
tartar, decayed teeth and mucosal irritation, were evaluated by the
interviewer through inspection of the mouth. The questionnaire
also included information on sociodemographic characteristics,
prior occurrence of sexually transmitted diseases and other infec-
tions, family history of cancer and a dietary questionnaire.
The present project was reviewed and approved by the Ethical
Committee of IARC and the local ethical and research committees.
Odds ratios (ORs) and corresponding 95% confidence intervals
(CIs) were computed for the 3 centers together using unconditional
multiple logistic regression models. Men and women were as-
sessed separately. All models included terms for center, age quin-
quennium, educational years and chewing habit in addition to other
variables as specified. Detailed evaluation of and adjustment for
smoking and drinking habits was restricted to men, since very few
women reported any consumption of cigarettes or alcoholic bev-
erages (Table I). Attributable risk fractions were computed, sepa-
rately for men and women, according to a method that implies
knowledge of the risk estimates and of the joint distribution of risk
factors among cases only, and is therefore applicable to hospital-
based case-control studies.
16
RESULTS
Oral cancer cases reported significantly fewer years of education
than control subjects. The difference was more marked in women
(OR for 0 versus ⱖ7 years of education 5.5) than men (OR 2.1).
Industrial manual workers and farmers were at an approximately
2-fold increased risk compared with clerical workers in either
gender. Housewives represented the majority of occupations in the
“other”category. A direct association also emerged between can-
cer risk and spouse’s education (OR for 0 versus ⱖ7 years of
education 1.9; 95% CI 1.1–3.4 in men and 1.6; 95% CI 0.6 –4.4 in
TABLE I –DISTRIBUTION AND ODDS RATIOS (OR) AND CORRESPONDING 95% CONFIDENCE INTERVALS (CI) FOR CANCER OF THE ORAL CAVITY BY
SELECTED CHARACTERISTICS AND GENDER (591 CASES AND 582 CONTROLS, INDIA, 1996 –1999)
1
Men Women
Cases Controls OR
2
(95% CI) Cases Controls OR
2
(95% CI)
Age (yr)
⬍55 126 136 109 159
55–64 103 92 98 77
ⱖ65 80 64 75 54
Education (years)
ⱖ7
3
101 163 1 13 112 1
1–6 138 88 1.89 (1.24–2.88) 45 72 1.09 (0.44–2.69)
0 70 41 2.06 (1.21–3.49) 222 104 5.52 (2.36–12.90)
1
2
for trend 9.83; p⫽0.002 20.12; p⬍0.001
Number of siblings
⬍3
3
50 54 1 87 73 1
3–4 58 56 1.32 (0.72–2.43) 62 54 0.98 (0.45–2.11)
ⱖ5 55 75 0.84 (0.46–1.55) 58 94 0.97 (0.46–2.01)
1
2
for trend 0.47; p⫽0.49 0.04; p⫽0.85
Religion
Hindu or buddhist
3
199 193 1 120 120 1
Christian 27 21 1.88 (0.90–3.91) 10 14 0.86 (0.22–3.37)
Muslim 25 16 1.30 (0.60–2.83) 20 18 1.14 (0.38–3.39)
Occupation
Clerical
3
44 89 1 13 23 1
Industrial workers 89 82 2.19 (1.26–3.78) 108 103 2.29 (0.80–6.58)
Farmers 153 90 2.76 (1.62–4.70) 57 21 2.18 (0.62–7.66)
Others 23 29 1.69 (0.77–3.70) 102 140 1.50 (0.51–4.42)
Smoking habit
Never
3
86 127 1 274 285 1
Ever 223 165 1.77 (1.17–2.69) 8 5 3.18 (0.58–17.46)
Drinking habit
Never
3
137 232 1 273 285 1
Ever 172 90 2.18 (1.43–3.33) 6 5 0.31 (0.07–1.40)
1
Distribution: some strata do not add up to the total because of missing values.–
2
Estimates from unconditional regression equations, including
terms for age, center, education and chewing habits and (men only) smoking and drinking habits.–
3
Reference category.
441ORAL CANCER IN SOUTHERN INDIA
women, not shown). Number of siblings was unrelated to oral
cancer risk in either gender, whereas Christian men, but not
Christian women, were at a 1.9-fold greater risk than Hindus or
Buddhists. Tobacco smoking was associated with oral cancer risk
among men (OR 1.8) and women (OR 3.2), but less than 3% of
female cases had ever smoked. Consumption of alcoholic bever-
ages was associated with an OR of 2.2 among men, but no risk
increase was detected among the few drinking women (2% of
female cases).
Smoking and drinking habits in men only are considered in
detail in Table II. Fifty-three percent of cases and 39% of controls
were current smokers. The majority of them smoked bidi, alone or
in combination with cigarettes or cigars (OR for ⱖ20 bidi or
equivalent/day versus never smokers 2.5; 95% CI 1.4 –4.4). Only
28 cases and 40 controls smoked cigarettes only (OR 1.1). Age at
starting among current smokers was relatively late (median age
starting at 20 years among both cases and controls), and it was not
related to oral cancer risk. Quitting smoking was associated with a
nonsignificant decline in risk compared with current smokers (OR
for ⱖ10 years after quitting 0.7), but former smokers were few.
Tobacco snuffing was rare (7% of male cases and 5% of controls)
and not significantly associated with oral cancer risk (not shown).
Current drinkers of alcoholic beverages were 32% among male
cases, and 19% among male controls (Table II). A significant trend
of increase in oral cancer risk with increasing number of drinks per
week was found (
2
⫽6.0; p⫽0.01). Toddy accounted for 38%
of the alcohol consumption, whereas arrack and liquors such as
whisky or gin represented 33 and 28%, respectively, of the total
amount. Only 1% of alcohol intake came from wine and beer.
Neither age at start drinking nor cessation of the habit were related
to oral cancer risk.
Table III shows paan chewing habits in men and women sepa-
rately. Among cases, 59% of men and 90% of women were
ever-chewers (OR 5.1; 95% CI 3.4 –7.8 and 42.4; 95% CI 23.8 –
75.6, respectively). Ninety-one percent of chewers, in both gen-
ders, reported the use of paan with tobacco (OR 6.1 in men and
45.9 in women). However, a significantly elevated risk was also
found in the few subjects who reported chewing paan without
tobacco (OR 4.2 in men and 16.4 in women). Among chewers of
paan without tobacco, 9 male cases and 4 male controls, but no
women, reported tobacco smoking. Median number of paan con-
sumed per day was 5 in either female or male cases. A significant
trend of increase in oral cancer risk by number of paan per day was
seen in both genders. The OR for ⱖ10 paans per day was sub-
stantially greater in women (OR 112) than in men (OR 7.9).
Women reported starting at an earlier age (median 20 years) than
men (median 22 years), and early starting of chewing (⬍20 ver-
sus ⱖ25 years of age) was associated with a 5-fold elevated OR
in women, but not in men. There were few former chewers. No
clear decline of oral cancer risk was seen after chewing cessation
in either gender.
TABLE II –ODDS RATIOS (OR) AND CORRESPONDING 95% CONFIDENCE INTERVALS (CI) FOR CANCER
OF THE ORAL CAVITY IN MEN BY SMOKING AND DRINKING HABITS
(309 CASES AND 292 CONTROLS, INDIA, 1996 –99)
1
Cases Controls OR
2
(95% CI)
Smoking habit
Never smokers 86 127 1
3
Former smokers 59 50 1.38 (0.78–2.47)
Current smokers
Cigarettes only 28 40 1.08 (0.56–2.09)
Cigars only 8 1 10.17 (1.12–92.18)
Bidi or equiv. (no./day)
⬍20 55 33 2.04 (1.10–3.79)
ⱖ20 73 41 2.50 (1.41–4.42)
Age started smoking (yr)
4
ⱖ23 54 34 1
3
20–22 63 46 0.82 (0.42–1.61)
⬍20 47 35 0.84 (0.41–1.73)
1
2
for trend 0.23; p⫽0.63
Years since quit smoking
4
Current smoker 164 115 1
3
⬍10 39 33 0.71 (0.37–1.34)
ⱖ10 20 17 0.73 (0.32–1.68)
1
2
for trend 1.07; p⫽0.30
Drinking habit
5
Abstainers 102 152 1
3
Former drinkers 65 34 1.78 (0.97–3.28)
Current drinkers (drinks/wk)
6
⬍3 29 18 2.17 (1.00–4.69)
3–13 22 13 2.14 (0.89–5.19)
ⱖ14 29 12 1.97 (0.85–4.57)
1
2
for trend 6.02; p⫽0.01
Age at start drinking
4,5
(yr)
ⱖ31 26 13 1
3
23–30 29 12 2.11 (0.69–6.48)
⬍23 25 18 0.67 (0.20–2.26)
1
2
for trend 0.08; p⫽0.78
Years since quit drinking
4,5
Current drinkers 84 44 1
3
⬍10 49 27 0.94 (0.43–2.09)
ⱖ10 16 7 0.62 (0.19–2.05)
1
2
for trend 0.36; p⫽0.55
1
Some strata do not add up to the total because of missing values.–
2
Estimates from unconditional
regression equations, including terms for age, center, education, smoking, drinking and chewing habits.–
3
Reference category.–
4
Current smokers or drinkers only.–
5
Information not available for Bangalore.–
6
One
drink corresponds to approximately 150 ml of wine, 450 ml of beer and 40 ml of liquor (i.e., 15gof
ethanol).
442 BALARAM ET AL.
To elucidate the difference between genders, the influence of
paan chewing was examined separately in men who, like the vast
majority of women in our study, never smoked or drank alcoholic
beverages (63 cases and 110 controls, not shown). ORs were more
elevated (OR for ⱖ5versus 0 paan/day 18; 95% CI 6.2–53.8) than
in the total male population but were still lower than among
women. When the gender-specific ORs for paan chewing were
examined in 3 separate strata of education, no difference was
found between male (OR 5.2) and female (OR 3.7) chewers who
reported 7 years of education or more.
Various indicators of oral hygiene and dentition are shown in
Table IV according to gender. Female, but not male, cases reported
that they cleaned their teeth less often than controls. For this
purpose, the majority of study participants, most notably women,
TABLE IV –ODDS RATIOS (OR) AND CORRESPONDING 95% CONFIDENCE INTERVALS (CI) FOR CANCER OF THE ORAL CAVITY BY INDICATORS OF
ORAL HYGIENE AND DENTITION AND GENDER (591 CASES AND 582 CONTROLS, INDIA, 1996 –99)
1
Men Women
Cases Controls OR
2
(95% CI) Cases Controls OR
2
(95% CI)
Self-reported:
Tooth cleaning (times/day)
ⱖ2
3
53 60 1 33 73 1
ⱕ1 254 232 0.96 (0.59–1.59) 244 217 3.39 (1.65–6.98)
Instrument used
Tooth brush
3
96 177 1 35 177 1
Finger 183 103 1.75 (1.11–2.76) 236 109 3.40 (1.80–6.45)
Other 30 12 3.65 (1.50–8.84) 11 4 2.87 (0.54–15.40)
Wearing dentures
No
3
296 276 1 274 263 1
Yes 11 16 0.86 (0.35–2.06) 4 26 0.26 (0.05–1.25)
Dental check-ups
Never
3
252 217 1 246 198 1
Yes 52 72 0.89 (0.56–1.42) 31 88 0.41 (0.19–0.87)
Gum bleeding
No
3
199 238 1 124 198 1
Yes 108 53 2.83 (1.71–4.68) 154 92 3.35 (1.82–6.15)
Interviewer-reported
Missing teeth
ⱕ5
3
161 235 1 114 229 1
⬎5 145 56 3.89 (2.46–6.17) 164 60 7.61 (3.89–14.88)
General oral condition
Good or average
3
127 232 1 68 218 1
Poor 177 58 4.90 (3.09–7.78) 209 72 5.99 (3.00–11.96)
1
Some strata do not add up to the total because of missing values.–
2
Estimates from unconditional regression equations, including terms for
age, center, education and (men only) smoking and drinking habits.–
3
Reference category.
TABLE III –ODDS RATIOS (OR) AND CORRESPONDING 95% CONFIDENCE INTERVALS (CI) FOR CANCER OF THE ORAL CAVITY BY PAAN CHEWING
HABITS AND GENDER (591 CASES AND 582 CONTROLS, INDIA, 1996 –99)
1
Men Women
Cases Controls OR
2
(95% CI) Cases Controls OR
2
(95% CI)
Chewing habit
Never chewers
3
127 232 1 29 251 1
Ever chewers 182 60 5.12 (3.38–7.76) 253 39 42.40 (23.78–75.59)
Type of paan
With tobacco 139 37 6.10 (3.84–9.71) 222 31 45.89 (25.02–84.14)
Without tobacco 15 6 4.16 (1.46–11.83) 14 5 16.42 (4.77–56.48)
No. of paan/day
Former chewers
⬍5 28 11 4.24 (1.87–9.63) 17 6 20.24 (6.40–63.94)
ⱖ5 31 9 5.77 (2.53–13.16) 31 3 60.42 (15.83–230.67)
Current chewers
⬍5 40 18 3.06 (1.58–5.91) 51 13 22.10 (10.06–48.52)
5–9 46 12 8.15 (3.93–16.90) 101 13 58.58 (26.61–128.99)
ⱖ10 34 7 7.91 (3.23–19.41) 51 3 112.41 (30.85–409.55)
1
2
for trend 18.37; p⬍0.001 71.21; p⬍0.001
Age started chewing (yr)
4
ⱖ25
3
51 21 1 56 13 1
20–24 42 10 1.53 (0.56–4.18) 74 12 1.92 (0.69–5.34)
⬍20 27 6 1.54 (0.47–5.02) 73 4 5.43 (1.50–19.65)
0.73; p⫽0.39 6.86; p⫽0.01
Years since quit chewing
Current chewer
3
120 37 1 203 29 1
⬍10 45 14 1.02 (0.45–2.29) 31 6 0.72 (0.23–2.21)
ⱖ10 14 6 0.75 (0.23–2.52) 17 3 0.97 (0.23–4.11)
1
2
for trend 0.50; p⫽0.48 0.17; p⫽0.68
1
Some strata do not add up to the total because of missing values.–
2
Estimates from unconditional regression equations, including terms for
age, center, education, chewing and (men only) smoking and drinking habits.–
3
Reference category.–
4
Current chewers only.
443ORAL CANCER IN SOUTHERN INDIA
reported using fingers (OR 1.8 in men and 3.4 in women) or other
instruments (OR 3.7 in men and 2.9 in women), instead of a
toothbrush. A few subjects reported using a soft wooden stick.
Regular toothpaste was used by 25% of oral cancer cases and 60%
of control subjects. Few cases and controls reported wearing
dentures and having dental check-ups. Dental check-up seemed to
be significantly protective in women (OR 0.4), but not in men.
Conversely, gum bleeding (OR 2.8 and 3.4 in men and women,
respectively), having 6 or more missing teeth (OR 3.9 in men and
7.6 in women) and interviewer-reported poor general oral condi-
tion (OR 4.9 in men and 6.0 in women) were associated with a
significantly increased risk in both genders.
The combined effects of chewing with smoking, alcohol drink-
ing and toothbrush use (as an indicator of oral hygiene) are shown
in Table V, for men only. Men who smoked 20 bidi or equivalents
per day or more and chewed paan had a 6.7-fold (95% CI 2.5–
18.3) increased oral cancer risk. This OR is consistent with a
significant negative interaction of smoking and chewing on a
multiplicative scale (
2
⫽7.27; p⬍0.05). Conversely, the com-
bined effects of chewing and drinking (OR 8.6) and chewing and
no use of a toothbrush (OR 11.8) show no significant departure
from risk-product multiplicativity.
DISCUSSION
In our present case-control study, paan-tobacco chewing was
confirmed to be the most important determinant of oral cancer in
Southern India. The fraction of the disease attributable to this habit
was 49% in men and over 87% in women (Table VI). Among
women, tobacco smoking and alcohol drinking have a negligible
influence, whereas among men, smoking and drinking accounted
for 21 and 26% of oral cancer cases, respectively. A lack of oral
hygiene, as indicated by no use of toothbrush, accounted for 32%
of oral cancer in men and 64% in women. All together, the factors
above seemed to explain 76% of oral cancer in males and 95% in
females (Table VI).
The ORs we found for various levels of smoking and alcohol
drinking among men are consistent with those shown before in
India
10–12,17–20
and in Europe
13
and North America.
21
Bidi is
confirmed to be at least equally harmful as regular cigarettes.
Studies conducted in India have shown that bidis produce more
carbon dioxide, nicotine, tar and alkaloids than regular ciga-
rettes.
22,23
Furthermore, the filterless design of the bidi combined
with low combustibility may contribute to higher toxin yields than
with regular cigarettes.
22
It is, however, worth noting that most
Indian men in our present study started smoking relatively late, at
20 years or older. Heavy alcohol intake was not common, and the
corresponding attributable risk was well below the ones found
elsewhere.
21,24
For the combination of drinking and smoking in
men, the attributable risk was approximately 80% in the United
States and Europe and Latin America
14,21,24
versus 35% in our
present study (Table VI).
Our present ORs for paan chewing in men are similar to those
reported by Nandakumar et al.
10
and Sankaranarayanan et al..
11
In
the latter study, the fraction of oral cancer attributable to chewing
(73%) in Trivandrum in the mid-1980s was greater than in our
present investigation, whereas the smoking-attributable fraction
was lower (19%, bidi only). In agreement with our findings con-
cerning different types of paan, a study from Pakistan
6
showed an
OR of 12.5 for paan-tobacco chewing and of 5.2 for chewing paan
without tobacco. Interestingly, areca nut, 1 of the main ingredients
of paan, is considered the strongest risk factor for oral submucous
fibrosis, a precancerous condition very common in India.
6,25
Thus,
our findings, albeit based on relatively few exposed subjects,
contribute to the evaluation of carcinogenicity of paan without
tobacco, which was still deemed to be inadequate in an IARC
monograph.
3
Women showed substantially higher ORs at any level of paan
chewing than men. This difference was found consistently in the 3
participating centers after allowance for town or village of living,
in different age groups and when the comparison between men and
women was restricted to men who had never smoked or drunk
alcoholic beverages. The only 2 Indian studies in which the 2
genders were analyzed separately also showed more elevated ORs
in women than men,
10,19
although the difference was less marked
than in our present study. In a large cross-sectional study on 927
cases of oral leukoplakia and 47,772 controls, interviewed in the
framework of an oral cancer screening trial in the Trivandrum
district, tobacco chewers showed an OR of 3.4 (95% CI 2.8 –4.1)
among men, but 37.7 (95% CI 24.2–58.7) among women.
26
A
TABLE V –ODDS RATIOS (OR) AND CORRESPONDING 95% CONFIDENCE INTERVALS (CI) OF ORAL CAVITY CANCER ACCORDING TO VARIOUS
COMBINATIONS OF CHEWING AND SMOKING, DRINKING AND ORAL HYGIENE IN MEN (309 CASES AND 292 CONTROLS, INDIA, 1996 –99)
1
Paan chewing
Never Current chewers
Cases/controls OR
2
(95% CI) Cases/controls OR
2
(95% CI)
Tobacco smoking
Never smokers 25/106 1
3
49/16 9.19 (4.38–19.28)
Current smokers (cig./day)
1–19 33/55 1.78 (0.93–3.47) 35/10 8.86 (3.60–21.83)
ⱖ20 48/35 3.69 (1.89–7.23) 22/8 6.69 (2.45–18.27)
Alcohol drinking
Never drinker 64/174 1
3
48/18 7.31 (3.79–14.10)
Current drinker 48/38 2.83 (1.58–5.09) 46/13 8.62 (4.12–18.06)
Toothbrush use
Yes 42/152 1
3
31/18 4.65 (2.27–9.54)
No 85/80 2.52 (1.49–4.24) 89/19 11.82 (6.15–22.74)
1
Some strata do not add up to the total because of missing values.–
2
Estimates from unconditional regression equations, including terms for
age, center, education, oral hygiene, chewing and smoking and drinking habits, as appropriate.–
3
Reference category.
TABLE VI –PERCENT OF CANCER OF THE ORAL CAVITY ATTRIBUTABLE
TO SELECTED HABITS BY GENDER (591 CASES AND 582 CONTROLS,
INDIA, 1996 –99)
Factor Attributable risk percentage (95% CI)
1
Men Women
Tobacco smoking 21 (⫺2–44) —
Alcohol drinking 26 (13–39) —
Smoking and drinking 35 (15–55) —
Paan chewing 49 (40–57) 87 (83–92)
Paan chewing and smoking 68 (53–82) —
Poor oral hygiene 32 (15–49) 64 (47–80)
Chewing and hygiene 50 (22–78) 95 (91–98)
All above 76 (65–86) 95 (91–98)
1
Estimates from a multiple logistic regression model including
terms for gender, age, center, education and the main effects of the
factors above. Ranges are in parentheses.
444 BALARAM ET AL.
greater susceptibility to the oral damage of pan-tobacco chewing in
females is thus possible, as has been reported already for alcohol
drinking.
26,27
It is also worth noting that women reported starting
chewing on average 2 years earlier than men.
The percentage of ever chewers among female controls in our
present study (13%), however, was lower than expected. In the
aforementioned oral cancer screening trial, for instance, 22% of
65,792 women 35 years or older were pan-tobacco chewers.
28
More than half of control women were chewers in previous case-
control studies in Trivandrum
28
and Bangalore.
10
It is conceivable
that the poorest, illiterate women, among whom chewing is com-
monest, do go to the hospital for advanced oral cancer (stage 3 and
4 in 80% of female cases in our present study), but they seldom
attend as outpatients for less severe diseases or go to hospital in
order to visit relatives and friends. Such scope for selection bias
among female hospital controls should be taken into account in
future planning of case-control studies in poor countries.
A gender-related difference was also found in respect to risk
related to years of education and, to some extent, oral hygiene, on
which our present study provides the first data in an Indian pop-
ulation. The great majority of study participants cleaned their teeth
once per day or less, did not use a toothbrush and never had dental
check-ups. The number of individuals missing more than 5 teeth or
wearing a denture was, however, substantially lower than in stud-
ies done with the same protocol in Italy
13
and Cuba.
14
Among
indicators of dental care, the use of a toothbrush, gum bleeding and
number of missing teeth were associated with oral cancer risk after
adjustment for smoking, drinking and chewing habits. These find-
ings are in agreement with those from the Americas,
14,29
China
30
and Europe.
13,31
As in Talamini et al.
13
the strongest association
emerged for general oral conditions reported by trained interview-
ers who performed oral inspection. Since inspection was per-
formed before cancer treatment, however, interviewers could not
be blinded about case-control status, and results must be inter-
preted cautiously.
In conclusion, our present study offers an up-to-date picture of
major causes of oral cancer in Southern India. Traditional methods
for mouth cleaning, such as the use of finger or wooden sticks,
seem less effective than the use of a toothbrush. Paan chewing
represents the most important cause of oral cancer in men and,
most notably, in women. Among men, however, 35% of cases are
attributable to the combination of smoking and alcohol drinking.
Aggressive campaigns aimed at eliminating paan chewing are thus
warranted, in addition to continued efforts to prevent the spread of
tobacco smoking. Types of paan that do not include tobacco (e.g.,
some types of paan-masala) should not be marketed as safe alter-
natives to paan-tobacco chewing.
ACKNOWLEDGEMENTS
The authors thank Dr, K. Chaudry for useful comments and Dr.
R. Ortiz Reyes and Mrs. A. Arslan for technical assistance.
REFERENCES
1. Parkin DM, Whelan SL, Ferlay J, et al. Cancer incidence in five
continents, vol. VII. IARC Scientific Publications No. 143. Lyon:
IARC, 1997.
2. Franceschi S, Bidoli E, Herrero R, et al. Comparison of cancers of the
oral cavity and pharynx worldwide: etiological clues. Oral Oncol
2000;36:106 –15.
3. IARC. Monographs on the evaluation of the carcinogenic risks to
humans, vol. 37. Tobacco habits other than smoking; betel-quid and
areca-nut chewing; and some related nitrosamines. Lyon: IARC,
1985.
4. Mack T. The new pan-Asian paan problem. Lancet 2001;357:1638 –9.
5. Gupta P. Chewing and smoking: the underestimated epidemic. In:
Proceedings of the Seventh World Conference on Tobacco and
Health, Perth, 1990.
6. Merchant A, Husain SSM, Hosain M, et al. Paan without tobacco: an
independent risk factor for oral cancer. Int J Cancer 2000;86:128 –31.
7. Corrao MA, Guindon GE, Sharma N, et al. Tobacco control country
profiles. Atlanta, GA: American Cancer Society, 2000.
8. National Sample Survey Organization. Sarvekshana, Journal of the
National Sample Survey Organization. Department of Statistics, Min-
istry of Planning, Government of India, July–September 1991;XV:
375, 406.
9. National Sample Survey Organization. Sarvekshana, Journal of the
National Sample Survey Organization. Department of Statistics, Min-
istry of Planning, Government of India, January–March 1998;76.
10. Nandakumar A, Thimmasetty KT, Sreeramareddy NM, et al. A pop-
ulation-based case-control investigation on cancers of the oral cavity
in Bangalore, India. Br J Cancer 1990;62:847–51.
11. Sankaranarayanan R, Duffy SW, Padmakumary G, et al. Risk factors
for cancer of the buccal and labial mucosa in Kerala, southern India.
J Epidemiol Comm Health 1990;44:286 –92.
12. Dikshit RP, Kanhere S. Tobacco habits and risk of lung, oropharyn-
geal and oral cavity cancer: a population-based case-control study in
Bhopal, India. Int J Epidemiol 2000;29:609 –14.
13. Talamini R, Vaccarella S, Barbone F, et al. Oral hygiene, dentition,
sexual habits and risk of oral cancer. Br J Cancer 2000;83:1238 –42.
14. Fernandez-Garrote L, Herrero R, Ortiz Reyes RM, et al. Risk factors
for cancer of the oral cavity and oro-pharynx in Cuba. Br J Cancer
2001;85:46 –54.
15. Franceschi S, Mu˜
noz N, Snijders PFJ. How strong and how wide is
the link between HPV and oropharyngeal cancer? Lancet 2000;356:
871–2.
16. Mezzetti M, Ferraroni M, Decarli A, et al. Software for attributable
risk and confidence interval estimation in case-control studies. Com-
put Biomed Res 1996;29:63–75.
17. Jussawalla DJ, Deshpande VA. Evaluation of cancer risk in tobacco
chewers and smokers: an epidemiologic assessment. Cancer 1971;28:
244 –52.
18. Notani PN. Role of alcohol in cancers of the upper alimentary tract:
use of models in risk assessment. J Epidemiol Comm Health 1988;
42:187–92.
19. Sankaranarayanan R, Duffy SW, Day NE, et al. A case-control
investigation of cancer of the oral tongue and the floor of the mouth
in Southern India. Int J Cancer 1989;44:617–21.
20. Sankaranarayanan R, Duffy SW, Padmakumary G, et al. Tobacco
chewing, alcohol and nasal snuff in cancer of the gingiva in Kerala,
India. Br J Cancer 1989;60:638 –43.
21. Blot WJ, McLaughlin JK, Winn DM, et al. Smoking and drinking in
relation to oral and pharyngeal cancer. Cancer Res 1988;48:3282–7.
22. Pakhale SS, Jayant K, Bhide SV. Chemical analysis of smoke of
Indian cigarettes, bidis and other indigenous forms of smoking—
levels of steam-volatile phenol, hydrogen cyanide and benzo-
(a)pyrene. Ind J Chest Dis Allied Sci 1990;32:75–-81.
23. Pakhale SS, Mary GB. Distribution of major and minor alkaloids in
tobacco, mainstream and sidestream smoke of popular Indian smoking
projects. Food Chem Toxicol 1998;36:1131–8.
24. Negri E, La Vecchia C, Franceschi S, et al. Attributable risk of oral
cancer in northern Italy. Cancer Epidemiol Biomarkers Prev 1993;2:
189 –93.
25. Maher R, Lee AJ, Warnakulasuriya KA, et al. Role of areca nut in the
causation of oral submucous fibrosis: a case-control study in Pakistan.
J Oral Pathol Med 1994;23:65–9.
26. Hashibe M, Sankaranarayanan R, Thomas G, et al. Alcohol drinking,
body mass index and the risk of oral leukoplakia in an Indian popu-
lation. Int J Cancer 2000;88:129 –34.
27. Franceschi S, Bidoli E, Negri E, et al. Alcohol and cancers of the
upper aerodigestive tract in men and women. Cancer Epidemiol
Biomark Prev 1994;3:299 –304.
28. Sankaranarayanan R, Mathew B, Jacob BJ, et al. for the Trivandrum
Oral Cancer Screening Study Group. Early findings from a commu-
nity-based cluster-randomized, controlled oral cancer screening trial
in Kerala, India. Cancer 2000;88:664 –73.
29. Velly AM, Franco EL, Schlecht N, et al. Relationship between dental
factors and risk of upper aerodigestive tract cancer. Oral Oncol
1998;34:284 –91.
30. Zheng T, Boyle P, Hu H, et al. Dentition, oral hygiene, and risk of oral
cancer: a case-control study in Beijing, People’s Republic of China.
Cancer Causes Control 1990;1:235–41.
31. Bundgaard T, Wildt J, Frydenberg M, et al. Case-control study of
squamous cell cancer of the oral cavity in Denmark. Cancer Causes
Control 1995;6:57–67.
445ORAL CANCER IN SOUTHERN INDIA
