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Oral Cancer and Mouthwash 1

William J. Blot, 2,3 Deborah M. Winn,2 and Joseph F. Fraumeni, Jr. 2, 4

ABSTRACT -As part of a case-control study in North Carolina involv- groups of women with differing risks (3): nonusers of to-
ing 206 women with oral and pharyngeal cancers and 352 controls, bacco, snuff users, and smokers who did not use snuff (few
questions were asked concerning the patterns of mouthwash use. No women both smoked and dipped snuff). Summary RR
significant overall increase in risk was found among users; the relative adjusting for tobacco habits and other indices and corre-
risk, adjusted for snuff dipping and smoking habits, was 1.15 [lower, sponding 95% CI were calculated according to the method
upper limits of the 95% confidence interval (95% CI)=0.8, 1.7]. The described by Gart (5) and Thomas (6).
relative risk associated with mouthwash use was increased to 1.94
(95% CI=0.8, 4.7), however, among women abstaining from tobacco. RESULTS
Although consistent dose-response relationships were not observed
for this subgroup, these findings and other reports of an increased risk
A total of 558 completed supplemental questionnaires
among persons ordinarily at low risk of this disease raise the possibility
were obtained, representing 89% of the cases and 86% of the
that mouthwash may contribute to oral and pharyngeal cancers.-JNCI
controls from whom a telephone interview was sought and

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1983; 70:251-253.
74% of the original target population. Thus the analysis was
based on supplemental interview data from 206 cases and
352 controls. The 2 groups were similar with respect to age
To evaluate the possibility that commercial mouthwashes (median, 67 yr) and race (85% white) because of the design
may be involved in the etiology of cancers of the mouth and employed and were also generally alike with respect to
throat, particularly among females (1, 2), we examined past residence (nearly equally divided between urban and rural
patterns of mouthwash use among women with oral cancer areas) and place of birth (82% were born in North Carolina).
in an area of the United States where mortality rates for Overall, 44% of the cases were reported to be regular
this disease are exceptionally high. mouthwash users, 48% were said not to have used mouth-
wash on a regular basis, and for 8% it was not known
METHODS whether they had used these products. The 1 cancer patient
who started using mouthwash after diagnosis was considered
Respondents from our previously reported (3) case-con- a nonuser. The corresponding percentages were 45, 49, and
trol study of oral cancer among women in North Carolina 6% among women with cancer of the oral cavity and 39, 48,
were recontacted by telephone for information on mouth- and 13% among women with cancer of the pharynx. Among
wash use. Details of the survey methods are presented the controls, 42% were regular users, 53% were nonusers,
elsewhere (3). Female patients with oral and pharyngeal and 5% were of unknown status. The overall RR of oral and
cancers (8th revision ICD codes 141, 143-146, 148, 149) and pharyngeal cancers among women who used mouthwash
two controls per case of similar age, race, county of residence, relative to women who did not was 1.15 (95% CI=0.8, 1.7).
and source of ascertainment were identified from hospital Among controls, mouthwash was used more often by
medical records and death certificates for the 1975-78 study smokers (50%) and snuff dippers (42%) than by abstainers
period. Prospective controls were ineligible if they had a from tobacco products (37%). The percentage of positive
diagnosis of mental disorder (ICD 290-315), neoplasm of responses to the question on regular use of mouthwash was
the oral cavity, pharynx, esophagus, or larynx (ICD 140- also higher in self (53%) than in next-of-kin (35%) interviews;
150, 161), or other oral or pharyngeal diseases (ICD 500- 90% of the next of kin were husbands, siblings, parents, or
502,508,523,528,529). Cases and controls were interviewed children who were generally able to provide first-hand
in their homes by use of a structured questionnaire for knowledge of the study subjects' habits. The RR remained
information on tobacco, alcohol, occupation, medical and unchanged at 1.15 (95% CI=0.8, 1.7) upon controlling for
dental history, and other variables. A next of kin served as both respondent type and tobacco use, but there was consid-
an informant when the subject herself could not be inter-
The 642 subjects who had completed the home interview ABBREVIATIONS USED: 95% CI=lower, upper limits of the 95% confidence
were recontacted for the 5-minute questionnaire on mouth- interval; ICD=International Classification of Diseases; RR=relative risk(s).
wash use. Mouthwash use was determined by response to
the question "Before 1975, did you (did she) ever use
mouthwash on a regular basis?" Those responding positively 1 Received June 3, 1982; accepted October 19, 1982.
were then asked a series of questions regarding patterns of 2 Environmental Epidemiology Branch, Division of Cancer Cause and
Prevention, National Cancer Institute, National Institutes of Health, Public
mouthwash use.
Health Service, U.S. Department of Health and Human Services, Bethesda,
On the basis of responses from this supplemental survey,
Md. 20205.
we calculated (4) odds ratios as estimates of the RR of oral 3 Address reprint requests to Dr. Blot, Landow Building, Room 3C09,
cancer associated with mouthwash use. RR were determined National Institutes of Health, Bethesda, Md. 20205.
for length of use (years used and duration of retention in 'We thank Patricia Hartge of the National Cancer Institute for her
the mouth), frequency of use, and concentration. RR asso- advice and Westat, Inc. (Rockville, Md.), for providing assistance in data
ciated with mouthwash use were calculated separately for 3 collection.

251 JNCI, VOL. 70, No.2, FEBRUARY 1983

252 Blot, Winn, and Fraumeni

TABLE 1.-RR of oral and pharyngeal cancers associated with use TABLE 2.-RR of oral and pharyngeal cancers by years of
of mouthwash according to tobacco use and type ofrespondent mouthwash use according to type ofrespondent
Ever use Years Self interviews" Next-of-kin interviews"
mouthwash used
Tobacco Respondent Case Control RR b
on regular mouth-
Case Control RRc Case Control RRc
basis" wash
None Next of kin No 14 51 1.3 Nonuser 26 69 1.0 73 117 1.0
Yes 9 26 0-4 0 4 0.0 7 2 5.5
DK 3 7 5-9 0 4 0.0 4 4 1.2
10-24 4 12 1.0 13 10 2.0
Self No 1 33 8.3 ~25 13 48 0.7 18 30 0.9
Yes 7 28
DK 0 0 Excluded are 5 cases and 9 controls with unknown duration of use.

Excluded are 27 cases and 26 controls with unknown duration of

Snuff Next of kin No 35 45 1.9 use and 16 cases and 17 controls for whom mouthwash status was
Yes 40 27 unknown.
DK 4 5 Adjusted for tobacco habits.

Self No 10 12 0.4
Yes 6 18 mouthwash among users of tobacco [the overall RR adjusted

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DK 0 0 for respondent type was 1.00 (95% CI=0.6, 1.6)]; however,
the RR was 1.90 (95% CI=0.9, 3.9) among snuff users when
Smoker" Next of kin No 24 21 0.9 interviews were conducted with the next of kin. Higher
Yes 20 19
DK 9 5
excess risks for mouthwash use were observed for women
with fewer than 30 years of snuff use (RR=3.0) compared
Self No 15 24 0.5 to women dipping snuff for 30-49 years (RR=1.5) or 50
Yes 9 31 years or more (RR=1.0). Risks were not elevated for smokers
DK 0 0 of less than a pack of cigarettes per day (RR=0.2), 20-29
UDK=don't know. cigarettes per day (RR=0.7), or 30 cigarettes or more per
b Risk of cancers of the mouth and throat among women reported to day (RR=0.8).
use mouthwash relative to those reported not to use mouthwash. Four indices were used to evaluate dose-response relation-
C Excludes those who used snuff..
ships. As shown in table 2, the RR did not rise with
increasing years of mouthwash use, nor were there consistent
erable variation in risk among the several tobacco and trends with daily frequency of mouthwash use, length of
respondent groups (table 1). The RR associated with mouth- time the mouthwash was usually retained in the mouth, or
wash among women who did not use tobacco products, usual concentration (full strength vs. diluted) of mouthwash.
adjusted for respondent type, was 1.94 (95% CI=0.8, 4.7); Table 3 shows the RR for these indices among the 3 groups
the RR varied from 1.26 (95% CI=O.4, 3.6) for next-of-kin with elevated risks associated with mouthwash use, i.e., the
interviews to 8.25 (95% CI=0.9, 189) for interviews with the next-of-kin and directly interviewed subjects who abstained
subject herself. The latter figure is high since 7 of the 8 from tobacco and the next-of-kin interviewed subjects who
directly interviewed patients among tobacco abstainers re- used snuff. No clear-cut patterns were evident.
ported use of mouthwash. All but one of these patients also The percentage of mouthwash users among controls was
abstained from alcohol. Table 1 also shows no influence of higher among those who wore dentures (46%) than those

TABLE 3.-RR of oral and pharyngeal cancers associated with years of mouthwash use, daily frequency of use, time usually held in the
mouth, and concentration, for selected tobacco and respondent categories
Tobacco abstainers
Snuff users: Next-of-kin interviews
Index Next-of-kin interviews Self interviews

Case Control RR a Case Control RR a Case Control RR a

Years of use:
<25 3 5 2.2 0 9 0 15 7 2.8
~25 1 12 0.3 6 18 11.0 10 11 1.2
Daily frequency:
<2 6 8 2.7 5 12 13.8 12 10 1.6
~2 2 9 0.8 2 16 4.1 21 9 3.1
Time retained:
"Few seconds" 3 18 0.6 4 22 6.0 25 19 1.7
More than "few seconds" 3 4 2.7 3 6 16.6 10 8 1.7
Diluted 6 5 4.4 4 7 18.9 17 5 4.5
Full strength 2 16 0.5 3 21 4.7 21 18 1.5
All risks
aU All risks were
were relative
relative to
to women
women of
of the
the same
same tobacco-respondent
tobacco-respondent type
type category
category reported
reported to
to have
have never
never used
used mouthwash.
mouthwash. Those
Those with
with an
unknown value
unknown value for the exposure
for the exposure index
index are
are excluded
excluded from
from the
the calculations
calculations for
for that
that index.

JNCl, VOL. 70, No.2, FEBRUARY 1983

Oral Cancer and Mouthwash 253

who did not (37%). Controlling for denture use, however, It is not clear why an association with mouthwash use was
did not markedly change the RR in the various respondent detected only among women unexposed to tobacco and
and tobacco groups. In the group with the highest observed alcohol, the major risk factors for oral and pharyngeal
risk, directly interviewed women who used mouthwash but cancers (7, 8). Although chance is an obvious explanation,
not tobacco, only 1 of the 7 cancer patients had worn particularly in view of the small number of subjects in-
dentures. Mouthwash use also varied by education; the volved, the finding is consistent with two other studies
percentages of regular users were 45, 42, and 39% for control conducted in different areas of the United States (1, 2).
women with education levels of grade school, high school, Persons who abstain from tobacco and alcohol may share
and beyond high school, respectively. There was some var- with mouthwash users certain characteristics that increase
iation by age, with the highest percentage of users (49%) their risk of oral cancer, but few factors other than tobacco
among those of ages 60-69 years. Adjusting for educational and alcohol are known to be related to this cancer. Adjusting
or age differences also did not materially reduce the RR in for the confounding influences of denture wearing (9) and
the 3 groups with elevated risks. socioeconomic status, as measured by education level, al-
tered the findings only minimally. If mouthwash is indeed
DISCUSSION a risk factor for oral cancer, its effect may be comparatively
small, obscured by the more potent risk factors of tobacco
Two epidemiologic studies of oral and pharyngeal cancers
and alcohol and thus more easily detected in an otherwise
have reported that regular use of mouthwash may be an

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low-risk population.
etiologic factor (1, 2). In both studies the excess risks related
to mouthwash use occurred primarily in subgroups of the
general population with a low base-line incidence, i.e., non-
smoking and nondrinking individuals (1) and females (2). REFERENCES
Results from our study among women in North Carolina
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JNCI, VOL. 70, No.2, FEBRUARY 1983