smoked. The study of Canadian veterans (9) also contained evidence
of a dose-response in mortality by amount smoked for cigar smokers.
No dose-response relationship was observed among pipe smokers (table
8). Kahn (50) reported a consistent increase in overall mortality
with an increase in the amount smoked for both pipe and cigar smokers
(table 9). Hammond (38) found no consistent relationship between
overall mortality and the number of cigars or pipefuls smoked
(table 10).

Tase 7.—Mortality ratios for total deaths of cigar and pipe smokers by
amount smoked— Hammond and Horn

 

Number of deaths

Amount smoked
Observed Expected Mortality ratio

 

Nonsmoker.......-_-_------------------ 1, 664 1, 664 1. 00
Cigar only:
Total... ---- 2 - ee 653 598 1. 09
1 to 4 cigars... 2-22 ee 410 400 1. 03
> 4 cigars. 222-222 eee eee 229 185 1. 24
Pipe only:
Total_____----- 2 ---- 609 560 1.09
1 to 10 pipefuls.______- Lene ene ee- 391 374 1. 05
> 10 pipefuls__-.- 22 ee 204 172 1.19

 

8ource: Hammond, E.C., Horn, D. (40).

Tas_Le 8.—Mortality ratios for total deaths of cigar and pipe smokers
by amount smoked—Best

 

Number of deaths

 

Amount smoked

 

Observed Expected Mortality ratio
Nonsmoker______.____.....__-_---e eee eee ee ee eee 1. 00
Cigar only:
: Total..____._.-.---.----------- 90 82. 07 1.10
1 to 2 cigars__.________.._------ 64 56. 05 1.44
3 to 10 cigars_.._____._-.------- 23 19. 40 1.19
> 10 cigars... ----- 1 1. 59 . 63
Pipe only:
Total. 22. eee 570 566. 99 1. 00
1 to 10 pipefuls_.._.___.--------- 374 370. 09 1.01
10 to 20 pipefuls_____._.-------- 141 140. 84 1. 00
> 20 pipefuls___.__.._..-------- 36 35. 90 1.00

 

Source: Best, E. W. BR. (#).

551
The above evidence suggests that a dose-response relationship may
exist between the number of cigars and pipefuls smoked and overall
mortality. However, because of the high-mortality rate of ex-smokers
of cigars and pipes, it is difficult to interpret the data presented with-
out including this group with the continuing smokers. Without data
which examines patterns of both daily rate of smoking and inhalation
at various age levels, no firm conclusions can be drawn as to the nature

of this dosage relationship.

TABLE 9.—Mortality ratios for total deaths of cigar and pipe smokers
by age and amount smoked—Kahn

 

Mortality ratio, age
Amount smoked

 

55 to 64 63 to 74

Nonsmoker___...__----------------------------- 1. 00 1. 00
Cigar only:

Total___. 22-2 1. OL 1. 08

1 to 4 cigars per day.____.__-_-__.----------- . 89 1. 00

5 to 8 cigars per day_._______-----_---------- 1. 14 1. 23

>8 cigars per day_._._..._------------------ 1.65 1. 28
Pipe only:

Total___ 22-2 ee -- 1. 08 1. 06

1 to 4 pipefuls per day_____-__--------------- 1. 16 -91

5 to 19 pipefuls per day__.__-.--------------- 1. 04 1.10

1.18

>19 pipefuls per day__...------------------- ----------

Bource: Kahn, H. A. (50}.

TasLE 10.—Mortality ratios for total deaths of cigar and pipe smokers
by amount smoked—Hammond

Amonant smoked Mortality Amount smoked Mortality
ratlo ratlo

1. 00} Current pipe smokers:

Nonsmoker__._-------------

Current cigar smokers: Total_....--------------- 1. 04
Total_.____-__.__--------- 1. 09 1 to 9 pipefuls per day_.__- 1. 08
1 to 4 cigars per day_._-_-- 1. 03 >9 pipefuls per day_.----- . 92
> 4 cigars per day.....---- 1.18

 

Source: Hammand, B.C. (98).

552
INHALATION

Inhalation of tobacco smoke directly exposes the bronchi and the
lungs to smoke and results in the absorption of the soluble constituents
of the gas and particulate phases Without inhalation tobacco smoke
only reaches the oral cavity and the upper digestive and respiratory
tracts and does not reach the lungs where further direct effects and
systemic absorption of various chemical compounds can occur.

Although the smoker has some voluntary control over the inhalation
of smoke, the physical and chemical properties of tobacco smoke to a
degree determine its acceptability and “inhalability.”

The condensate of pipe and cigar smoke is generally found to be
alkaline when the pH is measured by suspending a Cambridge filter
in CO,-free water. Cigarette condensate is slightly acidic as measured
by this method. Since alkaline smoke is more irritating to the respira-
tory tract, it has been assumed that the more alkaline smoke of pipes
and cigars was in part responsible for the lower levels of inhalation
reported by pipe and cigar smokers. Brunnemann and Hoffmann (/5)
have analyzed the pH of whole, mainstream smoke of cigarettes and
cigars on a pull-by-puff basis using a pH electrode suspended in main-
stream smoke. Smoke from several U.S. brands of cigarettes was found
to be acidic throughout the entire length of the cigarette. Of interest
was the finding that cigar smoke also had an acidic pH for the first
two-thirds of the cigar and became alkaline only in the last 20 to 40
percent of the puffs from the cigar. Available epidemiological evidence
indicates that most cigar smokers do not inhale the smoke and most
cigarette smokers do. The fact that smoke from the first half or more
of a cigar is acidic, near the range of pH values commonly found in
cigarette smoke, and becomes alkaline only toward the end of the
cigar might suggest that the pH of the smoke of a tobacco product
may not be the only factor that influences inhalation patterns. Per-
haps “tar” and nicotine levels as well as the concentration of other
“irritating” chemicals also affect the degree to which a tobacco smoke
will be inhaled.

Nicotine is rapidly absorbed into the blood stream from the lungs
when tobacco smoke is inhaled. The amount of nicotine absorbed from
the lungs is primarily a function of the nicotine concentration in the
smoke and the depth of inhalation. Some nicotine may also be ab-
sorbed through the mucous membranes of the mouth. This is more
likely to occur under alkaline conditions when nicotine is unprotonated
(3, 15, 79). This suggests that cigar smokers may be able to absorb
some nicotine through the oral cavity without having to inhale, par-
ticularly during the time that the smoke from the cigar is alkaline.

553
With the development of sensitive measures of serum nicotine levels
(48) the extent to which nicotine is absorbed through the membranes
of the mouth in pipe and cigar smokers can be more accurately
determined.

Inhalation patterns of smokers were determined in several of the
large prospective and some of the retrospective epidemiological studies.
Inhalation was usually determined by the administration of a ques-
tionnaire that required a subjective evaluation of one’s own patterns
of inhalation. Although the accuracy of these questionnaires has not
been confirmed by an objective measure of inhalation, such as carboxy-
hemoglobin or serum nicotine levels, their reliability is supported by
mortality data which demonstrate higher overall and specific death
rates with self-reported increases in the depth of inhalation.

Doll and Hill (26) and Hammond (38) presented information on
inhalation patterns of pipe, cigar, and cigarette smokers (figs. 1, 2, 3,
and table 12). Some 80 to 90 percent of cigarette smokers reported
inhaling, with the majority of individuals inhaling moderately or
deeply, whereas most pipe and cigar smokers denied inhaling at all.
Pipe smokers reported slightly more inhalation than cigar smokers.
For each type of smoking, less inhalation was reported by older
smokers. This change may represent less awareness of inhalation,
differences in smoking habits of successive cohorts of smokers, or it
may reflect the operation of selective factors which favor survival of
noninhalers,

The Tobacco Research Council of the United Kingdom has, since
1957, periodically reported the use of tobacco products by the British.

Figure 1.—Inhalation among pipe smokers by age.

 

No

inhalation

Some
inhalation

 

 

Age

SOURCE: Hammond, E. C. (38).

 

554
Figure 2.—Inhalation among cigar smokers by age—Hammond.

 

 

 

 

No
inhalation
Some 185
inhalation 26.4 22.9 17.1 13.7 .
Age 40 50 60 70 80

SQURCE: Hammond, E. C. (38).

Figure 3.—Depth of inhalation among cigarette smokers by age.—Hammond.

 

None

Slight
inhalation

Moderate
inhalation

 

41.1

31.9

Deep
i i 29.1
inhalation 23.9

17.4 121 oD

 

4

Age 40
SOURCE: Hammond, E. C. (38).

50 60 70 8&0

Recent reports edited by Todd have contained data on the inhalation
pattern of cigar, pipe, and cigarette smokers (92, 93, 94). Table 11
shows that most cigarette smokers inhale a “lot” of “fair amount”
whereas most pipe and cigar smokers do not inhale at all or “just a
little.” Little change is observed in the inhalation patterns of.a given
product since 1968. ,

Best (9) reported inhalation data among male cigarette smokers by
smoking intensity and age group, but did not report the inhalation

555
patterns of pipe and cigar smokers. The overall mortality rates of
current pipe smokers who inhaled at least slightly were reported by
Hammond (38) as being somewhat higher than for men who never
smoked regularly. The overall mortality rates of current cigar smokers
who reported inhaling at least slightly were appreciably higher than
for men who never smoked regularly (table 13).

Available evidence indicates that cigarette smokers inhale smoke
to a greater degree than smokers of cigars or pipes. Once a smoker has
learned to inhale cigarettes, however, there appears to be a tendency
to also inhale the smoke of other tobacco products. For cigars, this is
evidently true whether one smokes both cigarettes and cigars or
switches from cigarettes to cigars (tables 14, 15, 16).

Bross and Tidings (14) examined the inhalation patterns of
smokers of large cigars, cigarettes, and those who switched from one
tobacco product to another (table 15). Nearly 75 percent of those who
were currently smoking only cigarettes reported inhaling “almost every
puff” and only 7 percent never inhaled. The opposite was true for per-
sons who had always smoked only cigars among whom 4 percent re-

TapLe 11.—-The extent of inhaling pipes, cigars, and cigarettes by
British males aged 16 and over in 1968 and 1971

Tobacco product

 

 

 

 

Cigars Pipes Cigarettes
Amount of inhalation
1968 1971 1968 1971 1958 1971
Inhale a lot_._.___._.-------------- 23 19 8 8 47 47
Inhale a fair amount.__.------------ 16 19 10 8 3k 30
Inhale just a little.___...----------- 27 27 24 26 13 15
Do not inhale at all.__.-_----------- 34 35 59 58 9 8
Total___.___--.-------------- 100 100 100 100 100 100

 

Source: Todd, G. F. (93, 94).

TapLe 12.—Inhalation among cigar, pipe, and cigarette smokers by
age—Doll and Hill

Percentage of Inhalers, age

 

 

Smoking type tow Btu 45tabi SStosd G5to 74 >
Cigar and pipe---------------- 12.00 1000 7.00 5.00 4.00 4. 00
Mixed (cigarette and other)..... 74.00 60.00 47. 00 36.00 30.00 26.00
Cigarette only.--.------------ 90.00 85.00 75.00 66.00 58. 00 41.00

 

 

 

Source: Doll, R., Hil, A. B. (£6).

556
ported inhaling almost every puff and 89 percent said they never
inhaled. Cigar smokers who also smoked cigarettes reported inter-
mediate levels of inhalation between the cigar only and cigarette only
categories. Inhalation patterns were similar whether the individual
continued to smoke both products, stopped smoking cigarettes but
continued smoking cigars, or stopped smoking cigarettes and
switched to cigars. In all three groups, about 20 percent reported
inhaling “almost every puff.” This suggests that once an individual’s
inhalation patterns are established on cigarettes, he may be more likely
to inhale cigar smoke if he switches to cigars, or uses both cigars and
cigarettes, than the cigar smoker who has not smoked cigarettes.
Todd (93) reported similar data for a sample of smokers in the
United Kingdom (table 16). The prevalence of inhaling a “lot” or
“fair amount” of smoke was highest among cigarette smokers who were
currently smoking cigarettes (77 percent) and lowest among current
cigar smokers who had previously smoked only cigars or pipes (18
percent). Individuals who switched from cigarettes to cigars main-

TaBLe 13.—Mortality ratios for total deaths of cigar and pipe smokers
by age and inhalation—-Hammond

 

Mortality ratfo, age
Inhalation

 

45 to 64 85 to 84

Nonsmoker___._____-_2 eee eee ee 1. 00 1. 00
Cigar only:

Total... oe eee 1. 09 . 98

No inhalation.___-___ eee 1.02 .9l

Some inhalation.___________.__.________--______. 1. 28 1. 37
Pipe only:

Total. oe ee pepe eee eee 1. 04 - 95

No inhalation__.-._-__.____._________.-__-.-_-__- . 98 . 87

Some inhalation._._______________.______-- ee 1. 21 Lit

 

Bource: Hammond, E. C. (38).

TABLE 14.—Percentage of British male cigar smokers who reported
inhaling a lot or a fair amount by type of product smoked

 

1968 1971

 

Type of product
Number of Percent Number of Percent

 

individuals individuals
Cigars only___._____2_ 222-2 2-2 706 =. 23.0 11 27.0
Cigars and cigarettes-._____..--_--_ 1,193 42.0 277 44.0
Cigars and pipes._--. 22.22 -- 596 35.0 109 32. 0
Cigars, cigarettes, and pipes________.. 26 «52.0 15 32.0

 

Bource: Todd, G. F. (83, 84).

557
tained somewhat higher levels of cigar smoke inhalation than those
cigar smokers who had never smoked cigarettes (30 percent).

Todd (93) examined further the relationship between the inhalation
of cigarette and cigar smoke. In general, cigarette smokers who
switched to cigars were much less likely to report inhaling cigar
smoke than cigarette smoke; however, those who in the past reported
inhaling cigarette smoke a “lot” or “fair amount” were much more
likely to report inhaling cigar smoke to the same degree than those ex-
cigarette smokers who in the past did not inhale the smoke of their
cigarettes (table 17).

TasLe 15.—Percentage of individuals reporting inhalation of “almost
every puff” of tobacco smoke by current and previous tobacco usage and
type of tobacco used

 

 

 

 

Confidence
Type of tobacco smoked Number Percen- Umits

of Type inhaled tae —_-—_—_—_—-

Current usage Previous usage patients {nhsled Lower Upper

Cigarettes only_... Cigarettes only____ 2,359 Cigarette... 74.8 73.1 76.6

Cigars only_______ Cigars only______ 649 Cigars_____ 45 3.0 60

Cigarettes and Cigarettes and 520 ____. do... _ 20.4 105 28.0

cigars. cigars. .

Cigars... 22.22. Cigarettes and 93 ____. do_____ 13.3 90 30.0
cigars.

None__.. 2-22. Cigarettes and 186 _____ do_____ 215 17.8 24.2
cigars.

Cigars.__.2_2 22 Cigarettes only ____ 64 Le do__... 17.2 16.0 28.0

 

 

Bource: Bross, I. D.J., Tidings, J. (14).

TasLe 16.—Percentage of British males who reported inhaling a lot or
fair amount of cigar smoke by current and previous tobacco usage and
type of tobacco previously smoked (1963)

 

 

 

 

 

Type of tobacco smoked Number of Percentage
individuals Type inhaled Inhaled ~

Current usage Previous usage
Cigarettes only_.____ | Cigarettes only______ 2,586 Cigarette_____ 77.7
Cigars only___________ Nonsmoker_________ 306 Cigars_______ 18.0
Cigars only..____-____ Cigarettes only_______ 321 LLL do___.__. 30. 0

 

8ource: Todd, G. F. (94).

558
TABLE 17.—Extent of reported inhalation of cigar smoke by British
male cigar smokers who were ex-cigarette smokers in 1568, analyzed
by extent of reported inhalation of cigarette smoke when previously

smoking cigarettes

 

Extent of inhaling cigars

Extent of inhaling cigarettes

 

 

 

Inhale a lot Inhale a little
or fair amount or not at all
Percent Peoveent
Inhale a lot or fair amount_.__.__._..-.___.______. 44.0 5. 0
Inhale a little or not at all..--_-_-- ee 56. 0 95. 0
Total. ___.2 eee 100. 0 100. 0
Sample size_____-.--_-_. 2222-2 244 56

 

Source: Todd, G. F. (gn).

Specific Causes of Mortality

Cancer

Several prospective epidemiological studies have shown a signifi-
cantly higher overall cancer mortality among pipe and cigar smokers
compared to the cancer mortality of nonsmokers (table 18).

Pipe and cigar smokers have much higher rates of cancer at certain
sites than at others. The upper airway and upper digestive tracts
appear to be the most likely target organs. The relationship of pipe
and cigar smoking to the development of specific cancers is detailed

in the following sections.

TABLE 18.—Mortality ratios for total cancer deaths in cigar and pipe

smokers. A summary of prospective epidemiological studies

Author, reference

Nonsmoker

Type of smoking
Pipeonly Total pipe Cigarette

 

Hammond and Hom (40)___-
Best (9)________
Hammond (88)____--_._____
Kabn (60)______.2____-__-

1. 00
1. 00
1.00
1. 00

and cigar only
1.44 22 LL -ee 1.97
1.38 ~.-L_--- 2. 06
wee eeee 1. 21 1. 76
1. 25 1.25 2. 21

 

559
Cancer of the Lip

Approximately 1,500 new cases of cancer of the lip are reported
each year. Because of the possibility of early detection and surgical
accessibility of cancers in this area, there are less than 200 deaths from
cancer of the lip each year in the United States. Some of the earliest
scientific investigations exploring the association between tobacco use
and disease examined the smoking patterns of individuals with cancer
of the lip.

Broders (73) in 1920 examined the smoking habits of patients in
a retrospective study of 526 cases of epithelioma of the hp and 500
controls. Of the cancer cases, 59 percent smoked pipes, whereas this
was true for only 28 percent of the controls. No association was found
between cigar or cigarette smoking and cancer of the lip.

In a restrospective study of 439 clinic patients with cancer of the
Jip and 300 controls conducted in Sweden, Ebenius (32) reported a
significant association between pipe smoking and cancer of the lip.
A total of 61.8 percent of the lip cancer cases smoked pipes, while
only 22.9 percent of the controls smoked pipes. No association was
found between the use of cigarettes, cigars, or chewing tobacco and
cancer of the lip.

In other retrospective studies, Levin, et al. (60) reviewed a series
of 143 cases of cancer of the lip, and Sadowsky, et al. (77) reviewed
571 cases of cancer of the lip. In both studies, a strong association was
found between pipe smoking and cancer of the lip. No significant
association was found between the use of tobacco in ether forms and
cancer at this site.

In a study of environmental factors in cancer of the upper alimen-
tary tract, Wynder, et al. (413) found an association between pipe
smoking, cigarette smoking, and cancer of the lip. There were only 15
cases of cancer of the lip in this study.

Staszewski (87) examined the smoking habits of 394 men with
carcinoma or precancerous lesions of the lips. An association was
found between the smoking of pipes and cigars and cancer of the lip,
but this was only of doubtful significance. A significant association
was found between the use of cigarettes and cancer of the hp.

Keller (51) conducted a study of lip cancers in which he considered
a number of factors including histologic types, survival, race, occupa-
tions, habits, and associated diseases. A total of 304 patients with
primary basal cell or squamous cell carcinoma of the lip and 304
controls from the same hospital matched for age and race were con-
sidered in this series. A significant association was found between
smoking in all forms and combinations and carcinoma of the lip. It
was also found that increasing age and outdoor occupations with
exposure to the sun were equally significant factors in the etiology of

lip cancer.

560
In summary. it appears that there are several factors involved in
the etiology of cancer of the lip. Among the various forms of tobacco
use, pipe smoking either alone or in combination with other forms of
smoking seems to be a cause of cancer of the hip. Table 19 summarizes
the results of these retrospective studies.

Oral Cancer

The lips, oral cavity, and pharynx are the first tissues exposed to
tobacco smoke drawn in through the mouth. Variations in inhalation
during the smoking of various tobacco products result in different pat-
terns of distribution of smoke throughout the respiratory tree. How-
ever, the oral cavity and adjacent tissues are the sites most consistently
exposed to tobacco smoke. For this reason, differences in inhalation
should result in less variation in exposure to tobacco smoke for these
sites than for the lower trachea and the lung. The inherent carcinogen-
icity of pipe, cigar, and cigarette smoke is most reliably compared at
those tissue sites where dosage and exposure to tobacco smoke are most
nearly equal. Data from the epidemiological studies suggest that little
difference exists between the smoking of cigarettes, pipes, or cigars and
the risk of developing oral cancer.

Hammond and Horn (40) examined the association between smok-
ing in various forms and cancer of the combined sites of lip, mouth,
pharynx, larynx, and esophagus. The mortality ratios were 5.00 for
cigar smokers, 3.50 for pipe smokers, and 5.06 for cigarette smokers
compared to nonsmokers. All the deaths from cancer of the lip, oral cav-
ity, and pharynx reported by Doll and Hill (26) occurred in smokers.
The death rates from cancer at these sites were 0.04 per 1,000 for pipe
and cigar smokers, 0.10 per 1,000 for mixed smokers, and 0.05 per 1,000
for cigarette smokers. A fairly detailed analysis of oral cancer was pre-
sented by Kahn (50) who differentiated between cancer of the oral
cavity and cancer of the pharynx. The mortality ratios for oral cancers
were 1.00 for those who never smoked, 3.89 for all pipe and cigar
smokers, and 4.09 for cigarette smokers. A further breakdown of the
pipe and cigar smokers demonstrated a mortality ratio of 4.11 for
cigar smokers, 3.12 for pipe smokers, and 4.20 for smokers of pipes and
cigars. For cancer of the pharynx, the mortality ratios were 1.00 for
those who never smoked, 3.06 for all pipe and cigar smokers, and 12.5
for cigarette smokers. No deaths occurred among those who smoked
only cigars. The mortality ratio was 1.98 for pipe smokers and 7.76
for smokers of pipes and cigars. Hammond (38) combined cancers of
the hip, oral cavity, and pharynx. The pipe and cigar smokers had a
mortality ratio of 4.94 and the cigarette smokers a mortality ratio of
9.90 compared to nonsmokers.

561
29S

Tale 19.—Melative risk of lip cancer for men, comparing cigar, pipe, and ciyarette smokers with nongsmokerstel summary
of retrospective studies

 

Rolutive rlak cally nnd percentage of cases and coutruls by typeof sucking

 

 

Author, referenicy Number Nonsmoker Ciguronly Plpvonly Total pipe Cigarette Mired
and clyor only
Broders (13): Relative risk... 2222.8. 1.0 0.8 4.3 ...0...-. O _.-...-e-
Casts. .... 202-2 eee ee eee §37 Percent cayes._..--.---. 7 19 [ ) Lo oleae ee
Controls... eee eee eee eee 500 Percent controly....2.... 4 16 6 Lee ee eee 2600 Lotte eee
Ebenius (32): Relative risk....-...22.-- 1.0 7 4.1 0.5 Llo. tee eee e eee
Cuscs_ oo... eee eee eee ee 439 Percent cases-.....2---- 49 6 41 4 nen e cee e ewes
Controls. oo... eee eee ee eee 300 Percent controls.......2- 65 12 13 1000 Loe eee wee ee eee
Levin, et al. (G0): Relative risko..0 22 leek 1.0 1.9 2.9 ...-0---e |
Cases. oe ae eae eee ee eee ee 143 Percent cases... 2.22200. 15 27 48 Lac eee ee 450 Le eee
Controlg.o22 22 22e eee eee eee 554 Percent controly....2222- 22 20 24 eee e eee 460 Lee eee
Sadowsky, et al. (77): Ielative riskoo.c.eeele 1.0 Li 4.3 2.6 L4 0. 4
Causes. ... 0 0.0 ee eee eee eee 571 Percent cases... eee. ee 8 2 18 6 44 22
Controly. 22222 ee eee eee G15 Percent controlg..2. 2222. 13 3 7 4 53 19
Wynder,! et al. (178): Relative riskoo. leek 0 8 | ar 1.0 2.2
Cases... ...... 00 eee eee eee 14 Poreent cases...2--- 2... 0 7 290 faa a eee 36 29
Controls... 2.2.2.0 22--- eee 115 Percent controls.....222- 24 9 16 Ltt... 36 13
Staszewski (87): Relative risk. oe 1.0 coe lle 2.1 2.4 ..2------
Cases... 2.022222 eee euee eee 394 Percent cases__....---..- Gee ennece anceeee 12 1 an
Controls.....2 2... .00 0 eee 912 Percent controls___-_-- 2. . 130 Leelee eee eee i a
Keller: (61): Relative risk__-- 00.00 1.0 14 4.0 2.6
Cases- 220... ee eee een e neces 301 Percent cases_..2.22. 7 eee 7 2 6 1 60 6
Controlg....0.020-0--002------ 265 Percent controlg_.....-_- 17 4 3 0 53 0

 

§ Percentage based on loss than 20 pationts. Rutlus: relative to cighretto smokors,
These studies are summarized in table 20. They demonstrate that
smokers experience a large and Significant risk of developing cancer
of the oral cavity compared to nonsmokers. This risk seems to be about
the same for all smokers whether an individual uses a Pipe, cigar, or
cigarette,

A number of retrospective studies have examined the relationship
between smoking in various forms and cancer of the oral cavity. The
results of these studies are presented in table 21. Some of the variations
in relative risk of developing oral cancer observed in the retrospective
studies is probably due to the Jack of a uniform definition of oral cancer
by anatomical site and the various means used in selecting and defin-
ing cases and controls. It appears, however, that a significant risk of
developing oral cancer exists for smokers compared to nonsmokers
and this risk is similar for smokers of pipes, cigars, and cigarettes.

Several epidemiological investigations have demonstrated an asso-
ciation between the combined use of aleohol and tobacco and the
development of oral cancer. A few of these studies (52, 62, 63, 109)
contain data on pipe and cigar smokers. Heavy smoking and heavy
drinking are associated with higher rates of oral cancer than are seen

with either habit alone.

TABLE 20.—AMfortality ratios for oral cancer in cigar and pipe smokers.
A summary of prospective epidemiological studies

 

 

 

Smoking type
Author, reference
Non- Cigar Pi Total pipe Cigarette Mixed
smoker only only and cigar only
Hammond and Horn'(40)_ 1.00 5.00 3.50 _______. 5.06 _____2.
Doll and Hill? (26, 27)-__ 000 ---- 22. LLL Lee 0. 80 1. 00 2. 00
Hammond (88)..___.___. 1,00 .---2 8. LLL 4.94 3990 .._.___L
Kahn (60):
Oral #_ 2-2 1.00 4.11 3. 12 3. 89 4.09 .-_. LLL
Pharynx_._.-_._ 1,00 ___.____ 8 3.06 12.54 ___.. LL

 

' Combines data for oral, larynx, and esopbagus.

1 Rauos: relative to cigarette smokers.

» Mortallty ratics for ages 45 to & only are presented.
4 Excludes pharynx.

Cancer of the Larynx

The larynx is situated at the upper end of the trachea. Because of
its proximity to the oral cavity, the larynx probably has a similar
exposure to smoke drawn through the mouth as the buccal cavity and
pharynx. Tobacco smoke that is not inhaled may still reach ag far as
the larynx and upper trachea. Pipe and cigar smokers develop cancer
of the larynx at rates comparable to those of cigarette smokers. These

563
79S

TABLE 21.—Relative risk of oral cancer for men, comparing cigar, pipe, and cigarette smokers uith nonsmokers. A summary of retrospective

 

 

 

sludtes
Relative risk ratio wid percentage of cases and controls by typo of smoking
Author, reference Number
Nonamoker Clyurouly Pipeonly Totul plpo — Clyurette Mirod
and clyur only

Mills and Porter (65): Relative risk.....__.. 008. LO eee Leelee 7.0 41 cele.
Cases__ 2-2. eee eee 124 Percent cases_____.-_22.. 10 nee eee ee Lee eae 55 3600 eee eee
Controls... 2.0.02 0 eee eee 185 Percent controls.__....... 88 Lee tle eee 30 820 eee
Sadowsky, et al. (77): Relative risk_.....2.2 0. 1,0 2.0 re 14 2.1

Cases... 22.2222 e eee eee 1,136 Percent cases_......-_... 4 18 Leelee 42 28

Controls....222202. beeen n eee 615 Percent controls.._....._. 13 3 TO eee 53 23
Schwartz, et al. (83): Relative risk__.-.... 08. 10 .2lle Lele 16 wo... lle 16 Lele
“Cases. lll. 332 Percent cases..._.._..... 160 Leelee 3 Leelee i
Controls.......2222 0.20022. 608 Percent controls....___... 23 17 8 Leelee 58 ok. wae
Wynder, et al. (109): Relative risk_...2.2_2.2.. 1.0 3.6 i 3.0 3.3

Cases... 22. eee eee 543 Percent cases_.____...... 20 Vb Lee 57 8

Controls... 0.02.2 eel 207 Percent controls..._..._.. 10 13 G6 Leelee. 63 8
Wynder, et al. (113): Relative risk_......-..0.- 10 17 a: 1,2 14

Cases. eel 115 Percent cases___...__ 8. 23 13 20 Ll. 37 16

Controls... ee. 115 Percent controls..___._... 26 9 16 eee ee 36 13
S9S

Wynder, ct al. (116):

~ Cases. oo. eee eee eee 178
: Controls. .... cee cee eee 220
Pernu (73):
r LO 1, 400
[ Controls......022 eee eee 713
= Staszewski (87):
Cases... 0. ee - eee 383
Controls... 912
Keller (62):
Cases... eee eee 408
Controls....02 22... 408
Martinez (62):
Cases... eee eee 170
Controls... eee 510
Martinez ! (63):
Cases. 2... e eee 346
Controls......0.2....-00-- 8. 346

1.0
12
22

 

'This study combines data for oral caucer and cancer of the esophagus,
rates are several times the rates of nonsmokers. The similarity of the
mortality ratios of cancer of the larynx for smoking in various fomns
suggests that the carcinogenic potentials of the smoke from cigars,
pipes, and cigarettes are quite alike at this site.

Several of the prospective epidemiological studies include data on
deaths from cancer of the larynx for pipe and cigar smokers as well
as for cigarette smokers. Hammond and Horn (40) combined data for
cancer of the larynx with cancer of the esophagus and oral cavity.
The mortality ratios compared to nonsmokers were 5.00 for cigar
smokers, 3.50 for pipe smokers, and 5.06 for cigarette smokers. There
were no deaths from carcinoma of larynx among nonsmokers in
the study of British physicians by Doll and Hill (26) ; however, the
death rate for cancer of the larynx among pipe and cigar smokers was
0.10 per 1,000 while the death rate for cigarette smokers was 0.05 per
1,000. Kahn (50) reported mortality ratios for cancer of the larynx of
10.33 for cigar smokers, 9.44 for pipe and cigar smokers, 7.28 for al]
pipe and cigar categories combined, and 9.95 for cigarette smokers. No
deaths from cancer of the larynx occurred in pipe smokers. Hammond
(38) reported a mortality ratio of 3.37 for all pipe and cigar smokers
and a mortality ratio of 6.09 for cigarette smokers in the age category
45 to 64. These studies are, summarized in table 22.

Several retrospective studies have examined the smoking habits of
patients with cancer of the larynx and appropriately matched controls.
The small number of pipe and cigar smokers in each study results in
relative risk ratios that are quite unstable; however, it appears that
pipe and cigar smokers experience a risk of developing cancer of the
larynx that is similar to the risk observed among cigarette smokers
(table 18).

Tas.e 22.—Mortality ratios for cancer of the larynz in cigar and pipe
smokers. A summary of prospective epidemiological studies

 

Smoking type

 

Author, reference

 

 

Non- Cigaronly Pipeonly Total Pipe Cigarette Mixed

 

smoker and cigar only
Hammond and Horm !

(40)_ 22 1. 00 5. 00 3.50 2.2L 5.06 -_..
Doll and Hill? (26, £7)... 0.00 _...... _.__.. 2. 00 1. 00 0. 60
Hammond (38)__________ 100 2222. LLL. 3.37 36.09
Kahn (60)_._-.---_ 100 1033 __ 7. 28 9.95 -. LLL

 

 

1 Combines data for oral, larynx, and eso bagus.
? Ratios: relauve to cigarette smokers. P
* Only mortality ratios far Bges 45 Co 64 are presented.

566
Wynder, et al. (708, 1/3) distinguished between intrinsic and ex-
trinsic larynx cancers. For smokers the relative msk of developing
cancer of the intrinsic larynx was similar to the relative risk of lung
cancer whereas the relative risk of developing extrinsic larynx cancer
was more like the relative risk of cancer of the upper digestive tract.

Histologic changes of the larynx in relation to smoking in various
forms were described by Auerbach, et al. (5). Microscopic sections of
the larynx from 942 subjects were examined for the presence of
atypical nuclei and proliferation of cell rows. Sections were taken |
from four separate areas of the larynx in each case. Among those who
smoked cigars and pipes but not cigarettes, only 1 percent had no
atypical cells and more than 75 percent of the subjects had lesions
with 50 to 69 percent atypical cells. Four of the cigar and pipe smokers
had carcinoma in situ and in one of these four cases early invasion
was seen in three of the sections. Of those who never smoked regu-
larly, 75 percent had no atypical cells. The cigar and pipe smokers had
a similar percentage of cells with atypical nuclei as cigarette smokers
who smoked one to two packs per day. With respect to the prolifera-
tion of cell rows in the basal layer of the true vocal cord, the least
proportion of .cases with eight or more cell rows was found in men
who never smoked, and the greatest proportion was found in heavy
cigarette smokers. Pipe and cigar smokers had a distribution of cell
rows that was comparable to that of cigarette smokers who consumed
about a pack a day.

Several retrospective studies have reported an association between
the combined use of tobacco and alcohol and cancer of the larynx. A
study by Wynder, et al. (£08) included some information on pipe and
cigar smoking in relation to drinking habits and the development of
cancer of the larynx, but because of the limited number of pipe and
cigar smoking subjects this relationship could not be adequately

determined.

Cancer of the Esophagus

The esophagus is not directly exposed to tobacco smoke drawn into_ .
the mouth; however, the esophagus does have contact with that portion ~
of tobacco smoke that is condensed on the mucous membranes of the
mouth and pharynx and then swallowed. The esophagus is also ex-
posed to a portion of tobacco smoke that is deposited in the mucus
cleared from the lung by the ciliary mechanism or by coughing. Varia-
tions in inhalation of a tobacco product may not appreciably alter the
exposure the esophagus receives from smoke dissolved in mucus and
saliva. This suggestion receives support from the prospective and
retrospective epidemiological studies which demonstrate similar mor-
tality rates for cancer of the esophagus in smokers of cigars, pipes, and

cigarettes.
567
89S

TABLE 23.—Relative risk of cancer of the larynx for men, comparing cigar, pipe, and cigarette smokers with nonsmokers.
A summary of retrospective studies

Relative risk ratio and percentage of cases and controls by type of smoking

 

 

Author, reference Number
Nonsmokor Cigar only Pipe only Total pips Clearatte Mired
and clgar only

Schrek, et al. (81): Relative risk... 22.208. 1.0 0 Ld celle 23 celle
Cases. _ 2. eel 73 Percent caseg___.__.___- 14 0 To eke eee 80 Lee
Controls... 2 ee 522 Percent controls..___._._ 24 10 Vb cell 1)
Sadowsky, et al. (77): Relative risk....2-2.0 oo. 1.0 2,2 23 Lo... 3.7 4.1

Cases... 2.22 eel 273 Percent cases___.._.._.. 2 GB nee ate 60 29

Controls._....2220 ee 615 Percent controls..._..... 13 3 Fo eee 53 23
Wynder, et al. (108): Relative risk... 2.008. 1.0 15.5 27,7 ll 24.6 2 lle
ASOS- eee elle 209 Percent cases.__-._. 8. 5 8 5 1 8B Lee
Controls._....22- 22 209 Percent controls......_.. 1] 10 4 (.
Wynder, et al. (113): Relative risk_..2. 20008. 1.0 9.7 4.5 woe 6.3 6.3

Cases... 60 Percent cases..._...___. 5 17 Wo Leelee 47 17

Controls_....2 0. e el 271 Percent controls_.._.._.. 24 9 Wo Leelee 36 13
Wynder, et al. (116): Relative risk.....20 8. 1.0 14.5 16.0 .... lll le 22.0 16. 0

Cases... eee 142 Percent cases....__...._ 1 20 bee 62 16

Controls... eo oo 220 Percent controls.....__.. 16 22 Yo eel 45 16
69S

Pernu (78):

Relative risk... 02222.
Percent cases
In the prospective epidemiological studies, cigar, pipe, and cigarette
smokers all had similar mortality ratios from cancer of the esophagus.
Hammond and Horn (40) combined the categories of carcinoma of
the esophagus, larynx, pharynx, oral cavity, and lip and described
mortality ratios of 5.00 for cigar smokers, 3.50 for pipe smokers, and
5.06 for cigarette smokers. Doll and Hill (26) reported an esophageal
sancer mortality ratio of 2.0 for pipe and cigar smokers, 4.8 for mised
smokers, and 1.5 for cigarette smokers. Kahn (50) reported the fol-
lowing mortality ratios for smoking in various forms compared to non-
smokers: cigar only, 5.33; pipe only, 1.99; pipe and cigar, 4.17; all
pipes and cigars combined, 4.05; and cigarettes only, 6.17. The results
of these prospective studies are summarized in table 24,

Several retrospective investigations have also examined the associa-
tion between smoking in various forms and cancer of the esophagus.
These studies have been summarized in table 25. The evidence sug-
gests that cigar, pipe, and cigarette smokers develop cancer of the
esophagus at rates substantially higher than those seen in nonsmokers,
and that little difference exists between these rates observed in smokers
of pipes and cigars and cigarettes.

Histologic changes in the esophagus in relation to smoking in vari-
ous forms were investigated by Auerbach, et al. (7), who looked for
atypical nuclei, disintegrating nuclei, hyperplasia, and hyperactive
esophageal glands. A total of 12,598 sections were made from tissues
obtained from 1,268 subjects. For each of the parameters investigated,
pipe and cigar smokers demonstrated significantly more abnormal
histologic changes than nonsmokers; however, these changes were not
as severe or as frequent. as those seen in cigarette smokers.

Several retrospective studies conducted in the United States and
other countries have examined the synergistic roles of tobacco use and
heavy alcohol intake on the development of cancer of the esophagus.
Four of these investigations contain data on pipe and cigar smoking
(72, 62, 63, 107). It appears that smoking in any form in combination
with heavy drinking results in especially high rates of cancer of the
esophagus.

TaBLe 24.—Mortality ratios for cancer of the esophagus in cigar and
pipe smokers. A summary of prospective epidemiological studies

 

 

 

 

 

 

 

 

 

 

Smoking type
Author, reference Non- Clear Pi Total Cigarette
smoker only only Pipe and only Mixed
cigar
Hammond and Horn! (40) _ 1.00 5. 00 3.50 -._- Le 5.06 __.222
Doll and Hill (26, 27). 1.00 -22--222 LL 2. 00 1.50 4. 80
Hammond (38)_._.______ 100-2222 LLL 3.97 74.17 _._____.
Kahn (60)___-.-___. 1. 00 5. 33 1.99 4.05 6.17 _L.- Le

 

 

 

' Combines data for oral, larynx, and esophagus.
1 Mortality ratio for ages 45 to 64. P .

570
TLS

TAaune 25.—Nelative risk of cancer of the esophagus for men, comparing cigar, pipe, and cigarette smokers with nonsmokers,

‘l swonmary of retrospective studies

 

 

 

Relatlvo risk ratio and percentage of cases and controls by typo of smoking
Author, reference Number
Nonsinukee Clyar only — Pipe only Total plpo — Ctynretto Misod
ond cipar only
Sadowsky, et al. (77); Relative risk...--- 28 10 4.8 3.8 5.1 3, 8 3.3
Cases... 2. eel. 104 Percent cases..-..2 2 2. 4 5 8 6 60 18
Controls.....0222200..-00 8. 615 Percent controls...._.... 13 3 7 4 53 19
Wynder, et al. (113); Relative risk_-.20. 0. 1,0 31 21 ce. e lee 2.6 4
Cases_- 2... ee 39 Percent cases... 8] 13 15 18 wee ° 3
Controls... eee 115 Percent controls.....__.. 24 9 WW lee 13
Pernu (78): Relative risk.-...- 0-2 .. 10 Leelee 3.0 lel le. 27 5.9
Cases... eee 202 Percent casegs_....__. 8. Wo elle. TO ee aee eee 59 18
Controls__... 2.2 - 713 Percent controls__..._..- 39) le 6 Leet eee 50 7
Schwartz, et al. (84) Relative risk_..-2 020028. |) 2.6 ... 2 ll ll. 11.7 8.6
Cusos. ee eel 249 Percent cases__.__..._.- 2 Leelee 2 Leelee 88 7
Controls... 2.2 eee 249 Percent controls__..._.._. Wo eel Tease eens 67, 7
Wynder and Bross (107): Relative risk... 2008 - 1.0 3.6 9.0 6.0 2.8 3.7
Cases... 2222.2 eee 150 Percent casey__...00.0.. 5 19 9 4 51 I
Controlg._oe ee 150 Percent controls....-.._. 15 16 3 2 59 9
cls

Tasie 25—Relative risk of cancer of the esophagus for men, comparing cigar, pipe, and cigarette smokers with nonsmokers.
A summary of retrospective studies —Continued

 

Rolatlve risk ratio and porcentago of cnses and controls by type of smoking

 

 

Author reference Number
Nonsmoker Cigaronly Plpeonly Total pips Clyarotte Mixed
and cigar only
Bradshaw and Schonland (12): Relative risk............ 10 ...-.-2e- 4.8 os. -2ee 2.3 ..--..-.-
Cases_.-2.------- en eee ee eee 117 Percent cases.......---- | 4.00 Lol ellen 63 oleate eeee
Controlg..__.-22 2-2. ee eee 366 Percent controls.....-.-- 320 eee ene 1B keene 58 wee ee eee
Martinez (62): Relative risk... .- 22228. 1.0 2.0 pec ne cee eee 1.5 2, 2
Cases... eee wwe wee ee eee 120 Percent cases......----- 8 9 Leen ee teen eee 31 43
Controls... 2-2 oe eee ene 360 Percent controls......... 14 Beene ee eee eee 34 34
Martinez ! (68): Relative risk.......--... 1.0 2,0 2.8 we------ 1,7 2.5
Cases...-.-------------0e--- 346 Percent cases......--..- 21 10 15 eee 34 34
Controls... 22-2. ee nncee ee nne 346 ‘Percent controls__....2. 22 9 Lo teen eee 36 25

 

1 This study combines data for oral cancer and cancer of the esophagus.
Lung Cancer

Abundant evidence has accumulated from epidemiological, experi-
mental, and autopsy studies establishing that cigarette smoking is the
major cause of lung cancer. Several prospective epidemiological
studies have demonstrated higher lung cancer mortality ratios for pipe
and cigar smokers than for nonsmokers, but the risk of developing lung
cancer for pipe and cigar smokers is less than for cigarette smokers.
Table 26 presents a summary of these prospective studies. Dose-
response relationships such as those that helped demonstrate the nature
of the association between cigarette use and lung cancer could not be
as thoroughly studied for pipe and cigar smokers because of the rela-
tively few smokers in these categories. Although the number of deaths
were few, Doll and Hill (26) reported increased death rates from lung
cancer for pipe and cigar smokers with increasing tobacco consump-
tion (table 27). Kahn (50) also demonstrated a dose-response relation-
ship for lung cancer by the amount smoked (table 28).

A few of the retrospective studies contained enough smokers to allow
an examination of dose-response relationships for pipe and cigar smok-
ing and lung cancer (J, 61, 74, 77). An increased risk of developing
lung cancer was demonstrated with the increased use of pipes and
cigars as measured by amount smoked and inhalation. The retrospec-
tive investigation of Abelin and Gsell (1) is of particular interest. The
smoking habits of 118 male patients with cancer of the lung from a
rural area of Switzerland were compared with those reported in a sur-
vey of all male inhabitants of a town in the same region. About 20
percent of the population of this area were regular cigar smokers, the
most popular cigar being the Stiimpen, a small Swiss-made machine-
manufactured cigar cut at both ends with an average weight of 4.5 g.
In this investigation, cigar smokers experienced a risk of developing
lung cancer that was similar to the risk of cigarette smokers. A dose-
response relationship was demonstrated for inhalation and amount
smoked. These data suggest that the heavy smoking of certain cigars
may result in a risk of lung cancer that is similar to that experienced
by cigarette smokers.

Several pathologists have reported histologic changes in the
bronchial epithelium in relation to smoking in various forms. Knudt-
son (57) examined the bronchial mucosa of 150 lungs removed at au-
topsy and correlated the histologic changes noted with the history
of smoking, age, occupation, and residence. Specimens obtained from
the six cigar and pipe smokers demonstrated basal cell hyperplasia;
however, there was no squamous or atypical proliferative metaplasia
as 18 frequently seen in the heavy cigarette smokers.

Sanderud (78) examined histologic sections from the bronchial tree
of 100 male autopsy cases for the presence of squamous epithelial

573
metaplasia. In this study, 39 percent of the population were non-
smokers, 20 percent were pipe smokers, and 38 percent smoked cig-
arettes. A total of 80 percent of the pipe smokers and cigarette smokers
demonstrated squamous metaplasia of the bronchial tree, whereas only
54 percent of the nonsmokers had this abnormality.

Auerbach, et al. (6) examined 36,340 histologic sections obtained
from 1,522 white adults for various epithelial lesions including:
presence or absence of ciliated cells, thickness or number of cell rows,
atypical nuclei, and the proportion of cells of various types. The
pathologic findings in the bronchial epithelium of pipe and cigar
smokers are compared to those found in nonsmokers and cigarette
smokers (table 25). Pipe and cigar smokers had abnormalities that
were intermediate between those of nonsmokers and cigarette smokers,
although cigar smokers had pathologic changes that in some categories
approached the changes seen in cigarette smokers.

TaBLe 26.—AMortality ratios for lung cancer deaths in male cigar and
pipe smokers. A summary of prospective studies

 

 

 

Type of smoking
Author, reference
Non- Cigar Pipe Total pipe Cigarette Mixed
smoker only only and cigar ouly
Hammond and Horn (40). 1. 00 3. 35 8.50 ..2 2 8. 23. 12 19. 71
Doll and Hill (26, 27).... 1.00 _...._.. __._.. 6.14 13.29 7. 43
Best (9)_-22 2222 1. 00 2. 94 435 -. 1 __. 14.91 __.. LLL
Hammond (88)___._.._._ 1. 00 1. 85 2. 24 1.97 9. 20 7.39
Kahn (60)___. 1. 00 1. 59 1. 84 1. 67 12.14 _-_ ole

 

TABLE 27.—Lung cancer death rates for cigar and pipe smokers by amount
smoked—Doll and Hill

 

 

Smoking type Death rate per 100 Number of deaths
Nonsmoker_______._-.__-_-___. 0. O7 3
Cigar and pipe:

ltol4g. perday___.--.-. oe. - 42 12
15 to 24 g. perday____.-__... - 45 6
>24 g.perday__.__-.- - 96 3
Cigarette only._.---- - 96 143

 

Sources: Doll, R., Hill, A. B. (28).

574
TaBLe 28.—Lung cancer mortality ratios for cigar and pipe smokers by
amount smoked— Kahn

 

Smoking types Mortality ratlo Number of deaths

Nonsmoker__..._...----------------+-------- 1. 00 78

Cigar smokers:

<5 cigars per day_____-__.-------------- 1.14 12

5 to & cigars per day.____.-_-.----------- 2. 64 il

>8 cigars per day____-.----------------- 2. 07 2
Pipe smokers:

<5 pipefuls per day___.--_-------------- -T7 2

5 to 19 pipefuls per day.._-.------------- 2.¢ 12

>19 pipefuls per day..--.--------------- 2.47 3
Cigar and pipe:

8 or less cigars, 19 or less pipefuls._...---- 1. 62 18

>8 cigars, >19 pipefuls_....--.---------- 2.19 2

 

Source: Kahn, H. A. (50).

575