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Trends in the incidence of endometrial cancer in the United States
GYNECOLOGIC
2, 130-143
ONCOLOGY
Trends
(1974)
in thk- Incidence of Endometrial Cancer &NYthe United States
W. CRAMER,
DANIEL
AND
M.D.,’ SIDNEY BARBARA CHRISTINE,
J. CUTLER, M.D.
SC.D,
Biometry Branch, National Cancer Institute, Bethesda, Maryland 20014 and State Department of Health, Hartford, Connecticut 06115 Received March 7,1974 The incidence of endometrial carcinoma is examined in national surveys from 1947 and 1970 and the Connecticut Registry operating since 1935. Cases coded “uterus unspecified” present a classification problem but evidence from several lines suggest they belong with endometrial carcinoma, at least for the white females. Rates corrected for these cases indicate no significant increase in the absolute incidence of endometrial carcinoma in either whites or blacks, although the current incidence of endometrial carcinoma is greater than that of invasive cervical cancer in white females over 50. Thus, the incidence of endometrial cancer in whites has increased relative to invasive cervical cancer due to the declining incidence of the latter. In black women, invasive cancers of the cervix are still occurring more frequently than cancers of the endometrium at all ages. An additional finding in blacks is that one-fourth of the cancers of the corpus are myometrial sarcomas, which suggests that rates for cancer of the corpus should not be considered equivalent to rates for endometrial cancer in blacks. Finally, several factors which might influence the incidence of endometrial carcinoma were discussed.
The notion of a rising incidence of endometrial carcinoma has been firmly established in two decades of literature on the subject [l-5]. This impression was often based upon series from hospitals rather than true incidence data from a well-defined population. The issue was further obscured by the traditional method of reporting endometrial incidence by its ratio to cervical cancer. Data from surveys and state registries provided little more information since there were often a large number of cases coded “uterus unspecified,” unclear whether primary in the corpus or cervix. In this paper, we take a critical look at the incidence of endometrial carcinoma, utilizing data from two national surveys and the Connecticut Registry. MATERIALS
AND
METHODS
We examined detailed data from the Second National Cancer Survey (SNCS), the Third National Cancer Survey (SNCS), and the Connecticut Registry. The 2NCS was completed in 1947-1948 and collected incidence data for a single year while the 3NCS collected data from 1969 through 1971. A contin’ Present
address:
Boston
Hospital
for Women, 130
Copyright
@ 1974 by Academic
All rights of reproduction
Press,
Inc.
in any form reserved.
Boston,
Massachusetts.
ENDOMETRIAL
CANCER
IN
THE
UNITED
131
STATES
uous picture is available from the Connecticut Registry, which has collected statewide incidence data since 1935. Reports describing the particulars of data collection and the population surveyed in each operation have been published previously [6-81. Essentially, information is abstracted on individuals with cancer from hospital charts, pathology reports, autopsy records, outpatient clinic records, cancer registries, hospital diagnostic indices, and death certificates. Cancers reported in the 3NCS were classified by site and type according to the 1968 edition of the Manual of Tumor Nomenclature and Coding [9]. Cancers reported in the 2NCS and to the Connecticut Registry have been coded by site based upon the International Classification of Diseases and by type according to the 1951 Manual of Tumor Nomenclature [lo-l 11. We selected the cases originally coded “corpus” and “uterus unspecified” and utilized the reported histology to more accurately define endometrial carcinoma (Table I). All carcinomas and malignant tumors of unspecified histology of the corpus, plus adenocarcinomas of “uterus unspecified” were considered endometrial in origin. Sarcomas and mixed tumors of the corpus and “uterus unspecified” were considered myometrial in origin. Excluding epidermoid carcinomas of “uterus unspecified” as cervical in origin left only cancers of unspecified histology in the “uterus unspecified” category. We also examined separately “in situ carcinomas” of the endometrium. These were identified by a malignancy code of 2 in the 3NCS, and a stage 0 in the Connecticut data. It is appropriate to assume that all reported cases in the 2NCS were malignant [71. Age-specific rates and rates adjusted to the age distribution of the 1950 or 1970 U.S. populations have been calculated and reported in cases per
DEFINITION MYOMETRIUM,
OF ANALYTICAL AND “UTERUS
Category
TABLE I CATEGORJES FOR CANCERS OF THE UNSPECIFIED”: BNCS, SNCS, AND
Description
Codes-3NCS”
Endometrium
Includes all carcinomas and unspecified cancers of the corpus plus adenocarcinoma of “uterus unspecified’
Site code 1820 with types 800-867 or site code 1829 with type code 814:857
Myometrium
Includes tumors “uterus
Site code 1820 or 1829 with type code 880:995,911
Uterus unspecified
Includes all cancers specified histologic “uterus unspecified”
a See Ref. b See Ref.
[8]. [9, lo].
sarcomas and mixed of the corpus and unspecified” of untype of
Site code 1829 with type code 800:805 or 999
ENDOMETRIUM, CONNECTICUT Codes-2NCS Connecticutb
and
Site code 172 with type code 00: 19, 98,99, plus site codes 174 with type codes 00:09 Site code 172 or 174 with type codes 66 through 79,82 through 88 Site code 174 with a type code 18, 19, 98,99
132
CRAMER,
CUTLER
AND
CHRISTINE
100,000. Statistical methodology has been described in previous publications [6-81. It should be noted that in examining trends for the national data, only the seven areas common to both surveys were utilized to minimize geographic differences, as described in a previous publication [121. Furthermore, only 1969 and 1970 data from the 3NCS has been used, since 1971 data was preliminary at the time of this report. We examine separately the trends for white and black females in the national data, but only the trend for all females is available from Connecticut. This, however, is equivalent to the trend for white females because of the small black population in Connecticut-about 4% [8]. Finally, the rates given for in situ carcinoma of the endometrium are referred to as “reported” rather than incidence rates. Incidence rates for in situ carcinoma can be obtained only when the precise relationship of the lesion to the screening procedure(s) that identified it are known, as described by Dunn for cervical cancer [ 131. RESULTS
“Uterus
Unspecified”
Cases
The study of the morbidity and mortality of gynecologic cancers is complicated greatly by the fact that medical records and death certificates often do not indicate the exact organ of origin of uterine tumors. These “uterus unspecified’ cases are particularly numerous in the early years of registries though less of a problem now. Several investigators have done retrospective studies on these cases in predominantly white populations and have reached similar conclusions concerning their assignment. A 1950 survey of cancer in Iowa showed that 72% of 175 cases originally coded “uterus” were, in fact, corpus in origin [14]. In a series of cases from the Connecticut Registry, Bailar found that 90% of cancers coded “uterus” were in reality from the corpus and noted that no major errors would result from simply assigning all of these to the corpus 1151. We have reduced the number of these “uterus unspecified” cases by assigning them on the basis of histology to cervix, endometrium, or myometrium, but still must deal with those cases with unspecified histology. An examination of the distribution of cases comprising total uterus in our national surveys, including in situ carcinomas, may be enlightening. In Fig. 1 we see that in white females in 1947, cervix accounted for 64% of all uterine cancers and 66% in 1969-1970 when in situ cases are included. Clearly, if the “uterus unspecified” cases are included with corpus, then the percentage of corpus cancers will also have remained constant-36% in I947 and 34% in 1969-1970. In Fig. 2 we examine the distribution in black females. Here the percentage of cervical carcinomas, including in situs among the total uterine cases, is much greater89% in 1970. To obtain constancy in the proportions, it is reasonable to combine the I947 “uterus unspecified” cases with the cervix. Then the proportions are 87% cervix, 13% corpus in 1947 and 90% cervix and 10% corpus in 1970. - Though admittedly a simplistic approach, Figs. 1 and 2 suggest a reasonable
ENDOMETRIAL
CANCER
IN
THE
UNITED
133
STATES
CORPUS INSITU (2%)
UT. NOS 0x1
TOTAL
FIG.
1. Distribution
= 2071
TOTAL
of cancers
within
the total
uterus
= 10,091
for the national
surveys,
white
females.
method for handling the “uterus unspecified” cases in examining trends. For the white females in our studies, they should be included with corpus or its close equivalent endometrium. For black females the “uterus unspecified” cases more likely belong with cervix, but certainly should not be included with corpus in examining the trend for endometrial cancer. Trends
in Endometrial
Cancer
Zncidence
Age-adjusted rates. With the “uterus unspecified” cases distributed as described in the foregoing section, the trends in the age-adjusted rates for endometrial cancer for whites and blacks are shown in Table II and Fig. 3. The national survey rate for white females was 21.1 cases/lOO,OOO in 1947 and 20.4 cases/lOO,OOO in 1970-essentially no difference. The rates for white females in Connecticut suggest there have been some fluctuations in the incidence for endometrial cancer since 1935; but there is no evidence of an overall increase
1947
1969.1970 UT. NOS 0x1
TOTAL
FIG.
2. Distribution
= 412
of cancers
TOTAL
within
the total
uterus
= 2320
for the national
surveys,
black
females.
134
CRAh4ER,
CUTLER
AND
TABLE
CHRISTINE II
NUMBER OF CASES AND AVERAGE ANNUAL AGE ADJUSTED (1950) RATES FOR ENDOMETRIAL CANCER: NATIONAL SURVEYS AND CONNECTICUT Endometial
cancer
Cases White females 2NCS 3NCS Black Females 2NCS 3NCS Connecticut (white females) 1935-39 1940-44 1945-49 1950-54 1955-59 1960-64 1965-69
Age-adjusted
rate
705 2976
21.1 20.4
45 166
13.4 8.7
734 769 897 1124 1229 1306 1390
18.0 15.9 16.7 18.5 18.1 16.8 16.2
in incidence. In fact there has been a slight decrease in the age-adjusted rate since 1955. The national data suggest the rate for black females has decreased; but we do not believe this represents a statistically significant trend. Computed by the method of Chiang 1161, the 95% confidence limits on the rates for black females was 9.4 to 17.4 in 1947, overlapping with the limits 7.4 to 10.0 in 1970. Age-specific rates. In Tables III and IV, we present the age-specific rates
I
L 1935
1940
1945
, 1950
1955
c 1960
1965
1970
Years
FIG. 3. Trend and Connecticut.
in the age-adjusted
rates (1950)
for endometial
cancer
from
the national
surveys
ENDOMETRIAL
CANCER
IN
TABLE
THE
UNITED
135
STATES
III
AVERAGE ANNUAL AGE-SPECIFIC RATES FOR ENDOMETRIAL CARCINOMA FROM NATIONAL SURVEYS ~5
5-9
lo-14
15-19
20-24
25-29
30-34
35-39
40-44
45-49
50-54
55-59
60-64
6569
70-74
75+
0 0
0 0
0 0.1
0 0
0.7 0.3
1.0 0.9
4.3 2.2
5.7 6.2
15.6 13.0
37.3 29.6
52.6 64.6
76.7 78.6
60.9 79.3
98.0 92.9
72.6 81.4
85.1 59.8
0 0
0 0
0 0
0 0
0 0
0 1.3
0 0.8
2.1 3.1
5.3 3.0
6.3 11.4
46.6 23.2
50.5 19.6
46.0 39.9
94.2 39.2
55.2 59.4
51.5 35.4
White
2NCS 3NCS Black ZNCS 3NCS
from the national surveys and Connecticut. The rates for white females in the national surveys are presented graphically in Fig. 4. The curves are virtually identical, except for some discrepancy in the oldest age group. For comparable time periods (1945-1949 compared to 1965-1969), the age-specific rates for white females in Connecticut are shown in Fig. 5. Again the curves are noticeably similar except for the variance in the oldest age groups. Both sets of curves indicate no change in incidence for endometrial carcinoma, confirming the age-adjusted incidence data. Both sets of curves indicate a steep rise in endometrial cancer in the menopausal years 45-55, with a peak incidence in late 60’s and some decline thereafter. Figure 6 presents the age-specific rates for endometial carcinoma in black females. We point out that the rates are lower and the peak incidence at a later TABLE
IV
AVERAGE ANNUAL AGE-SPECIFIC RATES FOR ENDOMETRIAL CARCINOMA FROM CONNECTICUT Time Age group <5 5-Q 10-14 15-19 20-24 25-29 30-34 35-39 40-44 45-49 50-54 55-59 60-64 65-69 70-74 75-79 80-84 85+
1935-39 0 0 0 0 0.3 1.7 0.6 4.7 9.7 23.1 40.9 55.6 78.3 69.2 99.5 96.3 92.8 164.2
1940-44 0 0 0 0 0.2 0 1.4 4.1 11.6 22.4 34.0 60.2 60.3 67.1 87.3 66.7 85.3 139.8
1945-49 0 0 0 0 0 0.5 1.2 4.7 11.9 21.7 47.4 62.6 61.9 74.6 74.8 58.1 82.6 132.1
period
1950-54
1955-59
1960-64
1965-69
0 0 0 0 0.3 0.4 3.5 4.7 12.5 32.6 51.3 66.3 77.0 79.2 52.5 84.8 105.9 67.8
0 0 0 0 0.3 0.7 1.1 5.1 11.0 25.6 43.6 75.0 77.2 78.2 68.9 71.7 84.4 67.5
0 0 0 0 0 0.7 3.3 4.6 13.1 30.1 44.9 53.3 67.1 71.2 75.1 80.9 76.4 64.0
0 0 0 0 0.4 0.6 0.7 4.3 12.9 23.7 46.0 57.7 63.9 76.0 73.8 67.3 56.9 50.3
136
CRAMER,
CUTLER
---. So-
AND
2NCS
-3NCS
20
30
40
50
Age
FIG.
4. Age-specific
rates
for endometrial
I"
cancer
-----
,945
-
1965-69
20
5. Age-specific
60
70
80
yenrs
in white
females
from
the national
49
30
40
rates for endometrial
1 60
so nqe
FIG.
CHRISTINE
i”
cancer
70
so
I 93
years
in white
females
from
Connecticut.
surveys.
ENDOMETRIAL
FIG.
6. Age-specific
rates
CANCER
for endometrial
IN
cancer
THE
in black
UNITED
females
137
STATES
from
the national
surveys.
age than for white females. The curves are more irregular, reflecting the fact that the population and the number of cases is smaller which leads to more variability in the observed rates. Because of this we are unable to say that a statistically significant change has occurred even though the observed decreases are very suggestive. In situ carcinomas of the endometrium. In Fig. 1, we saw that approximately 2% of total uterine cancers in whites were in situ carcinomas of the endometrium. Table V reveals that the reported rates for these in situ carcinomas have shown an apparent increase since the 1950’s in Connecticut. Over the same period there has been a slight decrease in the rate for invasive endometrial cancer. The significance of these observations will be further discussed.
TABLE
V
REPORTED AGE-ADJUSTED 1950 INCIDENCE RATES FOR in Situ CARCINOMA OF THE ENDOMETRIUM IN CONNECTICUT Time
period
1950-54 1955-59 1960-64 1965-69
No. of cases 22 39 57 101
Age-adj. 0.4 0.4 0.8 1.2
rate
CRAMER,
138
Current
Incidence
CUTLER
of Endometrial
AND
CHRISTINE
Carcinoma
In a previous paper, Cramer and Cutler discussed the 3NCS and the annual incidence of cancers of the female genital organs in 1969-1970 1121.The rates presented for cancer of the corpus in that paper have been divided into endometrium and myometrium in Table VI. Since the “uterus unspecified” cases represent only 1% of the total uterine cases (Fig. l), they have simply been excluded in Table VI. Furthermore, we are using the entire 3NCS survey areas instead of the seven areas common to the 2NCS which was our population base in discussing trends. Thus, the rates in Table VI are based on a total of 4924 cases diagnosed in 1969 and 1970 out of some 10 million females. The rates for endometrial carcinoma in whites are twice as great as those for blacks -an age-adjusted rate of 20.1 compared to 9.3. Ninety-three percent of invasive cancers of the corpus originate in the endometrium in whites in contrast to only 76% in blacks. Not only are the age-adjusted rates for myometrial tumors greater in blacks (2.9 compared to 1.5 in whites); but, because of the smaller rate for endometrial cancer, the myometrial sarcomas comprise onefourth of all cancers of the corpus in blacks. This suggests that, while rates for cancer of the corpus may be considered equivalent to rates for endometrial cancer in whites such is not the case in blacks. The 3NCS age-specific rates for invasive cancers of the cervix and ovary [ 121compared with those for endometrium provide an important perspective. Figure 7 shows this comparison for white females. As can be seen, cervical cancer still predominates in the early years before age 50. A sharp rise in endometrial and ovarian cancer occur during the years 45-55 and thereafter endometrial cancers predominate. Even ovarian cancers are more frequent than invasive cervical cancers in white females over 50. Thus, the ratio of cervical to endometrial cancer varies with age but clearly endometrial cancer is now the dominant site among invasive cancers of the female genital organs in whites. As documented previously the incidence of invasive cervical cancer has decreased [12]. It is this event that is responsible for the apparent emergence of endometrial cancer in whites rather than the increasing incidence of endometrial cancer. Figure 8 presents similar data for black females. Though the incidence of invasive cervical cancer has also decreased in blacks 1121, at this point in time they still predominate in all age groups among invasive cancers of the genital organs in blacks. Only in the 70’s do endometrial cancers approach the rates for cervical cancer. DISCUSSION We are unable to confirm the general impression that the incidence of endometrial carcinoma is increasing. It may be true that clinicians are seeing more endometrial carcinoma today on the basis of a larger postmenopausal population but this does not represent an increased incidence in the true sense of the term. Furthermore, Christopherson pointed out that, if the ratio of cervical to endometrial carcinoma is taken as an indicator of incidence, then endometrial carcinoma will appear to be increasing simply because invasive
THIS
TAELE
IS
BASED
1.3 1.4 0.3
INSITU CARCINJIAS ENDOKETRIUK ALL 1.3 URITE 1.4 BLACK 0.4
*
33.6 39.9 16.7
21.4 22.5 9.6
0.0 0.0 0.0
0.0 0.0 0.0
0.0 0.0 0.0
0.0 0.0 0.0
00 -04
ADJUSTED IUVASIVE
ON A TOTAL
2.1 2.2 0.6
2.6 2.4 4.0
1.5 1.5 2.3
2Q*
31.0 32.5 12.7
A;B
19.3 21.0 7.3
CRUDE RATES ALL
6.
INVASIVE CANCERS ENDOCIETRIQK ALL 19.6 PHITE 20.1 BLACK 9.3 KPOKETRIQII ALL 1.6 UHITE 1.5 BLACK 2.9 TOTAL CORPUS 4LL 21.2 WHITE 21.6 BLACK 12.2
AGE ADJ 1970
FABLE
OF
0.0 0.0 0.3
0.0 0.0 0.3
3.3 0.0 0.0
0.0 0.0 0.0
05 -09
U.924
0.0 0.0 0.0
0.0 0.1 0.0
0.0 0.1 0.0
0.0 0.0 0.0
10 -14
(1970). CANCERS
CASES:
0.0 0.0 0.0
0.1 0.1 0.0
0.0 0.0 0.0
0.1 0.1 0.0
15 -19
CRUDE, OF THE
NOT
0.1 0.1 0.0
0.4 0.4 0.0
0.2 0.2 0.0
0.2 0.2 0.0
20 -24
INCLUDED
0.5 0.5 0.0
1.1 0.8 3.1
0.3 0.2 1.9
0.7 0.7 1.2
-:;
AGE
IN
0.1 0.0 0.7
2.9 3.1 1.5
1.1 1.2 0.7
1.8 1.9 0.7
THE
0.6 0.5 0.0
6.9 7.2 5.3
1.8 1.9 1.5
5.0 5.3 3.8
RATES
1.5 1.5 0.7
13.7 14.3 8.1
2.3 2.0 4.4
11.4 12.3 3.7
ARE
40 -uu
113
4.1 4.2 0.8
30.6 30.9 15.0
3.2 3.0 3.2
27.U 28.0 11.8
:ASES
6.3 6.5 2.7
63.4 65.0 31.7
3.7 3.3 8.1
59.7 61.7 23.5
55 -59
OF
3.5 3.2 5.2
3.8 U-2 0.0
78.0 79.4 44.0
'UTERUS
6.2 6.5 1.1
75.7 70.9 23.4
3.7 3.3 4.2
74.5 76.1 38.8
60 -64
UNSPECIFIED.'
1.8 1.7 1.5
89.6 91.9 48.9
6.9 6.6 9.2
82.7 85.3 39.7
65 -69
CASBS PER 100,000 CARCIN3SAS,1969-1970*
72.0 75.6 19.1
RATES IN FOR INSITU
A ATES 45 -u9
ANNUAL INCIDENZE AND REPORTXD RATES
SPECIFIC 30 35 -34 -39
AND A3E SPECIFIC ENDJlIYOHETRIUfl
1.7 1.8 0.0
81.0 80.2 75.8
6.2 5.2 18.4
74.8 75.0 57.u
70 -7u
75 -79
0.7 0.7 0.0
70.2 69.3 64.9
4.3 3.8 19.1
65.3 65.5 45.9
FEHALES
30 -84
0.4 0.0 0.0
53.7 5U.l 27.7
2.9 3.0 0.0
50.9 51.0 27.7
FOR
0.0 0.0 0.0
33.7 33.5 32.7
3.6 2.8 16.4
30.1 30.7 16.4
B5+
140
CRAMER,
CUTLER
AND CHRISTINE
--- cewtxIns -.-.- O"O,Y
al
-
t
Endometf
AqeI” years FIG. 7. Annual age-specific incidence for cancers of the cervix, endometrium and ovary in white females, 1969-1970.
90 8.
---.-.-
i
Cervix Invasive ovary Endometrlum
mg s
60-
$ ; 8 u
so40-
30-
ZO-
10
a
30
40
50 60 Age tn yeor~
70
80
90
FIG. 8. Annual age-specific incidence for cancers of the cervix, endometrium, and ovary in black females, 1969-1970.
ENDOMETRIAL
CANCER
IN
THE
UNITED
STATES
141
cervical cancer is decreasing 117,181. In his studies of endometrial carcinoma in Louisville, Kentucky, Christopher-son observed a slight but not significant increase in endometrial carcinoma over the period 1953-1967 [17,18]. Unpublished data from Louisville on the incidence of endometrial carcinoma in 1968-1970 are even more in line with the 1953 level [191. In our study of trends in the incidence of endometrial carcinoma, we have the advantage of a larger population but the disadvantage of a less precise definition for endometrial carcinoma. In particular, many cases were coded “uterus unspecified” in the 1947 national survey and the early years of the Connecticut Registry; and the handling of these cases is crucial to the assessment of the trend for endometrial carcinoma. Published studies and our own examination of these cases suggested that the “uterus unspecified” cases belonged with endometrial carcinoma for the whites but not for the blacks [14,15]. The rates so corrected for whites suggest no significant change in the incidence of endometrial carcinoma since 1935. No statistically significant change was observed for the blacks but we have less confidence in the 1947 rates because of the smaller population and number of cases. Having just pointed out that we believe there has been no recent change in the incidence of endometrial carcinoma let us briefly examine some factors which might have an influence. Based on a study by the American Cancer Society, Hammond concluded that the frequency of hysterectomies “has increased greatly” since 1946 1201. When a hysterectomy is performed for reasons other than endometrial carcinoma, it removes a woman from the population at risk and this should eventually cause a decrease in the observed incidence of endometrial carcinoma. But Hammond pointed out that if occult endometrial cancer is found in the hysterectomy specimens, this might lead to an apparent increase rather than a decrease in endometrial carcinoma. Also, if the woman at greatest risk of receiving an elective hysterectomy is not the type most liable to develop endometrial carcinoma, then we might expect little effect of hysterectomy on the frequency of endometrial cancer. Multiparity is not believed to have an association with endometrial cancer but is certainly one factor in the selection of patients who receive hysterectomies. Obviously, the question is complicated and solid data on the matter lacking; but hysterectomy is one factor which should be considered in epidemiological studies of endometrial cancer. The Department of Commerce estimates the total value of estrogens shipped by drug manufacturers at 17 million dollars in 1962 and 58 million in 1971, providing one indicator of the widespread and increasing use of estrogen in this country [21]. It is reasonable to ask if this has had an influence on the incidence of endometrial carcinoma, since the suspicion persists that excessive estrogen exposure may be an etiologic factor 1221. If our data are accurate, then the failure to observe an increase in endometrial carcinoma, particularly in the younger age groups, could indicate several things. First, there is no etiologic relationship between exogenous estrogen and endometrial carcinoma. Second, the increase may not yet have manifested itself and
142
CRAMER,
CUTLER
AND
CHRISTINE
may require more time or third, the increase is counterbalanced by other factors. Obviously, we cannot settle the issue with the present data but hopefully it may serve as a baseline in future inquiries. Finally, we wish to comment on the role of cervical cytology in the trend in incidence for endometrial carcinoma. There is general agreement that cervical cytology is inefficient in detecting endometrial carcinoma [S]. Christopherson felt that cervical cytology contributed little to the control of endometrial carcinoma except perhaps by increasing physician-patient contact 1181.Nevertheless, the data from Connecticut indicate an apparent increase in the reported rates for in situ carcinoma of the endometrium at the same time a slight decrease has occurred in the rates for invasive endometrial cancer. This has taken place since 1955, corresponding to the period when cervical cytology has burgeoned. The increasing popularity of the diagnosis, in situ carcinoma, may account for this coincidence. It is very likely that there has been among pathologists a shift in classification or at least greater awareness of in situ lesions of the endometrium because of emphasis on the early diagnosis of cervical cancer. REFERENCES 1. SPEERT, H. Corpus cancer. Cancer 1,584 (1948). 2. WALL, J. Endometrial carcinoma. Clin. Obstet. Gynecol. 4,599 (1961). 3. HERTIC, A. T., GORE, H. Atlas of tumor pathology, Armed Forces Institute of Pathology, Washington, D.C. (1960). 4. NASH, A. E. Symposium on endometrial cancer. Amer. J. Obstet. Gynecol. 81, 1169 (1961). 5. KISTNER, R. W., KRANTZ, K. E., LEBHERZ, T. B., LEWIS, G. L., REAGAN, J. W., SMITH, J., TOBIN, J. J., AND WIED, G. L., ET AL. Endometrial cancer: Rising incidence, detection and treatment. J. Reprod. Med. 10, 1 (1973). 6. Preliminary report, Third National Cancer Suruey, 1969 Incidence, DHEW Publication No. (NIH) 72-128, September 9, (1971). 7. DORN, H. F., AND CUTLER, S. J. Morbidity from cancer in the United States, Public Health Monogr. No. 56, Washington, DC. (1959). 8. GRISWOLD, M. H., WILDER, C. S., CUTLER, S. J., AND POLLACK, E. S. Cancer in Connecticut 1935-1951, Connecticut State Department of Public Health, Hartford, Connecticut, 1955. 9. Manual of tumor nomenclature and coding, 1968 Edition, American Cancer Society, Inc., 1968. 10. Manual of the International Statistical Classification of Diseases, Injuries and Causes of Death, 6th Rev., World Health Organization, Geneva, Switzerland, 1949. 11. Manual of tumor nomenclature and coding, 1951 Ed., American Cancer Society, Inc., 1951. 12. CRAMER, D. W., AND CUTLER, S. J. Incidence and histopathology of malignancies of the female genital organs in the United States. Accepted Amer. J. Obstet. Gynecol. (1973). 13. DUNN, J. E. The relationship between carcinoma in situ and invasive cervical carcinoma. Cancer 6,873 (1953). 14. HAENSZEL, W., MARCUS, S. C., AND ZIMMER, E. G.: Cancer morbidity in urban and rural Iowa. Public Health Monogr. No. 37, U.S. Government Printing Office (1956). 15. BAILAR, J. C., AND EISENBERG, H.: Uterine tumors of unspecified origin. Cancer 18, 589 (1965). 16. CHIANG, C. L. Vital statistics selected reports, Vol. 47, No. 9, DHEW (1961). 17. CHRISTOPHERSON, W. M., MENDEZ, W. M., LUDIN, F. E., AND PARKER, J. E. A ten-year study of endometrial carcinoma in Louisville, Kentucky. Cancer 18,554 (1965). 18. CHRISTOPHERSON, W. M., MENDEZ, W. M., PARKER, J. E., LUDIN, F. E., AND AHUJA, E. M. Carcinoma of the endometrium: A study of changing rates over a 1Syear period. Cancer 27, 1695 (1971).
ENDOMETRIAL
CANCER
IN
THE
UNITED
STATES
143
19. CHFUSTOPHERSON, W. M. Personal Communication. 29. HAMMOND, E. C. The early diagnosis of uterine cancer. In the early diagnosis of cancer of the cervix (J. M. Riggott, Ed.), British Association for Cancer Research (1970). 21. Current Industrial Reports: Pharmaceutical preparations except biological. Department of Commerce, Bureau of Census, Industrial Division Series, Ma-28G (62-l) and (71-1) (1962 and 1971). 22. RICHARDSON, G. S. Endometrial cancer as an estrogen-progesterone target. N. Engl. J. Med. 286,645 (1972).
2, 130-143
ONCOLOGY
Trends
(1974)
in thk- Incidence of Endometrial Cancer &NYthe United States
W. CRAMER,
DANIEL
AND
M.D.,’ SIDNEY BARBARA CHRISTINE,
J. CUTLER, M.D.
SC.D,
Biometry Branch, National Cancer Institute, Bethesda, Maryland 20014 and State Department of Health, Hartford, Connecticut 06115 Received March 7,1974 The incidence of endometrial carcinoma is examined in national surveys from 1947 and 1970 and the Connecticut Registry operating since 1935. Cases coded “uterus unspecified” present a classification problem but evidence from several lines suggest they belong with endometrial carcinoma, at least for the white females. Rates corrected for these cases indicate no significant increase in the absolute incidence of endometrial carcinoma in either whites or blacks, although the current incidence of endometrial carcinoma is greater than that of invasive cervical cancer in white females over 50. Thus, the incidence of endometrial cancer in whites has increased relative to invasive cervical cancer due to the declining incidence of the latter. In black women, invasive cancers of the cervix are still occurring more frequently than cancers of the endometrium at all ages. An additional finding in blacks is that one-fourth of the cancers of the corpus are myometrial sarcomas, which suggests that rates for cancer of the corpus should not be considered equivalent to rates for endometrial cancer in blacks. Finally, several factors which might influence the incidence of endometrial carcinoma were discussed.
The notion of a rising incidence of endometrial carcinoma has been firmly established in two decades of literature on the subject [l-5]. This impression was often based upon series from hospitals rather than true incidence data from a well-defined population. The issue was further obscured by the traditional method of reporting endometrial incidence by its ratio to cervical cancer. Data from surveys and state registries provided little more information since there were often a large number of cases coded “uterus unspecified,” unclear whether primary in the corpus or cervix. In this paper, we take a critical look at the incidence of endometrial carcinoma, utilizing data from two national surveys and the Connecticut Registry. MATERIALS
AND
METHODS
We examined detailed data from the Second National Cancer Survey (SNCS), the Third National Cancer Survey (SNCS), and the Connecticut Registry. The 2NCS was completed in 1947-1948 and collected incidence data for a single year while the 3NCS collected data from 1969 through 1971. A contin’ Present
address:
Boston
Hospital
for Women, 130
Copyright
@ 1974 by Academic
All rights of reproduction
Press,
Inc.
in any form reserved.
Boston,
Massachusetts.
ENDOMETRIAL
CANCER
IN
THE
UNITED
131
STATES
uous picture is available from the Connecticut Registry, which has collected statewide incidence data since 1935. Reports describing the particulars of data collection and the population surveyed in each operation have been published previously [6-81. Essentially, information is abstracted on individuals with cancer from hospital charts, pathology reports, autopsy records, outpatient clinic records, cancer registries, hospital diagnostic indices, and death certificates. Cancers reported in the 3NCS were classified by site and type according to the 1968 edition of the Manual of Tumor Nomenclature and Coding [9]. Cancers reported in the 2NCS and to the Connecticut Registry have been coded by site based upon the International Classification of Diseases and by type according to the 1951 Manual of Tumor Nomenclature [lo-l 11. We selected the cases originally coded “corpus” and “uterus unspecified” and utilized the reported histology to more accurately define endometrial carcinoma (Table I). All carcinomas and malignant tumors of unspecified histology of the corpus, plus adenocarcinomas of “uterus unspecified” were considered endometrial in origin. Sarcomas and mixed tumors of the corpus and “uterus unspecified” were considered myometrial in origin. Excluding epidermoid carcinomas of “uterus unspecified” as cervical in origin left only cancers of unspecified histology in the “uterus unspecified” category. We also examined separately “in situ carcinomas” of the endometrium. These were identified by a malignancy code of 2 in the 3NCS, and a stage 0 in the Connecticut data. It is appropriate to assume that all reported cases in the 2NCS were malignant [71. Age-specific rates and rates adjusted to the age distribution of the 1950 or 1970 U.S. populations have been calculated and reported in cases per
DEFINITION MYOMETRIUM,
OF ANALYTICAL AND “UTERUS
Category
TABLE I CATEGORJES FOR CANCERS OF THE UNSPECIFIED”: BNCS, SNCS, AND
Description
Codes-3NCS”
Endometrium
Includes all carcinomas and unspecified cancers of the corpus plus adenocarcinoma of “uterus unspecified’
Site code 1820 with types 800-867 or site code 1829 with type code 814:857
Myometrium
Includes tumors “uterus
Site code 1820 or 1829 with type code 880:995,911
Uterus unspecified
Includes all cancers specified histologic “uterus unspecified”
a See Ref. b See Ref.
[8]. [9, lo].
sarcomas and mixed of the corpus and unspecified” of untype of
Site code 1829 with type code 800:805 or 999
ENDOMETRIUM, CONNECTICUT Codes-2NCS Connecticutb
and
Site code 172 with type code 00: 19, 98,99, plus site codes 174 with type codes 00:09 Site code 172 or 174 with type codes 66 through 79,82 through 88 Site code 174 with a type code 18, 19, 98,99
132
CRAMER,
CUTLER
AND
CHRISTINE
100,000. Statistical methodology has been described in previous publications [6-81. It should be noted that in examining trends for the national data, only the seven areas common to both surveys were utilized to minimize geographic differences, as described in a previous publication [121. Furthermore, only 1969 and 1970 data from the 3NCS has been used, since 1971 data was preliminary at the time of this report. We examine separately the trends for white and black females in the national data, but only the trend for all females is available from Connecticut. This, however, is equivalent to the trend for white females because of the small black population in Connecticut-about 4% [8]. Finally, the rates given for in situ carcinoma of the endometrium are referred to as “reported” rather than incidence rates. Incidence rates for in situ carcinoma can be obtained only when the precise relationship of the lesion to the screening procedure(s) that identified it are known, as described by Dunn for cervical cancer [ 131. RESULTS
“Uterus
Unspecified”
Cases
The study of the morbidity and mortality of gynecologic cancers is complicated greatly by the fact that medical records and death certificates often do not indicate the exact organ of origin of uterine tumors. These “uterus unspecified’ cases are particularly numerous in the early years of registries though less of a problem now. Several investigators have done retrospective studies on these cases in predominantly white populations and have reached similar conclusions concerning their assignment. A 1950 survey of cancer in Iowa showed that 72% of 175 cases originally coded “uterus” were, in fact, corpus in origin [14]. In a series of cases from the Connecticut Registry, Bailar found that 90% of cancers coded “uterus” were in reality from the corpus and noted that no major errors would result from simply assigning all of these to the corpus 1151. We have reduced the number of these “uterus unspecified” cases by assigning them on the basis of histology to cervix, endometrium, or myometrium, but still must deal with those cases with unspecified histology. An examination of the distribution of cases comprising total uterus in our national surveys, including in situ carcinomas, may be enlightening. In Fig. 1 we see that in white females in 1947, cervix accounted for 64% of all uterine cancers and 66% in 1969-1970 when in situ cases are included. Clearly, if the “uterus unspecified” cases are included with corpus, then the percentage of corpus cancers will also have remained constant-36% in I947 and 34% in 1969-1970. In Fig. 2 we examine the distribution in black females. Here the percentage of cervical carcinomas, including in situs among the total uterine cases, is much greater89% in 1970. To obtain constancy in the proportions, it is reasonable to combine the I947 “uterus unspecified” cases with the cervix. Then the proportions are 87% cervix, 13% corpus in 1947 and 90% cervix and 10% corpus in 1970. - Though admittedly a simplistic approach, Figs. 1 and 2 suggest a reasonable
ENDOMETRIAL
CANCER
IN
THE
UNITED
133
STATES
CORPUS INSITU (2%)
UT. NOS 0x1
TOTAL
FIG.
1. Distribution
= 2071
TOTAL
of cancers
within
the total
uterus
= 10,091
for the national
surveys,
white
females.
method for handling the “uterus unspecified” cases in examining trends. For the white females in our studies, they should be included with corpus or its close equivalent endometrium. For black females the “uterus unspecified” cases more likely belong with cervix, but certainly should not be included with corpus in examining the trend for endometrial cancer. Trends
in Endometrial
Cancer
Zncidence
Age-adjusted rates. With the “uterus unspecified” cases distributed as described in the foregoing section, the trends in the age-adjusted rates for endometrial cancer for whites and blacks are shown in Table II and Fig. 3. The national survey rate for white females was 21.1 cases/lOO,OOO in 1947 and 20.4 cases/lOO,OOO in 1970-essentially no difference. The rates for white females in Connecticut suggest there have been some fluctuations in the incidence for endometrial cancer since 1935; but there is no evidence of an overall increase
1947
1969.1970 UT. NOS 0x1
TOTAL
FIG.
2. Distribution
= 412
of cancers
TOTAL
within
the total
uterus
= 2320
for the national
surveys,
black
females.
134
CRAh4ER,
CUTLER
AND
TABLE
CHRISTINE II
NUMBER OF CASES AND AVERAGE ANNUAL AGE ADJUSTED (1950) RATES FOR ENDOMETRIAL CANCER: NATIONAL SURVEYS AND CONNECTICUT Endometial
cancer
Cases White females 2NCS 3NCS Black Females 2NCS 3NCS Connecticut (white females) 1935-39 1940-44 1945-49 1950-54 1955-59 1960-64 1965-69
Age-adjusted
rate
705 2976
21.1 20.4
45 166
13.4 8.7
734 769 897 1124 1229 1306 1390
18.0 15.9 16.7 18.5 18.1 16.8 16.2
in incidence. In fact there has been a slight decrease in the age-adjusted rate since 1955. The national data suggest the rate for black females has decreased; but we do not believe this represents a statistically significant trend. Computed by the method of Chiang 1161, the 95% confidence limits on the rates for black females was 9.4 to 17.4 in 1947, overlapping with the limits 7.4 to 10.0 in 1970. Age-specific rates. In Tables III and IV, we present the age-specific rates
I
L 1935
1940
1945
, 1950
1955
c 1960
1965
1970
Years
FIG. 3. Trend and Connecticut.
in the age-adjusted
rates (1950)
for endometial
cancer
from
the national
surveys
ENDOMETRIAL
CANCER
IN
TABLE
THE
UNITED
135
STATES
III
AVERAGE ANNUAL AGE-SPECIFIC RATES FOR ENDOMETRIAL CARCINOMA FROM NATIONAL SURVEYS ~5
5-9
lo-14
15-19
20-24
25-29
30-34
35-39
40-44
45-49
50-54
55-59
60-64
6569
70-74
75+
0 0
0 0
0 0.1
0 0
0.7 0.3
1.0 0.9
4.3 2.2
5.7 6.2
15.6 13.0
37.3 29.6
52.6 64.6
76.7 78.6
60.9 79.3
98.0 92.9
72.6 81.4
85.1 59.8
0 0
0 0
0 0
0 0
0 0
0 1.3
0 0.8
2.1 3.1
5.3 3.0
6.3 11.4
46.6 23.2
50.5 19.6
46.0 39.9
94.2 39.2
55.2 59.4
51.5 35.4
White
2NCS 3NCS Black ZNCS 3NCS
from the national surveys and Connecticut. The rates for white females in the national surveys are presented graphically in Fig. 4. The curves are virtually identical, except for some discrepancy in the oldest age group. For comparable time periods (1945-1949 compared to 1965-1969), the age-specific rates for white females in Connecticut are shown in Fig. 5. Again the curves are noticeably similar except for the variance in the oldest age groups. Both sets of curves indicate no change in incidence for endometrial carcinoma, confirming the age-adjusted incidence data. Both sets of curves indicate a steep rise in endometrial cancer in the menopausal years 45-55, with a peak incidence in late 60’s and some decline thereafter. Figure 6 presents the age-specific rates for endometial carcinoma in black females. We point out that the rates are lower and the peak incidence at a later TABLE
IV
AVERAGE ANNUAL AGE-SPECIFIC RATES FOR ENDOMETRIAL CARCINOMA FROM CONNECTICUT Time Age group <5 5-Q 10-14 15-19 20-24 25-29 30-34 35-39 40-44 45-49 50-54 55-59 60-64 65-69 70-74 75-79 80-84 85+
1935-39 0 0 0 0 0.3 1.7 0.6 4.7 9.7 23.1 40.9 55.6 78.3 69.2 99.5 96.3 92.8 164.2
1940-44 0 0 0 0 0.2 0 1.4 4.1 11.6 22.4 34.0 60.2 60.3 67.1 87.3 66.7 85.3 139.8
1945-49 0 0 0 0 0 0.5 1.2 4.7 11.9 21.7 47.4 62.6 61.9 74.6 74.8 58.1 82.6 132.1
period
1950-54
1955-59
1960-64
1965-69
0 0 0 0 0.3 0.4 3.5 4.7 12.5 32.6 51.3 66.3 77.0 79.2 52.5 84.8 105.9 67.8
0 0 0 0 0.3 0.7 1.1 5.1 11.0 25.6 43.6 75.0 77.2 78.2 68.9 71.7 84.4 67.5
0 0 0 0 0 0.7 3.3 4.6 13.1 30.1 44.9 53.3 67.1 71.2 75.1 80.9 76.4 64.0
0 0 0 0 0.4 0.6 0.7 4.3 12.9 23.7 46.0 57.7 63.9 76.0 73.8 67.3 56.9 50.3
136
CRAMER,
CUTLER
---. So-
AND
2NCS
-3NCS
20
30
40
50
Age
FIG.
4. Age-specific
rates
for endometrial
I"
cancer
-----
,945
-
1965-69
20
5. Age-specific
60
70
80
yenrs
in white
females
from
the national
49
30
40
rates for endometrial
1 60
so nqe
FIG.
CHRISTINE
i”
cancer
70
so
I 93
years
in white
females
from
Connecticut.
surveys.
ENDOMETRIAL
FIG.
6. Age-specific
rates
CANCER
for endometrial
IN
cancer
THE
in black
UNITED
females
137
STATES
from
the national
surveys.
age than for white females. The curves are more irregular, reflecting the fact that the population and the number of cases is smaller which leads to more variability in the observed rates. Because of this we are unable to say that a statistically significant change has occurred even though the observed decreases are very suggestive. In situ carcinomas of the endometrium. In Fig. 1, we saw that approximately 2% of total uterine cancers in whites were in situ carcinomas of the endometrium. Table V reveals that the reported rates for these in situ carcinomas have shown an apparent increase since the 1950’s in Connecticut. Over the same period there has been a slight decrease in the rate for invasive endometrial cancer. The significance of these observations will be further discussed.
TABLE
V
REPORTED AGE-ADJUSTED 1950 INCIDENCE RATES FOR in Situ CARCINOMA OF THE ENDOMETRIUM IN CONNECTICUT Time
period
1950-54 1955-59 1960-64 1965-69
No. of cases 22 39 57 101
Age-adj. 0.4 0.4 0.8 1.2
rate
CRAMER,
138
Current
Incidence
CUTLER
of Endometrial
AND
CHRISTINE
Carcinoma
In a previous paper, Cramer and Cutler discussed the 3NCS and the annual incidence of cancers of the female genital organs in 1969-1970 1121.The rates presented for cancer of the corpus in that paper have been divided into endometrium and myometrium in Table VI. Since the “uterus unspecified” cases represent only 1% of the total uterine cases (Fig. l), they have simply been excluded in Table VI. Furthermore, we are using the entire 3NCS survey areas instead of the seven areas common to the 2NCS which was our population base in discussing trends. Thus, the rates in Table VI are based on a total of 4924 cases diagnosed in 1969 and 1970 out of some 10 million females. The rates for endometrial carcinoma in whites are twice as great as those for blacks -an age-adjusted rate of 20.1 compared to 9.3. Ninety-three percent of invasive cancers of the corpus originate in the endometrium in whites in contrast to only 76% in blacks. Not only are the age-adjusted rates for myometrial tumors greater in blacks (2.9 compared to 1.5 in whites); but, because of the smaller rate for endometrial cancer, the myometrial sarcomas comprise onefourth of all cancers of the corpus in blacks. This suggests that, while rates for cancer of the corpus may be considered equivalent to rates for endometrial cancer in whites such is not the case in blacks. The 3NCS age-specific rates for invasive cancers of the cervix and ovary [ 121compared with those for endometrium provide an important perspective. Figure 7 shows this comparison for white females. As can be seen, cervical cancer still predominates in the early years before age 50. A sharp rise in endometrial and ovarian cancer occur during the years 45-55 and thereafter endometrial cancers predominate. Even ovarian cancers are more frequent than invasive cervical cancers in white females over 50. Thus, the ratio of cervical to endometrial cancer varies with age but clearly endometrial cancer is now the dominant site among invasive cancers of the female genital organs in whites. As documented previously the incidence of invasive cervical cancer has decreased [12]. It is this event that is responsible for the apparent emergence of endometrial cancer in whites rather than the increasing incidence of endometrial cancer. Figure 8 presents similar data for black females. Though the incidence of invasive cervical cancer has also decreased in blacks 1121, at this point in time they still predominate in all age groups among invasive cancers of the genital organs in blacks. Only in the 70’s do endometrial cancers approach the rates for cervical cancer. DISCUSSION We are unable to confirm the general impression that the incidence of endometrial carcinoma is increasing. It may be true that clinicians are seeing more endometrial carcinoma today on the basis of a larger postmenopausal population but this does not represent an increased incidence in the true sense of the term. Furthermore, Christopherson pointed out that, if the ratio of cervical to endometrial carcinoma is taken as an indicator of incidence, then endometrial carcinoma will appear to be increasing simply because invasive
THIS
TAELE
IS
BASED
1.3 1.4 0.3
INSITU CARCINJIAS ENDOKETRIUK ALL 1.3 URITE 1.4 BLACK 0.4
*
33.6 39.9 16.7
21.4 22.5 9.6
0.0 0.0 0.0
0.0 0.0 0.0
0.0 0.0 0.0
0.0 0.0 0.0
00 -04
ADJUSTED IUVASIVE
ON A TOTAL
2.1 2.2 0.6
2.6 2.4 4.0
1.5 1.5 2.3
2Q*
31.0 32.5 12.7
A;B
19.3 21.0 7.3
CRUDE RATES ALL
6.
INVASIVE CANCERS ENDOCIETRIQK ALL 19.6 PHITE 20.1 BLACK 9.3 KPOKETRIQII ALL 1.6 UHITE 1.5 BLACK 2.9 TOTAL CORPUS 4LL 21.2 WHITE 21.6 BLACK 12.2
AGE ADJ 1970
FABLE
OF
0.0 0.0 0.3
0.0 0.0 0.3
3.3 0.0 0.0
0.0 0.0 0.0
05 -09
U.924
0.0 0.0 0.0
0.0 0.1 0.0
0.0 0.1 0.0
0.0 0.0 0.0
10 -14
(1970). CANCERS
CASES:
0.0 0.0 0.0
0.1 0.1 0.0
0.0 0.0 0.0
0.1 0.1 0.0
15 -19
CRUDE, OF THE
NOT
0.1 0.1 0.0
0.4 0.4 0.0
0.2 0.2 0.0
0.2 0.2 0.0
20 -24
INCLUDED
0.5 0.5 0.0
1.1 0.8 3.1
0.3 0.2 1.9
0.7 0.7 1.2
-:;
AGE
IN
0.1 0.0 0.7
2.9 3.1 1.5
1.1 1.2 0.7
1.8 1.9 0.7
THE
0.6 0.5 0.0
6.9 7.2 5.3
1.8 1.9 1.5
5.0 5.3 3.8
RATES
1.5 1.5 0.7
13.7 14.3 8.1
2.3 2.0 4.4
11.4 12.3 3.7
ARE
40 -uu
113
4.1 4.2 0.8
30.6 30.9 15.0
3.2 3.0 3.2
27.U 28.0 11.8
:ASES
6.3 6.5 2.7
63.4 65.0 31.7
3.7 3.3 8.1
59.7 61.7 23.5
55 -59
OF
3.5 3.2 5.2
3.8 U-2 0.0
78.0 79.4 44.0
'UTERUS
6.2 6.5 1.1
75.7 70.9 23.4
3.7 3.3 4.2
74.5 76.1 38.8
60 -64
UNSPECIFIED.'
1.8 1.7 1.5
89.6 91.9 48.9
6.9 6.6 9.2
82.7 85.3 39.7
65 -69
CASBS PER 100,000 CARCIN3SAS,1969-1970*
72.0 75.6 19.1
RATES IN FOR INSITU
A ATES 45 -u9
ANNUAL INCIDENZE AND REPORTXD RATES
SPECIFIC 30 35 -34 -39
AND A3E SPECIFIC ENDJlIYOHETRIUfl
1.7 1.8 0.0
81.0 80.2 75.8
6.2 5.2 18.4
74.8 75.0 57.u
70 -7u
75 -79
0.7 0.7 0.0
70.2 69.3 64.9
4.3 3.8 19.1
65.3 65.5 45.9
FEHALES
30 -84
0.4 0.0 0.0
53.7 5U.l 27.7
2.9 3.0 0.0
50.9 51.0 27.7
FOR
0.0 0.0 0.0
33.7 33.5 32.7
3.6 2.8 16.4
30.1 30.7 16.4
B5+
140
CRAMER,
CUTLER
AND CHRISTINE
--- cewtxIns -.-.- O"O,Y
al
-
t
Endometf
AqeI” years FIG. 7. Annual age-specific incidence for cancers of the cervix, endometrium and ovary in white females, 1969-1970.
90 8.
---.-.-
i
Cervix Invasive ovary Endometrlum
mg s
60-
$ ; 8 u
so40-
30-
ZO-
10
a
30
40
50 60 Age tn yeor~
70
80
90
FIG. 8. Annual age-specific incidence for cancers of the cervix, endometrium, and ovary in black females, 1969-1970.
ENDOMETRIAL
CANCER
IN
THE
UNITED
STATES
141
cervical cancer is decreasing 117,181. In his studies of endometrial carcinoma in Louisville, Kentucky, Christopher-son observed a slight but not significant increase in endometrial carcinoma over the period 1953-1967 [17,18]. Unpublished data from Louisville on the incidence of endometrial carcinoma in 1968-1970 are even more in line with the 1953 level [191. In our study of trends in the incidence of endometrial carcinoma, we have the advantage of a larger population but the disadvantage of a less precise definition for endometrial carcinoma. In particular, many cases were coded “uterus unspecified” in the 1947 national survey and the early years of the Connecticut Registry; and the handling of these cases is crucial to the assessment of the trend for endometrial carcinoma. Published studies and our own examination of these cases suggested that the “uterus unspecified” cases belonged with endometrial carcinoma for the whites but not for the blacks [14,15]. The rates so corrected for whites suggest no significant change in the incidence of endometrial carcinoma since 1935. No statistically significant change was observed for the blacks but we have less confidence in the 1947 rates because of the smaller population and number of cases. Having just pointed out that we believe there has been no recent change in the incidence of endometrial carcinoma let us briefly examine some factors which might have an influence. Based on a study by the American Cancer Society, Hammond concluded that the frequency of hysterectomies “has increased greatly” since 1946 1201. When a hysterectomy is performed for reasons other than endometrial carcinoma, it removes a woman from the population at risk and this should eventually cause a decrease in the observed incidence of endometrial carcinoma. But Hammond pointed out that if occult endometrial cancer is found in the hysterectomy specimens, this might lead to an apparent increase rather than a decrease in endometrial carcinoma. Also, if the woman at greatest risk of receiving an elective hysterectomy is not the type most liable to develop endometrial carcinoma, then we might expect little effect of hysterectomy on the frequency of endometrial cancer. Multiparity is not believed to have an association with endometrial cancer but is certainly one factor in the selection of patients who receive hysterectomies. Obviously, the question is complicated and solid data on the matter lacking; but hysterectomy is one factor which should be considered in epidemiological studies of endometrial cancer. The Department of Commerce estimates the total value of estrogens shipped by drug manufacturers at 17 million dollars in 1962 and 58 million in 1971, providing one indicator of the widespread and increasing use of estrogen in this country [21]. It is reasonable to ask if this has had an influence on the incidence of endometrial carcinoma, since the suspicion persists that excessive estrogen exposure may be an etiologic factor 1221. If our data are accurate, then the failure to observe an increase in endometrial carcinoma, particularly in the younger age groups, could indicate several things. First, there is no etiologic relationship between exogenous estrogen and endometrial carcinoma. Second, the increase may not yet have manifested itself and
142
CRAMER,
CUTLER
AND
CHRISTINE
may require more time or third, the increase is counterbalanced by other factors. Obviously, we cannot settle the issue with the present data but hopefully it may serve as a baseline in future inquiries. Finally, we wish to comment on the role of cervical cytology in the trend in incidence for endometrial carcinoma. There is general agreement that cervical cytology is inefficient in detecting endometrial carcinoma [S]. Christopherson felt that cervical cytology contributed little to the control of endometrial carcinoma except perhaps by increasing physician-patient contact 1181.Nevertheless, the data from Connecticut indicate an apparent increase in the reported rates for in situ carcinoma of the endometrium at the same time a slight decrease has occurred in the rates for invasive endometrial cancer. This has taken place since 1955, corresponding to the period when cervical cytology has burgeoned. The increasing popularity of the diagnosis, in situ carcinoma, may account for this coincidence. It is very likely that there has been among pathologists a shift in classification or at least greater awareness of in situ lesions of the endometrium because of emphasis on the early diagnosis of cervical cancer. REFERENCES 1. SPEERT, H. Corpus cancer. Cancer 1,584 (1948). 2. WALL, J. Endometrial carcinoma. Clin. Obstet. Gynecol. 4,599 (1961). 3. HERTIC, A. T., GORE, H. Atlas of tumor pathology, Armed Forces Institute of Pathology, Washington, D.C. (1960). 4. NASH, A. E. Symposium on endometrial cancer. Amer. J. Obstet. Gynecol. 81, 1169 (1961). 5. KISTNER, R. W., KRANTZ, K. E., LEBHERZ, T. B., LEWIS, G. L., REAGAN, J. W., SMITH, J., TOBIN, J. J., AND WIED, G. L., ET AL. Endometrial cancer: Rising incidence, detection and treatment. J. Reprod. Med. 10, 1 (1973). 6. Preliminary report, Third National Cancer Suruey, 1969 Incidence, DHEW Publication No. (NIH) 72-128, September 9, (1971). 7. DORN, H. F., AND CUTLER, S. J. Morbidity from cancer in the United States, Public Health Monogr. No. 56, Washington, DC. (1959). 8. GRISWOLD, M. H., WILDER, C. S., CUTLER, S. J., AND POLLACK, E. S. Cancer in Connecticut 1935-1951, Connecticut State Department of Public Health, Hartford, Connecticut, 1955. 9. Manual of tumor nomenclature and coding, 1968 Edition, American Cancer Society, Inc., 1968. 10. Manual of the International Statistical Classification of Diseases, Injuries and Causes of Death, 6th Rev., World Health Organization, Geneva, Switzerland, 1949. 11. Manual of tumor nomenclature and coding, 1951 Ed., American Cancer Society, Inc., 1951. 12. CRAMER, D. W., AND CUTLER, S. J. Incidence and histopathology of malignancies of the female genital organs in the United States. Accepted Amer. J. Obstet. Gynecol. (1973). 13. DUNN, J. E. The relationship between carcinoma in situ and invasive cervical carcinoma. Cancer 6,873 (1953). 14. HAENSZEL, W., MARCUS, S. C., AND ZIMMER, E. G.: Cancer morbidity in urban and rural Iowa. Public Health Monogr. No. 37, U.S. Government Printing Office (1956). 15. BAILAR, J. C., AND EISENBERG, H.: Uterine tumors of unspecified origin. Cancer 18, 589 (1965). 16. CHIANG, C. L. Vital statistics selected reports, Vol. 47, No. 9, DHEW (1961). 17. CHRISTOPHERSON, W. M., MENDEZ, W. M., LUDIN, F. E., AND PARKER, J. E. A ten-year study of endometrial carcinoma in Louisville, Kentucky. Cancer 18,554 (1965). 18. CHRISTOPHERSON, W. M., MENDEZ, W. M., PARKER, J. E., LUDIN, F. E., AND AHUJA, E. M. Carcinoma of the endometrium: A study of changing rates over a 1Syear period. Cancer 27, 1695 (1971).
ENDOMETRIAL
CANCER
IN
THE
UNITED
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