Ph.D.
Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland.
U.S. Surveillance, Epidemiology, and End Results (SEER) Program were used to
compute incidence rates for cervical carcinoma diagnosed during 1976 2000 by
histologic subtype (SCC and AC), race (black and white), age, and disease stage (in
situ, localized, regional, or distant).
RESULTS. In black women and white women, the overall incidence of invasive SCC
declined over time, and the majority of tumors that are detected currently are in
situ and localized carcinomas in young women. The incidence of in situ SCC
increased sharply in the early 1990s. AC in situ (AIS) incidence rates increased,
especially among young women. In black women, invasive AC incidence rose
linearly with age.
CONCLUSIONS. Changes in screening, endocervical sampling, nomenclature, and
improvements in treatment likely explain the increased in situ cervical SCC incidence in white women and black women. Increasing AIS incidence over the past 20
years in white women has not yet translated into a decrease in invasive AC
incidence. Etiologic factors may explain the rising invasive cervical AC incidence in
young white women; rising cervical AC incidence with age in black women may
reect either lack of effective screening or a differential disease etiology. Cancer
2004;100:1035 44. 2004 American Cancer Society.
Address for reprints: Sophia S. Wang, Ph.D., Hormonal and Reproductive Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, 6120 Executive Boulevard,
EPS MSC No. 7234, Bethesda, MD 20892-7234;
Fax: (301) 402-0916; E-mail: wangso@mail.nih.
gov
Received October 6, 2003; revision received December 11, 2003; accepted December 11, 2003.
2004 American Cancer Society
DOI 10.1002/cncr.20064
1036
and End Results (SEER) Program registry have supported the observation of increasing cervical AC incidence rates in young white women1,5,13 with further
indication of a birth-cohort effect.14 Given the simultaneous decline in SCC incidence, the resulting ratio
of cervical AC to SCC has increased.1,15 It is likely that
the increasing AC incidence can be attributed in part
to screening,3 reecting increased recognition and,
thus, detection of AC lesions that previously were undiagnosed or were not categorized as AC. Although
this is supported by a comparable decrease in the
incidence of subtypes (specied and not otherwise
specied [NOS]) other than SCC and AC,1 it is not yet
supported by increased rates of cervical AC in situ
(AIS). Although recent studies have focused on AC, to
our knowledge none published to date have compared
the incidence of SCC with AC directly or have examined their relation to changes in screening practices.
To assess the role of screening in cervical SCC and AC
incidence rates in the U.S., we used the SEER registry
database to determine cervical carcinoma incidence
rates by histologic subtype, disease stage, race, age,
and birth cohort. We used in situ carcinoma as a
surrogate for screening effectiveness and assessed its
impact on invasive carcinoma incidence rates for both
SCC and AC. In the current report, we also discuss in
depth the various events that have occurred during
this time period, including changes in nomenclature,
screening practices, endocervical sampling, and improved treatments.
RESULTS
A total of 27,016 incident invasive cervical carcinomas
were diagnosed among white women and black
women in the 9 SEER areas between January 1, 1976
and December 31, 2000. Of those tumors, 19,703 were
SCC and 3895 were AC. The remaining were adenosquamous carcinomas (n 956 tumors), carcinomas
NOS (n 2341 tumors), and carcinoma OS (n 116
tumors). Overall, in situ SCC incidence among white
women increased from 19.6 per 100,000 woman-years
in 1976 1980 to 41.4 per 100,000 woman-years in
19911995 (Table 1), compared with decreasing incidence of invasive malignant SCC from 8.7 per 100,000
woman-years in 1976 1980 to 5.4 per 100,000 womanyears in 1996 2000; the in situ to invasive SCC rate
ratio increased from 2.3 in 1976 1980 to 6.7 in 1991
1995. Among black women, in situ SCC rates declined
from 24.8 to 14.7 per 100,000 woman-years in 1986
1037
TABLE 1
Age-Adjusted Surveillance, Epidemiology, and End Results Incidence Rates and Rate Ratios for In Situ and Invasive Cervical Carcinoma by
Histologic Subtype, Race, and Year of Diagnosisa
White
In situ
Year of diagnosis
Squamous cell carcinoma
19761980
19811985
19861990
19911995
19962000
Adenocarcinoma
19761980
19811985
19861990
19911995
19962000
a
b
Black
Invasive
In situ
Invasive
Black:white rate
ratio
Rate
Count
Rate
Count
In situ
invasive
rate ratio
19.6
18.84
21.23
41.44
b
8859
9391
11,098
21,748
b
8.73
7.15
6.89
6.19
5.37
3660
3216
3293
3151
2850
2.25
2.63
3.08
6.69
b
24.77
18.26
14.72
30.63
b
1333
1108
1028
2421
b
21.76
16.25
13.19
10.6
9.63
834
723
667
640
669
1.14
1.12
1.12
2.89
b
1.26
0.97
0.69
0.74
b
2.49
2.27
1.91
1.71
1.79
0.21
0.31
0.61
1.25
b
86
136
296
645
b
1.23
1.23
1.59
1.57
1.76
511
535
740
798
943
0.17
0.25
0.38
0.80
b
0.08
0.19
0.22
0.31
b
3
10
13
22
b
1.39
1.71
1.59
1.6
1.36
48
69
78
87
86
0.06
0.11
0.14
0.19
b
0.38
0.61
0.36
0.25
b
1.13
1.39
1.00
1.02
0.77
Rate
Count
Rate
Count
In situ
invasive
rate ratio
In situ
Invasive
1990 but increased sharply to 30.6 per 100,000 woman-years in 19911995. Because invasive SCC rates
steadily declined over time from 21.8 to 9.6 per
100,000 woman-years, the resulting in situ-to-invasive
rate ratio increased from 1.1 throughout 1976 1995 to
2.9 in 19911995. Invasive SCC incidence rates were
higher in black women compared with white women,
although the black-to-white ratios declined from 2.5 to
1.8. The black-to-white ratio for in situ SCC declined
from 1.3 to 0.7 due to the more rapid increase among
white women. AIS increased steadily among both
white women and black women, and AC increased
steadily among white women. The increase in AIS
incidence outpaced that for AC, resulting in a rising in
situ-to-invasive rate ratio among white women from
0.2 to 0.8. The rising AC rates among white women
decreased the AC black-to-white rates from 1.1 to 0.8.
Age-adjusted localized, regional, and distant-stage
SCC incidence rates declined from 1976 1980 to
1996 2000 in white women and black women, as did
in situ SCC among black women until about 1990 (Fig.
1A and 1B). In situ SCC rates rose rapidly after 1990 in
both groups. The incidence of in situ SCC was highest,
followed by localized, regional, and distant-stage SCC.
AIS incidence increased rapidly among white women
and black women, as did the incidence of localized,
regional, and distant AC among white women, but not
among black women (Fig. 1C,D).
Incidence trends by period and age revealed that
incidence rates of in situ SCC in white women increased steadily in women age 55 years. Although
FIGURE 1.
1038
DISCUSSION
The data presented from the past 25 years of incidence
reporting by 9 SEER registries demonstrate a clear
screening effect on SCC of the cervix in white women
and black women. The high incidence of in situ SCC in
young women reects a displacement of invasive SCC
1039
1040
1041
1042
25 years.3,47 Because of the relatively modest risk estimates observed to date, these risk factors most likely
would not affect incidence trends signicantly on their
own but may do so together.
The striking linear increase in age-specic incidence rates for invasive AC among black women, compared with the plateau among white women, suggests
a different disease etiology and/or lack of effective
screening and treatment. Recent surveys indicate that
nulliparity and OC use are higher in white women
compared with black women.52 Although we cannot
rule out the potential for a hormonal role, it appears
that added difculties in screening as well as physiologic effects related to obesity may be differential between black women and white women53 and, thus,
potentially play a role in the differential rates of invasive AC in black women; recent national data indicate
a higher prevalence of obese and overweight black
women compared with white women.54 Currently, it is
unknown whether HPV-18 infections or their subtypes
vary by race; however, as stated earlier, it is likely that
these risk factors act in concert and that any one risk
factor (e.g., obesity) may be enhanced by the presence
of other risk factors.
Although numerous surveys have indicated similar Pap smear screening practices among black and
white women in the U.S.,25,5557 the quality of screening may differ by race and socioeconomic status. If
differences within the three SEER registries are
present, and if screening quality differs, then it is
possible that their effects would manifest in a rare and
difcult to sample tumor, such as cervical AC; differences also may be reected by the higher SCC rates in
black women compared with white women. However,
if cervical sampling, in fact, is equivalent in black and
white women, then the possibility of etiologic differences between AC in black and white women must be
considered. Furthermore, because SCC rates plateaued after ages 4550 years even before screening, it
is possible that true etiologic differences are more
likely to explain this nding rather than screening
differences and changes.
Despite the noted limitations in the reporting of in
situ carcinoma between SEER registries from changing
terminology and practices over time, as well as the
assumptions made between detection of preinvasive
lesions through cytology and SEER reporting by histology, our results for in situ and invasive SCC appear
to reect accurately the expected association between
in situ and invasive carcinomas28 with regard to time
and age. Coupled with data regarding disease stage,
our rates appear to reect the expected effects of
screening. Although we did not adjust for hysterectomy rates in the current analyses, the rates likely
8.
9.
10.
11.
12.
13.
14.
15.
16.
17.
18.
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