Gynecologic Oncology 82, 504 –509 (2001)
doi:10.1006/gyno.2001.6316, available online at http://www.idealibrary.com on
A Comparison of Ovarian Metastasis between Squamous Cell
Carcinoma and Adenocarcinoma of the Uterine Cervix
Toru Nakanishi, M.D., 1 Kenji Wakai, M.D.,* Hisatake Ishikawa, M.D., Akihiro Nawa, M.D., Yuka Suzuki, M.D.,
Shigeo Nakamura, M.D.,† and Kazuo Kuzuya, M.D.
Department of Gynecology, †Department of Pathology and Clinical Laboratory, Aichi Cancer Center Hospital, and
*Department of Preventive Medicine, Nagoya University School of Medicine, Nagoya 464-8681, Japan
Received February 12, 2001
Objective. The purpose of our study was to investigate a possible
difference in ovarian metastasis between squamous cell carcinoma
and adenocarcinoma of the uterine cervix and to confirm clinico-
pathological variables associated with the metastases.
Methods. Clinical and pathological variables of 1064 patients
with invasive squamous cell carcinoma and 240 with adenocarci-
noma were studied.
Results. Ovarian metastasis was found in 14 patients (1.3%)
with squamous cell carcinoma and 15 (6.3%) with adenocarci-
noma. The mean age of patients with ovarian metastasis of squa-
mous cell carcinoma was 57.4 years, compared to 50.2 years for
adenocarcinoma. Ovarian metastasis of adenocarcinoma was
more likely to be visible (40.0%) and present in both ovaries
(66.7%), while these two characteristics occurred in only 21.4 and
36.7% of patients with squamous cell carcinoma. A logistic regres-
sion analysis with clinical variables indicated that clinical stage
beyond IIb was a significant variable of squamous cell carcinoma,
and more than 30-mm tumor size was significant in adenocarci-
noma.
Conclusion. The incidence of ovarian metastasis of adenocarci-
noma of the uterine cervix was significantly higher than that of
squamous cell carcinoma. The incidence of adenocarcinoma was
associated more closely with tumor size than clinical stage,
whereas it was more associated with clinical stage in squamous cell
carcinoma. The results thus suggested that the differences in
ovarian metastases were caused by the different characteristics of
the two types of carcinoma. © 2001 Academic Press
Key Words: cervical cancer; ovarian metastasis.
INTRODUCTION
Since it was reported that ovarian metastases were more
commonly found in association with adenocarcinoma than with
squamous cell carcinoma and the incidence was 5.5–12.5%
[1– 4], the incidence of ovarian metastasis of adenocarcinoma
of the uterine cervix has been considered much higher than that
1
To whom correspondence should be addressed at Department of Gynecol-
ogy, Aichi Cancer Center Hospital, 1-1 Kanokoden, Chikusa-ku, Nagoya
464-8681, Japan. Fax: 001-81-52-763-5233.
0090-8258/01 $35.00 504
Copyright © 2001 by Academic Press
All rights of reproduction in any form reserved.
of squamous cell carcinoma. Recently, however, some studies
showed that ovarian metastases were rare in early invasive
adenocarcinoma of the uterine cervix (1.7–2.5%) [4 –7]. The
reported incidence was almost equal to that of early-stage
squamous cell carcinoma of the uterine cervix, which rarely
metastasizes to the ovary (0 – 0.71%) [4 –9]. When compared in
clinical stage Ib disease [4, 5], the incidence of ovarian me-
tastasis of adenocarcinoma was slightly higher than that of
squamous cell carcinoma. Since the differences in the charac-
teristics of ovarian metastasis from squamous cell carcinoma
and adenocarcinoma have not been sufficiently studied, the
clinicopathological variables associated with the metastases
remain unclear.
This is a retrospective study of ovarian metastasis from
cervical cancer over the past 27 years at Aichi Cancer Center.
We attempted to determine possible differences in ovarian
metastases from squamous cell carcinoma and adenocarcinoma
of the uterine cervix and to confirm their clinical characteristics
and any variables associated with the metastases.
PATIENTS AND METHODS
The clinical and pathological records of all patients diag-
nosed with invasive cervical cancer at Aichi Cancer Center
between 1974 and 2000 were reviewed. All patients who
underwent hysterectomy, pelvic lymphadenectomy, and oo-
phorectomy of one or both sides as primary treatment at the
Aichi Cancer Center during these years, and whose primary
cervical lesion was diagnosed as squamous cell carcinoma or
adenocarcinoma, were included in this study. Patients whose
clinical or pathological records were not available, and those
with adenocarcinoma in which a primary site could not be
differentiated from a site of endometrial origin, were excluded
from this study. A total of 1304 patients formed the basis of the
study. Of these patients, 1134 underwent bilateral oophorec-
tomy, 62 oophorectomy on one side and wedge resection on
the other, and 108 oophorectomy on only one side. Because of
benign ovarian disease or ectopic pregnancy, one ovary had
 OVARIAN METASTASIS OF CERVICAL CANCER
been already removed in 55 of 108 patients undergoing oopho-
rectomy on one side. One ovary of 115 patients, who were 45
years old or less and diagnosed as having early invasive car-
cinoma, was conserved. Besides these, all patients received
hysterectomy and pelvic lymphadenectomy; 1151 underwent
radical hysterectomy, 134 simple hysterectomy, and 19 pelvic
exenteration. Informed consent was obtained from each patient
regarding the use of clinicopathological variables.
The age of patients at the initial evaluation, their menopausal
state, presence or absence of obesity, and year of treatment
were obtained from clinical records. Obesity was defined ac-
cording to the criteria of the Japan Society of Obesity, i.e., a
body mass index of more than 26.4. Primary disease was
staged at the initial evaluation according to the staging system
of the International Federation of Gynecology and Obstetrics
(FIGO) and was adopted as the clinical stage of disease.
Sixteen patients whose disease had not invaded the pelvic wall
but had caused hydronephrosis were diagnosed as clinical stage
IIIb, and 1 whose disease had invaded the lower third of the
vaginal wall was diagnosed as clinical stage IIIa. Tumor size
was determined from pathological slides. For patients with
gross tumors, the maximum diameter was noted. All available
pathological slides were reviewed for the diagnosis of histo-
logical subtype, presence or absence of pathological parame-
trial invasion, vaginal invasion, lymph node metastasis, endo-
metrial invasion, and ovarian metastasis. Histological
specimens of each ovary were made by cutting it vertically,
and at least two sections were made for examination. Ovarian
metastasis was considered present if viable tumor cells were
observable in ovarian tissue or vessels. Histological diagnosis
of squamous cell carcinoma included both the keratinizing and
the nonkeratinizing types, and adenocarcinoma included both
the endocervical and the endometrioid types as well as adeno-
squamous carcinoma and clear cell adenocarcinoma.
In comparing the age of patients, Student’s t test analysis
was used. Pearson’s ␹ 2 test was used to examine the signifi-
cance of variables in relation to histology and to the ovarian
metastasis. Logistic regression analysis was carried out with
ovarian metastasis as the dependent variable and with the other
variables listed in Table 2 as the independent ones for patho-
logical analysis. The reliability of the analysis was validated
using a likelihood ratio step-forward and step-backward fitting
procedure. All variables were assessed for analyses according
to the categories listed in Table 2. All tests were two tailed; a
P value of ⬍0.05 was considered statistically significant. The
statistical analysis was performed using the SPSS software
version 6.1J.
RESULTS
All patients in this study were Japanese with a mean age at
presentation of 50.3 years (age range, 24.2 to 79.8 years). In
total, 29 (2.0%) patients had ovarian metastases from cervical
505
TABLE 1
Clinical Presentation of Ovarian Metastasis of Cervical Cancer
Squamous cell
carcinoma Adenocarcinoma
Total 1064 240
Mean age (Range) 50.5 (24.2 ⫺ 79.8) 49.5 (25.3 ⫺ 78.2)
Ovarian metastasis 14 15
Mean age (Range) 57.4 (36.8 ⫺ 73.5) 50.2 (30.0 ⫺ 70.1)
Unilateral 9 5
Bilateral 5 10
Enlarged ovary 2 4
Visible 1 2
Microscopic 11 9
cancer. Of 1064 patients with squamous cell carcinoma, 14
(1.3%) had metastases and 15 of 240 (6.3%) with adenocarci-
noma had metastases (Table 1). Histologically, 2 were kera-
tinizing type squamous cell carcinoma, 12 nonkeratinizing
type, 11 endocervical type adenocarcinoma, 1 endometrial
type, 2 clear cell, and 1 adenosquamous carcinoma. While 1 of
14 patients with squamous cell carcinoma had no other extra-
cervical spread pathologically, all patients with adenocarci-
noma had spread. The mean age of all patients with squamous
cell carcinoma was not different from that of patients with
adenocarcinoma (P ⫽ 0.194). Patients with metastasis of
squamous cell carcinoma had a higher mean age than those
with adenocarcinoma, but the difference was not statistically
significant (P ⫽ 0.072). The mean age of patients with
metastasis was significantly older than that of all patients with
squamous cell carcinoma (P ⫽ 0.029), whereas the mean age
was not different in adenocarcinoma (P ⫽ 0.819). Although
10 of 15 (66.7%) adenocarcinoma cases involved both ovaries,
5 of 14 (35.7%) metastases of squamous cell carcinoma were
found in both ovaries. Ovaries of 4 (26.7%) patients with
adenocarcinoma were enlarged due to metastases and 2
(13.3%) had a visible metastatic tumor of adenocarcinoma on
normal-size ovaries, while 11 of 14 (78.6%) of the squamous
cell carcinomas had microscopic metastases. While 4 of 6
(66.7%) visible metastases of adenocarcinoma involved both
ovaries, 1 of 3 (33.3%) metastases of squamous cell carcinoma
involved both. Other ovarian diseases were found in 55 pa-
tients, 1 with an endocervical type adenocarcinoma of the
uterine cervix coexisting with ovarian cancer of stage IIIc
(endometrioid type) and the others with benign adenomas,
mature cystic teratomas, or endometrial cysts.
The findings from our comparison of clinicopathological
variables in squamous cell carcinoma and adenocarcinoma are
summarized in Table 2. While the mean age of all patients did
not differ between squamous cell carcinoma and adenocarci-
noma patients, the incidence in adenocarcinoma patients
younger than 50 years of age was significantly higher than for
squamous cell carcinoma patients. The incidence of adenocar-
cinoma patients in the premenopausal state was also signifi-
506 NAKANISHI ET AL.

TABLE 2
Comparison of Clinicopathological Variables between Squamous Cell Carcinoma and Adenocarcinoma of the Uterine Cervix

Squamous cell carcinoma Adenocarcinoma

n % n % P

Clinical variables
Age (years) ⫺40 147 13.8 52 21.7 0.003
41–50 367 34.5 86 35.8
51⫹ 550 51.7 102 42.5
Postmenopausal state No 556 52.3 146 60.8 0.016
Yes 508 47.7 94 39.2
Obesity No 965 90.7 213 88.8 0.357
Yes 99 9.3 27 11.3
FIGO clinical stage Ia–IIa 862 81.0 204 85.0 0.149
IIb⫹ 202 19.0 36 15.0
Treatment year ⫺1985 620 58.3 83 34.6 ⬍0.001
1986⫹ 444 41.7 157 65.4
Tumor size (mm) ⫺30 654 61.5 151 62.9 0.435
31–50 324 30.5 65 27.1
51⫹ 86 8.1 24 10.0
Pathological variables
Vaginal invasion No 821 77.2 201 83.8 0.002
Yes 243 22.8 39 16.3
Parametrial invasion No 817 76.8 190 79.2 0.427
Yes 247 23.2 50 20.8
Endometrial invasion No 947 89.0 201 83.8 0.023
Yes 117 11.0 39 16.3
Pelvic lymph node metastasis No 789 74.2 178 74.2 0.997
Yes 275 25.8 62 25.8
Depth of invasion (mm) ⫺10 555 52.2 132 55.0 0.571
10–15 240 22.6 55 22.9
15⫹ 269 25.3 53 22.1

cantly higher. The incidence of adenocarcinoma has increased
in recent years, as described previously [10, 11]. In the present
study, the incidence of pathological vaginal invasion of squa-
mous cell carcinoma was significantly higher than that of
adenocarcinoma, while the incidence of endometrial invasion
of squamous cell carcinoma was significantly lower. The inci-
dence of pathological parametrial invasion of squamous cell
carcinoma was slightly higher than that of adenocarcinoma, but
the difference was not statistically significant. The incidences
of large tumor maximum diameter greater than 30 mm, pelvic
lymph node metastasis, and deep stromal invasion were not
significantly different between squamous cell carcinoma and
adenocarcinoma.
The associations of ovarian metastases with clinicopatho-
logical variables are summarized in Table 3. While the inci-
dences of the metastases of clinical stage Ia, Ib, and IIa
squamous cell carcinoma were 0.8% (1/132), 0.5% (3/614),
and 0.9% (1/116), respectively, the incidence increased imme-
diately to 4.0% (7/175) in clinical stage IIb and to 7.4% (2/27)
in stage III–IV. The incidence of stage Ib adenocarcinoma was
4.0% (7/178), compared to 14.8% (4/27) in stage IIb and
44.4% (4/9) in stage III–IV. No ovarian metastasis was found
in 15 patients with clinical stage Ia and in 11 with stage IIa
adenocarcinoma. When classified by tumor size, the meta-
static incidence of adenocarcinoma of 0% (0/102) in tumors
smaller than 20 mm and of 2.0% (1/49) in 21- to 30-mm
tumors increased immediately to 10.8% in 31- to 50-mm
tumors and 29.2% in tumors larger than 51 mm (Table 3).
The incidence of squamous cell carcinoma was 0.2% (1/
444) in tumors smaller than 20 mm, 1.9% (11/583) in 21- to
60-mm tumors, and 5.4% (2/37) in tumors larger than 61
mm in diameter.
The logistic regression analysis with clinicopathological
variables revealed that the presence of pathological endo-
metrial invasion and lymph node metastasis were the sig-
nificant variables associated with ovarian metastasis of
squamous cell carcinoma of the uterine cervix (Table 4). In
the analysis of adenocarcinoma, pathological endometrial
invasion, lymph node metastasis, and pathological parame-
trial invasion were significant. When analyzed with clinical
variables only, clinical stage beyond IIb was a significant
variable of squamous cell carcinoma, and a tumor size of
more than 30 mm was a significant variable in adenocarci-
noma (Table 4).
 OVARIAN METASTASIS OF CERVICAL CANCER 507

TABLE 3
Comparison of Clinicopathological Variables and Ovarian Metastasis between Squamous Cell Carcinoma
and Adenocarcinoma of the Uterine Cervix

Squamous cell carcinoma Adenocarcinoma

Ovarian metastasis Ovarian metastasis

Total Total
n n % n n % P

Total 1064 14 1.3 240 15 6.3 ⬍0.001

Age (years)
⫺40 147 1 0.7 52 1 1.9 0.440
41–50 367 2 0.5 86 9 10.5 ⬍0.001
51⫹ 550 11 2.0 102 5 4.9 0.082
Postmenopausal state
No 556 4 0.7 146 10 6.8 ⬍0.001
Yes 498 10 2.0 94 5 5.3 0.003
FIGO clinical stage
Ia–IIa 862 5 0.6 204 7 3.6 ⬍0.001
IIb⫹ 202 9 4.5 36 8 23.5 ⬍0.001
Treatment year
⫺1985 620 7 1.1 83 6 7.2 ⬍0.001
1986⫹ 444 7 1.6 157 9 5.7 0.005
Tumor size (mm)
⫺30 654 6 0.9 151 1 0.7 0.895
31–50 324 5 1.5 65 7 10.8 ⬍0.001
51⫹ 86 3 3.5 24 7 29.2 ⬍0.001
Pathological vaginal invasion
No 821 7 0.9 201 5 2.5 0.054
Yes 243 7 2.9 39 10 25.6 ⬍0.001
Pathological parametrial invasion
No 817 6 0.7 190 3 1.6 0.265
Yes 247 8 3.2 50 12 24.0 ⬍0.001
Pathological endometrial invasion
No 947 7 0.7 201 5 2.5 0.027
Yes 117 7 6.0 39 10 25.6 ⬍0.001
Pelvic lymph node metastasis
No 789 2 0.3 175 3 1.7 0.016
Yes 275 12 4.4 62 12 19.4 ⬍0.001

DISCUSSION Comparison of the clinicopathological variables revealed no

Although some recent studies showed that ovarian metas-
tases were rare (1.7–2.5%) in early invasive adenocarci-
noma of the uterine cervix [4 –7], several authors reported
that the incidence of ovarian metastases (5.5–12.5%) was
higher in association with adenocarcinoma than with squa-
mous cell carcinoma [1– 4]. In the present study, the inci-
dence of ovarian metastasis from adenocarcinoma of 6.3%
was significantly higher than that of squamous cell carci-
noma. When the comparison was limited only to early
invasive disease, the incidence of adenocarcinoma was sig-
nificantly higher than that of squamous cell carcinoma (Ta-
ble 3), suggesting that clinical behavior of an ovarian me-
tastasis from adenocarcinoma might be different from that
of squamous cell carcinoma. We compared clinicopatholog-
ical variables to determine possible differences in clinical
behavior between squamous cell carcinoma and adenocar-
cinoma.
clear differences. Although adenocarcinoma tended to attack
young patients under 50 years of age, this could be explained
by the decrease in the number of older patients [12–14] and the
increase in adenocarcinoma, as described previously [10, 11].
Squamous cell carcinoma seemed to invade the vaginal wall
and adenocarcinoma the endometrium, yet the incidence of
ovarian metastasis of adenocarcinoma was still higher than for
squamous cell carcinoma in comparison with the incidence of
vaginal invasion, as well as that of endometrial invasion (Table
3). These results suggested that the higher incidence of ovarian
metastasis of adenocarcinoma would be caused by the different
characteristics of the two types of carcinoma.
If the characteristics of ovarian metastasis from adenocarci-
noma of the uterine cervix were different from those of squa-
mous cell carcinoma, the variables associated with such me-
tastasis would also be different. Thus, we performed a separate
logistic regression analysis in squamous cell carcinoma and
508 NAKANISHI ET AL.

TABLE 4
Comparison of Logistic Regression Analysis of Ovarian Metastasis between Squamous Cell Carcinoma
and Adenocarcinoma of the Uterine Cervix

Squamous cell carcinoma Adenocarcinoma

OR 95% CI P OR 95% CI P

Clinicopathological variables
Pelvic lymph node metastasis
No 1.00 0.001 1.00 0.034
Yes 12.66 2.71–59.15 4.81 1.13–20.57
Pathological endometrial invasion
No 1.00 0.011 1.00 0.008
Yes 4.19 1.39–12.69 5.43 1.56–18.97
Parametrial invasion
No NS 1.00 0.025
Yes 5.37 1.23–23.42
Clinical variables
FIGO clinical stage
Ia–IIa 1.00 ⬍0.001 NS
IIb⫹ 7.99 2.65–24.12
Tumor size
⬍30 mm NS 1.00 ⬍0.001
31–50 mm 18.06 2.18–149.72
⬎51 mm 61.62 7.16–530.29

Note. OR, odds ratio; 95% CI, 95% confidence interval.

adenocarcinoma. Although the independent significant vari-
ables were not different in the clinicopathological analysis, the
analysis using clinical variables indicated a difference. While
an independent significant variable in the analysis of squamous
cell carcinoma was clinical stage beyond IIb, a tumor size of
more than 30 mm was the variable in adenocarcinoma. Indeed,
the incidence of ovarian metastasis was increased in tumors
larger than 30 mm. These results suggest that the clinical
variables associated with ovarian metastasis differ between
squamous cell carcinoma and adenocarcinoma and that the
incidence of metastasis of adenocarcinoma associates more
closely with tumor size than clinical stage.
The present study also revealed other characteristics of ovar-
ian metastasis of adenocarcinoma that are different from those
of squamous cell carcinoma. One of 14 patients with metasta-
ses of squamous cell carcinoma had no other extracervical
spread, whereas all with adenocarcinoma had spread. Patients
with metastases of squamous cell carcinoma had a higher mean
age than those with adenocarcinoma. Although 66.7% of ovar-
ian metastases of adenocarcinoma were observed in both ova-
ries, only 35.7% of patients with squamous cell carcinomas had
metastases in both. Some 40.0% of the metastases of adeno-
carcinoma were visible, compared to only 21.4% for squamous
cell carcinoma. This proportion did not change when analyzing
patients with metastasis in both ovaries. However, these dif-
ferences were not significant because of the small number of
patients with ovarian metastasis. Further studies should be
conducted on a large patient sample with ovarian metastases.
The results also suggested that the characteristics of ovarian
metastasis from adenocarcinoma would be different from those
from squamous cell carcinoma.
In conclusion, the incidence of the ovarian metastasis of
adenocarcinoma uterine cervix was 6.3%, compared to 1.3%
for squamous cell carcinoma. Logistic regression revealed that
the independent significant variable for squamous cell carci-
noma was clinical stage beyond IIb, while the variable for
adenocarcinoma was a tumor size of greater than 30 mm.
These results suggested that the incidence of ovarian metastasis
from cervical cancer would be rare in patients with disease
earlier than clinical stage IIa squamous cell carcinoma and with
small adenocarcinoma less than 30 mm in maximum diameter
and that characteristics of ovarian metastasis would differ
between squamous cell carcinoma and adenocarcinoma.
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