Gynecologic Oncology 125 (2012) 287–291

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Gynecologic Oncology
journal homepage: www.elsevier.com/locate/ygyno

Prognostic significance of adenocarcinoma histology in women with cervical cancer

Vijaya Galic a, Thomas J. Herzog a, d, Sharyn N. Lewin a, d, Alfred I. Neugut b, c, d, William M. Burke a,
Yu-Shiang Lu a, Dawn L. Hershman b, c, d, Jason D. Wright a, d,⁎
a
Department of Obstetrics and Gynecology, Columbia University College of Physicians and Surgeons, United States
b
Department of Medicine, Columbia University College of Physicians and Surgeons, United States
c
Department of Epidemiology, Mailman School of Public Health, United States
d
Herbert Irving Comprehensive Cancer Center, United States

a r t i c l e i n f o a b s t r a c t

Article history: Objectives. We performed a population-based analysis to determine the effect of histology on survival for
Received 29 November 2011 women with invasive cervical cancer.
Accepted 11 January 2012 Methods. The Surveillance, Epidemiology and End Results database was used to identify women with
Available online 18 January 2012 stage IB-IVB cervical cancer treated from 1988 to 2005. Patients were stratified by histology (squamous, ad-
enocarcinoma, and adenosquamous). Clinical characteristics, patterns of care, and outcomes were analyzed
Keywords:
using multivariable logistic regression and Cox proportional hazards models.
Cervical cancer
Cervical carcinoma
Results. A total of 24,562 patients were identified including 18,979 (77%) women with squamous cell car-
Adenocarcinoma cinomas, 4103 (17%) with adencarcinomas, and 1480 (6%) with adenosquamous tumors. Women with ade-
Squamous cell carcinoma nocarcinomas were younger, more often white, and more frequently married than patients with squamous
Histology cell tumors (p b 0.0001 for all). Patients with adenocarcinomas were more likely to present with early-
stage disease (p b 0.0001). At diagnosis, 26.7% of women with adenocarcinomas had stage IB1 tumors com-
pared to 16.9% of those with squamous cell carcinomas. Among women with early-stage (IB1-IIA) tumors,
patients with adenocarcinomas were 39% (HR = 1.39; 95% CI, 1.23–1.56) more likely to die from their tumors
than those with squamous cell carcinomas. For patients with advanced-stage disease (stage IIB-IVA) women
with adenocarcinomas were 21% (HR = 1.21; 95% CI, 1.10–1.32) more likely to die from their tumors than
those with squamous neoplasms. Five-year survival for stage IIIB neoplasms five-year survival was 31.3%
(95% CI, 29.2–33.3%) for squamous tumors vs. 20.3% (95% CI, 14.2–27.1%) for adenocarcinomas.
Conclusion. Cervical adenocarcinomas are more common in younger women and white patients. Adeno-
carcinoma histology negatively impacts survival for both early and advanced-stage carcinomas.
© 2012 Elsevier Inc. All rights reserved.

Introduction Oncology Group (GOG) found no difference in outcome for squamous

Approximately 20–25% of cervical carcinoma is comprised of adeno-
carcinomas [1]. Unlike squamous cell carcinoma, which has progressive-
ly declined in incidence, adenocarcinomas have increased [2]. The
increased incidence of adenocarcinomas is likely multifactorial, although
difficulties in detecting these lesions by cytology and variability in diag-
nosing the precursor in-situ lesion likely play a substantial role [3–5].
The effect of tumor histology on outcomes for women with cervi-
cal cancer has been actively debated with conflicting results. While
some studies have shown that survival for the two histologies is
equivalent, other data has suggested that adenocarcinomas are
more aggressive and associated with decreased survival [6–11]. A
study of women with stage IB tumors conducted by the Gynecologic
cell carcinomas and adenocarcinomas [10]. Many of these studies in-
clude small numbers of patients, are from single institutions, or in-
clude patients treated over long periods of time. Additionally, the
majority of published studies have focused on early-stage tumors,
data specifically examining women with advanced stage disease has
been limited.
Given the rising incidence of adenocarcinomas the effect of histol-
ogy on outcome is of particular importance. If adenocarcinomas are
more aggressive than their squamous counterparts histology- specific
protocols or inclusion of histology as a risk factor in treatment algo-
rithms may be warranted. The goal of our study was to examine the
effect of histology on survival for women with invasive cervical
cancer.

Materials and methods

⁎ Corresponding author at: Division of Gynecologic Oncology, Department of Obstetrics
and Gynecology, Columbia University College of Physicians and Surgeons, 161 Fort
Washington Ave, 8th Floor, New York, NY 10032, United States. Fax: +1 212 305 3412. Data from the National Cancer Institute's Surveillance, Epidemiology,
E-mail address: jw2459@columbia.edu (J.D. Wright). and End Results (SEER) database was analyzed [12]. SEER is a

0090-8258/$ – see front matter © 2012 Elsevier Inc. All rights reserved.
doi:10.1016/j.ygyno.2012.01.012
288 V. Galic et al. / Gynecologic Oncology 125 (2012) 287–291
population-based registry that encompasses 17 geographically distinct
tumor registries and includes approximately 26% of the United States
population [13].
Women diagnosed with stage IB1-IVB invasive cervical cancer
from 1988 to 2005 were analyzed. Patients were classified based
on their tumor histology into the following groups: squamous, ad-
enocarcinoma or adenosquamous carcinoma. Demographic data
collected included age at diagnosis (b40, 40–65, > 65 years), race
(white, black or other), and marital status (married, single, un-
known). The year of diagnosis was classified as 1988–1993,
1994–1999, or 2000–2005. The geographic residence at the time
of diagnosis was categorized into one of the following United
States regions: east (Connecticut, New Jersey, Atlanta, rural Geor-
gia) central (Detroit, Iowa, Kentucky, Louisiana, Utah), and west
(Alaska, California, Hawaii, Los Angeles, New Mexico, San Fran-
cisco, San Jose, Seattle). Tumor grade (1, 2, or 3) was recorded
for each patient. Stage was assigned based on the reported SEER
extent of disease codes and American Joint Cancer Committee
(AJCC) criteria. The primary treatment modality (radiation, surgery
or no treatment) as well as whether lymphadenectomy was per-
formed were also recorded.
Frequency distributions for categorical variables were com-
pared using chi square tests. Cancer specific and overall survival
were analyzed using multivariable Cox proportional hazards
models. Separate models were developed to analyze early-stage
(IB1-IIA) and advanced-stage (IIB-IVA) patients. All analyses
were performed with SAS version 9.2 (SAS Institute Inc., Cary,
North Carolina).
Results
A total of 24,562 patients were identified including 18,979 (77.3%)
women with squamous cell carcinomas, 4103 (16.7%) with adenocar-
cinomas, and 1480 (6.0%) with adenosquamous tumors. Table 1 dis-
plays the demographic characteristics of the cohort. At the time of
diagnosis, women with adenocarcinomas were younger, more often
white, and more frequently married than patients with squamous
cell tumors (p b 0.0001 for all). Women with adenocarcinomas were
more likely to present with early-stage disease (p b 0.0001). At diag-
nosis, 26.7% (n = 1094) of women with adenocarcinomas had stage
IB1 tumors compared to 16.9% (n = 3214) of those with squamous
cell carcinomas, while 5.8% (n = 238) of those with adenocarcinomas
had stage IIIB disease vs. 13.5% (n = 2568) of patients with squamous
lesions. Primary treatment consisted of surgery in 2852 (69.5%) pa-
tients with adenocarcinomas and in 9452 (49.8%) of women with
squamous cell carcinomas (p b 0.0001).
The characteristics of patients with early-stage (IB1-IIA) neo-
plasms are displayed in Table 2. Compared to women with squamous
cell carcinomas, the multivariable odds ratio for death from cervical
cancer was 1.39 (95% CI, 1.23–1.56) for women with adenocarci-
nomas and 1.55 (95% CI, 1.32–1.82) for adenosquamous tumors. Sim-
ilar trends were noted for overall survival. Other adverse prognostic
factors for women with early-stage tumors included black race,
higher tumor grade, treatment with radiation, and higher stage. In a
Kaplan-Meier analysis, cancer-specific survival for women with
stage IB1 adenocarcinomas and adenosquamous tumors was inferior
to that of stage matched patients with squamous cell carcinomas
(p = 0.001) (Fig. 1).
Among women with advanced-stage disease (stage IIB-IVA),
histology continued to have an effect on survival (Table 3). The
multivariable odds ratio for cancer-specific survival for women
with adenocarcinomas was 1.21 (95% CI, 1.10–1.32) and 1.03
(95% CI, 0.91–1.18) for adenosquamous carcinomas. Overall sur-
vival was also lower for patients with adenocarcinomas
(OR = 1.22; 95% CI, 1.13–1.33). Other factors associated with de-
creased cancer-specific survival for women with stage IIB-IVA
tumors included higher tumor grade and more advanced stage.
In a Kaplan–Meier analysis of cancer-specific survival for patients
with stage IIIB neoplasms, survival of women with adenocarci-
nomas was inferior to that of patients with squamous cell tumors
(p = 0.014) (Fig. 2).
Five-year survival was then examined. For women with stage IB1
tumors, survival was 88.2% (95% CI, 86.9–89.5%) for squamous le-
sions, 84.8% (95% CI, 82.0–87.3%) for adenocarcinomas, and 81.7%
(95% CI, 76.7–85.8%) for adenosquamous cancers (Table 4). For
stage IIIB neoplasms five-year survival was 31.3% (95% CI, 29.2–
33.3%) for squamous tumors, 20.3% (95% CI, 14.2–27.1%) for adeno-
carcinomas, and 24.6% (95% CI, 15.7–34.5%) for adenosquamous
carcinomas.
Discussion
Our findings suggest that tumor histology has an important im-
pact on survival for women with cervical cancer. While a number of
prior reports have examined the influence of histology on outcome,
our analysis specifically explored the influence of adenocarcinoma
histology on outcome stratified by stage. For both early and
advanced-stage disease women with adenocarcinomas had poorer
survival.
For women with early-stage cervical cancer survival is similar fol-
lowing radical hysterectomy or primary radiotherapy [14]. While pa-
tients treated surgically who have high-risk tumor features (nodal
involvement, positive margins, parametrial spread) benefit from ad-
juvant therapy, the postoperative management of women with inter-
mediate risk tumors remains controversial [15]. While adjuvant
radiation has not been shown to improve survival for women with in-
termediate risk tumors, the recurrence rate in patients with adeno-
carcinomas and adenosquamous carcinomas decreased from 44% to
9% in a prospective trial of adjuvant radiation. In contrast, the recur-
rence rate in squamous tumors decreased from 28% to 20%, suggest-
ing that adenocarcinomas as a subset may derive the greatest
benefit from postoperative radiation [16]. Our findings suggest that
among women with stage IB-IIA with adenocarcinomas have an infe-
rior prognosis to women with squamous lesions. Women with early-
stage adenocarcinomas were nearly 40% more likely to die from their
disease than patients with squamous cell carcinomas. Our findings as
well as the data from the Gynecologic Oncology Group's study of ad-
juvant radiotherapy suggest that physicians should take into account
histology in treatment planning in patients with early-stage disease
managed surgically.
Little data has been reported to examine whether histology has
an influence on outcome for women with advanced stage disease.
Curative intent therapy for most women with stage IIB-IVA cervi-
cal cancer is chemoradiation [17,18]. We noted that even for pa-
tients with advanced stage disease histology had an impact on
survival. Five-year survival for women with stage IIIB squamous
tumors was 31% compared to only 20% for women with adenocar-
cinomas. An important consideration is the influence on the addi-
tion of chemotherapy to radiation for the treatment of advanced
stage disease and how this impacts the influence of histology on
survival. Although SEER lacks data on chemotherapy, we per-
formed a sensitivity analysis and examined patients treated from
1988 to 1999 (before chemoradiation) as well as those treated
after the intronduction of chemoradiation (2000–2005). In both
subgroups women with adenocarcinomas had an statistically sig-
nificantly lower survival even after adjustment for other demo-
graphic and treatment characteristics. These findings suggest that
advanced stage cervical adenocarcinomas are inherently more ag-
gressive than squamous cell tumors.
We also explored the outcomes of women with adenosquamous
tumors. Prior studies have reported have reported inferior outcomes
for women with adenosquamous tumors [10,19]. In a prospective
 V. Galic et al. / Gynecologic Oncology 125 (2012) 287–291 289

Table 1
Association between tumor histology and demographic and clinical characteristics.

Squamous cell (n = 18,979) Adenocarcinoma Adenosquamous (n = 1480)

(n = 4103)

N (%) N (%) N (%) p-value

Age at diagnosis b 0.0001

b40 4575 (24.1) 1091 (26.6) 447 (30.2)
40–65 10,151 (53.5) 2168 (52.8) 786 (53.1)
>65 4253 (22.4) 844 (20.6) 247 (16.7)
Race b 0.0001
White 14,012 (73.8) 3278 (79.9) 1165 (78.7)
Black 2912 (15.3) 312 (7.6) 149 (10.1)
Other 1975 (10.4) 487 (11.9) 163 (11.0)
Unknown 80 (0.4) 26 (0.6) 3 (0.2)
Year of diagnosis 0.0001
1988–1993 4261 (22.5) 829 (20.2) 326 (22.0)
1994–1999 5237 (27.6) 1109 (27.0) 458 (31.0)
2000–2005 9481 (50.0) 2165 (52.8) 696 (47.0)
SEER registry b 0.0001
West 10,506 (55.4) 2369 (57.7) 904 (61.1)
Central 4828 (25.4) 961 (23.4) 304 (20.5)
East 3645 (19.2) 773 (18.8) 272 (18.4)
Marital status b 0.0001
Married 7958 (41.9) 2166 (52.8) 721 (48.7)
Single 10,240 (54.0) 1768 (43.1) 720 (48.7)
Unknown 781 (4.1) 169 (4.1) 39 (2.6)
Tumor grade b 0.0001
1 775 (4.1) 951 (23.2) 43 (2.9)
2 6111 (32.2) 1350 (32.9) 306 (20.7)
3 7223 (38.1) 1008 (24.6) 822 (55.5)
Unknown 4870 (25.7) 794 (19.4) 309 (20.0)
Primary treatment b 0.0001
Surgery 9452 (49.8) 2852 (69.5) 994 (67.2)
Radiation 8480 (44.7) 1020 (24.9) 422 (28.5)
No treatment 1047 (5.5) 231 (5.6) 64 (4.3)
Lymphadenectomy b 0.0001
Yes 7149 (37.7) 2182 (53.2) 843 (57.0)
No 11,830 (62.3) 1921 (46.8) 637 (43.0)
Stage b 0.0001
IB1 3214 (16.9) 1094 (26.7) 383 (25.9)
IB2 1701 (9.0) 343 (8.4) 168 (11.4)
IB NOS 3978 (21.0) 1359 (33.1) 331 (22.4)
IIA 1488 (7.8) 202 (4.9) 84 (5.7)
IIB 3754 (19.8) 424 (10.3) 236 (16.0)
IIIA 695 (3.7) 80 (2.0) 25 (1.7)
IIIB 2568 (13.5) 238 (5.8) 111 (7.5)
IVA 622 (3.3) 82 (2.0) 30 (2.0)
IVB 959 (5.1) 281 (6.9) 112 (7.6)

GOG study of patients with IB1 cervical cancer treated with radical
hysterectomy, overall survival was worse for adenosquamous carci-
noma than for other histologies [10]. A similar observation was
made in a more recent retrospective study, which included IB1 cervix
cancer patients stratified according to surgicopathological risk factors.
In otherwise low risk patients with IB1 tumors, patients with adenos-
quamous histology were more likely to have a poorly differentiated
tumor and both shorter disease free survival and overall survival
rates compared to patients without adenocarcinomas [19]. Our find-
ings were notable in that while survival for early-stage adenosqua-
mous tumors was inferior to that of squamous cells carcinomas,
survival was similar for the two histologies in women with advanced
stage disease.
There is considerable evidence to suggest that the molecular
mechanisms underlying the pathogenesis of adenocarcinomas and
squamous carcinomas are distinct. A gene expression array analysis
has shown that adenocarcinomas may be reliably distinguished
from squamous cell carcinomas based on their expression signature
[20,21]. Notably, the algorithm devised by Hall and colleagues for cer-
vical cancer correctly classified a set of lung squamous and adenocar-
cinomas, suggesting that gene expression profiles may affect behavior
more so than tissue of origin [21]. Methylation studies have demon-
strated hypermethylation of growth-inhibitory genes such as
NOGOR in adenocarcinomas but not squamous carcinomas [22]. Final-
ly, adenocarcinomas may differ from squamous carcinomas with re-
spect to the role of human papillomavirus (HPV). While a causal
relationship has been established between both HPV 16 and 18 infec-
tion and subsequent development of cervical adenocarcinoma, HPV
18 infection is more common in adenocarcinomas than squamous
carcinomas [23,24].
While our study benefits from the inclusion of a large number
of subjects, we recognize a number of important limitations. Like
all administrative datasets, central pathology review is not per-
formed for patients registered in SEER. While we limited our
study to the most common histologic variants of cervical cancer,
we cannot exclude the possibility that some patients were mis-
classified. SEER lacks data on some important pathologic parame-
ters including lymphovascular space invasion, margin status, and
parametrial spread that may have provided additional insight
into the findings we noted. Finally, SEER lacks data on timing
and distribution of recurrences. As such, our study was limited
to analyzing cancer-specific survival.
Our findings support the hypothesis that adenocarcinomas are a
distinct clinical entity from squamous cell carcinomas. There are sev-
eral possible explanations for the inferior outcomes of both early and
advanced stage adenocarcinomas. It has been previously argued that
290 V. Galic et al. / Gynecologic Oncology 125 (2012) 287–291

Table 2 Table 3
Survival for patients with stage IB1-IIA cervical cancer. Survival for stage IIB-IVB cervical cancer.

Cancer-specific survival Overall survival Cancer-specific survival Overall survival

N (%) N (%)

Histology Histology
Squamous cell 10,381 (72.4) Referent Referent Squamous cell 8598 (84.2) Referent Referent
Adenocarcinoma 2998 (20.9) 1.39 (1.23–1.56) 1.16 (1.05–1.27) Adenocarcinoma 1105 (10.8) 1.21 (1.10–1.32) 1.22 (1.13–1.33)
Adenosquamous 966 (6.7) 1.55 (1.32–1.82) 1.36 (1.19–1.55) Adenosquamous 514 (5.0) 1.03 (0.91–1.18) 1.02 (0.91–1.15)
Age at diagnosis Age at diagnosis
b40 4581 (31.9) Referent Referent b40 1532 (15.0) Referent Referent
40–65 7316 (51.0) 1.04 (0.93–1.15) 1.40 (1.28–1.54) 40–65 5789 (56.7) 0.94 (0.86–1.02) 1.02 (0.94–1.10)
>65 2448 (17.1) 1.42 (1.25–1.62) 3.17 (2.87–3.51) >65 2896 (28.3) 1.10 (1.00–1.20) 1.49 (1.37–1.62)
Race Race
White 10,970 (76.5) Referent Referent White 7485 (73.3) Referent Referent
Black 1764 (12.3) 1.36 (1.20–1.54) 1.33 (1.21–1.45) Black 1609 (15.7) 1.17 (1.08–1.27) 1.17 (1.10–1.26)
Other 1518 (10.6) 0.98 (0.85–1.14) 0.85 (0.76–0.96) Other 1107 (10.8) 0.81 (0.73–0.90) 0.80 (0.73–0.88)
Unknown 93 (0.7) 0.21 (0.05–0.83) 0.34 (0.15–0.76) Unknown 16 (0.2) 1.86 (0.97–3.58) 1.57 (0.84–2.91)
Year of diagnosis Year of diagnosis
1988–1993 3343 (23.3) Referent Referent 1988–1993 2073 (20.3) Referent Referent
1994–1999 4105 (28.6) 0.85 (0.76–0.95) 0.94 (0.86–1.02) 1994–1999 2699 (26.4) 0.92 (0.86–1.00) 0.91 (0.85–0.98)
2000–2005 6897 (48.1) 0.89 (0.80–1.00) 0.96 (0.87–1.05) 2000–2005 5445 (53.3) 0.82 (0.76–0.89) 0.83 (0.78–0.88)
SEER registry SEER registry
West 8134 (56.7) Referent Referent West 5645 (55.3) Referent Referent
Central 3543 (24.7) 1.08 (0.97–1.20) 1.07 (0.98–1.16) Central 2550 (25.0) 1.06 (0.99–1.14) 1.07 (1.01–1.14)
East 2668 (18.6) 1.00 (0.89–1.13) 0.99 (0.90–1.09) East 2022 (19.8) 0.98 (0.91–1.07) 0.97 (0.91–1.04)
Marital status Marital status
Married 6990 (48.7) Referent Referent Married 3855 (37.7) Referent Referent
Single 6736 (47.0) 1.07 (0.98–1.18) 1.25 (1.16–1.34) Single 5992 (58.6) 1.09 (1.02–1.16) 1.13 (1.07–1.20)
Unknown 619 (4.3) 0.82 (0.64–1.05) 0.96 (0.80–1.15) Unknown 370 (3.6) 1.18 (1.01–1.38) 1.15 (1.00–1.32)
Tumor grade Tumor grade
1 1280 (8.9) Referent Referent 1 489 (4.8) Referent Referent
2 4724 (32.9) 1.80 (1.44–2.24) 1.38 (1.18–1.62) 2 3043 (29.8) 1.11 (0.96–1.29) 1.11 (0.97–1.27)
3 4981 (34.7) 2.47 (1.98–3.09) 1.77 (1.52–2.08) 3 4072 (39.9) 1.38 (1.20–1.60) 1.36 (1.19–1.55)
Unknown 3360 (23.4) 1.35 (1.07–1.70) 1.24 (1.06–1.46) Unknown 2613 (25.6) 1.11 (0.95–1.30) 1.15 (1.00–1.31)
Primary treatment Primary treatment
Surgery 10,665 (74.4) Referent Referent Treatment 9370 (91.7) Referent Referent
Radiation 3185 (22.2) 2.24 (2.03–2.49) 2.07 (1.91–2.23) No treatment 847 (8.3) 2.51 (2.29–2.76) 2.53 (2.33–2.75)
No treatment 495 (3.5) 3.54 (2.89–4.36) 3.82 (3.31–4.40) Stage
Stage IIB 4414 (43.2) Referent Referent
IB1 4691 (32.7) Referent Referent IIIA 800 (7.8) 2.06 (1.84–2.31) 1.85 (1.67–2.04)
IB2 2212 (15.4) 2.08 (1.80–2.40) 1.87 (1.67–2.10) IIIB 2917 (28.6) 2.26 (2.10–2.44) 2.04 (1.91–2.18)
IB NOS 5668 (39.5) 1.26 (1.10–1.43) 1.29 (1.17–1.43) IVA 734 (7.2) 3.51 (3.14–3.91) 3.12 (2.84–3.44)
IIA 1774 (12.4) 2.66 (2.30–3.09) 2.07 (1.84–2.32) IVB 1352 (13.2) 4.87 (4.46–5.32) 4.10 (3.79–4.44)

adenocarcinomas tend to be diagnosed at a later stage, presumably
because screening is less effective. The present study, however, con-
trolled for this by analyzing survival controlling for stage. The second
hypothesis is that adenocarcinomas are more likely to metastasize to
the regional nodes than squamous carcinomas. This too is less likely
given that the rate of pelvic lymph node metastasis following radical
hysterectomy in early stage disease is similar between squamous and
adenocarcinomas [25]. In sum, this data would suggests that adeno-
carcinomas and squamous carcinomas are fundamentally different
on a molecular level. Further prospective studies to confirm the pre-
sent findings in both early and late stage adenocarcinomas would
be of great value. While current screening and management guide-
lines do not take histology into account, recognizing that adenocarci-
nomas may be distinct may provide an opportunity for improving

Fig. 1. Kaplan–Meier analysis of cancer-specific survival for women with stage IB1 cervical Fig. 2. Kaplan–Meier analysis of cancer-specific survival for women with stage IIIB cervical
cancer (p= 0.001). Solid line-squamous cell carcinoma, dashed line-adenocarcinoma, cancer (p= 0.014). Solid line-squamous cell carcinoma, dashed line-adenocarcinoma,
short-dashed line adenosquamous carcinoma. short-dashed line adenosquamous carcinoma.
 V. Galic et al. / Gynecologic Oncology 125 (2012) 287–291 291

Table 4 [10] Look KY, Brunetto VL, Clarke-Pearson DL, et al. An analysis of cell type in patients
Five-year survival stratified by stage. with surgically staged stage IB carcinoma of the cervix: a Gynecologic Oncology
Group study. Gynecol Oncol 1996;63:304–11.
Squamous Adenocarcinoma Adenosquamous [11] Webb JC, Key CR, Qualls CR, Smith HO. Population-based study of microinvasive
adenocarcinoma of the uterine cervix. Obstet Gynecol 2001;97:701–6.
IB1 88.2% (86.9–89.5%) 84.8% (82.0–87.3%) 81.7% (76.7–85.8%) [12] Surveillance, Epidemiology, and End Results, SEER*Stat Database: Incidence-
IB2 69.0% (66.3–71.4%) 68.3% (62.0–73.8%) 65.1% (56.4–72.6%) SEER 9 Regs Limited-Use, Nov 2006 Sub (1973–2004), National Cancer Institute,
IBNOS 77.9% (76.4–79.2%) 83.7% (81.4–85.8%) 77.5% (72.2–81.8%) DCCPS, Surveillance Research Program, Cancer Statistics Branch, released April
IIA 58.3% (55.3–61.1%) 45.5% (37.3–53.3%) 42.0% (29.5–54.0%) 2007, based on the November 2006 submission. http://.seer.cancer.gov.
IIB 55.1% (53.2–56.9%) 46.3% (40.6–51.9%) 55.2% (47.5–62.2%) Accessed October, 2007.
IIIA 33.7% (29.7–37.8%) 15.6% (7.8–25.8%) 33.8% (12.4–56.9%) [13] The Surveillance, Epidemiology, and End Results (SEER) Program, Data Quality.
IIIB 31.3% (29.2–33.3%) 20.3% (14.2–27.1%) 24.6% (15.7–34.5%) National Cancer Institute; 2007 http://seer.cancer.gov/about/ [Accessed October,
IVA 17.1% (13.8–20.7%) 8.0% (2.3–16.9%) 10.4% (2.1–26.7%) 2007].
IVB 5.9% (4.4–7.7%) 9.4% (6.0–13.7%) 8.7% (4.0–15.8%) [14] Landoni F, Maneo A, Colombo A, et al. Randomised study of radical surgery versus
radiotherapy for stage Ib-IIa cervical cancer. Lancet 1997;350:535–40.
[15] Sedlis A, Bundy BN, Rotman MZ, Lentz SS, Muderspach LI, Zaino RJ. A randomized
trial of pelvic radiation therapy versus no further therapy in selected patients
outcomes through the development of histology-specific with stage IB carcinoma of the cervix after radical hysterectomy and pelvic lym-
phadenectomy: A Gynecologic Oncology Group Study. Gynecol Oncol 1999;73:
interventions. 177–83.
[16] Rotman M, Sedlis A, Piedmonte MR, et al. A phase III randomized trial of postop-
erative pelvic irradiation in Stage IB cervical carcinoma with poor prognostic fea-
tures: follow-up of a gynecologic oncology group study. Int J Radiat Oncol Biol
Conflict of interest Phys 2006;65:169–76.
The authors declare that there are no conflicts of interest. [17] Rose PG, Bundy BN, Watkins EB, et al. Concurrent cisplatin-based radiotherapy
and chemotherapy for locally advanced cervical cancer. N Engl J Med 1999;340:
1144–53.
[18] Whitney CW, Sause W, Bundy BN, et al. Randomized comparison of fluorouracil
References plus cisplatin versus hydroxyurea as an adjunct to radiation therapy in stage
IIB-IVA carcinoma of the cervix with negative para-aortic lymph nodes: a Gyneco-
[1] Young RH, Clement PB. Endocervical adenocarcinoma and its variants: their mor- logic Oncology Group and Southwest Oncology Group study. J Clin Oncol 1999;17:
phology and differential diagnosis. Histopathology 2002;41:185–207. 1339–48.
[2] Chan PG, Sung HY, Sawaya GF. Changes in cervical cancer incidence after three decades [19] Lea JS, Coleman RL, Garner EO, Duska LR, Miller DS, Schorge JO. Adenosquamous
of screening US women less than 30 years old. Obstet Gynecol 2003;102:765–73. histology predicts poor outcome in low-risk stage IB1 cervical adenocarcinoma.
[3] Smith HO, Tiffany MF, Qualls CR, Key CR. The rising incidence of adenocarcinoma Gynecol Oncol 2003;91:558–62.
relative to squamous cell carcinoma of the uterine cervix in the United States–a [20] Contag SA, Gostout BS, Clayton AC, Dixon MH, McGovern RM, Calhoun ES. Com-
24-year population-based study. Gynecol Oncol 2000;78:97–105. parison of gene expression in squamous cell carcinoma and adenocarcinoma of
[4] Sherman ME, Wang SS, Carreon J, Devesa SS. Mortality trends for cervical squamous the uterine cervix. Gynecol Oncol 2004;95:610–7.
and adenocarcinoma in the United States. Relation to incidence and survival. Cancer [21] Hall JS, Leong HS, Armenoult LS, et al. Exon-array profiling unlocks clinically and
2005;103:1258–64. biologically relevant gene signatures from formalin-fixed paraffin-embedded tu-
[5] Ioffe OB, Sagae S, Moritani S, Dahmoush L, Chen TT, Silverberg SG. Proposal of a mour samples. Br J Cancer 2011;104:971–81.
new scoring scheme for the diagnosis of noninvasive endocervical glandular le- [22] Lee EJ, McClelland M, Wang Y, Long F, Choi SH, Lee JH. Distinct DNA methylation
sions. Am J Surg Pathol 2003;27:452–60. profiles between adenocarcinoma and squamous cell carcinoma of human uterine
[6] Kleine W, Rau K, Schwoeorer D, Pfleiderer A. Prognosis of the adenocarcinoma of cervix. Oncol Res 2010;18:401–8.
the cervix uteri: a comparative study. Gynecol Oncol 1989;35:145–9. [23] Dahlstrom LA, Ylitalo N, Sundstrom K, et al. Prospective study of human pap-
[7] Baalbergen A, Ewing-Graham PC, Hop WC, Struijk P, Helmerhorst TJ. Prognostic illomavirus and risk of cervical adenocarcinoma. Int J Cancer 2010;127:
factors in adenocarcinoma of the uterine cervix. Gynecol Oncol 2004;92:262–7. 1923–30.
[8] Park JY, Kim DY, Kim JH, Kim YM, Kim YT, Nam JH. Outcomes after radical hyster- [24] Tase T, Okagaki T, Clark BA, et al. Human papillomavirus types and localization in
ectomy in patients with early-stage adenocarcinoma of uterine cervix. Br J Cancer adenocarcinoma and adenosquamous carcinoma of the uterine cervix: a study by
2010;102:1692–8. in situ DNA hybridization. Cancer Res 1988;48:993–8.
[9] Eifel PJ, Morris M, Oswald MJ, Wharton JT, Delclos L. Adenocarcinoma of the uterine [25] Kasamatsu T, Onda T, Sawada M, et al. Radical hysterectomy for FIGO stage I-IIB
cervix. Prognosis and patterns of failure in 367 cases. Cancer 1990;65:2507–14. adenocarcinoma of the uterine cervix. Br J Cancer 2009;100:1400–5.