ADENOCARCINOMA OF THE CERVIX
DiSaia: Clinical Gynecologic
Oncology, 6th ed., 2002
Approximately 85%–90% of cervical cancers
are squamous cell, and most of the
remaining 10%–15% are adenocarcinomas. There appears to be an
increase in the frequency
of cervical adenocarcinomas, but this may be a result of the decrease in
the incidence of invasive squamous cell lesions. Adenocarcinoma arises
from the endocervical mucous-producing gland cells; and because of its
origin within the cervix, it may be present for a considerable time before
it becomes clinically evident. These lesions are
characteristically bulky neoplasms
that expand the cervical canal and create the so-called barrel-shaped
lesions of the cervix. The spread pattern of these lesions is similar to
that of squamous cell cancer, with direct extension accompanied by
metastases to regional pelvic nodes as the primary routes of
dissemination. Local recurrence is more common in these lesions, and this
has resulted in the commonly held belief that they are more radioresistant
than are their squamous counterpart. It seems more likely, however, that
the bulky, expansive nature of these endocervical lesions, rather than a
differential in radiosensitivity, accounts for the local recurrence. This
problem has led many oncologists to advocate combined radiotherapy and
surgery for optimal control of the central lesion.
Although debated as an entity, the term
microinvasive adenocarcinoma of the cervix is appearing more frequently in
the literature. Authors are reporting their experience using the 1994 FIGO
definition of stage Ia cervical cancer. Kaku and associates reported 30
patients who had <5 mm invasion (21 with <3 mm), but 15 had horizontal
spread >7 mm. None of the patients with <3 mm stromal invasion recurred.
Östör and colleagues, in the largest and most extensive review, identified
77 women with <5 mm invasion. None of the 48 who had pelvic node
dissection or the 23 in whom 1 or both adnexa were removed had metastasis.
Twenty patients did have >7 mm horizontal spread, and LSI was present in
only 7; 4, however, had <3 mm invasion. None of the 24 hysterectomy
specimens showed residual disease if conization margins were free. There
were two recurrences, but both were in women with >7 mm horizontal spread.
Schorze and associates reported 21 patients with stage Ia1 adenocarcinoma
of the cervix. None of the patients had LSI. No lymph node metastasis was
noted in 16 patients, and none of the 21 patients experienced a
Two debatable issues continue with regard
to adenocarcinoma of the cervix. Does this cell type carry a worse
prognosis than squamous or adenosquamous cell types? For early stage
disease, which therapy (radical surgery or radiation) is superior or is
there a place for combined treatment?
Most studies suggest no difference
in survival when adenocarcinomas are compared to squamous carcinomas after
correction for stage. The 1998 FIGO Annual Report, which reported
>10,000 squamous carcinomas and 1138 adenocarcinomas using multivariant
analysis, noted no difference in survival in stage I cancers.
In a study by Chen and associates of 302
adenocarcinomas, it was noted that in early stages, multivariant analysis
noted better survival in patients treated with radical surgery compared
with those treated with radiation therapy.
Kjorstad and Bond investigated the
metastatic potential and patterns of dissemination in 150 patients with
stage Ib adenocarcinoma of the cervix treated from 1956–1977. All cases
were treated with a combination of intracavitary radium followed by
radical hysterectomy with pelvic lymph node dissection. The incidence of
pelvic metastases and distant recurrences and the survival rates were the
same as those given in previously published reports for squamous cell
carcinoma treated in the same manner. In one respect, the adenocarcinomas
showed a significant difference from the squamous cell cancers. The
incidence of residual tumor in the hysterectomy specimens after
intracavitary treatment was much higher (30% vs 11%). Kjorstad and Bond
considered that this was a strong argument for surgical treatment of
patients with early stages of adenocarcinoma of the cervix.
Berek and colleagues reported on 100
patients with primary adenocarcinoma of the uterine cervix. Of 48 stage I
patients, 13 were treated with radical surgery, 16 with radiation alone,
and 19 with combination therapy. Analysis of stage I patients by Berek and
colleagues showed no significant difference in survival compared with
those treated with radical surgery or combination therapy. However, both
of these groups had >5-year survival (P > .05) than those treated with
radiation alone. A higher tumor grade was associated with poorer survival
for each stage regardless of treatment. More complications were associated
with radiation therapy than with radical therapy. Radiation therapy alone
did not appear to be sufficient therapy for patients with stage I or stage
Moberg and colleagues reported on 251
patients at Radiumhemmet in Stockholm with adenocarcinoma of the uterine
cervix. The 5-year survival rate was compared with that in the total of
cervical epithelial malignancies, and the rate was lower in the
adenocarcinoma cases, with respective crude 5-year survival rates of 84%,
50%, and 9% in stages I, II, and III. Combined treatment consisting of two
intracavitary radium treatments with an interval of 3 weeks followed by a
radical hysterectomy with pelvic lymphadenectomy done within 3 months gave
improved 5-year survival in a nonrandomized series. Prempree and
colleagues also suggested combined therapy for stage II lesions or for
those >4 cm.
A large series of 367 cases of
adenocarcinoma of the cervix was reported by Eifel and associates. Their
conclusions were that the central control of adenocarcinomas with
radiation therapy is comparable to that achieved for squamous cell
carcinomas of comparable bulk. They found no evidence that combined
treatment (radiation therapy plus hysterectomy) improved local regional
control or survival. In their study, radiation therapy alone was as
effective a treatment for most patients with stage I disease. They noted,
as others have, that patients with bulky stage I (>6 cm), stage II, or
stage III disease, particularly with poorly differentiated lesions or
evidence of nodal spread, had a very high rate of extrapelvic disease
Eifel reported the results of 160 patients
with adenocarcinoma of the cervix. Of those patients, 84 were treated with
radiation therapy alone; 20 were treated with external and intracavitary
radiation followed by hysterectomy; and 56 were treated with radical
hysterectomy. Survival was strongly correlated with tumor size and grade.
There was a 90% survival rate for lesions <3 cm. After 5 years, 45% of the
patients treated with radical hysterectomy had a recurrence. These
recurrences were strongly correlated with lymph/vascular space invasion
and poorly differentiated lesions, as well as larger tumor size.
Chen and associates from Taiwan reviewed
3678 cases of cervical cancer treated between 1977 and 1994 of which 302
(8.5%) were adenocarcinoma. A higher proportion of cases with
adenocarcinoma were of the lower stages and in the younger patient even
within a given stage. Survival was better in all stages in patients with
squamous compared with adenocarcinoma (81% vs 76% in stage I, P = .0039).
When surgery was primary therapy, there was no difference in survival in
stage I (83% vs 80.3% survival of squamous and adenocarcinoma,
respectively). Survival with radiation therapy noted 71% vs 49%,
respectively (P = .0039), in stage I. Survival decreased as age increased
within a given stage.
The Anderson group compared 1538 patients
with squamous cell carcinoma with 229 adenocarcinoma patients, all stage
IB who were treated with radiation. In patients with ≥4 cm tumors,
multivariant analysis confirmed that those patients with adenocarcinoma
had a significantly poorer survival than did those with squamous carcinoma
(59% vs 73%). In a study by the GOG, 813 stage Ia2 and Ib cancers were
evaluated. All were treated with radical hysterectomy. There were 645
squamous, 104 adenocarcinoma, and 64 adenosquamous cancers. Radiation was
given postoperatively to 16% squamous, 13% adenocarcinomas, and 20% of
adenosquamous patients. After adjusting for multiple risk factors,
survival was worst for adenosquamous cancer compared with squamous and
adenocarcinoma (71.8%, 82.1%, 88%, respectively). A similar finding was
noted in a study from Taiwan in which 134 stage IB or II cervical
adenocarcinomas or adenosquamous cancers were compared with 757 similarly
staged squamous carcinomas treated with radical hysterectomy. The overall
survival was 72.2% for the former compared with 81.2% for the squamous
cancers. The histology was an independent prognostic factor for
recurrence-free survival and overall survival.
Adenocarcinoma of uterine
cervix -- prognostic significance of clinicopathologic parameters.
Nola M, Croat Med J.
Department of Pathology, Zagreb Croatia
The 5-year survival for this group of patients was 75%. The following
parameters proved to be statistically significant in a univariate
analysis: clinical stage (P=0.042), architectural grade (P=0.009), and
nuclear grade (P=0.002). In the multivariate analysis,
the nuclear grade (P=0.007) turned
out to be the only statistically significant parameter.
According to the nuclear grade,
the five-year survival was 80% in the prognostically favorable and only
30% in the unfavorable group of patients. CONCLUSION: Our data
showed that in patients with adenocarcinoma of the uterine cervix the
nuclear grade, clinical stage, and architectural grade of the tumor
represent the most important prognostic parameters. The analysis of DNA
ploidy and proliferative activity had no prognostic significance.
Stage I adenocarcinoma of
the cervix: does lesion size affect treatment options and prognosis?
Am J Clin Oncol. 1998 Oct;21(5):431-5.
Department of Gynecologic Oncology, The Roswell Park Cancer Institute,
A retrospective analysis of 93 patients with International Federation of
Gynecology and Obstetrics stage I adenocarcinoma of the cervix was
performed to determine the significance of tumor size, patient age, tumor
grade, lymph node status, and primary treatment modality as prognostic
variables of 5-year survival and 5-year progression-free survival (PFS).
Multivariate analysis demonstrated that patient age and tumor grade were
significant variables prognostic of survival (p < 0.01 and p = 0.01,
respectively). Tumor size was a significant (p < 0.01) prognostic variable
of PFS in a multivariate model that included tumor size and patient age.
An important advantage in survival
and PFS for patients with lesions smaller than 3 cm compared with those
patients with lesions 3 cm or more was observed (92% vs. 76% and 89% vs.
67%, respectively). Among surgically treated patients, survival and
PFS among patients with lesions smaller than 3 cm were significantly
improved compared with patients with tumors 3 cm or more (97% vs. 77% [p =
0.03] and 90% vs. 69% [p = 0.03], respectively). Significant improvement
in survival and PFS was observed among patients with lesions smaller than
3 cm who were treated with surgery compared with those who received
radiation therapy (97% vs. 77% [p = 0.03] and 90% vs. 77% [p = 0.048],
Adenocarcinoma of the
uterine cervix. Prognosis and patterns of failure in 367 cases.
Eifel PJ, Cancer. 1990 Jun
Division of Radiotherapy, University of Texas M. D. Anderson Cancer
Between 1965 and 1985, 367 patients received initial treatment for
adenocarcinoma of the uterine cervix at the M. D. Anderson Cancer Center (MDACC).
Of the 334 patients treated with curative intent, 223 had International
Federation of Gynecology and Obstetrics (FIGO) Stage I, 60 had Stage II,
and 51 had Stage III/IV disease.
The 5-year and 10-year relapse-free survival (RFS) rates for all patients
treated for Stage I disease were 73% and 70%, respectively. RFS was
strongly correlated with initial bulk of disease (P = 0.002), although
locoregional control (LRC) was good in all groups: 91 patients with a
normal-sized cervix (tumor less than 3 cm) had a 5-year RFS rate of 88%
and an actuarial LRC rate of 94%; 102 patients with lesions 3 to 5.9 cm in
diameter had an RFS rate of 64% and an LRC rate of 82%; and 22 patients
with bulky lesions greater than 6 cm in diameter had a comparable LRC rate
of 81%, but an RFS rate of only 45%. Decreased RFS also was strongly
correlated with positive lymphangiogram (LAG) results (P = 0.02) and
poorly differentiated lesions (P = 0.0014). When initial primary tumor
size was taken into account, there was no significant difference in RFS or
LRC between patients treated with radiation (RT) alone or RT plus
extrafascial hysterectomy (R + S).
The 5-year and 10-year RFS rates of 60 patients who received curative
therapy for Stage II disease were 32% and 25%, respectively, with an LRC
rate of 62% at 5 years. Patients with bulky Stage II disease did
particularly poorly, with a 5-year RFS rate of 15%. Decreased RFS was
correlated with positive LAG results and poorly differentiated tumors.
Most Stage II patients whose disease relapsed died with distant metastases
(73%). Forty-eight patients with
Stage III/IV disease treated with curative intent had a 5-year survival
rate of 31% and a 5-year pelvic disease control rate of 52%. In
summary, patients with small volume Stage IB lesions have excellent LRC
and survival with RT alone. RT achieves good LRC of bulkier Stage I
lesions, but survival decreases with increasing primary tumor size. R + S
holds no apparent advantage over RT alone. Patients with more advanced
disease have a high rate of relapse with frequent distant metastasis. In
particular, the survival of patients with FIGO Stage II disease is much
lower than what we have observed after treatment of comparable stage
Histologic subtype has
minor importance for overall survival in patients with adenocarcinoma of
the uterine cervix: a population-based study of prognostic factors in 505
patients with nonsquamous cell carcinomas of the cervix.
Alfsen GC, Cancer. 2001 Nov 1;92(9):2471-83.
Department of Pathology, The Norwegian Radium Hospital, N-0310 Oslo,
BACKGROUND: The incidence of
adenocarcinoma of the uterine cervix is increasing. For better
prognostic information, the authors studied all nonsquamous cell
carcinomas (non-SCCs) in the Norwegian population over a total of 15
years. METHODS: All non-SCCs from three 5-year periods (1966-1970,
1976-1980, and 1986-1990) were reviewed and classified according to the
World Health Organization classification system, and histopathologic and
clinical parameters were registered. Tissue blocks were available from all
patients. RESULTS: Of 505 patients, 417 had tumors classified as
adenocarcinoma, and 88 had tumors classified as other non-SCC. The mean
ages were 53 years and 52 years for patients with adenocarcinoma and non-SCC,
respectively. Sixty-two percent of the staged patients had clinical Stage
I disease according to the classification system of the International
Federation of Gynecology and Obstetrics (FIGO). In univariate analyses,
histology, architectural and nuclear grade, extension to the vagina or
corpus uteri, tumor length (> 20 mm) or tumor volume (> 3000 mm(3)),
infiltration depth (in thirds of the cervical wall), thickness of the
remaining wall (< 3 mm), vascular invasion, lymph node metastases,
treatment, and patient age were significant variables in patients with
FIGO Stage I disease. Variables with no significance in patients with
Stage I disease were number of mitoses, state of resection margins,
infiltration to ectocervix, tumor thickness, lymphoid reaction, earlier or
concomitant cervical intraepithelial neoplasia, stump carcinoma, DNA
ploidy or DNA index, or time period. Multivariate analyses of patients
with FIGO Stage I disease
identified small cell carcinoma, corpus infiltration, vascular invasion,
and positive lymph nodes as independent prognostic factors.
CONCLUSIONS: Small cell carcinoma was the only histologic subgroup
of independent importance for prognosis in patients with non-SCC of the
uterine cervix. No significant difference between major subtypes of
adenocarcinoma favored a simplified classification. Extension to the
corpus in patients with early-stage disease was of independent
significance and should be acknowledged in planning treatment.
Is there really a
difference in survival of women with squamous cell carcinoma,
adenocarcinoma, and adenosquamous cell carcinoma of the cervix?
Shingleton HM, Cancer. 1995 Nov
Emory University, Atlanta, Georgia, USA.
The authors' aim was to assess whether there is a difference in biologic
behavior and survival in comparing
adenocarcinoma (AdCA), squamous cell carcinoma (SCC), and adenosquamous
carcinoma (Ad/SC) of the cervix. METHODS. Cancer registrars at 703
hospitals submitted anonymous data on 11,157 patients with cervical cancer
diagnosed and/or treated in 1984 and 1990 for a Patient Care Evaluation
Study of the American College of Surgeons. Among these patients, 9351
(83.8%) had SCC; 1405 (12.6%), AdCA; and 401 (3.6%), Ad/SC cancers. There
were no significant changes in percentages of the different histologic
types between the study years 1984 and 1990, nor was the patient
distribution different regarding age, race/ethnicity, and socioeconomic
background for each histologic group. Furthermore, the distribution of
patients who had had a hysterectomy did not change between 1984 and 1990.
RESULTS. A larger percent of patients with SCC (63.8%) than those with
Ad/SC (59.8%) or AdCA (50.2%) had tumors larger than 3 cm at greatest
dimension. Early stage patients (IA, IB, IIA) often were treated by
hysterectomy alone (45.5%) or combined with radiation (21.1%). The
remaining patients (21.9%) received radiation alone. Of the patients with
clinical stage I disease, 7.6% of Ad/CA patients, 15.5% of Ad/SC patients
and 12.6% of SCC patients had positive nodes. Although patients with SCC
had higher survival rates for all four clinical stages (I-IV), the
differences were only significant for Stage II patients. Patients with
clinical stage IB SCC and AdCA treated by surgery alone were found to have
significantly better survival rates (93.1% and 94.6% at 5 years,
respectively) than women treated by either radiation alone or a
combination of surgery and radiation (P < 0.001, both histologic
comparisons). For women with Ad/SC tumors, however, the 5-year survival
rate was 87.3% for those receiving combined treatment compared with those
receiving surgery alone (69.2%) or radiation alone (79.2%). However, these
survival curves were not significantly different (P = 0.496). One hundred
six patients with positive nodes were available for analysis. The 5-year
survival rate of patients with SCC and positive nodes was 76.1%.
Surprisingly, patients with Ad/SC and positive nodes had the highest
5-year survival rate (85.7%), whereas, women with AdCA and positive nodes
had a sharply reduced 5-year survival rate (33.3%). The curves were
significantly different (P < 0.01). For patients with clinical stage I,
the risk factors for age, tumor size, nodal status, histologic features,
and treatment were analyzed with Cox's multivariate regression. In this
analysis, subset IB, greater tumor size, age 80 or older, and positive
nodal status were each independently significant for poorer survival.
Patients who were treated by surgery alone had a significantly better
survival than patients who had other types of treatment or no treatment.
Histologic characteristics had no significant effect on survival. In the
analysis of patients with pathologic stage I disease, those with SCC had
significantly poorer survival and those with Ad/SC had significantly
better survival than patients with Ad/CA. Positive nodes had no
significant independent effect on survival. In another analysis, tissue
type was not found to be an important factor in recurrence time.
CONCLUSIONS: 1. Ad/CA and Ad/SC
tumors were found to represent 12.6% and 3.6%, respectively, of a large
series (N = 11,157) of cervical cancers diagnosed in 1984 and 1990 and
reported to the Commission on Cancer of the American College of Surgeons.
2. Two thirds of women with early clinical stage disease (IA, IB, IIA) had
hysterectomy as all or part of their primary therapy. 3. No significant
differences were found in 5-year survival among the three tissue types in
any clinical stage except American Joint Committee on Cancer stage II.
Obesity as a potential risk factor for adenocarcinomas and squamous cell
carcinomas of the uterine cervix
James V. Lacey Jr
Hormonal factors may play a more prominent
role in cervical adenocarcinoma than squamous cell carcinoma. The authors
evaluated whether obesity, which can influence hormone levels, was
associated with adenocarcinoma and squamous cell carcinoma. This
case-control study included 124 patients with adenocarcinoma, 139 matched
patients with squamous cell carcinoma, and 307 matched community control
participants. All participants completed interviews and provided
cervicovaginal samples for human papillomavirus (HPV) testing.
Height, weight, BMI, and WHR were positively associated with
30 kg/m2 (vs. BMI < 25 kg/m2; OR, 2.1 and 95% CI,
1.1-3.8) and WHR in the highest tertile (vs. the lowest tertile; OR, 1.8
and 95% CI, 0.97-3.3) were associated with adenocarcinoma. Neither height
nor weight was found to be associated with squamous cell carcinoma, and
associations for BMI
30 kg/m2 (OR, 1.6) and WHR in the highest tertile (OR, 1.6)
were weaker and were not statistically significant. Analyses using only
HPV positive controls showed similar associations. The data were adjusted
for and stratified by screening, but higher BMI and WHR were associated
with higher disease stage at diagnosis, even among recently and frequently
screened patients with adenocarcinoma. Thus, residual confounding by
screening could not be excluded as an explanation for the associations.
Obesity and body fat distribution
were associated more strongly with adenocarcinoma than with squamous cell
carcinoma. Although questions about screening remain, obesity may
have a particular influence on the risk of glandular cervical carcinoma.
The Rising Incidence of
Adenocarcinoma Relative to Squamous Cell Carcinoma of the Uterine Cervix
in the United States—A 24-Year Population-Based Study
Oncology Volume 78, Issue 2 , August 2000, Pages 97-105
The aim of this study was to compare the age
adjusted incidence and survival for invasive adenocarcinoma and squamous
cell carcinoma of the uterine cervix using population-based data. The
SEER database was used to identify all cases of cervical cancer
registered between 1973 and 1996.
Results. The age-adjusted incidence rates
per 100,000 for all invasive cervical cancers decreased by 36.9% over 24
years [12.35 (1973–1977) vs 7.79 (1993–1996)]. Similarly, the
e-adjusted incidence rates for
squamous cell carcinoma declined by 41.9% [9.45 (1973–1977) vs
5.49 (1993–1996)]. In contrast, the age-adjusted incidence rates for
adenocarcinoma increased by
29.1% [1.34 (1973–1977) vs 1.73 (1993–1996)]. The proportion of
adenocarcinoma increased 107.4% relative to all cervical cancer, 95.2%
relative to squamous cell carcinoma, and 49.3% relative to the
population of women at risk [10.8% vs 22.4% (P < 0.001), 12.4% vs 24.0%
(P < 0.001), and 1.40 vs 2.09 per 100,000 women (P < 0.001),
respectively]. Observed survival
rates for adenocarcinoma vs squamous cell carcinoma were poorer for
regional (P = 0.04), but not localized or distant disease.
Conclusions. Over the past 24 years, the
incidence of all cervical cancer and squamous cell carcinoma has
continued to decline. However, the proportion of adenocarcinoma relative
to squamous cell carcinoma and to all cervical cancers has doubled, and
the rate of adenocarcinoma per population at risk has also increased.
These results suggest that current screening practices in the United
States are insufficient to detect a significant proportion of
adenocarcinoma precursor lesions.