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CARCINOMA OF THE ENDOMETRIUM
Definition
Endometrial cancer arises from the glandular tissue within the
uterine lining.
Prevalence
Endometrial cancer is the most common of the gynecologic malig-
nancies. Approximately 2% to 3% of women in the United States will
develop cancer of the endometrium at some point during their lives.
With an estimated 37,000 new cases last year, it is the fourth most
common malignancy among women. It predominantly affects older
women, with 75% of cases occurring in the postmenopausal years.
Pathophysiology
Endometrial cancer is a heterogeneous disease that is believed to have
two biologically different subtypes, implying two different mecha-
nisms for its origin.
Low-Risk Subtype
The most common subtype is a well-differentiated carcinoma (grade
1 or 2 endometrioid histology) that behaves in an indolent fashion,
causes bleeding symptoms in its early stages, and is curable in most
cases. Risk factors for this low-risk subtype are well known and are
related to an increase in circulating estrogens: obesity, chronic
anovulation and nulliparity, estrogen replacement therapy (un­­
opposed by progesterone), and tamoxifen use.
High-Risk Subtype
The high-risk subtype accounts for a minority of endometrial malig-
nancies. These poorly differentiated tumors (grade 3 endometrioid,
clear cell, and papillary serous carcinoma) are not associated with
increased circulating estrogens. Rather, they appear to occur spon-
taneously in postmenopausal women without clearly defined risk
factors. These tumors metastasize early and account for a dispropor-
tionate number of mortalities from endometrial malignancy. Modes
of spread include local invasion and lymphatic and vascular embo-
lization. The most common metastatic sites include the cervix,
adnexa, and retroperitoneal lymph nodes.
Signs and Symptoms
Endometrial cancer usually manifests with abnormal uterine bleed-
ing. It should be suspected in any postmenopausal woman with
bleeding symptoms. Pre- or perimenopausal women might have
bleeding abnormalities such as menorrhagia or metrorrhagia.
Less commonly, asymptomatic women can present with an
abnormal Papanicolaou (Pap) smear revealing atypical or malignant
endometrial cells. A normal Pap smear in a symptomatic woman,
however, must never be relied on to exclude endometrial pathology.
Diagnosis
A complete physical examination is the first step in the evaluation of
a woman with suspected endometrial cancer. Inspection of the vulva,
anus, vagina, and cervix is necessary to evaluate for metastatic lesions.
A biopsy should be done for any suspicious genital tract lesions
detected on examination. Bimanual and rectovaginal examination to
evaluate the uterus, cervix, adnexa, parametria, and rectum is essen-
tial. Palpation of the inguinal and supraclavicular nodes may reveal
enlargement in advanced cases with metastatic disease.
Histologic evaluation of endometrial tissue is necessary. An endo-
metrial biopsy can be performed safely and easily in the office setting
in most symptomatic patients. The sensitivity for detecting endome-
trial carcinoma approaches that of a dilation and curettage (D&C)
and avoids the expense and morbidity of an operative procedure.
Several biopsy instruments are available for use, including the Pipelle
sampler and Novak curette.
Occasionally, D&C is necessary to obtain tissue for histologic
evaluation. Cervical stenosis and patient discomfort are common
indications for D&C. This outpatient surgical procedure may be
performed using a paracervical block with sedation; however, in
some cases, general or regional anesthesia may be preferred. Hyster-
oscopy and saline infusion sonography visualize endometrial lesions,
such as polyps, within the uterine cavity and can be useful adjuncts
to endometrial sampling techniques.
If endometrial cancer is confirmed, further studies are needed to
optimize treatment planning, including a chest x-ray to rule out
metastatic disease. Other studies may be performed based on a
patient’s risk factors and symptoms at presentation. These include
computed tomography (CT) scans of the abdomen and pelvis with
oral and intravenous contrast (for preoperative assessment of extra-
uterine tumor spread in high-grade endometrial malignancies); sig-
moidoscopy, colonoscopy, or barium enema; intravenous pyelogram;
and serum cancer antigen 125 (CA 125) assay for papillary serous
carcinoma.
Treatment
Treatment is based on the surgically determined disease stage and on
assessment of prognostic features.1
Staging of endometrial cancer is
defined by the International Federation of Gynecology and Obstet-
rics (FIGO) criteria outlined in Table 1. Surgical staging by ex­­
ploratory laparotomy requires a peritoneal cytology assessment,
intraoperative inspection of the abdominal and pelvic organs (dia-
phragm, liver, omentum, pelvic and aortic lymph nodes, peritoneal
surfaces) for evaluation of metastatic disease, hysterectomy with
bilateral salpingo-oophorectomy, and retroperitoneal lymph node
sampling.2
Surgery
Although endometrial cancer is traditionally managed by laparot-
omy, increasing evidence supports the safety and efficacy of laparo-
scopic hysterectomy in appropriately selected patients at low risk for
extrauterine tumor spread.
Adjuvant Treatment
The need for adjuvant therapy is based on disease stage and on risk
factors for tumor recurrence.
Stage I Disease. For disease confined to the uterus, patients are
placed in low-, intermediate-, and high-risk categories, and adjuvant
therapies are based on pathologic features. In general, stage I tumors
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Cervical Cancer
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present with metastatic disease and account for a disproportionate
number of endometrial cancer deaths.
CANCER OF THE OVARY
Definition
Ovarian cancer is a heterogeneous group of malignancies that arises
from the various cell types that compose the organ.
Epithelial
Nearly 90% of ovarian malignancies are classified as epithelial
ovarian carcinomas. These cancers arise from the germinal epithe-
lium lining the ovary. Epithelial ovarian cancer can be further
subdivided into several histologic cell types: serous, mucinous, endo-
metrioid, clear cell, transitional, and undifferentiated carcinomas.
The risk of epithelial ovarian cancer increases with age and is found
predominantly in postmenopausal women. Epithelial tumors of low
malignant potential (borderline ovarian carcinoma) are a histologic
variant that is less aggressive than their invasive epithelial counter-
parts, are found in younger women, and are often confined to the
ovary at diagnosis.
Germ Cell
Germ cell tumors account for approximately 5% of all ovarian
cancers and recapitulate the developing embryo or placental struc-
tures. Histologic subtypes include dysgerminoma (most common),
endodermal sinus tumor, immature teratoma, choriocarcinoma, and
embryonal carcinoma. Germ cell ovarian cancer can occur in women
of any age, but approximately 80% of these are diagnosed in women
younger than 30 years.
Sex Cord–Stromal
Sex cord–stromal tumors, which account for approximately 5% of
all ovarian cancers, develop in the connective tissue and supporting
ovarian stroma. These tumors are generally less aggressive and often
produce steroid hormones, including estrogen, progesterone, and
testosterone. Some patients with hormone-producing tumors
present with signs and symptoms of steroid excess, such as vaginal
bleeding or hyperandrogenism.
Prevalence
According to the American Cancer Society, there were more
than 23,000 new cases of ovarian cancer and 14,000 deaths from
the disease in the United States in 2001. It is estimated that a
woman has a 1% to 2% lifetime risk for developing ovarian cancer.
that are higher grade and more deeply invasive into the myometrium
have a greater risk for recurrence and benefit from adjuvant therapy
postoperatively.
Whole-pelvis radiotherapy, with or without vaginal cuff
brachytherapy, is the most commonly used adjuvant postoperative
treatment modality. Patients with the histologic variant papillary
serous carcinoma, an aggressive endometrial lesion with a high risk
for extrapelvic recurrence, are generally offered chemotherapy to
reduce postoperative recurrence risk, although this treatment is
controversial.
Stage II Disease. For disease involving the uterine cervix, there
are several treatment options. When unsuspected cervical stromal
involvement is found during surgery, postoperative external-beam
radiotherapy with vaginal cuff brachytherapy is indicated. If cervical
involvement is known preoperatively, various combinations of
surgery and radiotherapy have been used:
● Hysterectomy, bilateral salpingo-oophorectomy, and node sam-
pling followed by postoperative irradiation
● Preoperative intracavitary and external-beam radiation therapy
followed by hysterectomy and bilateral salpingo-oophorectomy
● Radical hysterectomy and pelvic lymphadenectomy
Unfortunately, there is no standard treatment for stage II endome-
trial cancer, and the equivalence of these strategies has not been
assessed in comparative randomized trials.
Stage III Disease. In general, postoperative whole-pelvis radio-
therapy (vaginal cuff brachytherapy) is indicated when disease
involves adnexal structures or retroperitoneal nodes. Patients
with para-aortic involvement might benefit from extended-field
radiotherapy.
Stage IV Disease. The site of metastatic disease and associated
symptoms dictate the appropriate treatment of stage IV endometrial
cancer. For bulky pelvic disease, radiation therapy consisting of a
combination of intracavitary and external beam irradiation is used.
When distant metastases are present, systemic therapy is indicated.
Satisfactory tumor responses to hormonal treatment with progesta-
tional agents can often be achieved in well-differentiated (grades 1
and 2) tumors. Useful chemotherapeutic agents include doxorubicin
and paclitaxel.
Outcomes
Endometrial cancer is one of the most curable of the gynecologic
cancers because most patients have well-differentiated tumors and
present with symptoms early in the disease process (Table 2). Five-
year survival rates are much poorer in patients with the less common
and poorly differentiated tumor histologies. These patients often
Table 1 FIGO Staging for Endometrial Carcinoma
Stage Definition
I Carcinoma confined to the corpus uteri
II Carcinoma that involves the corpus and the cervix but has
not extended outside the uterus
III Carcinoma that extends outside the uterus but is confined
to the true pelvis and/or retroperitoneal lymph nodes
IV Carcinoma that involves the bladder or bowel mucosa or
that has metastasized to distant sites
FIGO, International Federation of Gynecology and Obstetrics.
Table 2 Endometrial Carcinoma: Stage at Presentation and 5-year
Relative Survival Rate
Disease Extent Stage Distribution (%) Survival (%)
All stages — 84
Localized 73 96
Regional 13 66
Distant 9 27
Unstaged 4 53
Adapted from Ries LAG, Kosary CL, Hankey BF, et al (eds): SEER Cancer Statistics
Review, 1973-1995. Bethesda, National Cancer Institute, 1998.

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another common finding. The distended abdomen is dull to percus-
sion and an omental cake may be palpated in the upper abdomen.
Further diagnostic workup is necessary to establish extent of disease
and exclude other causes of an adnexal mass, carcinomatosis, or
ascites.
Imaging Studies
Transvaginal ultrasound uses higher-frequency sound waves to
image the ovaries, allowing improved morphologic characterization.
The addition of color flow Doppler can further characterize the mass.
A vascular mass with low resistive indices supports a diagnosis of
malignancy. Chest x-ray might indicate pleural effusion, which is
common in patients with ovarian carcinomatosis. CT scans of the
abdomen and pelvis with intravenous and oral contrast characterize
tumor burden and assist in evaluating other causes of adnexal mass,
carcinomatosis, or ascites. Other studies may be performed based on
a patient’s risk factors and symptoms at presentation. These include
sigmoidoscopy, colonoscopy, or barium enema; upper gastrointesti-
nal endoscopy; and intravenous pyelogram.
Serum Tumor Markers
Serum tumor markers can assist in preoperative evaluation; however,
their limitations must be understood so they are not misinterpreted
or obtained inappropriately. Serum testing is essential to monitoring
treatment response for ovarian cancer, but its usefulness as a diag-
nostic tool is hindered by poor sensitivity and specificity. CA 125 is
a high-molecular-weight glycoprotein that is expressed by more than
80% of nonmucinous epithelial ovarian cancers. Although elevated
in most women with advanced ovarian cancer, only 50% of patients
with early-stage disease have an elevated CA 125, and mucinous
epithelial ovarian cancers express this antigen poorly. Furthermore,
an elevated CA 125 is not specific for ovarian cancer. Many nongy-
necologic and benign gynecologic conditions also are associated with
elevations in this serum antigen.
If nonepithelial ovarian cancer is suspected, other tumor markers
may be useful to assist in diagnosis. Alpha fetoprotein, human cho-
rionic gonadotropin, and lactic dehydrogenase may be expressed by
germ cell malignancies. If metastatic colon or pancreatic carcinoma
is suspected, serum carcinoembryonic antigen and CA 19-9 might
also be elevated. Limitations in the sensitivity and specificity of these
tests must be understood so they can be interpreted appropriately
for each patient.
Paracentesis
Malignant ascites is common in patients with metastatic epithelial
ovarian carcinoma. However, ascites due to other conditions such as
congestive heart failure and cirrhosis must be ruled out by careful
history and, if necessary, diagnostic testing.
Although paracentesis may be performed for cytologic examina-
tion, diagnostic paracentesis is not necessary for most patients if they
have already been deemed appropriate for exploratory surgery and
operative management. Furthermore, a negative cytology from pre-
operative paracentesis does not exclude the possibility of malignancy,
and differentiating the site of tumor origin is rarely possible on
cytologic examination. Large-volume therapeutic paracentesis,
however, may be useful for palliation of symptoms of abdominal
distention and associated respiratory compromise due to diaphrag-
matic elevation.
Consultation
If a reasonably high probability for ovarian malignancy exists,
consultation with a gynecologic oncologist is essential to ensure
appropriate preoperative counseling and preparation, operative
management, and postoperative care.
Ovarian carcinoma is the fifth most frequent cause of cancer death
in women, and one half of all cases occur in women older than 65
years.
Pathophysiology
The cause of ovarian cancer is poorly understood; however, risk
factors and mode of spread have been well described.
Risk Factors
The most significant risk factor for ovarian cancer is a positive family
history. When two or more first-degree relatives have or have had
ovarian cancer, a woman’s lifetime risk for developing this cancer is
7%. If a heritable cancer syndrome is identified, this lifetime risk can
increase 17- to 50-fold. Three dominantly inherited mutations are
known to be associated with the development of approximately 10%
of all ovarian carcinomas: breast-ovarian cancer syndrome, which is
associated with mutations in BRCA-1 and BRCA-2 genes; site-
specific ovarian carcinoma; and hereditary nonpolyposis colorectal
cancer (Lynch syndrome II), which is associated with mutations in
mismatch repair genes.Advanced age is also associated with increased
risk, whereas high parity, oral contraceptive use, tubal ligation, and
hysterectomy decrease one’s risk.
Mode of Spread
Ovarian cancer usually spreads via cellular shedding into the perito-
neal cavity followed by implantation on the peritoneal surface. Local
invasion of the bowel and bladder is common in advanced cases.
Tumor cells also may block diaphragmatic lymphatics. The resulting
impairment of lymphatic drainage of the peritoneum is believed to
play a role in development of ascites in ovarian cancer. Transdia-
phragmatic spread and seeding of the pleura with pleural effusion
are also common in advanced cases.
Signs and Symptoms
Unfortunately, most patients with epithelial ovarian cancer experi-
ence few or no symptoms until the disease has widely metastatasized.
Manifesting symptoms usually relate to an increasing intra-
abdominal tumor burden and ascites and are often vague, mimicking
other more common diseases. Symptoms include fatigue; bloating or
a feeling of fullness; abdominal swelling or pain; early satiety; vague
but persistent gastrointestinal complaints, such as gas, nausea, and
indigestion; frequency or urgency of urination; change in bowel
habits; unexplained weight loss or gain; shortness of breath; and
obstructive symptoms, such as nausea, vomiting, and constipation
or obstipation.
On the other hand, borderline, germ cell, and sex cord–stromal
tumors are often confined to the ovary at the time of diagnosis. They
may be quite large at presentation, and associated symptoms may be
related to their large size. These masses are occasionally detected
during the screening pelvic examination. More commonly, patients
feel the mass themselves or present with symptoms of acute abdomen
due to torsion of the adnexa or rupture of the tumor.
Diagnosis
A complete physical examination is the first step in the diagnosis
of ovarian cancer. Although pelvic examination is notoriously inef-
ficient at detecting presymptomatic early ovarian cancer, a pelvic
mass can often be palpated on examination in symptomatic patients.
The finding of a unilateral or bilateral nonmobile (fixed) mass is
characteristic of epithelial ovarian carcinoma. Cul-de-sac masses
may also be palpated with rectovaginal examination. Impingement
of the rectum and compromise of lumen diameter can also be appre-
ciated on this examination. Abdominal distention due to ascites is

4. 1230 Endometrial, Ovarian, and Cervical Cancer
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although some regimens are given over a period of several days,
requiring hospitalization.
For epithelial ovarian cancer, platinum-based therapy-either cis-
platin or carboplatin-in combination with paclitaxel has demon-
strated the highest activity of all agents studied.4
These agents are
generally given intravenously every 3 weeks for a total of six courses.
One study, however, suggests that continuation of single-agent pacl-
itaxel for 12 courses is associated with an improved disease-free
survival. Although its impact on overall survival is uncertain, these
findings have the potential to significantly affect recommended adju-
vant therapy for this disease.
Stage I Disease. Patients with stage Ia or Ib tumors that are
well-differentiated (grade 1) have an excellent prognosis, and the
addition of adjuvant chemotherapy has not been demonstrated to
improve survival in these patients. However, caution must be exer-
cised when considering withholding adjuvant therapy in patients
with presumed stage I disease who have not had the benefit of
adequate surgical staging. Reoperation for staging purposes is an
option in these patients. Patients with grades 2 and 3 tumors are at
increased risk for recurrence and appear to benefit from adjuvant
chemotherapy.
Stages II to IV Disease. The use of adjuvant chemotherapy has
survival and palliative benefits in patients with metastatic ovarian
carcinoma and a larger tumor burden. Adjuvant therapy for tumors
of borderline histology is generally not indicated. Little evidence
exists that postoperative chemotherapy or radiation therapy alters
the course of these tumors in any beneficial way.
All patients with germ cell tumors, except those with stage I, grade
1 immature teratoma and stage IA dysgerminoma, require postop-
erative chemotherapy.5
With platinum-based combination chemo-
therapy, the prognosis for patients with endodermal sinus tumors,
immature teratomas, embryonal carcinomas, choriocarcinomas, and
mixed tumors containing one or more of these elements has improved
dramatically.
Most patients with advanced ovarian cancer ultimately develop
progressive or recurrent disease after initial surgery and adjuvant
chemotherapy and require some form of palliative therapy.
Patients with recurrent ovarian carcinoma are considered either
platinum sensitive or platinum resistant, depending on whether
the response duration was less than or longer than 6 months
from prior therapy with a platinum-based agent. Potentially
platinum-sensitive patients often benefit from re-treatment with a
platinum-based agent. Owing to its favorable toxicity profile, carbo-
platin is ideally suited for palliative therapy in the appropriate
patient.
Platinum-resistant patients, on the other hand, generally have
more limited responses to alternative chemotherapeutic agents. A
number of second-line chemotherapeutic agents might have pallia-
tive benefit, including paclitaxel, liposomal doxorubicin, topotecan,
and gemcitabine. Because of poorer response rates in most patients
with platinum-resistant disease, participation in clinical trials evalu-
ating new therapies is also appropriate.
When disease-related symptoms can be palliated, such as the
reversal of intestinal obstruction, surgical intervention might
improve the quality of life. However, palliation is rarely achieved in
advanced disease when there are multiple areas of partial or complete
obstruction or when the transit time is prolonged due to diffuse
peritoneal carcinomatosis.
Outcomes
Survival in ovarian cancer is related to surgical stage and tumor
histology (Table 4). Patients with borderline tumors, germ cell
malignancies, and sex cord–stromal tumors often present with ear-
lier-stage disease and generally have improved prognoses.
Treatment
Ovarian cancer is initially managed with exploratory laparotomy to
confirm the diagnosis and determine the extent of disease (surgical
staging) and for tumor cytoreduction.
Histologic Identification
The availability of reliable intraoperative frozen section is essential
for optimal surgical decision making and management. For
example, fertility-sparing surgery may be an option in select
ovarian malignancies, such as germ cell tumors. In addition,
although tumor debulking appears to have survival benefit in
patients with ovarian malignancies, carcinomatosis related to an
extraovarian primary tumor does not necessarily benefit from such
measures.
Surgical Staging
Accurate staging determines both treatment and prognosis. Inade-
quate surgical staging is a common problem in patients with pre-
sumed early-stage disease when the operating surgeon does not
perform the necessary procedures for adequate staging. Therefore, it
is imperative that the operating surgeon is familiar with staging cri-
teria and has the surgical skills necessary to perform all the necessary
steps of the staging procedure. FIGO staging criteria are described in
Table 3.
Cytoreduction
Metastatic implants of ovarian cancer typically involve the peritoneal
surfaces and are often amenable to resection along with the primary
tumor mass. Although not documented by any randomized clinical
trial, optimal tumor cytoreduction (defined as removal of the
primary tumor and all gross metastatic implants to less than 1 cm
residual in largest diameter) is believed to improve chemotherapy
response and disease-free survival.3
To achieve these goals, surgical
techniques such as en bloc hysterectomy with resection of the recto-
sigmoid, small bowel, total omentum, spleen, and possibly more may
be necessary.
Aggressive resection of tumor does not appear to have any clini-
cal advantage unless all metastatic implants also can be optimally
reduced. The operating surgeon must exercise judgment as to
whether optimal tumor reduction is possible and can be safely
achieved without incurring significant complications that would
delay chemotherapy.
Adjuvant Treatment
Most, but not all, ovarian cancer patients require adjuvant chemo-
therapy after surgery. The importance of adequate surgical staging is
evident when making decisions regarding adjuvant therapy in stage
I disease. Most chemotherapy can be given on an outpatient basis,
Table 3 FIGO Staging for Ovarian Cancer
Stage Definition
I Growth limited to the ovaries
II Growth involves one or both ovaries with pelvic extension
III Tumor with peritoneal implants outside the pelvis, or
positive retroperitoneal or inguinal nodes, or both
IV Tumor involves one or both ovaries with distant metastasis
FIGO, International Federation of Gynecology and Obstetrics.

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Colposcopy is a technique of visually evaluating the cervix for
abnormalities. The colposcope is a magnifying device that aids the
examination of the cervix. Light filters and staining solutions are
used in combination to identify cervical dysplasia. If an abnormality
is identified, a biopsy may be recommended. Treatment is usually
based on the results of the biopsy. Referral to an expert familiar with
the colposcopy technique and the treatment of cervical dysplasia is
recommended.
When a colposcopic abnormality or a grossly visible cervical
lesion is identified, a biopsy is necessary for histologic evaluation.
Pap smear cytology is not adequate for diagnosis. Cervical biopsy
may be accomplished in an office setting using any number of instru-
ments, such as the Tischler-Morgan, Kevorkian, and mini-Townsend
biopsy instruments or even a loop electrode.
With documented invasive cervical carcinoma, further diagnostic
workup is necessary to establish the extent of disease. Cervical cancer
staging is defined clinically by FIGO criteria using physical examina-
tion and a limited number of diagnostic studies (Table 5).
A pelvic examination is necessary to assess tumor size and con-
figuration and to identify possible vaginal metastasis and parametrial
or pelvic sidewall involvement. Additionally, lymphatic metastasis is
common in advanced cervical cancer. Assessment of groin and
supraclavicular lymph nodes might reveal enlargement. Lower
extremity edema might also be present with an expanded tumor
diameter, significant pelvic lymphadenopathy, or both. Homans’
sign or a palpable cord may be identified if there is an associated deep
venous thrombosis.
Chest x-ray can identify pulmonary metastasis.Computed tomog-
raphy of the abdomen and pelvis (with oral, rectal, and intravenous
contrast) allows for more complete assessment of tumor extent within
the abdomen and pelvis. Although not part of FIGO clinical stage
criteria,it is useful for treatment planning.An intravenous pyelogram
may be obtained if ureteral obstruction or bladder involvement is
suspected. Cystoscopy or sigmoidoscopy may be obtained if bladder
involvement, rectal involvement, or both are suspected.
Treatment
Treatment and prognosis of cervical cancer are greatly affected by
the extent of disease at the time of diagnosis.
Stage 0 Disease (Carcinoma in Situ)
Invasive cervical carcinoma must be excluded with confidence before
therapy for preinvasive disease is undertaken. Standard treatment
options include excisional and ablative therapy. In general, excisional
therapies are preferred because they are associated with a lower
CANCER OF THE CERVIX
Definition
Cervical carcinoma has its origins at the squamocolumnar junction
or the cervix. The precursor lesion is dysplasia or carcinoma in situ
(cervical intraepithelial neoplasia III). Squamous cell carcinoma
accounts for 90% and adenocarcinoma accounts for 10% of cervical
cancers.
Prevalence
Last year, cervical cancer was diagnosed in approximately 14,000
women in the United States, and there were 4,700 deaths from the
disease. Peak incidence of cervical carcinoma is at 51 years of age,
whereas that for carcinoma in situ is approximately 10 years younger.
Pathophysiology
Epidemiologic studies convincingly demonstrate that the major risk
factor for preinvasive or invasive cervical carcinoma is infection with
the human papillomavirus (HPV). HPV DNA is detected in virtually
all cervical cancers, with HPV subtypes 16, 18, and 31 identified most
commonly. Other known risk factors include early age at first inter-
course, number of sexual partners, and a positive smoking history.
Cervical carcinoma spreads predominantly by local invasion and
lymphatic metastasis. The most common metastatic sites include the
vagina, parametrium, and pelvic lymph nodes.
Signs and Symptoms
Precancerous changes of the cervix rarely cause symptoms and are
generally detected by pelvic examination and Pap smear screening.
Symptoms usually do not appear until lesions become cancerous and
invade underlying cervical stroma. Postcoital vaginal spotting may
be one of the first symptoms of the disease. Ultimately, an enlarging
and vascular tumor mass can become ulcerated, leading to frank
vaginal bleeding, heavy vaginal discharge, or both. As the tumor
invades locally or spreads into the regional lymphatics, patients
develop pain, lower extremity edema, and lower extremity deep
venous thrombosis.
Diagnosis
Cervical cancer may be detected in its early stages by the screening
Pap smear or by identification of larger lesions in the symptomatic
patient. The Pap smear is a screening test only. Patients whose Pap
smears indicate cytologic abnormalities suggestive of high-grade
lesions are at risk for invasive cancer and warrant further diagnostic
testing with colposcopy. Ablative procedures should not be per-
formed without a thorough colposcopic examination.
Table 4 Ovarian Carcinoma: Stage at Presentation and 5-Year
Relative Survival Rate
Disease Extent Stage Distribution (%) Survival (%)
All stages — 50
Localized 25 95
Regional 9 79
Distant 61 28
Unstaged 6 29
Adapted from Ries LAG, Kosary CL, Hankey BF, et al (eds): SEER Cancer Statistics
Review, 1973-1995. Bethesda: National Cancer Institute, 1998.
Table 5 FIGO Staging for Cervical Cancer
Stage Definition
0 Preinvasive disease (carcinoma in situ)
I Carcinoma strictly confined to the cervix
II Carcinoma that extends into the parametrium (but not onto
the pelvic sidewall) or the upper two thirds of the vagina
III Carcinoma that has extended onto the pelvic sidewall or
involves the lower one third of the vagina. All cases with
a hydronephrosis or nonfunctioning kidney should be
included, unless they are known to be due to other causes.
IV Carcinoma that has extended beyond the true pelvis to
distant organs or has clinically involved the mucosa of the
bladder, rectum, or both
FIGO, International Federation of Gynecology and Obstetrics.

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Suggested Readings
Creasman WT, Morrow CP, Bundy BN, et al: Surgical pathologic spread patterns of
endometrial cancer. A Gynecologic Oncology Group Study. Cancer 1987;60(Suppl
8):2035-2041.
Ferenczy A, Choukroun D, Arseneau J: Loop electrosurgical excision procedure for
squamous intraepithelial lesions of the cervix: Advantages and potential pitfalls.
Obstet Gynecol 1996;87:332-337.
Gershenson DM, Morris M, Cangir A, et al: Treatment of malignant germ cell tumors
of the ovary with bleomycin, etoposide, and cisplatin. J Clin Oncol 1990;8:715-720.
Hoskins WJ, Bundy BN, Thigpen JT, Omura GA: The influence of cytoreductive surgery
on recurrence-free interval and survival in small-volume stage III epithelial ovarian
cancer: A Gynecologic Oncology Group study. Gynecol Oncol 1992;47:159-166.
McGuire WP, Hoskins WJ, Brady MF, et al: Cyclophosphamide and cisplatin compared
with paclitaxel and cisplatin in patients with stage III and stage IV ovarian cancer.
N Engl J Med 1996;334:1-6.
National Cancer Institute: Long-term data support cisplatin-based chemoradiation for
cervical cancer. Available at http://www.cancer.gov/clinicaltrials/results/cisplatin-
cervical0507 (accessed March 20, 2009).
Omura GA: Chemotherapy for cervix cancer. Semin Oncol 1994;21:54-62.
Ries LAG, Kosary CL, Hankey BF, et al (eds): SEER Cancer Statistics Review, 1973-1995.
Bethesda: National Cancer Institute, 1998.
References
For a complete list of references, log onto www.expertconsult.com.
failure rate and provide tissue for histologic evaluation to assess
margins and exclude invasion. Excisional therapies include the loop
electrosurgical excision procedure (LEEP), laser conization, cold
knife conization, and extrafascial hysterectomy. Ablative therapies
include cryotherapy and laser ablation therapy.
In most cases, outpatient LEEP is preferred.6
LEEP uses a fine wire
loop with electrical energy flowing through it to remove the trans-
formation zone of the cervix or focal areas of dysplasia. It can quickly
and easily be performed in an office setting and generally requires
only local anesthesia, thus avoiding the risks associated with
general anesthesia. Cold knife or laser conization require general
anesthesia.
Stage Ia1 (Microinvasive Cervical Cancer)
Cervical cancer in its earliest stages of invasion is termed microinva-
sive carcinoma. It is defined as invasion of the stroma no greater than
3 mm deep and no wider than 7 mm in diameter with no lymph-
vascular space involvement.
Disease meeting this strictly defined criteria has a very limited risk
for lymphatic metastasis, and outcome is excellent with less-radical
therapies. Expert pathology review is essential when considering less
radical therapies for disease qualifying as microinvasive. Equivalent
treatment options include extrafascial hysterectomy, cervical coniza-
tion, and intracavitary radiation alone (without external beam
radiotherapy).
All Other Stage I and Stage IIa Disease
Risk for lymphatic metastasis is increased with larger and more
deeply invasive lesions. For this reason, radical therapies are neces-
sary, and referral to a qualified gynecologic oncologist is appropriate
and recommended.
Therapy selection depends on patient factors, tumor factors, and
surgical expertise. Radical hysterectomy with bilateral pelvic lymph-
adenectomy is one option; combined external beam radiotherapy
and brachytherapy with concurrent chemotherapy is an equivalent
option.
Several randomized phase III trials have shown an overall survival
advantage for cisplatin-based therapy given concurrently with radia-
tion therapy. As a result of these findings, the National Cancer Insti-
tute issued a clinical announcement suggesting that “strong
consideration should be given to the incorporation of concurrent
cisplatin-based chemotherapy with radiation therapy in women who
require radiation therapy for treatment of cervical cancer.”7
Stages IIb to IVa Disease
With tumor spread beyond the cervix and upper vagina, cure rates
for radical surgery decline. Stages IIb to IVa cervical cancer are best
treated by radiation therapy using combined external beam pelvic
radiation and concurrent cisplatin-based chemotherapy with intra-
cavitary brachytherapy or interstitial therapy.
Stage IVb Disease
Patients with distant metastasis are no longer amenable to cure by
radiation therapy. Unfortunately, response rates to standard chemo-
therapy are generally less than 20% and are typically brief.All patients
with distant metastasis or recurrent disease should be considered
appropriate candidates for phases I and II clinical trials investigating
new treatments.
Palliative treatment options include radiation therapy to relieve
pelvic disease and chemotherapy with agents such as cisplatin, ifos-
famide, paclitaxel, gemcitabine, and irinotecan.8
Table 6 Cervical Carcinoma: 5-Year Relative Survival Rate
Disease Extent Survival (%)
All stages 84
Localized 96
Regional 66
Distant 27
Adapted from Ries LAG, Kosary CL, Hankey BF, et al (eds): SEER Cancer Statistics
Review, 1973-1995. Bethesda, National Cancer Institute, 1998.
l Endometrial cancer is one of the most curable of the
gynecologic cancers because most patients have well-
differentiated tumors and present with symptoms early in
the disease process.
l A woman’s lifetime risk for developing ovarian cancer is
7% when two or more first-degree relatives have this
cancer. This lifetime risk can increase 17- to 50-fold if a
heritable cancer syndrome is identified.
l Unfortunately, most patients with epithelial ovarian cancer
experience few or no symptoms until the occurrence of
widespread metastatic disease.
l Serum tumor markers can assist in the preoperative
evaluation of ovarian cancer; however, their limitations
must be understood so they are not misinterpreted or
obtained inappropriately.
l Epidemiologic studies convincingly demonstrate that the
major risk factor for preinvasive or invasive cervical
carcinoma is infection with the human papillomavirus
(HPV).
Summary
Outcomes
If not diagnosed in its early stages, cervical cancer carries high mor-
tality (Table 6). Properly diagnosed and managed, tumor control of
in situ cervical carcinoma should be nearly 100%.