Académique Documents
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Prof. M. Addar
Introduction
Race
In the United States, cervical cancer is more
common in Hispanic, African American, and
Native American women than in white women.
Sex
Cervical cancer is found only in women.
Age
Cervical cancers usually affect women of middle
age or older, but it may be diagnosed in any
reproductive-aged woman.
Causes
Early epidemiological data demonstrated a direct causal
relationship between cervical cancer and sexual activity.
Major risk factors include:
sex at a young age,
multiple sexual partners,
promiscuous male partners,
history of sexually transmitted diseases.
the search for a potential sexually transmitted
carcinogen had been unsuccessful until breakthroughs in
molecular biology enabled scientists to detect viral
genome in cervical cells
Human papillomavirus
HPV is a heterogeneous group of viruses that
contain closed circular double-stranded DNA.
The viral genome encodes 6 early open reading
frame proteins (ie, E1, E2, E3, E4, E6, E7), which
function as regulatory proteins, and 2 late open
reading frame proteins (ie, L1, L2), which make up
the viral capsid.
To date, 77 different genotypes of HPV have been
identified and cloned, among which, types 6, 11, 16,
18, 26, 31, 33, 35, 39, 42, 43, 44, 45, 51, 52, 53, 54, 55,
56, 58, 59, 66, and 68 have the propensity to infect
anogenital tissues.
Studies have shown a higher prevalence of HPV in HIVseropositive women than in seronegative women, and the HPV
prevalence was directly proportional to the severity of
immunosuppression as measured by CD4 counts.
Differential Diagnoses
Cervilities is an inflammation of the uterine
cervix.
Infectious cervicitis might be caused by
Chlamydia trachomatis, Neisseria gonorrhea,
Trichomonas vaginalis, herpes simplex virus
(HSV), or human papillomavirus (HPV).
Noninfectious cervicitis might be caused by local
trauma, radiation, or malignancy.
The infectious etiologies are significantly more
common than the noninfectious causes, and all
possible infectious causes of cervicitis are
sexually transmitted diseases (STDs).
Endometrial Carcinoma
Corpus cancer is the most frequently
occurring female genital cancer.
Approximately 39,000 cases of corpus
cancer were predicted to occur in the
United States in 2007, making it the
fourth most common cancer among
women; of these women, approximately
7400 will die from the disease
Cervicitis/infection, particularly
granulomatous (rare)
Vaginal cancer
Metastatic cancer to cervix (rare)
Laboratory Studies
A Papanicolaou test should be performed in
every patient suggested to have a diagnosis
of cervical cancer.
The patient should be referred to a
gynecologist for colposcopy, direct biopsies,
and endocervical curettage.
After the diagnosis is established, a complete
blood cell count and serum chemistry for
renal and hepatic functions should be
ordered to look for abnormalities from
possible metastatic disease.
Imaging Studies
Once the diagnosis is established, imaging studies are
performed for staging purposes.
A routine chest radiograph should be obtained to help rule out
pulmonary metastasis.
CT scan of the abdomen and pelvis is performed to look for
metastasis in the liver, lymph nodes, or other organs and to
help rule out hydronephrosis/hydroureter.
In patients with bulky primary tumor, barium enema studies can
be used to evaluate extrinsic rectal compression from the
cervical mass.
The use of positron emission tomography (PET) scan is now
recommended for patients with stage IB2.
Other Tests
The International Federation of Gynecology and
Obstetrics (FIGO) guidelines for staging are
limited to colposcopy, biopsy, conization of
cervix, cystoscopy, and proctosigmoidoscopy.
In the United States, more complex radiologic
imaging, such as CT, MRI, and PET scans as
well as surgical staging, are often done to guide
therapeutic options.
Procedures
In patients with bulky primary tumor, cystoscopy and
proctoscopy should be performed to help rule out local
invasion of the bladder and the colon.
Clinical staging protocols can fail to demonstrate pelvic and
aortic lymph node involvement in 20-50% and 6-30% of
patients, respectively. For that reason, surgical staging
frequently is recommended. Pretreatment surgical staging is
the most accurate method to determine the extent of disease.
However, little evidence suggests an improvement in overall
survival with routine surgical staging. Therefore, pretreatment
surgical staging should be individualized after a thorough
nonsurgical workup, including fine-needle aspiration of lymph
nodes, has failed to demonstrate metastatic disease.
Histologic Findings
Precancerous lesions of the cervix usually are
detected via Papanicolaou test. The
Papanicolaou test classification system has
evolved over the years. In 1988, the National
Cancer Institute (NCI) sponsored a workshop to
standardize Papanicolaou test reporting.
Currently, cervical cytology results are reported
according to the 2001 Bethesda System.
Table 1. 2001 Bethesda System for Reporting
Cervical Cytologic Diagnoses
Treatment
Medical Care
The treatment of cervical cancer varies with the
stage of the disease. For early invasive cancer,
surgery is the treatment of choice. In more
advanced cases, radiation combined with
chemotherapy is the current standard of care. In
patients with disseminated disease,
chemotherapy or radiation provides symptom
palliation.
Stage IB or IIA
For patients with stage IB or IIA disease, treatment
options are either combined external beam radiation
with brachytherapy or radical hysterectomy with
bilateral pelvic lymphadenectomy.
Radical trachelectomy with pelvic lymph node
dissection is appropriate for fertility preservation in
stage IA2 and B1.
Most retrospective studies have shown equivalent
survival rates for both procedures, although such
studies usually are flawed due to patient selection
bias and other compounding factors. However, a
recent randomized study showed identical overall
and disease-free survival rates.
Stage IIB-IVA
For locally advanced cervical carcinoma (stages IIB, III, and
IVA), radiation therapy was the treatment of choice for many
years. However, the results from large randomized clinical trials
demonstrated a dramatic improvement in survival with the
combined use of chemotherapy and radiation.
For treatment with radiation alone, 5-year survival rates
reportedly are 65-75%, 35-50%, and 15-20% for stages IIB, III,
and IVA, respectively.
Radiation therapy begins with a course of external beam
radiation to reduce tumor mass to enable subsequent
intracavitary application. Brachytherapy is delivered using
afterloading applicators that are placed in the uterine cavity
and vagina
Surgical Care
Carcinoma in situ (stage 0) is treated with local
ablative measures such as cryosurgery, laser
ablation, and loop excision.
Hysterectomy should be reserved for patients with other
gynecologic indications to justify the procedure.
After local treatment, these patients require lifelong
surveillance.
Consultations
Consultations
The treatment of cervical cancer
frequently requires a multidisciplinary
approach involving a gynecologic
oncologist, radiation oncologist, and
medical oncologist.
Diet
Proper nutrition is important for patients with cervical cancer.
Every attempt should be made to encourage and provide
adequate oral food intake.
Nutritional supplements such as Ensure or Boost are used
when patients have had significant weight loss or cannot
tolerate regular food due to nausea caused by radiation or
chemotherapy.
In patients with severe anorexia, appetite stimulants such as
Megace can be prescribed.
For patients who are unable to tolerate any oral intake,
percutaneous endoscopic gastrostomy tubes are placed for
nutritional supplementation.
In patients with extensive bowel obstruction as a result of
metastatic cancer, hyperalimentation sometimes is used.
Medication
Chemotherapy should be administered in
conjunction with radiation therapy to most
patients with stage IB (high risk) to IVA. Cisplatin
is the agent used most commonly, although 5fluorouracil also is used frequently. For patients
with metastatic disease, cisplatin remains the
most active agent. Topotecan, ifosfamide, and
paclitaxel also have significant activity in this
setting. The combination of topotecan and
cisplatin improves overall survival. However,
acute toxicities are also increased.
Cisplatin (Platinol)
Intrastrand cross-linking of DNA and inhibition of
DNA precursors are among proposed
mechanisms of action. Used in combination with
radiation therapy.
5-Fluorouracil (Efudex, Adrucil, Fluoroplex)
Pyrimidine antagonist. Several mechanisms of
action have been proposed, including inhibition
of thymidylate synthase and inhibition of RNA
synthesis. Also is a potent radiosensitizer.
Ifosfamide (Ifex)
Forms DNA interstrand and intrastrand
bonds that interfere with protein synthesis.
Paclitaxel (Taxol)
Mechanisms of action are tubulin
polymerization and microtubule
stabilization.
Topotecan
Inhibits topoisomerase I, inhibiting DNA
replication. Patients who have received
prior chemotherapy should be given a
lower dose initially
Vaccines
A human papillomavirus (HPV) vaccine is now available for
prevention of HPV-associated dysplasias and neoplasias, including
cervical cancer, genital warts (condyloma acuminata), and
precancerous genital lesions. The immunization series should be
completed in girls and young women aged 9-26 years.
Adult
<26 years: 0.5 mL IM administered as 3
separate doses; administer second and
third doses 2 and 6 mo after first dose,
respectively
>26 years: Not established
Pediatric
<9 years: Not established
>9 years: Administer as in adults
Deterrence/Prevention
Screening of cervical cancer
For many years, the standard method for cervical cancer
screening has been the Papanicolaou test. Retrospective
data have shown that screening with a Papanicolaou test
reduces the incidence rate of cervical cancer by 60-90% and
the death rate by 90%.
The false-negative rate of a Papanicolaou test is 20%, which
mostly results from sampling error. Physicians can reduce
sampling error by ensuring adequate material is taken from
both the endocervical canal and the ectocervix. Smears
without endocervical or metaplastic cells must be repeated.
Upon physical examination, suspicious or grossly abnormal
cervical lesions should undergo biopsy regardless of
cytologic findings.
Complications
Complications from radiation alone
During the acute phase of pelvic radiation, the
surrounding normal tissues such as the
intestines, the bladder, and the perineum skin
often are affected.
Acute adverse gastrointestinal effects include
diarrhea, abdominal cramping, rectal discomfort,
or bleeding. Diarrhea usually is controlled by
either loperamide (Imodium) or atropine sulfate
(Lomotil). Small, steroid-containing enemas are
prescribed to alleviate symptoms from proctitis.
Prognosis
Prognosis of cervical cancer depends on disease stage.
In general, the 5-year survival rate for stage I disease is
higher than 90%, for stage II is 60-80%, for stage III is
approximately 50%, and for stage IV disease is less than
30%.
Patient Education
Cervical cancer is overrepresented among
underserved and minority groups in the United
States. It is imperative to increase awareness about
the benefits of Papanicolaou test screening in these
groups.