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Cervical
cancer is usually a squamous cell carcinoma that is caused by human
papillomavirus infection or an adenocarcinoma. Early cancer is asymptomatic;
the 1st symptom of later cancer is usually postcoital vaginal bleeding.
Diagnosis is by screening cervical Papanicolaou (Pap) test and biopsy.
Staging is clinical. Treatment usually includes surgical resection,
radiation therapy, and, unless cancer is localized, chemotherapy;
if cancer is widely metastasized, treatment is primarily
chemotherapy.
Cervical cancer is the 3rd most common gynecologic cancer and the 8th most common cancer among women in the US. Mean age at diagnosis is about 50, but the cancer can occur as early as age 20.
Cervical cancer results from cervical intraepithelial neoplasia (CIN), which appears to be caused by infection with human papillomavirus (HPV) type 16, 18, 31, 33, 35, or 39. Risk factors for cervical cancer include younger age at 1st intercourse, a high lifetime number of sex partners, and intercourse with men whose previous partners had cervical cancer. Other factors such as cigarette smoking and immunodeficiency also appear to contribute.
Pathology
CIN is graded as 1 (mild cervical dysplasia), 2 (moderate dysplasia), or 3 (severe dysplasia and carcinoma in situ). CIN 3 is unlikely to regress spontaneously; if untreated, it may, over months or years, penetrate the basement membrane, becoming invasive carcinoma.
About 80 to 85% of all cervical cancers are squamous cell carcinoma; most of the rest are adenocarcinomas. Sarcomas and small cell neuroendocrine tumors are rare.
Invasive cervical cancer usually spreads by direct extension into surrounding tissues or via the lymphatics to the pelvic and para-aortic lymph nodes. Hematogenous spread is possible.
Symptoms and Signs
CIN is usually asymptomatic. Early cervical cancer usually manifests as irregular vaginal bleeding; it is most often postcoital but may occur spontaneously between menses. Larger cancers are more likely to bleed spontaneously and may produce foul-smelling vaginal discharge or pelvic pain. More widespread cancer may produce obstructive uropathy, back pain, and leg swelling due to venous or lymphatic obstruction; examination may detect an exophytic necrotic tumor in the cervix.
Diagnosis
Cervical cancer is considered in women with visible cervical lesions, abnormal routine cervical Pap tests, or abnormal vaginal bleeding. Most CIN is evident on Pap tests, but about 50% of patients with cervical cancer have not had a Pap test for ≥ 10 yr. Patients at highest risk are the least likely to obtain regular preventive health care and to be tested regularly.
Reporting of cervical cytology results is standardized (see
Table 4: Gynecologic Tumors: Bethesda Classification of Cervical Cytology*  ). Further evaluation is indicated if atypical or cancerous cells are found, particularly in women at risk. If there is no obvious cancer, colposcopy (examination of the vagina and cervix with a magnifying lens) can be used to identify areas that require biopsy. Colposcopy-directed biopsy is usually diagnostic. If not, cone biopsy (conization) is required; a cone of tissue is removed using a loop electrical excision procedure (LEEP), laser, or cold knife.
Staging:
Cancers are clinically staged based on biopsy, physical examination, and chest x-ray results (see
Table 5: Gynecologic Tumors: Clinical Staging of Cervical Carcinoma*). If the stage is > IB1, CT or MRI of the abdomen and pelvis is also typically done to identify metastases, although results are not used for staging. Cystoscopy, sigmoidoscopy, and IV urography, when clinically indicated, may also be used for staging.
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Table 5
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Clinical Staging of Cervical
Carcinoma*
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Stage
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Description
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0
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Carcinoma in situ (CIN 3), intraepithelial carcinoma
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I
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Carcinoma strictly confined to the cervix (extension to the corpus should be disregarded)
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IA
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Preclinical carcinoma (diagnosed only by microscopy, with a depth of invasion < 5 mm from the surface)†
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IA1
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Measured invasion of stroma ≤ 3 mm in depth and ≤ 7 mm in width
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IA2
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Measured invasion of stroma > 3 mm and ≤ 5 mm in depth and ≤ 7 mm in width
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IB
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Clinically visible lesions confined to the cervix or preclinical lesions larger than those in stage IA2
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IB1
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Clinically visible lesions ≤ 4 cm
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IB2
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Clinically visible lesions > 4 cm
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II
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Extension beyond the cervix but not to the pelvic wall; involvement of the vagina but excluding the lower 1⁄3
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IIA
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No obvious parametrial involvement
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IIB
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Obvious parametrial involvement
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III
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Extension to the pelvic wall, with rectal examination detecting no cancer-free space between the tumor and pelvic wall; involvement of the lower 1⁄3 of the vagina; all cases with hydronephrosis or with a nonfunctioning kidney secondary to the carcinoma
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IIIA
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Extension to lower 1⁄3 of the vagina but not to the pelvic wall
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IIIB
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Extension to the pelvic wall, hydronephrosis, or a nonfunctioning kidney
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IV
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Extension beyond the true pelvis or clinical involvement of the bladder or rectal mucosa (bullous edema does not signify stage IV)
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IVA
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Spread to adjacent pelvic organs
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IVB
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Spread to distant organs
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*Based on staging established by the International Federation of Gynecology and Obstetrics (FIGO) and American Joint Committee on Cancer (AJCC), 1995, 1996, 1997.
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†Depth of invasion should be measured from the base of the epithelium (surface or glandular) from which it originates. Vascular space involvement (venous or lymphatic) should not alter staging.
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When imaging tests suggest that pelvic or para-aortic lymph nodes are grossly enlarged (> 2 cm), surgical exploration, typically with a retroperitoneal approach, is occasionally indicated. Its sole purpose is to remove enlarged lymph nodes.
Prognosis
and Treatment
In squamous cell carcinoma, distant metastases usually occur only when the cancer is advanced or recurrent. The 5-yr survival rates are 80 to 90% with stage I, 50 to 65% with stage II, 25 to 35% with stage III, and 0 to 15% with stage IV. Nearly 80% of recurrences manifest within 2 yr. Adverse prognostic factors include lymph node involvement, large tumor size and volume, deep cervical stromal invasion, parametrial invasion, vascular space invasion, and nonsquamous histology.
For patients with CIN or squamous cell carcinoma stage IA1, cone biopsy with LEEP, laser, or cold knife is usually sufficient treatment. Uncommonly, a hysterectomy is required.
If hysterectomy is done for stage IA1 cancer, simple (extrafascial) hysterectomy is usually sufficient when no adverse prognostic factors (nonsquamous histology or lymphatic or vascular invasion) are present because risk of recurrence and lymph node metastasis is < 1%. Pelvic lymph node dissection is not indicated. However, if adverse prognostic factors are present, radical hysterectomy is typically required; it includes bilateral pelvic lymphadenectomy and removal of all adjacent ligaments (cardinal, uterosacral) and parametria and the upper 2 cm of the vagina.
For stage IA2 to IIA, treatment may involve a radical hysterectomy or pelvic radiation therapy with concurrent chemotherapy. The 5-yr cure rates in stage IB or IIA are 85 to 90% with either treatment. Surgery provides additional staging data and preserves the ovaries. If extracervical spread is noted during surgery, postoperative radiation therapy may prevent local recurrence.
For patients with stage IIB to IVA cancer, radiation therapy is more suitable as primary therapy; radiation is also used for poor surgical candidates who would otherwise require hysterectomy. Surgical staging should be considered to determine whether para-aortic lymph nodes are involved and thus whether extended-field radiation therapy is indicated; a retroperitoneal approach is used. External beam radiation therapy shrinks the central tumor and treats regional lymph nodes; this therapy is followed by brachytherapy (local radioactive implants, usually using cesium) to the cervix, which destroys the central tumor. Acute complications of radiation therapy (eg, radiation proctitis and cystitis) may occur. Occasionally, late complications (eg, vaginal stenosis, intestinal obstruction, rectovaginal and vesicovaginal fistula formation) occur.
For stages IIB to IVA, chemotherapy is usually given with radiation therapy, often to sensitize the tumor to radiation. Treatment is often ineffective for bulky and advanced-stage tumors.
Although stage IVA cancers are usually treated with radiation therapy initially, pelvic exenteration (excision of all pelvic organs) may be considered. If after radiation therapy, cancer remains but is confined to the central pelvis, exenteration is indicated and cures up to 50% of patients. The procedure may include a continent urostomy, low anterior rectal anastomosis without colostomy, omental carpet to close the pelvic floor (J-flap), and vaginal reconstruction with gracilis or rectus abdominis myocutaneous flaps.
For widely metastatic or recurrent cancer, chemotherapy is the primary treatment, but the resulting response is brief and occurs in only 15 to 25% of patients. Cisplatin is the most active drug and the current standard. Paclitaxel , topotecan , gemcitabine , and vinorelbine are under study for treatment of recurrent squamous cell carcinoma. Paclitaxel is also used to treat recurrent or metastatic nonsquamous cancer. Metastases outside the radiation field appear to respond better to chemotherapy than does previously irradiated pelvic cancer.
Prevention
Routine cervical Pap tests are recommended yearly, starting the year of 1st sexual intercourse or by age 18. Pap test and HPV test can be done simultaneously. If both are normal or if 3 consecutive Pap tests are normal, some physicians test at 2- to 3-yr intervals. Testing continues until patients are age 65 to 70, have normal results for 10 yr, or have a hysterectomy. (See also the American Cancer Society guideline Early
detection of cervical neoplasia and cancer.) Vaccination against HPV to prevent cervical cancer is under study. Sexually active women are advised that condoms should be used during intercourse to prevent spread of HPV.
Last full review/revision November 2005
Content last modified November 2005
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