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 45, 51, 52, 56, 58, 59, 73, and 82. Types 16 & 18 cause about 70% of cervical cancers.  Together with type 31, they are the primary risk factors.  Genital wars are caused by various strains of HPV which are usually not related to cervical cancer.  Other risk factors include smoking, HIV infection Chlamydia infection, dietary factors, hormonal contraception, multiple pregnancies, DES (diethylstilbestrol) and a family history of cervical cancer (genetic risk associated with HLA-B7) 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.  About 80 to 85% of all cervical cancers are squamous cell carcinoma; most of the rest are adenocarcinomas (glandular cells). Sarcomas and small cell neuroendocrine tumors are rare.

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.

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 (spread to adjacent pelvic organs) 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.  Stage IV, spread beyond the true pelvis or clinical involvement of the bladder or rectal mucosa.  Stage IVA spread to adjacent pelvic organs.  Stage IVB, spread to distant organs.  Treatment is often ineffective for bulky and advanced stage tumors. 

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.  In June of 06, the FDA approved the combination of hycamtin and cisplatin for women with stage IVB.  Combination treatment has significant risk of neutropenia (decrease of neutrophils in the blood), anemia, and thrombocytopenia (decrease of  blood platelets) side effects.  Paclitaxel, topotecan, gemcitabine, and vinorelbine are under study for treatment of recurrent squamous cell carcinoma.  Paclitaxel is also used to treat recurrent or metastatic non-squamous cancer.  Metastases outside the radiation field appear to respond better to chemotherapy than does previously irradiated pelvic cancer. 

GARDASIL is the only cervical cancer vaccine that helps protect against 4 types of human papillomavirus (HPV): 2 types that cause 70% of cervical cancer cases, and 2 more types that cause 90% of genital warts cases. GARDASIL is for girls and young women ages 9 to 26.

Dysoplasia abnormal development or growth of tissues, organs, or cells.

Dysplasia is a term used in pathology to refer to an abnormality in maturation of cells within a tissue. This generally consists of an expansion of immature cells, with a corresponding decrease in the number and location of mature cells. Dysplasia is often indicative of an early neoplastic process. The term dysplasia is typically used when the cellular abnormality is restricted to the originating tissue, as in the case of an early, in-situ neoplasm....