In the United States, about 13,170 cases of invasive cervical cancer are diagnosed each year and 50,000 cases of carcinoma in situ are detected by Pap smear. Cervical cancer kills 4250 women a year, 85% of whom never had a Pap smear. It is a major cause of disease in underdeveloped countries and is more common in lower socioeconomic groups, in women with early sexual activity and/or multiple sexual partners, and in smokers. Human papilloma virus (HPV) types 16 and 18 are the major types associated with cervical cancer. The virus attacks the G1 checkpoint of the cell cycle; its E7 protein binds and inactivates Rb protein, and E6 induces the degradation of p53. Risk factors include a large number of sexual partners, early age at first intercourse, a history of venereal disease, HIV infection, and heavy smoking.
Women should begin screening when they begin sexual activity or at age 20. After two consecutive negative annual Pap smears, the test should be repeated every 3 years. Abnormal smears dictate the need for a cervical biopsy, usually under colposcopy, with the cervix painted with 3% acetic acid, which shows abnormal areas as white patches. If there is evidence of carcinoma in situ, a cone biopsy is performed, which is therapeutic.
Women, men, and children age 9–26 should obtain vaccination with Gardasil to prevent infection with two serotypes of virus (16 and 18) that cause 70% of the cervical cancer in the United States.
Pts present with abnormal bleeding or postcoital spotting or menometrorrhagia or intermenstrual bleeding. Vaginal discharge, low back pain, and urinary symptoms also may be present.
Staging is clinical and consists of a pelvic examination under anesthesia with cystoscopy and proctoscopy. Chest x-ray, IV pyelography, and abdominal CT are used to search for metastases. The staging system and its influence on prognosis are shown in Table 74-1. At presentation, 47% of pts are stage I, 28% are stage II, 21% are stage III, and 4% are stage IV.
Carcinoma in situ is cured with cone biopsy. Stage I disease may be treated with radical hysterectomy or radiation therapy. Stages II–IV disease are usually treated with radiation therapy, often with both brachytherapy and teletherapy, or combined-modality therapy. Pelvic exenteration is used uncommonly to control the disease, especially in the setting of centrally recurrent or persistent disease. Women with locally advanced (stage IIB–IVA) disease usually receive concurrent chemotherapy and radiation therapy. The chemotherapy acts as a radiosensitizer. Hydroxyurea, 5-fluorouracil (5FU), and cisplatin have all shown promising results given concurrently with radiation therapy. Cisplatin, 75 mg/m2 IV over 4 h on day 1, and 5FU, 4 g given by 96-h infusion on days 1–5 of radiation therapy, is a common regimen. Relapse rates are reduced 30–50% by such therapy. Advanced-stage disease is treated palliatively with single agents (cisplatin, irinotecan, ifosfamide). Bevacizumab may improve the antitumor effects of chemotherapy. Potentially active agents include mTOR inhibitors (temsirolimus) and immune checkpoint inhibitors, especially in the subset of pts with tumors defective in DNA repair.
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