Chapter 093. Gynecologic Malignancies (Part 7)

Patients with stage IV disease (outside the abdomen or invading the bladder or rectum) are treated palliatively with irradiation, surgery, and platinum-based chemotherapy. Progestational agents produce responses in ~10–20% of patients. Well-differentiated tumors respond most frequently, and response can be correlated with the level of progesterone receptor expression in the tumor. The commonly used progestational agents hydroxyprogesterone (Dilalutin), megestrol (Megace), and deoxyprogesterone (Provera) all produce similar response rates, and the antiestrogen tamoxifen (Nolvadex) produces responses in 10–25% of patients in a salvage setting. ...
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Chapter 093. Gynecologic Malignancies (Part 7) Chapter 093. Gynecologic Malignancies (Part 7) Patients with stage IV disease (outside the abdomen or invading the bladderor rectum) are treated palliatively with irradiation, surgery, and platinum-basedchemotherapy. Progestational agents produce responses in ~10–20% of patients.Well-differentiated tumors respond most frequently, and response can becorrelated with the level of progesterone receptor expression in the tumor. Thecommonly used progestational agents hydroxyprogesterone (Dilalutin), megestrol(Megace), and deoxyprogesterone (Provera) all produce similar response rates,and the antiestrogen tamoxifen (Nolvadex) produces responses in 10–25% ofpatients in a salvage setting. Chemotherapy is not very successful in advanced endometrial carcinoma.The most active single agents with consistent response rates of ≥20% includecisplatin, carboplatin, doxorubicin, epirubicin, and paclitaxel. Combinations ofdrugs with or without progestational agents have generally produced responserates similar to single agents. Cervix Cancer Incidence and Epidemiology Carcinoma of the cervix was once the most common cause of cancer deathin women, but over the past 40 years, the mortality rate has decreased by 50% dueto widespread screening with the Pap smear. In 2007, ~11,150 new cases ofinvasive cervix cancer occurred, and >50,000 cases of carcinoma in situ weredetected. There were 3670 deaths from the disease, and of those patients, ~85%had never had a Pap smear. Worldwide, cervical cancer is the third commonestcancer diagnosed, and it remains the major gynecologic cancer in underdevelopedcountries. It is more common in lower socioeconomic groups, in women withearly initial sexual activity and/or multiple sexual partners, and in smokers. Etiology and Genetics Venereal transmission of human papilloma virus (HPV) has an importantetiologic role. Over 66 types of HPVs have been isolated, and many are associatedwith genital warts. Those types commonly associated with cervical carcinoma are16, 18, 31, 33, 52, and 58, but 70% of cases are caused by HPV-16 and -18. These,along with many other types, are also associated with cervical intraepithelialneoplasia (CIN). The protein product of HPV-16, the E7 protein, binds andinactivates the tumor-suppressor gene Rb, and the E6 protein of HPV-18 hassequence homology to the SV40 large T antigen and the capacity to bind andinactivate the tumor-suppressor gene p53. E6 and E7 are both necessary andsufficient to cause cell transformation in vitro. These binding and inactivationevents may explain the carcinogenic effects of the viruses (Chap. 178). Screening and Prevention Vaccination against pathologic HPV appears to be an effective cervixcancer prevention strategy. Vaccines are made with inactivated virus-like particlesthat are noninfectious but highly immunogenic. The administration of aquadrivalent HPV vaccine against types 16, 18, 6, and 11 in a double-blind studyof 2392 women completely prevented infection with the virus, and no cases ofHPV-16–related CIN were seen in vaccinated women. This quadrivalent vaccinehas been approved for use by the FDA for patients 9–26 years old and must beadministered before HPV exposure to be effective. A second study with a bivalentvaccine (types 16 and 18) is underway. Both vaccines appear highly effective inpreventing their particular HPV infections, and protection has persisted for at least4.5 years after three injections over a 6-month period. Since not all oncogenicHPVs are targeted, patients will need to continue PAP smear surveillance. Uncomplicated HPV infection in the lower genital tract can progress toCIN. This lesion precedes invasive cervical carcinoma and is classified as low-grade squamous intraepithelial lesion (SIL), high-grade SIL, and carcinoma insitu. Carcinoma in situ demonstrates cytologic evidence of neoplasia withoutinvasion through the basement membrane and can persist unchanged for 10–20years, but most of these eventually progress to invasive carcinoma. The Pap smear is 90–95% accurate in detecting early lesions such as CINbut is less sensitive in detecting cancer when frankly invasive cancer or fungatingmasses are present. Inflammation, necrosis, and hemorrhage may produce false-positive smears, and colposcopic-directed biopsy is required when any lesion isvisible on the cervix, regardless of Pap smear findings. The American CancerSociety recommends that women after onset of sexual activity, or >age 20, havetwo consecutive yearly smears. If negative, smears should be repeated every 3years until age 65. The Pap smear can be reported as normal (includes benign,reactive, or ...