Mike F. Janicek

Cervical Cancer: Prevention, Diagnosis, and Therapeutics

Cervical cancer is a leading cause of cancer deaths in women worldwide. Because of its association with human papilloma virus infection, as well as the ability to screen for premalignant stages of the disease, it is now largely a preventable disease. This article describes the molecular basis for cervical cancer, and presents a clinical overview of current treatment approaches and technological advances, emphasizing the unique aspects of this viral disease as it relates to the immune system and vaccination or other immunotherapeutic strategies.

Epidemiology and biology of cervical cancer

Worldwide, cancer of the cervix is the second leading cause of cancer death in women: each year, an estimated 500,000 cases are newly diagnosed. Among populations, there are large differences in incidence rates of invasive cervical cancer: these reflect the influence of environmental factors, screening Papanicolaou (Pap) tests, and treatment of pre-invasive lesions. The high-risk human papillomavirus (HPV) subtypes 16, 18, 31, 33, and 51 have been recovered from more than 95% of cervical cancers. We have made great strides in understanding the molecular mechanism of oncogenesis of this virus, focusing on the action of the E6 and E7 viral oncoproteins. These oncoproteins function by inactivating cell cycle regulators p53 and retinoblastoma (Rb), thus providing the initial event in progression to malignancy. Cervical cancers develop from precursor lesions, which are termed squamous intraepithelial lesions (SIL) and are graded as high or low, depending on the degree of disruption of epithelial differentiation. Viral production occurs in low-grade lesions and is restricted to basal cells. In carcinomas, viral DNA is found integrated into the host genome, but no viral production is seen. The well-defined pre-invasive stages, as well as the viral factors involved at the molecular level, make cervical carcinoma a good model for investigating immune therapeutic alternatives or adjuvants to standard treatments.

The national cancer data base report on ovarian cancer

Background. Reports generated from the National Cancer Data Base (NCDB), a joint project of the American College of Surgeons Commission on Cancer and the American Cancer Society, have described trends in demographics, stage, treatment patterns, and survival for a variety of cancers. In this report, the most current (1991) data for ovarian cancer are presented and include some comparisons with 1985/1986 data.

Tumor angiogenesis as a prognostic factor in ovarian carcinoma

The growth of a malignant tumor requires the formation of new capillaries. Quantification of these microvessels is difficult. The purpose of this study was to establish an objective technique for quantifying angiogenesis and to evaluate whether microvessel quantity may predict tumor aggressiveness in patients with ovarian carcinoma.

Ovarian carcinoma: A review of the significance of familial risk factors and the role of prophylactic oophorectomy in cancer prevention

Women with a family history of ovarian cancer are at increased risk of ovarian cancer. Prophylactic oophorectomy (PO) remains the only effective method of ovarian cancer prevention. This study reviewed current data on the significance of family history and how prophylactic oophorectomy should be used in different risk groups. Approximately 7% of ovarian cancer patients have a positive family history of whom 3–9% may eventually manifest certain hereditary cancer syndromes. Women in direct genetic lineage of family cancer syndromes have up to a 50% lifetime risk of ovarian cancer. Because of the high risk, PO is indicated for women with familial cancer syndromes after childbearing or between the ages of 35–40 at the latest. The majority of women with a positive family history of ovarian cancer do not have one of the recognized syndromes. Women with one or two affected relatives have an increased lifetime risk of ovarian cancer from a baseline of 1.6 to 5–7%. This risk is not high enough to warrant PO for a large number of women. After being properly informed, the patient still chooses surgical prevention, she then receives PO. For women without a family history of ovarian cancer, the role of PO remains controversial. Assuming an annual incidence of 22,000 new cases of ovarian cancer, it is estimated that at least 1000 may be prevented if PO is diligently practiced during hysterectomy. Despite ovarian and breast cancer prevention, PO would lead to shorter life expectancy if estrogen therapy compliance were less than perfect. Thus, the decision on PO as a concurrent procedure should depend on the individual patient and her ability to comply with lifelong estrogen therapy. Cancer 1994; 74:545‐55.