To be suitable for screening, a disease must have a significant prevalence and be a significant cause of mortality. There must be a preclinical phase that can be detected, and the disease must be amenable to therapy. The screening test itself must have sufficient specificity, sensitivity, and positive predictive value (PPV) to be effective, and it must be cost-effective. In ovarian cancer, if one assumes a prevalence of 50/100,000, a test with 99 percent specificity and 100 percent sensitivity would yield only 1 in 21 women with a positive screen actually having the disease (i.e., PPV = 4.8 percent). It must be noted that currently available tests do not attain the aforementioned high level of sensitivity.
Three screening tests are in general use: bimanual rectovaginal pelvic examination, CA 125, and transvaginal ultrasonography (TVS). CDI is also being investigated in some centers regarding its role as an adjunct to TVS. Historically, rectovaginal pelvic examination has been the only method used to detect ovarian cancer at any stage. Although pelvic exam is an important part of routine gynecologic care, it has inadequate sensitivity and specificity as a screening test for ovarian cancer. CA 125 is an antigenic determinant detected by radioimmunoassay. It is elevated in 80 percent of epithelial ovarian cancers. However, only half of the patients with stage I cancers have elevated levels. Because detecting early disease is the goal of screening, CA 125 alone is not an adequate screening test. In addition, a significant proportion of healthy women and women with benign disease have elevations in CA 125 resulting in an unacceptably low specificity for this test.
Transabdominal ultrasound and TVS have been studied as noninvasive screening tools. TVS is currently the preferred modality. However, specificity of ultrasonography is not adequate for use as a single screening modality. For example, in a representative study, 5,479 women, 96 percent of whom were 45 years of age or older, were screened using abdominal ultrasound, and there were 338 positive screens. This resulted in exploratory laparotomy in 326 women, and five stage I ovarian cancers were found. Three had borderline histology, and, therefore, diagnosis at a later date may not have affected survival. Sixty-five laparotomies were performed for each case of ovarian cancer detected. In a similar screening study of women with a family history of ovarian cancer, 1,601 pre- and postmenopausal women were screened using TVS. Sixty-one operations detected five stage I ovarian cancers, three of which were of borderline histology. The combination of CA 125 screening and TVS significantly improves the specificity of screening and has reduced the proportion of women requiring unnecessary surgical intervention. However, there is a potential for significant anxiety related to abnormal screening test results as well as morbidity and even mortality from resultant surgical procedures in women with no significant pathology, which may outweigh any potential benefits.
