Challenges of Ovarian Cancer Screening

Developing an effective screening test for ovarian cancer in the general population poses many challenges. First, a distinct precursor lesion to ovarian cancer has yet to be identified. Therefore, ovarian cancer screening is limited to an attempt to detect early-stage disease. Initial laboratory data support a progression of early-stage disease to advanced-stage disease, which is important if screening is to be effective. Investigators have demonstrated that over 90% of sporadic ovarian cancers are clonal, and a similar pattern of abnormalities exists in high-grade stage I and stage III cancers.9-11

Investigators have also shown that up to 1.9 years may exist between the development of ovarian cancer and its clinical detection.12 However, the histologies of stage I ovarian cancer have a predominance of mucinous, clear cell, and endometrioid cancers, in contrast to advanced-stage disease, which has a predominance of serous cancers. In addition, population-based screening studies have demonstrated that the screen-detected stage I tumors have a predominance of borderline ovarian tumors, granulosa cell tumors, and germ cell tumors.13 Therefore, the question of whether a

Chapter 6 Ovarian Cancer Screening screening program would identify those invasive, poorly differentiated serous tumors when confined to the ovary is unknown.

Second, except for patients with an increased risk of ovarian cancer based on family history, identification of the appropriate groups in the general population to target for screening is problematic. The prevalence of ovarian cancer in the general population is 40 per 100,000 postmenopausal women. Therefore, the detection of early-stage ovarian cancer requires tests with high sensitivity and specificity because of the low prevalence of ovarian cancer in the general population. In general, a positive predictive value (PPV) of 10% has been proposed as a clinical cut-point for screening tests for ovarian cancer. Clinically, a PPV of 10% means that there will be 10 operations for every one case of ovarian cancer detected. Screening tests must, therefore, achieve a sensitivity of at least 75% and a specificity of greater than 99.6% to achieve a PPV of 10%.

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