Because the prevalence of cancer in a screening population is low, the number of true-positive tests is usually low. If, as noted previously (see Figure 12.2), only a fraction of the true-positive tests lead to extended life, then the number of people who could, over a period of years, potentially suffer the harms of a false positive screening test so far outnumbers the people who may reap the benefits that weighing benefit and harm overall is not straightforward.

As noted previously, improving the sensitivity of a screening test may or may not lead to increased benefits from screening. However, improving the specificity of a screening test often leads to less harm because there are fewer false-positive tests. A smaller number of false-positive tests gives less opportunity for adverse psychologic effects of screening and for adverse effects of negative workups. Thus, improving the specificity of screening tests should often be a priority.

For most tests, whether screening or diagnostic, sensitivity and specificity are inversely related. Thus, increasing the specificity of a screening test may well reduce the sensitivity. The optimal screening test, then, may be neither the most sensitive nor the most specific test, but rather the test (or test cut-point) that gives the optimal trade-off between benefits and harms.

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