The science behind the effectiveness of in vivo screening

Meta-analyses of studies examining the sensitivity of the Papanicolaou (Pap) smear have revealed that up to 50% evade detection by a single Pap test. Liquid-based preparation techniques have improved the false-negative rate; however, an apparent irreducible 20% false-negative rate still exists. Emerging data now show that aberrant expression of adhesion molecules is seen in a subset of dysplastic lesions of the cervix that fail to be detected by the Pap test, whereas normal patterns were observed in lesions that were Pap positive. These data have led to the hypothesis that there is a subset of lesions where dysplastic cells fail to exfoliate. In this model, the Pap test is extremely unlikely to detect such "nonshedding" lesions as the cells resist being harvested by the collection devices. However, despite their nonshedding behavior, these lesions remain readily identifiable by visual inspection of the cervix after application of acetic acid.