Pap Test Accuracy Screening for cervical cancer precursors using exfoliative cervico-vaginal cytology, the Pap test was successful in reducing the incidence of cervical cancer by 79% and the mortality by 70% since 1950 (50). However, 20% of women in the United States do not undergo regular screening and have not had a Pap test in the previous 3 years. The annual incidence rate dropped from 8 to 5 cases per 100,000 women, so approximately 8,200 women per year are diagnosed with cervical cancer (50–52). Some cases of cervical cancer continue to occur in patients who have regular Pap tests. A literature review of cervical cytology testing techniques was conducted by the Agency for Healthcare Research and Quality (53). The conclusion was that the sensitivity of conventional cytologic testing in detecting cervical cancer precursor lesions was 51%, with an estimated false-negative rate of 49%. In three reviews of the accuracy of cervical cytology assessment, the sensitivity of the Pap test in detecting CIN 2 or 3 ranged from 47% to 62% and the specificity ranged from 60% to 95% (54–56). Nearly 30% of new cancer cases each year occur among women who underwent Pap testing. Errors of sampling, fixation, interpretation, or follow-up may be responsible for the missed cases (57). Prior overestimates of Pap test sensitivity of approximately 80% led to erroneous recommendations of screening frequency (58).
The conventional Pap test technique needs to be improved in order to reduce false-negative errors. Sampling errors occur because a lesion is too small to exfoliate cells or the device did not pick up the cells and transfer them to the fixation media. Historically, preparation errors occurred because of poor fixation on the glass slide, leading to air drying and its consequences for interpretation. The slide preparations could be too thick and obscured by vaginal discharge, blood, or mucus. These problems were obviated with the widespread utilization of liquid-based media. Interpretive errors may still occur when the slide contains diagnostic cells that the screening technician or automated detection device fails to identify.
The ubiquitous use of liquid-based medium to collect the cytologic sample and preserve the collected cervical cells significantly decreased specimen sampling and preparation errors. With this technique, liquid samples are processed to provide a uniform, thin layer of cervical cells without debris on a glass slide. The Agency for Healthcare Research and Quality assessment of liquid-based cytology improved the sensitivity of the Pap test to the stated goal of 80%. The cell sample is collected with an endocervical brush used in combination with a plastic spatula or with a plastic broom. The sample is rinsed in a vial containing liquid alcohol-based preservative. With this technique, 80% to 90% of the cells are transferred to the liquid media, as compared with the 10% to 20% transferred to the glass slide with conventional cytologic testing. Using liquid-based media eliminates air drying. The cells are retrieved from the vial by passing the liquid through a filter, which traps the larger epithelial cells, separating them from the small blood and inﬂammatory cells. This process yields a thin layer of diagnostic cells properly preserved and more easily interpreted by the cytologist. This technique reduces by 70% to 90% the rate of unsatisfactory samples encountered with conventional cytologic testing (59). Liquid-based cytology is commonly performed by most of the laboratories in the United States.
Another technology approved by the FDA for primary screening and rescreening samples of cervical cytology initially interpreted as normal is the automated image-guided slide screening system. This technique uses an automated microscope coupled to a special digital camera. The system scans the slide and uses computer imaging techniques to analyze each field of view on the slide. Computer algorithms rank each slide on the probability that the sample may contain an abnormality. The selected slides are reviewed by a cytotechnologist or a cytopathologist. This technique reduced the false-negative rate by 32% (60).