To determine the sensitivity and specificity of the Pap smear, both a test threshold (i.e., the point at which the test will be considered to be "positive") and a reference-standard threshold (i.e., the point at which the reference standard is considered to be "positive") must be defined. In practice, ASCUS is often used as the test threshold, and CIN 1 is often used as the reference threshold. This combination gives a sensitivity of about 68% and a specificity of about 75%. A more appropriate test threshold may be LSIL, with a reference threshold of CIN 2-3. This combination gives a sensitivity of 70% to 80%, with a specificity of about 95%.
One important factor in the accuracy of the Pap test is the adequacy of the specimen obtained. Adequate training and using techniques such as the cytobrush may improve sensitivity.
New Screening Technologies
Newer techniques that employ liquid-based cytology (e.g., ThinPrep) have been developed to improve the sensitivity of screening. As with the Pap test, the optimal studies to determine the sensitivity and specificity of these technologies have not been done. Some less-than-optimal studies show that sensitivity is modestly higher for detecting any degree of CIN, with modestly lower specificity.[38,39] One careful study, however, showed that conventional Pap testing was slightly more sensitive and specific than liquid-based cytology.
The evidence is also mixed about whether liquid-based techniques improve rates of test adequacy.[38,39] One advantage of liquid-based cytology is that HPV testing can be done on the same preparation; one disadvantage is that liquid-based approaches are more expensive than conventional Pap testing. No study has examined whether liquid-based cytology actually reduces the number of women dying of cervical cancer compared with conventional Pap testing.
Screening Women Who Have Had a Hysterectomy
Women who have had a hysterectomy with removal of the cervix for benign disease rarely have important abnormalities found on Pap testing. Several studies have shown that the rate of high-grade vaginal lesions or vaginal cancer is less than 1 in 1,000 tests;[41,42] no study has shown that screening for vaginal cancer reduces mortality from this rare condition.
Because cervical cancer is slow growing, considerable uncertainty surrounds the issue of the optimal screening interval. The most direct evidence about this issue comes from a prospective cohort analysis of a randomized controlled trial. Among 2,561 women (mean age 66.7 years) with normal Pap tests at baseline, 110 had an abnormal Pap test within the next 2 years. No woman was found to have CIN 2-3 or invasive cancer, and only one had CIN 1-2. Thus the positive-predictive value (PPV) of screening 1 year after a negative Pap test was 0%; after 2 years, the PPV was 0.9%. The authors concluded that Pap tests should not be repeated within 2 years of a negative test.