This section of the chapter reviews the Pap (Papanicolaou) smear and adjunctive technologies that can be used to improve the accuracy of detection of cervical cancer. Alternative screening strategies, such as testing for human papillomavirus (HPV), testing for molecular biomarkers (e.g., fluorescent immunochemical labeling) (Patterson et al., 2001), and cervicography, are not reviewed.
A fundamental difficulty in the evaluation of screening tests for cervical cancer is the lack of reliability of the reference standard: cytological and histological interpretation of cervical specimens. Even among expert pathologists, interobserver variations in interpreting atypical squamous cells of undetermined significance and low-grade squamous intraepithelial lesions are substantial (Stoler and Schiffman, 2001).
A principal limitation of the Pap smear is its poor sensitivity. A recent meta-analysis calculated that the sensitivity and specificity of the Pap smear were 51 percent (95 percent CI, 37 to 66 percent) and 98 percent (95 percent CI, 97 to 99 percent), respectively (Agency for Health Care Policy and Research, 1999). False-negative results are due to both sampling errors (in obtaining the sample from the cervix and in cell collection and cell preparation techniques) and interpretation errors, with the latter accounting for about one-third of false-negative results. Efforts to improve sensitivity have included the introduction of the cytobrush, broom brushes, and plastic spatulas to gain better access to the squamocolumnar junction and endocervix. Other measures have been programmatic, such as federal legislation mandating manual reexamination of a portion of negative slides under the Clinical Laboratory Improvement Amendments.
New technologies have been introduced in recent years to improve the sensitivity and specificity of screening. These include thin-layer cytology (ThinPrep), computerized rescreening neural network technology (Papnet), and algorithm-based computer rescreening (AutoPap). Although these innovations offer the promise of improving the sensitivity and specificity of screening, a systematic review by the Agency for Health Care Policy and Research concluded that existing data for making comparisons were inadequate to reach conclusions about their incremental impacts on health outcomes (Agency for Health Care Policy and Research, 1999). Coupling Pap smears with screening for HPV infection has also been advocated, but