PAP SMEAR

The Papanicolaou (Pap) smear has been the most effective screening method developed in the prevention of cancer since the 1941 publication of The Diagnostic Value of Vaginal Smears in Carcinoma of the Uterus by George Papanicolaou and Herbert Traut. The Pap smear is a screening test in which a film of exfoliating cells from the lower genital tract is placed onto a slide for staining and microscopic evaluation by a qualified cytotechnologist. The advantage of the Pap smear is in the early detection and ultimate treatment of premalignant changes of the cervix. As a direct benefit of this technology, the incidence of invasive cervical cancer in the United States has been reduced 50 percent and the mortality has been decreased by more than 70 percent.

In 1999, unfortunately, 12,800 new cervical cancer cases were diagnosed in the United States resulting in 4,800 deaths. Between 50 and 60 percent of U.S. women with cervical cancer have either never had a Pap smear or have received Pap smears at irregular intervals, while almost 6,000 of the women who develop cervical cancer annually have had recent Pap smear screening. In those countries without the use of routine Pap smear screening, cervical cancer remains the primary malignancy in women that results in mortality. Since the widespread acceptance of the Pap smear, a dramatic decline in the incidence and mortality of cervical cancer has occurred. Since 1986, however, the incidence has slightly risen. This underscores the success of the Pap smear, as well as its inability to detect 100 percent of the cases.

In 1984, the American College of Obstetrics and Gynecology recommended annual screening for most women. Initial screening should begin at age eighteen, or when the individual becomes sexually active. High-risk women—those with a history of early sexual activity and multiple partners—should be screened yearly. Those with only one partner and who have two successive negative annual Pap smears might be considered low-risk and be screened every one to three years.

The inability to detect the presence of a case of disease in the screened population results in a false-negative cytologic finding. In January 1999, the Agency for Health Care Policy and Research (AHCPR) released the Evaluation of Cervical Cytology. The AHCPR estimated the true sensitivity of the Pap smear to be only 51 percent, which means that the test correctly identifies only half the actual cases. More alarming, from 70 to 90 percent of those Pap smear cases with false-negative cytologic findings have no cytologic abnormality even when reviewed. Therefore, the major factor in improving the reliability of the Pap smear may be adequate specimen collection, preparation, and fixation. Prior to 1988, the quality of a Pap smear was not reported. Currently, if a smear is interpretable but the quality is poor due to poor handling of the specimen, blood, infection, cellular debris, or inadequate sampling, the sample is termed "satisfactory but limited by." If the smear is uninterpretable, the sample is labeled "unsatisfactory."

Newer technologies to improve the detection of cervical disease in a premalignant state are being developed. These technologies include an automated computerized analyzer to evaluate Pap smears; liquid-based, thin-layer cytology; and tests to identify the presence of the human papillomavirus (HPV), which has been demonstrated to be a major cause of cervical abnormalities.

The automated computerized analyzer scans Pap smear slides. Cells on the slides are digitized and processed through an image interpretation algorithm that has been developed to distinguish between normal and abnormal cells. This methodology reduces the human error that occurs in the current manual cytologic interpretation. In the liquid-based, thin-layer cytologic system, cells are collected from the cervix and transferred to a liquid fixative rather than to a glass slide. Once the sample arrives at the laboratory, the cervical cells are uniformly transferred to a filter. This technology eliminates air-drying artifacts and other factors that interfere with interpretation, thereby improving the detectability of abnormalities.

Although newer technologies are aimed at reducing the false-negative rate of the Pap smear, the cytotechnologist will always find cells with no distinguishing characteristics. These cells are termed "undetermined." The management of these "atypical cells of undetermined significance" (ASCUS) is a major clinical dilemma. HPV testing has been proposed as a method to resolve this problem. HPV-positive women are at risk for cervical cancer and therefore require further clinical evaluation. HPV-negative women can be followed with a repeat Pap smear in the future. The liquid-based, thin-layer method readily allows for HPV testing, another major advantage over the standard Pap smear.

Thomas J. Rutherford

(see also: Cancer; Cervical Cancer; Human Papillomavirus Infection; Laboratory Services; Screening; Secondary Prevention )

Bibliography

Boyes, D. A. (1981). "The Value of Pap Smear and Suggestions for Its Implementation." Cancer 48:613.

Burke, L. (1997). "Evolution of Therapeutic Approaches to Cervical Intraepithelial Neoplasia." Journal of Lower Genital Tract Disease 4:267.

Kurman, R. I.; Henson, D. E.; Herbst, A. I. et al. (1994). "Interim Guidelines for the Management of Abnormal Cervical Cytology." Journal of the American Medical Association 271:1866.

Manos, M. M.; Kinney, W. K.; Hurley, L. B. et al. (1999). "Identifying Women with Cervical Neoplasia: Using Human Papillomavirus DNA Testing for Equivocal Papanicolaou Results." Journal of the American Medical Association 281(17):1605.

National Cancer Institute (1989). "The 1988 Bethesda System for Reporting Cervical/Vaginal Cytological Diagnosis." Journal of the American Medical Association 262(7):931.

Sidawy, M. K., and Tabbara, S. O. (1993). "Reactive Change and Atypical Squamous Cells of Undetermined Significance in Papanicolaou Smears: A Cytohistologic Correlation." Diagnostic Cytopathology 9:423.