Screening by the Pap Test

Cervical cancer is the third most common cause of cancer death among women worldwide but it is almost always curable if detected early. Cervical cancer is largely controlled in high income countries through regular screening by the Pap test. Since its introduction in the 1950s, the Pap test has reduced cervical cancer deaths by 70% in the United States but it is a screening technique, not a diagnostic test. This means that it is used on a general population to detect possible abnormalities. An abnormal Pap result indicates that the test should be repeated or that a diagnostic test should be performed. The diagnostic test consists of a microscopic examination of the suspect tissue, either directly on the cervix (colposcopy) or in a laboratory using tissue samples collected from the cervix (biopsy). The Pap test will give many ambiguous results and will miss true abnormals depending both on the proficiency of the examiner and the reliability of the lab analysis. Recent reviews have concluded that 40-47% of women who developed invasive cervical cancer have had adequate Pap screening histories within five years of detection. Some of these women had failed to follow up on an abnormal smear result while many had a history of negative smear results. Many later stage abnormalities are missed by the Pap test. In a survey of healthcare-insured women with invasive cervical cancer who had a Pap test within the previous 36 months, 71% of the cases were attributed to Pap test detection failure. Although cervical cancer is slow to develop, usually taking ten to fifteen years to progress from a localized abnormality to invasive cancer, there

is a small subset of rapidly progressive cervical cancers which are diagnosed within three years of a confirmed negative Pap test. These tumors occur in younger women with higher socioeconomic status. One third of these cancers originate in the cervical canal, which emphasizes the need for a complete cervical sampling. Several studies show that general practitioners performing Pap tests fail to collect cell samples from the endocervical

canal about 30% of the time.

More than fifty million women a year in the United States have Pap tests. According to the American Cancer Society, about three and a half million of these women get abnormal results and only 11,200 have cancer (see reference). In addition, about 10 percent of women with an obvious visible cancer have a normal reading on the Pap test. One million of the abnormal Pap smears are found to be low-grade tissue changes, often leading to colposcopy, biopsy, and office visits. The average cost of the standard management of such cases is more than $1,500 each. Especially alarming to about two million women each year is a Pap result of ASCUS (Atypical Squamous Cells of Undetermined Significance). This interpretation of a slide varies greatly from laboratory to laboratory. 10% to 15% of ASCUS readings eventually progress to high grade lesions, less often to invasive cancer. A repeat Pap test is indicated but since there is no record where on the cervix the initial sample originated or whether the entire cervix is well sampled by the second test, this repeat test may not resolve the ambiguity. Vaginitis or common infections frequently cause this type of Pap smear. The turnaround time for the laboratory analysis in the United States is about two weeks.

In the most extended survey to date, the conventional Pap test accurately detected malignant and pre-malignant lesions in only 51% of patients tested.  However, because cervical tissue changes are usually slow to progress, decades may pass from the introduction of the cancer-causing virus to the cervix before the development of invasive cancer.  The long development time of most versions of the disease has conferred a degree of adequacy on the Pap test.  Even with the low sensitivity of a single Pap test to detect serious disease, repeated testing at regular intervals throughout a woman’s life has a high likelihood of identifying those at risk for cancer. Awareness of Pap test deficiencies and a general movement to take personal control of health issues are leading women to seek more reliable test methods.

Automated cell preparation techniques can eliminate some of the Pap test errors by removing mucus and blood and producing a uniform cell distribution on a glass slide for microscopic examination.  However, the lack of feedback to the practitioner on thoroughness of technique remains an issue.  In low income countries, this collection factor and the variability of laboratory analysis of the slides combine with problems of access, cost, and susceptibility to allow this disease to kill women in large numbers.  Non-white South African women, for example, die of cervical cancer more than any other cancer.  Furthermore, the benefits of immediate diagnosis could allow mobile clinics in such locales to function as treatment centers without the need to return and locate women in rural areas for treatment or a retest after an ambiguous Pap test lab report.