Cervical Tissue Changes May Explain False Negative Pap Smears

Writing in the June issue of the American Journal of Obstetrics & Gynecology, physicians at the Keck School of Medicine of USC and colleagues in California and Taiwan are the first to suggest this explanation for the frequent occurrence of false negative Pap smears.

Nationwide, physicians perform about 55 million Pap tests every year to look for cervical cells that are becoming abnormal, a precursor to cancer. To perform such a smear, a physician inserts a swab through a patient's vagina and scrapes the cervix to collect a sample of cells shed from its surface. Pathologists analyze the cells under a microscope to see if they are healthy.

Unfortunately, as many as four in 10 test results come back negative even when a biopsy shows abnormal lesions, and researchers have not been able to conclusively explain the inconsistencies.

A substance called E-cadherin may lie at the heart of the problem, says the study's lead author, Juan C. Felix, M.D., professor of clinical pathology and obstetrics and gynecology at the Keck School of Medicine of USC.

E-cadherin is a molecule that helps cells in the cervical tissue stick together, Felix explains. Normally, E-cadherin can be found in cervical tissue, except on the cervix's surface (the superficial epithelial layers). With no E-cadherin there, older cells can detach and slough away from the surface of the cervix, much like dead cells are regularly exfoliated from the surface of the skin.

However, the researchers found that in some cervical lesions, E-cadherin also was abnormally present in cells on the cervix's surface, keeping the abnormal epithelial cells anchored to the cells beneath them. Researchers theorize that this bond keeps these telltale aberrant cells from being collected during testing.

"I am convinced that the findings of this study are extremely important in understanding the biology of the false negative Pap smear," Felix says. "Never before have we seen such clear evidence that barriers to exfoliation are linked to false negative Pap smears." The team conducted the study with tissue samples from 25 women known to have cervical dysplasia (aberrant cells preceding cancer). Researchers analyzed whether the tissue samples showed normal distribution of E-cadherin, and then compared each tissue sample to its corresponding Pap smear result.