Kaiser Permanente Study Shows Why Pap Smears Can Fail to Detect High Grade Cervical Cancer Precursors

A Kaiser Permanente study of women with abnormal cervical cells but whose Pap smears were false-negative showed altered distribution of the molecules that bind cells together affecting whether the cells would be shed and captured during the Pap smear. This condition may also be responsible for false negative Hybrid Capture II (HC II) test results in women who also may have had possibly pre-cancerous cervical cells. The study is published in the October edition of the Journal of Lower Genital Tract Disease.

“We are very interested in unraveling why some women with abnormal lesions on their cervix can become pre-cancerous or cancerous and yet remain undetected when we use tests relying on cells being shed and collected for analysis,” said Neal Lonky, MD, MPH, member of the Board of Directors of the Southern California Permanente Medical Group. “One theory is that some women’s lesions that are precursors to cancer are `stickier’ than others and do not shed their cells as easily.”

The 4600 women screened for the study were examined using a colposcope, an instrument that shines light on the cervix and magnifies the view for the doctor. “In this study, we investigated the a correlation between the distribution of adhesion molecules in new and abnormal growths on the cervix known to contain human Papillomavirus (HPV) and the ability of the HC II test for HPV-DNA to identify neoplastic virus in shed cells from patients with atypical Pap smear results,” said Lonky.

High risk human Papillomavirus (HPV) is associated with the development of cervical cancers and has led to the development of HPV-DNA testing to augment finding high-grade squamous intraepithelial lesions, established cervical cancer precursors.

Altered adhesion molecules are molecules that exist between cells that bind them to other neighboring cells and tissues. Their distribution in cervical tissue may interfere with the normal cell maturation and shedding process in women with cervical cancers and cause false negative test results.

“HPV infection is required for the development of cervical dysplasia, and should be found in pre-cancerous cells on the surface of the cervix. This test is useful because of its ability to detect the presence of HPV-DNA in the collected sample from each women studied,” said Lonky. “It has been presumed that if there is HPV in the tissue, cells containing viral DNA and RNA are freely released through the natural process of cell turnover. This is one of only a few studies which question if the cells collected from the surface of tissues truly reflect the underlying health or pathology of the tissues.”

In addition to Lonky, the study’s other authors are Juan Felix MD, University of Southern California; Girma Wolde Tsadik PhD, Kaiser Permanente Research and Evaluation; and Stewart Lonky MD, Trylon Corporation.

Kaiser Permanente is America’s leading integrated health plan. Founded in 1945, it is a not-for-profit, group practice prepayment program headquartered in Oakland, CA. The Kaiser Permanente Southern California Region has more than 3.1 million members. They are cared for by the 3,600 physicians of the Southern California Permanente Medical Group (SCPMG) and 47,300 Kaiser Foundation Health Plan and Hospitals and medical group employees. The Kaiser Permanente Southern California Region is served by 11 major medical centers.

www.kaiserpermanente.org

Neal M. Lonky, MD, MPH, is affiliated with Trylon Corporation as well as a previous inventor of technologies, co-founder prior to joining the Southern California Permanente Medical Group in 1986. No products other than Hybrid Capture II were evaluated in this study.