A jungle of healthy cells on a Pap smear may hide amid blood and mucus a few ominous distortions that portend a brutal death from cervical cancer.
Interpreting a Pap smear is something worse than the proverbial search for a needle in a haystack. Technologists, hunting for subtle clues on dozens of slides day after day, may miss as many as half the invasive cervical cancers, studies show. Women die who might have lived if medicine had better screening tools.
A few small companies are building safety nets to back up the imperfect Pap smear. Their products, in various stages of the Food and Drug Administration approval process, are triggering clinicians' interest. Some developing technologies include computers to seek out suspicious cells, systems to prepare better slides and lights to illuminate the cervix.
U.S. laboratories will read more than 70 million Pap smears this year, and thousands of women will endure radiation, surgery or chemotherapy to cure their cancer. About 4,600 will die from the disease.
Their numbers include the highly publicized case of 29-year-old Karin Smith. Her death in March led to murder charges against Chem-Bio Corp., an Oak Creek, Wis., laboratory that misread her Pap test (April 17, p. 6). Prosecutors say the firm was reckless and its technician had been reading more smears than professional standards recommend to achieve sufficient accuracy.
The case is one of the rare instances when criminal charges have been brought against a provider for a medical mistake, but public outcry following seemingly preventable tragedies is common in the field of cytopathology.
For example, in May 1993 federal and state officials ordered Newport (R.I.) Hospital to review about 20,000 Pap smears when a woman died of cervical cancer after years of negative tests (Oct. 4, 1993, p. 17).
"Every single laboratory, including every good, well-known laboratory, has false negative Pap smears sitting in their files," said Mary Nielsen, M.D., a pathologist in Wichita, Kan. "Every Pap smear has thousands and thousands of cells, and each cell has to be examined for abnormalities. It requires a kind of constant attention."
Public pressure to adopt new technology is great because cervical cancer, if caught in time, is curable. For laboratories, however, the decisionmaking will be complex. Federal law already requires laboratories to monitor the quality of their work. Meanwhile, they face extraordinary pressures to cut costs. Reading Pap smears, for example, is no longer a profitable business now that reimbursement ranges from $7 to $10 per smear. New technologies are likely to add costs to the tests.
Such products are designed to make up for a lapse in the technologist's attention. Take the computer system known as PapNet. Its maker-Suffern, N.Y.-based Neuromedical Systems-submitted clinical data to the FDA last fall. Its application for marketing approval is under review. Other companies also are at work on computer-aided screening, but no system has FDA approval.
PapNet is a neural network, a computer system that emulates the structure of the human brain. Such systems are expert at recognizing patterns. They learn the characteristics of a series of examples-in this case, the warning signs of cancer-but, unlike traditional computer systems, can apply their knowledge to new cases. PapNet should be able to identify an abnormal cell even though it's never seen that particular abnormality before.
Laboratories send slides to PapNet's central computer in Suffern via express mail. The computer identifies the 128 "most abnormal" cells on a slide, which is then returned to the laboratory. There, a technologist diagnoses abnormalities on a high-resolution video monitor. The process adds about $10 to the cost of the test, Neuromedical Systems said.
Other companies are trying to simplify the review of Pap smears by cleaning them up. Marlborough, Mass.-based Cytyc Corp. is running clinical trials on its ThinPrep Processor, a device that hasn't yet been priced. After brushing the cervix for cells, a clinician stirs the brush into a small vial of buffered alcohol solution. A machine gently rotates the vial to dissolve blood and mucus, and a vacuum-like device then sucks cells onto a membrane. It is pressed against a slide for an even layer of cells.
One product recently put on the market is called Pap Plus Speculoscopy, made by Torrance, Calif.-based Trylon Corp. The procedure is performed in addition to a Pap smear. In it, a clinician examines the cervix for lesions that might indicate cancer. A blue-white light shows lesions more clearly on a cervix magnified by a small telescope. The single-use product costs about $10. It's been sold through Upjohn Co. since last October.
Already, HMOs and other providers are trying to see if Pap Plus Speculoscopy lives up to its claims. Rush Prudential Health Plans in Chicago, for example, recently bought 200 lights so it can see if they result in better diagnoses and fewer Pap smears.
Good technology, however, is no replacement for quality controls. "You can have the best technology in the world, but if the patient isn't told the results of the test, you're really not staying on top of things," said Frank Campanella, supervisor of gynecology operations at Rush's central clinic.