Improving the Pap smear-the single most successful cancer test ever developed-is a tall order.
But a handful of companies, led by Cytyc Corp., Boxborough, Mass., have finally brought to market a host of new technologies to sharpen the venerable Pap smear. Clinicians credit the test, named after its inventor, George Papanicolaou, with virtually eliminating deaths from cervical cancer among women who are regularly screened.
Now, as these companies put their proverbial feet in hospitals' doors, they must convince healthcare executives and payers that the new techniques are worth their higher cost.
That's a challenge because for almost 50 years the economical Pap smear has rightfully been the gold standard in spotting cervical cancers while they can be successfully treated. "There's never been a cancer screening test that's done a better job than the Pap smear," says Kenneth Noller, M.D., professor of obstetrics and gynecology at University of Massachusetts Medical School in Worcester. "Mammography is good, but it's not even close."
More than 50 million Pap smears are performed annually, with prices ranging from $6 to $30, according to Cytyc, whose refined preparation of cervical-cell samples adds $9.75 in direct supply costs alone for each test performed.
Since Pap smear screening became widespread in the late 1940s, cervical cancer death rates have dropped more than 70%, federal researchers say. And the nearly 5,000 deaths still attributed to cervical cancer each year could be all but eliminated if screening were extended to poor women who are often overlooked, a National Institutes of Health consensus panel found last year.
Years in the making, several of the technologies are only now causing a commercial splash after recently getting the Food and Drug Administration's marketing go-ahead. Last fall, for instance, the FDA gave Cytyc the green light to say its ThinPrep test is "significantly more effective" than the regular Pap smear.
On a different tack, NeoPath, Redmond, Wash., and Neuromedical Systems, Suffern, N.Y., make computerized readers that automate Pap smear interpretation. Currently limited by the FDA to use in laboratory quality control and as second-line readers of ambiguous clinical samples, many experts nonetheless say that within a few years automated tests will likely overcome technical and regulatory hurdles to replace humans as the primary interpreters of Pap smears.
Finally, Digene Corp., Beltsville, Md., has developed a DNA test, approved by the FDA last year, that detects a virus linked with cervical cancer for use in sorting out whether women with inconclusive Pap smears have the disease.
Among the new-wave technologies, Cytyc's is the readiest for prime time.
Cytyc refined the preparation of the Pap smear slide, reducing the likelihood of later errors. That promises savings because equivocal Pap smears lead to repeat tests or more complicated patient exams.
In the classic Pap test, a doctor uses a swab to collect cervical cells and smears them onto a glass microscope slide where they are stained to ease later reading by a technologist. Inelegantly but accurately named, the Pap smear preparation invariably stacks cervical cells one on top of another. And the cells are frequently obscured by blood or mucus that contaminate the sample.
"The conventional test is like looking at a coin on the bottom of a swimming pool and trying to determine whether it's a nickel or a quarter or a dime," explains William Dupree, M.D., medical director of cytology at Health Network Laboratories, an affiliate of Lehigh Valley Hospital, Allentown, Pa.
As a result, conventional Pap smears, whose interpretation is almost as much art as science, are inconclusive about 5% of the time.
By using Cytyc's ThinPrep technology, the doctor puts the cervical cell sample in liquid suspension that is filtered before a thin film is applied to the glass microscope slide. The technique results in a one-cell layer free of debris. That reduces indeterminate results and cuts the time to analyze each slide by as much as a third, Dupree says.
Cytyc got a commercial boost in March when Laboratory Corporation of America became the first major clinical laboratory to make the ThinPrep Pap smear technique nationally available. And last November, United HealthCare Corp., a Minneapolis-based managed-care company, publicly said it would reimburse for the Cytyc test.
"It at least doubles or triples the (Pap smear) price," says James Cross, M.D., vice president and national medical director for United HealthCare. But the scientific literature supports Cytyc's claims that its test is superior and is associated with better outcomes, he says. "You should put your money where the quality of care is," he adds.
An early adopter of the Cytyc method, Lehigh Valley's Dupree says his lab's results have exceeded admittedly high expectations. Among the six hospitals the lab serves, Lehigh Valley has already switched to ThinPrep as its in-house standard of practice, Dupree says. Since instituting the Cytyc method, Lehigh Valley's rate of Pap smears with suspicious but undetermined significance (the bugaboo of the standard test) has dropped to 0.076% from 4.9%, Dupree says.
That has lowered the need for repeat Pap tests and more costly clinical examination and testing to rule out cancer, he adds.
"From the scientific, clinical and laboratory standpoints it has been a great success," Dupree says. "If there is a downside it's that we are currently in a transition period (waiting) for third-party payers to pay for the test."
Dupree says Lehigh Valley will stick by the ThinPrep test. The same clinical evidence that convinced him will eventually sway payers, he says.