The ultimate goal? It depends.

In this era of rapid scientific advancement, it is hard to imagine a medical technology that has essentially remained unchanged for more than 50 years. Until recently, the Pap smear. the screening method for cervical cancer, had stood this test of time. A yearly Pap smear has been credited with a 70 percent reduction in cervical cancer by identifying it in its earliest and most treatable stages. The incidence of invasive cervical cancer has declined by 36 percent since 1963 and, in 1995, it was estimated that only 4,800 Americans would die from cervical cancer.[1]

By all accounts, Pap smears have been the most effective cancer preventive health measure ever promoted. Both the disease and the procedure fit all the requirements for a successful screening test. Cervical cancer is considered a slow-growing disease with recognizable premalignant stages. The Pap smear is easy to perform, causes minimal discomfort to the patient, and is relatively inexpensive. Nevertheless, there are numerous flaws in the screening method, including barriers to access, inadequate sampling of the cervix, unrepresentative transfer of the collected material to the slide, and inaccurate interpretation by the cytotechnologist and pathologist. The knowledge that cervical cancer should be a preventable disease has provided the impetus to improve the Pap smear.

Now, for the first time in 50 years, two new computerized technologies are available that could change the way Pap smears are interpreted. Of course, these new innovations come at a price, perhaps doubling or tripling the cost. Cervical cancer screening is the highest volume screening program in the country, with about 50,000,000 Pap smears performed annually. By one estimate, the new technologies could add $1 billion per year to the total price tag.[2] The health policy issue is whether these innovations address the limitations of cervical cancer screening programs in an efficient way.

The AutoPap and Papnet systems were approved by the FDA in the latter half of 1995. Both computerized systems are intended to reduce the false negative rate in Pap smears. Interpreting Pap smears is a highly labor-intensive and complicated process. Conservatively, each Pap smear contains from 50,000 to 150,000 cells and thus, in the average five minutes allotted to screening each one, a cytotechnologist must make tens of thousands of decisions regarding the malignant potential of individual cells. In addition, approximately 95 percent of Pap smears will be normal, and screening them has been likened to searching for a needle in a haystack. It is not surprising that some abnormalities will be missed, particularly if there are only a small number of abnormal cells, leading to a false negative report.

Estimates of false negatives rates vary, but generally range from 10 to 30 percent. While on the surface of it, this false negative rate seems alarmingly high, yearly Pap smears should ensure that a timely diagnosis can still be made, given the slow progression of most cervical cancers. For example, assuming a false negative rate of 10 percent, the likelihood of four sequential falsely negative Pap smears would be 0.0001, representing a cumulative sensitivity of 99.9 percent. Nevertheless, there has been a focus on the false negative rate, in part fueled by adverse publicity and legal liability related to missed diagnoses. The AutoPap and Papnet were developed in response to these concerns.

Both the AutoPap and Papnet are computerized rescreening systems; they provide another opportunity to find the needle in the haystack. In 1988, the federal government mandated, through the Clinical Laboratory Improvement Act (CLIA), a 10 percent random rescreening rate. Some have argued that it would make more sense to adopt a targeted rescreening program of those slides most likely to be abnormal. The AutoPap system is a targeted rescreening program that scans slides to select those 10 percent of cases (or a higher percentage if desired) most likely to contain abnormal cells. The Papnet system is different in that it is used as a 100-percent rescreening tool. Slides are scanned by a computerized system that automatically selects 128 images that contain the most abnormal-appearing cells. These images are then projected on a video screen to be reviewed by a cytotechnologist, who can then choose which cases should be rescreened manually. Both techniques are associated with a reduction in the false negative rate.

A public health or individual patient care issue?

Assessing these technologies represents a complicated health policy issue. The resolution will depend on whether it is viewed from the public health or an individual patient care perspective. From a public health policy outlook, the current use of computerized rescreening would not be the most efficient use of finite resources. Since there are deficiencies in a cervical screening program, reducing the Pap smear false negative rate, unfortunately, will probably have a minimal effect on reducing mortality - the ultimate public health goal. It is estimated that only 3 percent of preventable cervical cancer deaths can be traced to laboratory error.[3]

It is true that the cost effectiveness of Pap smears represents a relative bargain. The Congressional Office of Technology Assessment estimated that Pap screening costs $1,666 per-life-year saved, compared to $13,200 per-life-year saved for mammography, and $35,054 for annual stool occult blood testing. Therefore, even if the cost of Pap screening increased 10- to 20-fold, its cost effectiveness would still be comparable to other commonly used screening tests. However., if the additional investment does not result in a significant reduction in mortality, these dollars would be wasted. The sad fact is that most women who die from cervical cancer have not had regular Pap tests. Thus, the biggest reduction in mortality rate should come from increased education and access to regular Pap testing.

The analysis is entirely different when cast as an individual patient care issue. Here the patient and physician, who serves as her advocate, want to use the best screening method. The goal is not how to best allocate resources to improve the health of the overall population, but instead how to get the best care for the individual patient. In this context, reductions in the false negative rate of Pap smears become more compelling. Convincing a patient that a 10- to 30-percent false negative rate of conventional Pap testing is a trivial issue, since any potential cancer would most likely be picked up in the ensuing three years, would lie a challenging educational effort - especially among women who are overwhelmed with the threat of cancer in general and have been educated about the importance of early diagnosis, particularly for breast cancer.

Pap testing was initially a public health recommendation, but it is funded primarily through employee-sponsored health plans, whose agenda is largely the health of its employees and not the health of the overall population. Thus, in its implementation, Pap testing has been converted from a public health issue to one of individual patient care, with a corresponding change in agendas. While some would argue that our health care resources are better spent in improving access to Pap smears to underserved women, resources for this type of initiative would largely come from the public health budget.

An additional factor to consider is the medical liability issue. False negative Pap smears are a frequent cause of lawsuits, based both on real laboratory error, but also on the misperception that Pap smear screening is an exact science and that any false negative test may be the result of negligence. In considering these cases, courts and juries would take the patient perspective and not the public health view. Therefore, techniques that may reduce the false negative rate of Pap screening may also reduce exposure to liability.

In addition, if automated rescreeners are rapidly adopted, they will become the new standard of care for Pap screening and laboratories may appear negligent if they do not use these technologies. It should be pointed out that 100 percent manual rescreening of all Pap smears has always been theoretically available and is, in fact, estimated to be a more effective and less costly method of reducing false negative results than the current use of automatic rescreeners.[3] However, this approach has not been pursued, due either to the high cost of the additional personnel required, or the shortage of available cytotechnologists, or the lack of a mandate in terms of CLIA requirements.

The advent of two new sophisticated computer technologies, backed by marketing and publicity budgets, will sharply focus attention once again on the issue of false negatives. Adopting these technologies will depend on whether a reduction in the levels of false negative Pap smears is considered a public health, individual patient, or medical liability issue.

Elizabeth Brown, MD, is Director of Technology Assessment and Clinical Guidelines at Aetna, Inc. in Chicago, Illinois. The opinions expressed in this column are those of the author and not necessarily those of Aetna, Inc. Dr. Brown can be reached at 312/441-3292.

References

[1.] Shingleton, H.M., Patrick. R.L.. Johnston. W.W., Smith R.A. The Current Status of the Papanicolaou Smear. CA Cancer J Clin 1995;45:305-20. [2.] Grohs, D.H. Challenges in Cervical Cancer Screening: What Clinicians. Patients and the General Public Need to Know. Acta Cytologica 1996;40:133-137. [3.] Hutchinson. M.L. Assessing the Costs and Benefits of Alternative Rescreening Strategies. Acta Cytologica 1996;40:4-8.

Key Concepts: Pap Smears/Adopting New Technologies/Technology Assessment/The Goal Depends on the Viewpoint: Public Health versus Individual Patient Care

The knowledge that cervical cancer should be a preventable disease has provided the impetus to improve the Pap smear. Now, for the first time in 50 years, two new computerized technologies are available - the AutoPap and Papnet systems - that could change the way they are interpreted. Of course, these new innovations come at a price, perhaps doubling or tripling the cost - by one estimate, the new technologies could add $1 billion per year. The health policy issue is whether these innovations address the limitations of cervical cancer screening programs in an efficient way. The analysis is entirely different when cast as an individual patient care issue. Here the patient and physician, who serves as her advocate, want to use the best screening method. The goal is not how to best allocate resources to improve the health of the overall population, but instead how to get the best care for the individual patient.