Screening patients for preclinical disease is an established part of day to day medical practice. Routine recording of blood pressure, urine testing, and preoperative chest radiography may all be regarded as screening activities. Increasingly, screening is now being extended to people who have not themselves requested medical aid. For example, general practitioners invite patients who would not otherwise be attending the surgery to undergo tests such as cholesterol measurement and cervical cytology. This places the doctor in a different role, and there is a special obligation to ensure that such screening is beneficial. To this end three questions must be answered, for which epidemiological data are required.
Lung cancers detected at an early stage in their development are more likely to be surgically resectable. Moreover, it is possible to identify such tumours when they are still asymptomatic by chest radiography and sputum cytology. However, a large study in the United States failed to demonstrate any clear reduction in mortality from lung cancer among heavy smokers who were offered fourmonthly screening by radiography and sputum cytology, despite the fact that more resectable tumours were detected in the screened population. As this example shows, the outcome of screening must be judged in terms of its effect on mortality or illness, and not simply by the number and severity of cases identified.
Assessing the benefits of early treatment is not always easy. One potential source of error is the phenomenon known as lead time.
Suppose that we wish to explore the scope for reducing mortality from breast cancer by early diagnosis. One approach might be to compare the survival of patients whose tumours were detected at screening with that of women who only present once their disease has become symptomatic. However, this could be misleading. Survival might be longer in the screened women not because early treatment is beneficial, but simply because their tumours are being diagnosed earlier in the natural history of their disease (fig).
Lead time (with screening (a) disease is diagnosed earlier than without screening (b) and survival is longer from diagnosis, but this does not necessarily imply that the time course of the disease has been modified.)
A further difficulty in comparisons of survival is that, apart from any effects of treatment, cases detected at screening tend to be more slowly progressive. Patients with aggressive disease are more likely to develop symptoms in the intervals between screening examinations and therefore present spontaneously.
Outcome is best assessed by systematically comparing the morbidity and mortality of a screened population with that of controls. Moreover, because people who attend for screening may have a different incidence of disease from those who do not, it is important to measure outcome in all of the population selected for screening and not only in those members who actually undergo investigation. Women from social classes IV and V have the highest rates of cervical cancer but the lowest uptake of cervical cytology. Thus an analysis restricted to women undergoing cervical screening would tend to indicate lower mortality even if in fact there was no advantage in early treatment.
Even if prognosis is improved by early treatment, screening is only worthwhile if a satisfactory diagnostic test is available. The test must detect cases in sufficient numbers and at acceptable cost, and it must not carry side effects that outweigh the benefits of screening. Because a screening test must be inexpensive and easy to perform, it is not usually the most valid diagnostic method for a disease. In screening, therefore, it has to be accepted that some cases will remain undetected. As with all diagnostic tests, there is a trade off between sensitivity and specificity, and the competing needs for each must be balanced.
In addition to its sensitivity and specificity, the performance of a test is measured by its predictive value. The predictive value of a positive result is the probability that a person who reacts positively to the test actually has the disease. Predictive value varies with the prevalence of disease in the population to whom the test is applied. If the prevalence is low then there are more false positive results than true positives, and predictive value falls. At the extreme, if nobody has the disease then the predictive value will be zero – all positive test results will be false positives. It follows that a test that functions well in normal clinical practice will not necessarily be useful for screening purposes. Sputum cytology has quite a high positive predictive value for bronchial carcinoma in patients presenting with haemoptysis, but if it is used to screen asymptomatic people most positive results will be false.
Because the average benefit to the individual from a screening programme is usually much smaller than from interventions in response to symptoms, screening tests need to be safer than those used in normal clinical practice. The radiation dose from a chest x ray examination is small, but if the investigation forms part of a screening programme for tuberculosis, then even the very small risk of complications may outweigh the benefits of early diagnosis. As the prevalence of pulmonary tuberculosis in the general population has declined, so mass radiographic screening has ceased to be justifiable.
The yield of a screening service is measured by the number of cases identified whose prognosis is improved as a result of their early detection. This must be related to the total number of tests performed. Theoretically, the yields of screening may be improved by restricting it to high risk groups, as has been suggested in the screening of infants for developmental and other abnormalities. But identifying relatively small high risk groups among whom most cases will be found is rarely feasible. If uptake of a screening procedure is low then yield will be correspondingly limited.
Ultimately the yields of a screening service have to be balanced against the costs, in terms of staff and facilities, of screening and making the confirmatory diagnoses. For breast cancer screening it has been found that identifying one case requires examining 170 women by palpation and mammography and taking nine biopsy specimens.