Chapter 4. Screening and Prevention of Disease

Screening and Prevention of Disease: Introduction
A primary goal of health care is to prevent disease or detect it early enough that intervention will be more effective. Strategies for disease screening and prevention are driven by evidence that testing and intervention are practical and effective. Currently, most screening tests are readily available and inexpensive. Examples include tests that are biochemical (e.g., cholesterol, glucose), physiologic (e.g., blood pressure, growth curves), or radiologic (e.g., mammogram, bone densitometry) or that involve tissue specimens (e.g., Pap smear). In the future, it is anticipated that genetic testing will play an increasingly important role in predicting disease risk (Chap. 63). However, such tests are not widely used except for individuals at risk for high-penetrancegenes on the basis of family or ethnic history (e.g., BRCA1, BRCA2). The identification of low-penetrance but high-frequency genes that cause common disorders such as diabetes, hypertension, and macular degeneration offers the possibility of new genetic tests. However, any new screening test, whether based on genetic or other methods, must be subjected to rigorous evaluation of its sensitivity, specificity, impact on disease, and cost-effectiveness. Physicians and patients are introduced continually to new screening tests, often in advance of complete evaluation. For example, the use of whole-body CT imaging has been advocated as a means to screen for a variety of disorders. Though it is appealing in concept, there is currently no evidence to justify this approach, which is associated with high cost and a substantial risk of false-positive results.
This chapter will review the basic principles of screening and prevention in the primary care setting. Recommendations for specific disorders such as cardiovascular disease, diabetes, and cancer are provided in the chapters dedicated to those topics.
Basic Principles of Screening
In general, screening is most effective when applied to relatively common disorders that carry a large disease burden (Table 4-1). The five leading causes of mortality in the United States are heart diseases, malignantneoplasms, accidents, cerebrovascular diseases, and chronic obstructive pulmonary disease. Thus, many prevention strategies are targeted at these conditions. From a global health perspective, these conditions are priorities, but malaria, malnutrition, AIDS, tuberculosis, and violence also carry a heavy disease burden (Chap. 2).

Table 4-1 Lifetime Cumulative Risk

Breast cancer for women 10% Colon cancer 6% Cancer of the cervix for womena 2% Domestic violence for women Up to 15% Hip fracture for white women 16%

aAssuming an unscreened population.

A primary goal of screening is the early detection of a risk factor or disease at a stage at which it can be corrected or cured. For example, most cancers have a better prognosis when identified as premalignant lesions or when they are still resectable. Similarly, early identification of hypertension or hyperlipidemia allows therapeutic interventions that reduce the long-term risk of cardiovascular or cerebrovascular events. However, early detection does not necessarily influence survival. For example, in some studies of lung cancer screening, tumors are identified at an earlier stage but the overall mortality rate does not differ between screened and unscreened populations. The apparent improvement in 5-year survival rates can be attributed to the detection of smaller tumors rather than to a real change in clinical course after diagnosis. Similarly, the detection of prostate cancer may not lead to a difference in the mortality rate because the disease is often indolent and competing morbidities, such as coronary artery disease, may ultimately cause mortality (Chap. 82).
Disorders with a long latency period increase the potential gains associated with detection. For example, cancer of the cervix has a long latency between dysplasia and invasive carcinoma, providing an opportunity for detection by routine screening. It is hoped that the introduction of new papillomavirus vaccines will provide additional disease prevention, ultimately reducing reliance on screening for cervical cancer. For colon cancer, an adenomatous polyp progresses to invasive cancer over 4–12 years, providing an opportunity to detect early lesions by fecal occult blood testing (FOBT) or endoscopy. In contrast, breast cancer screening in premenopausal women is more challenging—and controversial—because of the relatively short interval between development of a localized breast cancer and metastasis to regional nodes (estimated to be –12 months).
Methods of Measuring Health Benefits
It is not practical to perform all possible screening procedures. For example, screening for laryngeal cancer in smokers is not currently recommended. It is necessary to examine the strength of evidence in favor of screening measures relative to the cost and risk of false-positive tests. For example, should ultrasound be used to screen for ovarian cancer in average-risk women? It is currently estimated that the unnecessary laparotomies triggered by finding benign ovarian masses would cause more harm than the benefit derived from detecting the occasional curable ovarian cancer.
A variety of endpoints are used to assess the potential gain from screening and prevention interventions:

1. 
   The number of subjects screened to alter the outcome in one individual. It is estimated, for example, that 731 women ages 65–69 would need to be screened by dual-energy x-ray absorptiometry (DEXA) and then treated appropriately to prevent one hip fracture from osteoporosis.
   
2. 
   The absolute and relative impact of screening on disease outcome. A meta-analysis of Swedish mammography trials (ages 40–70) found that –1.2 fewer women per thousand would die from breast cancer if they were screened over a 12-year period. By comparison, –3 lives per 1000 might be saved from colon cancer in a population (ages 50–75) screened with annual FOBT over a 13-year period. Based on this analysis, colon cancer screening may actually save more womens lives than does mammography. The impact of FOBT (8.8/1000 versus 5.9/1000) might be stated either as 3 lives per 1000 or as a 30% reduction in colon cancer death; thus, it is important to consider both the relative impact and absolute impact on numbers of lives saved.
   
3. 
   The cost per year of life saved is used to assess the effectiveness of many screening and prevention strategies. Typically, strategies that cost <$30,000–50,000 per year of life saved are considered "cost-effective" (Chap. 3). For example, using alendronate to treat 65-year-old women with osteoporosis approaches this threshold of approximately $30,000 per year of life saved.
   
4. 
   Increase in average life expectancy for a population. Predicted increases in life expectancy for various screening procedures are listed in Table 4-2. It should be noted, however, that the increase in life expectancy is an average that applies to a population, not to an individual. In reality, the vast majority of the screened population does not derive any benefit and possibly incurs a slight risk from false-positive results. A small subset of patients, however, will benefit greatly from being screened. For example, Pap smears do not benefit the 98% of women who never develop cancer of the cervix. However, for the 2% who would develop localized cervical cancer, Pap smears may add as much as 25 years to their lives. Some studies suggest that a 1-month gain of life expectancy is a reasonable goal for a population-based preventive strategy.
   

Table 4-2 Estimated Average Increase in Life Expectancy for a Population

Screening Procedure Average Increase Mammography:   Women, 40–50 years 0–5 days   Women, 50–70 years 1 month Pap smears, age 18–65 2–3 months   Screening treadmill for a 50-year-old (asymptomatic) man 8 days   PSA and digital rectal exam for a man >50 years Up to 2 weeks   Getting a 35-year-old smoker to quit 3–5 years   Beginning regular exercise for a 40-year-old man (30 min 3 times a week) 9 months– 2 years

Abbreviation: PSA, prostate-specific antigen.

The U.S. Preventive Services Task Force (USPSTF) provides recommendations for evidence-based screening (Table 4-3). In addition to these population-based guidelines, it is reasonable to consider family and social history to identify individuals with special risk (www.ahrq.gov/clinic/uspstfix.htm). For example, when there is a significant family history of breast, colon, or prostate cancer, it is prudent to initiate screening about 10 years before the age at which the youngest family member developed cancer. Screening also should be considered for many other common disorders pending the development of further evidence. Three examples are screening for diabetes (using fasting blood glucose), domestic violence, and coronary artery disease in intermediate-risk asymptomatic individuals.

Table 4-3 Clinical Preventive Services for Normal-Risk Adults Recommended by the U.S. Preventive Services Task Force

Test or Disorder Population,a Years Frequency Chapter Reference Blood pressure, height and weight >18 Periodically 77 Cholesterol Men >35 Every 5 years 241 Women >45 Every 5 years Depression >18 Periodicallyb Diabetes >45 or earlier, if there are additional risk factors Every 3 years 344 Pap smearc Within 3 years of onset of sexual activity or 21–65 Every 1–3 years 82 Chlamydia Women 18–24 Every 1–2 years 176 Mammographya Women >50 Every 2 years 82, 90 Colorectal cancera >50 82, 91   fecal occult blood and/or Every year   sigmoidoscopy or Every 5 years   colonoscopy Every 10 years Osteoporosis Women >65>60 at risk Periodically 354 Abdominal aortic aneurysm (ultrasound) Men 65–75 who have ever smoked Once Alcohol use >18 Periodically 392 Vision, hearing >65 Periodically 28, 30 Adult immunization 122, 123   Tetanus-diphtheria (Td) >18 Every 10 years   Varicella (VZV) Susceptibles only, >18 Two doses   Measles mumps rubella (MMR) Women, childbearing age One dose   Pneumococcal >65 One dose   Influenza >50 Yearly   Human papillomavirus (HPV) Up to age 26 If not done prior

aScreening is performed earlier and more frequently when there is a strong family history. Randomized, controlled trials have documented that fecal occult blood testing (FOBT) confers a 15–30% reduction in colon cancer mortality. Although large randomized trials have not been performed for sigmoidoscopy or colonoscopy, well-designed case-control studies suggest similar or greater efficacy relative to FOBT. bIf staff support are available. cIn the future, Pap smear frequency may be influenced by HPV testing and the HPV vaccine. Note:Prostate-specific antigen (PSA) testing is capable of enhancing the detection of early-stage prostate cancer, but evidence is inconclusive that it improves health outcomes. PSA testing is recommended by several professional organizations and is widely used in clinical practice, but it is not currently recommended by the U.S. Preventive Services Task Force (Chap. 85). Source: Adapted from the U.S. Preventive Services Task Force, Guide to Clinical Prevention Services, 2009. http://www.ahrq.gov/clinic/uspstfix.htm.

Cost-Effectiveness
Screening techniques must be cost-effective if they are to be applied to large populations. Costs include not only the expense of testing but also time away from work, downstream costs from false-positive results, and other potential risks. When the risk-versus-benefit ratio is less favorable, it is useful to provide information to patients and factor their perspectives into the decision-making process. For example, many expert groups, including the USPSTF, recommend an individualized discussion about prostate cancer screening, as the decision-making process is complex and relies heavily on personal issues. Although the early detection of prostate cancer may seem desirable intuitively, risks include false-positive results that can lead to anxiety and unnecessary surgery. Randomized trials for prostate cancer screening have yielded mixed and relatively modest results. Potential complications from surgery and radiation treatment include erectile dysfunction, urinary incontinence, and bowel dysfunction. Some men may decline screening, whereas others may be more willing to accept the risks of an early-detection strategy. Another example of shared decision-making involves the choice of techniques for colon cancer screening (Chap. 82). In controlled studies, the use of annual FOBT reduces colon cancer deaths by 15–30%. Flexible sigmoidoscopy reduces colon cancer deaths by –60%. Colonoscopy offers the same benefit as or greater benefit than flexible sigmoidoscopy, but its use incurs additional costs and risks. These screening procedures have not been compared directly in the same population, but the estimated cost to society is similar: $10,000–25,000 per year of life saved. Thus, although one patient may prefer the ease of preparation, less time disruption, and the lower risk of flexible sigmoidoscopy, others may prefer the sedation and thoroughness of colonoscopy.
In considering the impact of screening tests, it is important to recognize that tobacco and alcohol use, diet, and exercise constitute the vast majority of factors that influence preventable deaths in developed countries. Perhaps the single greatest preventive health care measure is to help patients quit smoking (Chap. 395).
Commonly Encountered Issues
Despite compelling evidence that prevention strategies can have major health care benefits, implementation of these services is challenging because of competing demands on physician and patient time and because of gaps in health care reimbursement. Moreover, efforts to reduce disease risk frequently involve behavior changes (e.g., weight loss, exercise, seat belts) or the management of addictive conditions (e.g., tobacco and alcohol use) that are often recalcitrant to intervention. Public education and economic incentives are often useful, in addition to counseling by health care providers (Table 4-4).

Table 4-4 Counseling to Prevent Disease

Topic Chapter Reference Tobacco cessation 395 Drug and alcohol use 392, 393 Nutrition to maintain caloric balance and vitamin intake 73 Calcium intake in women >18 years 354 Folic acid: Women of childbearing age 74 Oral health 32 Aspirin use to prevent cardiovascular disease in selected men >45 years and women >55 years 241 Chemoprevention of breast cancer in women at high risk 90 STDs and HIV prevention 130, 189 Physical activity Sun exposure 56 Injury prevention (loaded handgun, seat belts, bicycle helmet) Issues in the elderly 9   Polypharmacy   Fall prevention   Hot water heater <120°   Vision, hearing, dental evaluations   Immunizations (pneumococcal, influenza)

Abbreviation: STDs, sexually transmitted diseases.

A number of techniques can assist physicians with the growing number of recommended screening tests. An appropriately configured electronic health record can provide reminder systems that make it easier for physicians to track and meet guidelines. Some systems give patients secure access to their medical records, providing an additional means to enhance adherence to routine screening. Systems that provide nurses and other staff with standing orders are effective for smoking prevention and immunizations. The Agency for Healthcare Research and Quality and the Centers for Disease Control and Prevention have developed flow sheets and electronic tools as part of their "Put Prevention into Practice" program (http://www.ahcpr.gov/clinic/ppipix.htm). Age-specific recommendations for screening and counseling are summarized in Table 4-5.

Table 4-5 Age-Specific Causes of Mortality and Corresponding Preventive Options

Age Group Leading Causes of Age-Specific Mortality Screening Prevention Interventions to Consider for Each Specific Population 15–24 1. Accident 2. Homicide 3. Suicide 4. Malignancy 5. Heart disease Counseling on routine seat belt use, bicycle/motorcycle/ATV helmets (1) Counseling on diet and exercise (5) Discuss dangers of alcohol use while driving, swimming, boating (1) Ask about vaccination status (tetanus, diphtheria, hepatitis B, MMR, rubella, varicella, meningitis, HPV) Ask about gun use and/or gun possession (2,3) Assess for substance abuse history including alcohol (2,3) Screen for domestic violence (2,3) Screen for depression and/or suicidal/homicidal ideation (2,3) Pap smear for cervical cancer screening, discuss STD prevention (4) Discuss skin, breast awareness, and testicular self-exams (4) Recommend UV light avoidance and regular sunscreen use (4) Measurement of blood pressure, height, weight, and body mass index (5) Discuss health risks of tobacco use, consider emphasis on cosmetic and economic issues to improve quit rates for younger smokers (4,5) Chlamydia screening and contraceptive counseling for sexually active females HIV, hepatitis B, and syphilis testing if there is high-risk sexual behavior(s) or any prior history of sexually transmitted disease 25–44 1. Accident 2. Malignancy 3. Heart disease 4. Suicide 5. Homicide 6. HIV As above plus consider the following: Readdress smoking status, encourage cessation at every visit (2,3) Obtain detailed family history of malignancies and begin early screening/prevention program if patient is at significant increased risk (2) Assess all cardiac risk factors (including screening for diabetes and hyperlipidemia) and consider primary prevention with aspirin for patients at >3% 5-year risk of a vascular event (3) Assess for chronic alcohol abuse, risk factors for viral hepatitis, or other risks for development of chronic liver disease Consider individualized breast cancer screening with mammography at age 40 (2) 45–64 1. Malignancy 2. Heart disease 3. Accident 4. Diabetes mellitus 5. Cerebrovascular disease 6. Chronic lower respiratory disease 7. Chronic liver disease and cirrhosis 8. Suicide Consider prostate cancer screen with annual PSA and digital rectal exam at age 50 (or possibly earlier in African Americans or patients with family history) (1) Begin colorectal cancer screening at age 50 with fecal occult blood testing, flexible sigmoidoscopy, or colonoscopy (1) Reassess vaccination status at age 50 and give special consideration to vaccines against Streptococcus pneumoniae, influenza, tetanus, and viral hepatitis Consider screening for coronary disease in higher-risk patients (2,5) 65 1. Heart disease 2. Malignancy 3. Cerebrovascular disease 4. Chronic lower respiratory disease 5. Alzheimers disease 6. Influenza and pneumonia 7. Diabetes mellitus 8. Kidney disease 9. Accidents 10. Septicemia As above plus consider the following: Readdress smoking status, encourage cessation at every visit (1,2,3,4) One-time ultrasound for AAA in men 65–75 who have ever smoked Consider pulmonary function testing for all long-term smokers to assess for development of chronic obstructive pulmonary disease (4,6) Vaccinate all smokers against influenza and S. pneumoniae at age 50 (6) Screen all postmenopausal women (and all men with risk factors) for osteoporosis Reassess vaccination status at age 65, emphasis on influenza and S. pneumoniae (4,6) Screen for dementia and depression (5) Screen for visual and hearing problems, home safety issues, and elder abuse (9)

Note: The numbers in parentheses refer to areas of risk in the mortality column affected by the specified intervention. Abbreviations: AAA, abdominal aortic aneurysm. ATV, all-terrain vehicle; HPV, human papillomavirus; MMR, measles-mumps-rubella; PSA, prostate-specific antigen; STD, sexually transmitted disease; UV, ultraviolet.

A routine health care examination should be performed every 1–3 years before age 50 and every year thereafter. History should include medication use (prescription and nonprescription), allergies, dietary history, use of alcohol and tobacco, sexual practices, and a thorough family history, if not obtained previously. Routine measurements should include assessments of height, weight (body mass index), and blood pressure, in addition to the relevant physical examination. The increasing incidence of skin cancer underscores the importance of screening for suspicious skin lesions. Hearing and vision should be tested after age 65, or earlier if the patient describes difficulties. Other sex- and age-specific examinations are listed in Table 4-3. Counseling and instruction about self-examination (e.g., skin, breast "awareness") can be provided during the routine examination.
Many patients see a physician for ongoing care of chronic illnesses, and this visit provides an opportunity to include a "measure of prevention" for other health problems. For example, a patient seen for management of hypertension or diabetes can have breast cancer screening incorporated into one visit and a discussion about colon cancer screening at the next visit. Other patients may respond more favorably to a clearly defined visit that addresses all relevant screening and prevention interventions. Because of age or comorbidities, it may be appropriate with some patients to abandon certain screening and prevention activities, although there are fewer data about when to "sunset" these services. The risk of certain cancers, such as cancer of the cervix, ultimately declines, and it is reasonable to cease Pap smears after about age 65 if recent Pap smears have been negative. For breast, colon, and prostate cancer, it is reasonable to reevaluate the need for screening after about age 75. For some older patients with advanced diseases such as severe chronic obstructive pulmonary disease and congestive heart failure and for those who are immobile, the benefit of some screening procedures is low, and other priorities emerge when life expectancy is <10 years. This shift in focus needs to be done tactfully and allows greater focus on the conditions likely to affect quality and length of life.