ACP medicine, 3rd Edition

Clinical Essentials

Adult Preventive Health Care

Mark Helfand MD, FACP¹

Associate Professor

¹Department of Medicine, Oregon Health and Science University

The author has no commercial relationships with manufacturers of products or providers of services discussed in this chapter.

May 2007

Over the past 20 years, prevention has become a major activity in primary care. During a typical day, primary care clinicians spend much of their time managing asymptomatic conditions in which the main goal is to prevent death or complications (e.g., hypertension, hyperlipidemia, osteoporosis). Many chapters in ACP Medicine include information on screening or prevention of specific disorders in asymptomatic patients or those at increased risk [see Table 1]. This chapter focuses primarily on preventive screening recommendations from the United States Preventive Services Task Force (USPSTF).

Table 1 Selected Prevention-Related Content in ACP Medicine

Chapter Relevant Content CE:III Reducing Risk of Injury and Disease Alcohol, tobacco, and other drug abuse; injury; violence; cites USPSTF CE:IV Diet and Exercise AHA recommendations CE:VII Health Advice for International Travelers CDC-recommended pretravel immunizations, other prophylactic measures 1:III Hypertension Prevention 1:VIII Acute Myocardial Infarction Secondary prevention; drugs and risk-factor modification 1:XI Valvular Heart Disease Prophylactic drug therapy for endocarditis; drugs and surgery for valvular disease 1:XVIII Venous Thromboembolism Primary and secondary prophylaxis 2:V Contact Dermatitis and Related Disorders Prevention 2:X Malignant Cutaneous Tumors Prevention 3:VI Diseases of Calcium Metabolism and Metabolic Bone Disease Osteoporosis prevention 4:VII Acute Viral Hepatitis Immunization 6:XIII Urticaria, Angioedema, and Anaphylaxis Prevention of anaphylaxis 6:XV Allergic Reactions to Hymenoptera Prevention 7:I Infections Due to Gram-Positive Cocci Prevention of spread of staphylococcal infection 7:II Infections Due to Mycobacteria Tuberculosis prevention 7:III Infections Due to Neisseria Prophylaxis for meningococcal disease 7:IV Infections Due to Gram-Positive Bacilli Prevention of diphtheria, listeria, anthrax 7:V Anaerobic Infections Tetanus prevention 7:VII Leptospirosis, Relapsing Fever, Rat-Bite Fever, and Lyme Disease Prevention of Lyme disease 7:X Infections Due to Haemophilus, Moraxella, Legionella, Bordetella, and Pseudomonas H. influenzae immunization and secondary prevention; pertussis immunization 7:XVII Infections Due to Rickettsia, Ehrlichia, and Coxiella Prevention of Rocky Mountain spotted fever, typhus 7:XVIII Infective Endocarditis Prevention for high-risk patients/procedures 7:XXII Vaginitis and Sexually Transmitted Diseases Screening recommendations for sexually transmitted diseases 7:XXV Respiratory Viral Infections Prevention of influenza and other respiratory viral infections 7:XXVI Herpesvirus Infections Prevention of herpes simplex, varicella-zoster, and cytomegalovirus infections 7:XXVIII Enteric Viral Infections Polio prevention 7:XXIX Measles, Mumps, Rubella, Parvovirus, and Poxvirus MMR, smallpox vaccination 7:XXXI Viral Zoonoses Vaccination for yellow fever, Japanese encephalitis, and rabies 7:XXXIII HIV and AIDS Prevention of HIV infection 7:XXXIV Protozoan Infections Prevention of malaria, toxoplasmosis, giardiasis, and amebiasis 7:XXXVIII Mycotic Infections in the Compromised Host Prevention of several opportunistic fungal infections 8:II Bites and Stings Prophylactic antibiotics for bites 8:IV Preoperative Assessment and Care of the Surgical Patient Assessing operative risk and preventing complications 8:V Bioterrorism Vaccination and postexposure prophylaxis 8:VIII Assessment of the Geriatric Patient Evidence-based preventive services, assessment of in-home hazards 8:IX Management of Common Clinical Disorders in Geriatric Patients Prevention of falls, incontinence, pressure ulcers, malnutrition, and iatrogenic illness 8:X Rehabilitation of Geriatric Patients Prevention of stroke complications 9:VI Diagnosis and Treatment of Dyslipidemia Primary and secondary prevention 9:II Diabetes Mellitus ADA screening recommendations, prevention of type 2 diabetes, prevention of diabetic complications 10:VI Acute Renal Failure Prevention 10:XII Nephrolithiasis Prevention of recurrent kidney stones 11:IV Cerebrovascular Disorders Risk reduction for stroke 11:VIII Headache Migraine prophylaxis 12:I Cancer Epidemiology and Prevention Screening of asymptomatic patients for prevention and early detection; ACS recommendations 12:V Colorectal Cancer Risk reduction, screening tests; ACS recommendations 12:VII Breast Cancer Screening and prophylaxis 12:VIII Lung Cancer Prevention 12:IX Prostate Cancer Risk reduction, screening; ACS recommendations 13:III Alcohol Abuse and Dependency Screening for alcoholism and treatment to prevent relapse 16:IX Medical Problems in Pregnancy Limited discussion of screening 16:XI Menopause Prevention and screening per USPSTF 16:XVI Approach to the Patient with an Abnormal Pap Smear Prevention and screening per USPSTF ACS—American Cancer Society   ADA—American Diabetes Association   AHA—American Heart Association   CDC—Centers for Disease Control and Prevention   MMR—measles, mumps, rubella vaccine   USPSTF—United States Preventive Services Task Force

Rationale and Evolution of Preventive Care Guidelines

The rationale for delivering preventive care during an office visit is strong. In 2002, life expectancy in the United States was 77.4 years, an all-time high.¹ Behavioral risk factors, including tobacco use, diet, and alcohol use, as well as factors such as hyperlipidemia and hypertension, contributed to the most frequent causes of death [see Table 2]. From the viewpoint of clinical preventive services, modifiable risk factors such as these, rather than the diseases they affect, are the true causes of death.²

Table 2 Major Causes of Death in the United States1*

Cause of Death Number of Deaths Age-Adjusted Death Rate (per 100,000 population) Diseases of the heart 695,754 204.4 Malignant neoplasms 558,847 194 Cerebrovascular diseases 163,010 56.3 Chronic lower respiratory diseases 125,500 43.7 Accidents (unintentional injuries) 102,303 35.3 Diabetes mellitus 73,119 25.4 Influenza and pneumonia 65,984 22.7 Alzheimer disease 58,785 20.2 *Preliminary data for 2002; these causes account for three quarters of all deaths.

Primary care visits provide an opportunity to assess risk, discuss options, and recommend behaviors and treatments that have been proved to reduce the risks of diseases and death. During 2002, an estimated 558 million visits were made to primary care physicians in the United States, an overall rate of about two visits per person per year.³ On average, these physicians spent 20 minutes with the patient at each visit.

In 1975, Frame and Carlson published a series of articles that examined the quality of evidence for periodic screening conducted in the routine physical examination.⁴ These authors argued that any preventive strategy should meet certain criteria of accuracy and usefulness [see Table 3]. The criteria are helpful in understanding the controversy about screening proposals. Several scholars have pointed out that clinical intuition about screening is often wrong, leading to errors in inference about the effects of screening. Some of these logical fallacies and hidden assumptions are now well recognized and even find their way into board examinations [see Table 4].

Table 3 Criteria for Evaluating a Screening Program

1. Does the program target a disease that causes serious morbidity and mortality that might be prevented by the service? 2. Can the screening test accurately identify healthy people who are at high risk for developing advanced disease? 3. Is the screening test feasible to use in primary care? 4. Does treatment given before symptoms occur result in better outcomes than treatment given later? 5. Do the overall benefits outweigh the harms of screening and treatment?

Table 4 Sample Board Examination Questions About Screening

Question Answer and Explanation A screening test correctly identifies 95% of patients who have prexerostosis and 95% of patients who are well. If 1 of every 500 patients has prexerostosis, what is the likelihood that a patient who has a positive test has the disease? The correct answer is 3%; the positive predictive value is commonly overestimated because of neglecting Bayes theorem. The 5-year survival of stage 0 lung cancer is 95%, versus 10% for more advanced stages. In usual care, 70% of patients present in advanced stages. When screening with a CT scan, 90% of patients have stage 0 disease. By how much will screening reduce mortality? The correct answer is that the effect of screening on survival cannot be determined; increasing detection of disease in a “curable stage” may improve 5-yr survival but does not necessarily reduce mortality because of overdiagnosis bias, length bias, and lead-time bias—for example, screening may detect slower-growing cancers that would never have become lethal. With improvements in treatment, mortality from advanced HIV infection has dropped by 63%. Because effective treatment is now available, screening and early treatment should result in even greater mortality reductions. True or false? The conclusion may be, but is not necessarily, true. If treatment of advanced disease is very effective, screening may not confer any additional advantage. Screening is most likely to improve outcomes when advanced disease is untreatable but treatment of earlier, asymptomatic disease can result in cure.

The work of Frame and Carlson gave rise to evidence-based decision making in prevention. The Canadian Task Force on the Periodic Health Exam used independent reviews of the scientific literature and a set of rules to grade the strength of evidence supporting a clinical service.

The USPSTF, founded in 1984, was modeled on the Canadian Task Force. It published its first set of guidelines for clinical preventive services in 1989.⁵ The current USPSTF has experts from the specialties of family medicine, pediatrics, internal medicine, obstetrics and gynecology, geriatrics, preventive medicine, public health, behavioral medicine, and nursing.

Other expert panels also make recommendations about prevention [see Table 5]. Despite general agreement that recommendations should be evidence based, opinions about the effectiveness of specific preventive services differ. These differences arise because interpretation of the evidence is ultimately a subjective process, especially regarding the balancing of benefits and risks—an equation that includes such disparate factors as mortality reduction, costs or burden of illness, and patient discomfort.

Table 5 Government-Sponsored Preventive Guidelines Programs

Organization Sponsorship Focus Web Site U.S. Preventive Services Task Force Agency for Healthcare Research and Quality Clinical preventive services http://www.ahrq.gov/clinic/uspstfix.htm Canadian Task Force on Preventive Health Care Health Canada (Canadian Federal Government) Clinical prevention, periodic health examination http://www.ctfphc.org Physician Data Query Program National Cancer Institute Cancer prevention http://cancernet.nci.nih.gov/cancertopics/pdq/screening Task Force on Community Preventive Services CDC Community, population, and health care system strategies http://www.thecommunityguide.org Advisory Committee on Immunization Practices DHHS and CDC Immunizations, bioterrorism response http://www.cdc.gov/nip/recs/adult-schedule.pdf National Heart, Lung, and Blood Institute National Institutes of Health Asthma, cholesterol, hypertension, obesity http://www.nhlbi.nih.gov/guidelines Board on Health Promotion and Disease Prevention Institute of Medicine Population-based public health measures and the public health infrastructure http://www.iom.edu/board.asp?id=3793 CDC—Centers for Disease Control and Prevention DHHS—Department of Health and Human Services

To avoid errors in judging the evidence and weighing benefits and harms, expert panels, as well as individual clinicians, should do the following: (1) use an independent systematic review to distinguish assertions based on evidence from those based on other grounds, (2) make the rationale for a recommendation explicit, and (3) be free from financial and political conflicts of interest. Although the use of these measures does not guarantee a correct decision, they represent the best safeguards against bias.

USPSTF Evidence Ratings

The USPSTF assigns an overall grade of A, B, C, D, or I to each prevention service. The grades reflect the overall strength of evidence and the magnitude of benefit, defined as benefits minus harms [see Table 6].⁶

Table 6 United States Preventive Services Task Force Grading System6

Grade* Strength of Evidence Magnitude of Benefit A Good Large B Good Moderate   Fair Moderate to large C Fair to good Small D Fair to good None I Poor None to large *A—Service strongly recommended  B—Service recommended  C—No recommendation for or against  D—Service not recommended  I—Insufficient evidence

A grade of A indicates services that have solid supporting evidence and at least a moderate net benefit. A grade of B suggests that there are information gaps (so-called fair evidence) or that the benefits are only moderately greater than the harms for all patients. A grade of C denotes a toss-up, whereas a D grade indicates a service that is either proven ineffective or unlikely to provide benefits that outweigh the harms.

When there is too little evidence to determine whether or not a service works, the USPSTF assigns a grade of I for insufficient evidence. Some of the services with an I grade make good clinical sense and some are very promising, but without better research, it is not possible to say with confidence that they improve outcomes. Other grade I services have uncertain benefits but definite harms.

Noncancer Prevention Imperatives

Several preventive measures have earned an A grade on the strength of their good supportive evidence, substantially greater benefits than harms, and broadest applicability to primary care practice [see Table 7]. Implementation of these measures is described in detail in otherACP Medicine chapters [see Table 1].

Table 7 Strongly Recommended Noncancer Preventive Services in Adults*

Service Candidates Established Benefits Aspirin for primary prevention of cardiovascular events Adults at high cardiovascular risk Reduces the risk of stroke Blood pressure screening All adults Reduces the risk of stroke Screening for lipid disorders Men 35 yr of age and older; women 45 yr of age and older; and younger adults at increased risk for coronary artery disease Reduces overall mortality, as well as mortality from cardiovascular disease Chlamydial infection screening Sexually active women 25 yr of age and younger; other asymptomatic women at increased risk for infection Reduced the risk of pelvic inflammatory disease in one randomized trial36 Hepatitis B virus (HBV) infection screening Pregnant women Reduces prenatal transmission of HBV Syphilis screening Persons at increased risk for infection; all pregnant women Penicillin treatment during pregnancy reduces the risk to the fetus of acquiring congenital syphilis HIV screening† Pregnant women Reduces prenatal transmission of HIV High-risk men and women Delays mortality from HIV disease and permits counseling to reduce transmission Screening for asymptomatic bacteriuria Pregnant women (urine culture at 12–16 weeks' gestation) Prevents symptomatic urinary tract infections, low birth weight, and preterm delivery *As per the United States Preventive Services Task Force. †As per the CDC.37,38

Immunization

The USPSTF has not issued recommendations about immunization since 1996, and those recommendations are now out of date. The Advisory Committee on Immunization Practices (ACIP), which consists of 15 experts in fields associated with immunization, is currently the only entity in the United States federal government that makes recommendations about immunizations. In contrast to the USPSTF, the ACIP does not use systematic reviews and does not usually describe the quality of evidence supporting a recommendation.

The ACIP publishes schedules for vaccination against certain infectious diseases in adults, depending on age and risk factors; these recommendations are discussed in individual ACP Medicine chapters and are available on the Internet (http://www.cdc.gov/nip/recs/adult-schedule.pdf). For example, general recommendations include a tetanus-diphtheria booster every 10 years in all adults, influenza vaccination every year in adults 50 years of age and older, and pneumococcal vaccination once in adults 65 years and older. The ACIP has made specific recommendations for vaccination of health care workers [see Table 8].⁷

Table 8 Recommended Vaccination Schedule for Health Care Workers7,37*

Vaccine Schedule Tetanus-diphtheria (Td) Every 10 yr after complete primary series or for persons lacking documentation of vaccination or   Tetanus-diphtheria-pertussis (Tdap) A single dose of Tdap as soon as feasible to reduce risk of transmitting pertussis; a 2-yr interval since last dose of Td is suggested but not required Influenza Annual Pneumococcal (polysaccharide) For persons with medical indications† or at risk for exposure Hepatitis B For persons lacking documentation of vaccination or evidence of disease Hepatitis A No data to support a recommendation Measles, mumps, rubella (MMR) For persons lacking documentation of vaccination or history of disease‡ Varicella For persons lacking documentation of vaccination or history of disease *As per the Advisory Committee on Immunization Practices. †Medical indications: Chronic pulmonary disorders, excluding asthma; cardiovascular disease; diabetes mellitus; chronic liver disease, including liver disease as a result of alcohol abuse (i.e., cirrhosis); chronic renal failure; chronic renal failure or nephrotic syndrome; functional or anatomic asplenia (e.g., sickle cell disease or splenectomy); lymphoma, multiple myeloma, generalized malignancy, or organ or bone marrow transplantation; chemotherapy with alkylating agents, antimetabolites, or long-term systemic corticosteroids; or cochlear implants. ‡Measles component: Adults born before 1957 can be considered immune to measles. Health care workers born during or after 1957 should receive two doses of MMR vaccine unless they have a medical contraindication. Mumps component: Health care workers who have received only one MMR dose previously should be given a second dose of a live mumps virus vaccine. Health care workers without a history of mumps vaccination or other evidence of immunity should receive two doses of a live mumps vaccine, with a minimum interval of 28 days between doses. Rubella component:Administer one dose of MMR vaccine to women whose rubella vaccination history is unreliable, and counsel women to avoid becoming pregnant for 4 wk after vaccination. For women of childbearing age, routinely determine rubella immunity and counsel regarding congenital rubella syndrome. Do not vaccinate pregnant women or those planning to become pregnant during the next 4 wk. For women who are pregnant and susceptible, vaccinate as early as possible in the postpartum period.

Cancer Prevention

Only two cancer screening tests meet the USPSTF criteria for a strong recommendation: (1) Papanicolaou (Pap) smears for cervical cancer and (2) fecal occult blood testing or endoscopic procedures for colorectal cancer [see Table 9]. With both of these conditions, the aim of screening is to remove precancerous lesions, which prevents invasive cancer, saves the involved organ, and reduces disease-specific mortality. By contrast, the more controversial cancer screening tests, such as prostate-specific antigen (PSA) and mammography, detect invasive cancers and lead to aggressive treatments (prostatectomy and mastectomy) that often destroy the involved organ and that have more substantial morbidity than cone biopsy for cervical cancer and polypectomy for colorectal cancer.

Table 9 Recommended and Strongly Recommended Measures for Cancer Prevention*

Service Recommendation Grade Candidates Comment Cervical cancer screening A Women who have been sexually active and have a cervix; begin screening within 3 yr of onset of sexual activity or at age 21 (whichever comes first) and screen at least every 3 yr, stopping at age 65 Reduces the risk of invasive cervical cancer and mortality from cervical cancer Colorectal cancer screening A Adults 50 yr and older (earlier in patients with a strong family history) Reduces the risk of invasive colon cancer and mortality from colon cancer Breast cancer screening B Women 40 yr and older Reduces mortality from breast cancer Breast cancer chemoprophylaxis B Women at high risk for developing breast cancer Reduces the incidence of invasive breast cancer *As per the United States Preventive Services Task Force [see Table 6].

Cervical Cancer

Although no data from randomized, controlled trials support the value of the Pap smear in reducing mortality from cervical cancer, indirect evidence suggests that it is among the most effective cancer screening techniques.⁸ By current standards, the sensitivity of traditional Pap testing is low (51%).^9,10 Cervical dysplasia is slow to progress to invasive carcinoma, however, so periodic screening can make up for the low sensitivity of a single exam.

The USPSTF recommends screening with Pap smears at least every 3 years, beginning within 3 years after the start of sexual activity or age 21 (whichever comes first). The Task Force recommends against annual screening. In women who have had consistently negative Pap smear results, continuing screening past age 65 is unnecessary because of the declining incidence of high-grade cervical lesions and an increased risk for potential harms, including false positive results and invasive procedures. The USPSTF also recommends against routine Pap smear screening in women who have had a total hysterectomy for benign disease.

The specificity of Pap smears for detection of dysplasia and cancer is 98%. False positive results occur infrequently, but Pap smears may correctly detect a large number of low-grade lesions that, without treatment, would remain stable or regress.¹¹ As a consequence, many women who would never develop invasive cervical cancer are subjected to anxiety and to colposcopy and biopsy.

In a systematic review, the effectiveness of liquid-based cytology, computerized rescreening, and algorithm-based screening have been compared with that of conventional Pap smear screening in reducing the incidence and mortality of invasive cervical cancer. The review concluded that the liquid-based monolayer preparation (ThinPrep) appears to offer higher sensitivity but lower specificity than conventional Pap smears.¹⁰ However, the USPSTF could not determine whether the potential benefits of the three new screening approaches relative to conventional Pap smears are sufficient to justify a possible increase in potential harm or cost. They also found insufficient evidence to recommend for or against the routine use of human papillomavirus testing as a primary screening test for cervical cancer.

Colorectal Cancer

Screening modalities for colorectal cancer include fecal occult blood testing (FOBT), sigmoidoscopy, double-contrast barium enema, colonoscopy, and computed tomographic colonography [see 12:V Colorectal Cancer]. FOBT is the only screening modality that has been shown in randomized controlled trials to reduce colorectal cancer mortality. In the Minnesota Colon Cancer Control Study, 33 volunteers 50 to 80 years of age were randomized to annual FOBT, biennial FOBT, or a control group. After 18 years of follow-up, colorectal cancer mortality was 33% lower in the annual FOBT group and 21% lower in the biennial group than in the control group.¹² In this study, the slides were rehydrated, a technique that increases sensitivity but reduces specificity; during the trial, 38% of patients in the annual FOBT group underwent colonoscopy because of a positive test result. Two randomized, controlled trials from Europe have demonstrated 16% and 18% reductions in colorectal cancer mortality using FOBT.^13,14 In the European trials, unlike in the Minnesota study, patients were drawn from the general population, the slides were not rehydrated, and all testing was biennial.

In the screening trials, FOBT reduced mortality from colon cancer but did not reduce all-cause mortality. For example, the Minnesota trial findings indicate that 10 years of screening would result in 12 (95% confidence interval, 1 to 24) fewer colon cancer deaths per 10,000 persons screened. In that trial, however, the 95% confidence interval for all-cause mortality was 334 to 350 with annual screening, 333 to 348 with biennial screening, and 336 to 351 in control subjects.¹²

Evidence for the efficacy of sigmoidoscopy comes from case-control studies, which suggest that the protective effect of a single sigmoidoscopy lasts at least 6 years. The results of a large United Kingdom trial of screening with flexible sigmoidoscopy are not yet complete. Preliminary results suggest that flexible sigmoidoscopy is safe and that about 5% of persons 55 to 64 years of age have high-risk polyps (three or more adenomas; size 1 cm or greater; villous, severely dysplastic, or malignant).¹⁵

Because of the imperfect sensitivity of FOBT and sigmoidoscopy and because many patients who undergo these procedures end up requiring colonoscopy anyway, many clinicians are advising their average-risk patients to undergo colonoscopy as a screening test, either as a one-time procedure or periodically (e.g., every 10 years) beginning at age 50. Colonoscopy is the most sensitive test for detecting polyps; however, as for other slow-growing lesions, such as cervical dysplasia, it is not clear whether improved sensitivity for polyps at a single point in time will translate into fewer invasive cancers in the long run.

In 2002, for the first time, the USPSTF included screening colonoscopy as an option, but with the qualification that the potential added benefits of colonoscopy may not always be great enough to justify the increased risks and inconvenience.¹⁶ All colon cancer screening tests have a low yield—over 500 patients must be screened to prevent one invasive cancer¹⁷—so even a slightly increased rate of serious complications with colonoscopy might negate the benefit. Several gaps in the evidence base for colonoscopy can also be mentioned. First, the frequency of one procedure every 10 years was arrived at by means of mathematical models; in fact, no one knows how many patients will develop invasive cancer less than 10 years after a negative colonoscopy. Second, surveys suggest that gastroenterologists overuse colonoscopy for surveillance in patients who have clinically insignificant hyperplastic polyps or low-risk lesions, such as small adenomas. As a result, colonoscopic screening may lead to the use of a scarce, expensive resource, primarily in patients who have little chance of benefit. Third, the accuracy of colonoscopy when performed by the so-called average colonos- copist is not known. The primary advantage of colonoscopy, visualization of the entire colon, is negated if the operator cannot reach the cecum consistently or does not view the entire circumference of the lumen during the procedure.

No direct evidence supports the use of double-contrast barium enema for screening, and patients find it more uncomfortable than other alternatives. CT colonography may prove to be more sensitive and better tolerated than double-contrast barium enema and safer than colonoscopy; as of yet, however, there are insufficient data to determine whether it would result in better outcomes.¹⁸

Breast Cancer

It was predicted that in the United States in 2004, invasive breast cancer would be diagnosed in an estimated 215,990 women; in situ disease would be diagnosed in 55,700 women; and 40,110 women would die of the disease.¹⁹ A 40-year-old woman has a 13.2% (approximately one in eight) chance of developing invasive breast cancer during her life, but her risk of developing breast cancer within 10 years is only 1.47% (approximately one in 68). Modalities for breast cancer screening include mammography, clinical breast examination, and breast self-examination.

Mammography

In 2000, a Danish meta-analysis of the major randomized trials of mammography concluded that there was no evidence that mammography reduced mortality from breast cancer.²⁰ However, another analysis of the same trials conducted for the USPSTF concluded that mammography reduced breast cancer mortality in women 40 to 70 years of age.²¹ The controversy centered on disagreement about the quality of the randomized trials of mammography: the Danish investigators excluded five of the eight trials that showed mammography to be beneficial, whereas the United States investigators excluded only two of those eight trials on grounds of quality.

The USPSTF demoted mammography from grade A to grade B to reflect their view that the quality of the evidence was fair and that the net benefit (benefits minus harms) was moderate. Coming after the widely publicized Danish study, the USPSTF recommendation of grade B for mammography received a mixed reception. One independent review, published in 2003, confirmed the USPSTF view that although the trials were flawed, the balance of the evidence still favored screening mammography in women 40 years of age and older at least every 2 years.²²Conversely, the National Cancer Institute's Physician Data Query program largely endorsed the idea that most of the mammography trials were seriously flawed.

The USPSTF's most controversial decision regarding mammography was to promote screening in women 40 to 50 years of age from a grade C to a grade B. This was done because with several additional years of follow-up since the previous recommendations, in 1996, the pooled risk reduction for women who began screening at this age had become statistically significant. Nevertheless, the number needed to screen is higher, and the balance of benefits and harms narrower, in women 40 to 50 years of age than in older women.

For clinicians, the most difficult question is how to present information about the risks and benefits clearly and fairly to patients. At the time of an earlier controversy over the effectiveness of mammography in women 40 to 49 years of age, a survey of 509 women in the United States found that most believed the controversy was really about cost.²³ Women may interpret the lifetime risk of one in eight to be their immediate risk of developing breast cancer if they defer or miss their next mammogram.²⁴ In deciding how to inform patients, clinicians should carefully consider the major criticisms of the USPSTF recommendation. These criticisms represent differences in values rather than disagreements over the facts. There are four principal issues:

1. Is reducing breast cancer mortality important? In the trials, which involved nearly half a million women, mammography clearly had no effect on all-cause mortality. The USPSTF, although fully aware of this fact, chose to base their assessment of the benefits on the narrower grounds of breast cancer mortality. They chose to let women decide for themselves whether reducing the risk of dying of breast cancer was important to them.
2. How large is the reduction in breast cancer mortality? Judging from the trials, about 1,200 women 40 to 70 years of age must be invited to be screened four to five times over 10 years to prevent one death from breast cancer. Of women 40 to 49 years of age, 1,792 (95% CI, 764 to 10,540) must be invited to be screened to prevent one death from breast cancer, a death that would not have occurred until about 20 years after screening began. The specification “invited to” is important: it is likely that the trials underestimated the true benefit because they are diluted by a large number of subjects who were assigned to have mammography but did not.²⁵Nevertheless, to benefit even one woman, a large number of women must have a large number of mammograms over many years.
3. Are these estimates from the randomized trials still valid? Evidence from the trials may be out of date. The first trial began in 1963, and the others began between 1976 and 1982. Improvements in mammography since then might translate into better outcomes than were seen in the trials. On the other hand, improved systemic treatment for clinically detected breast cancer may have eliminated the advantage that earlier detection conferred in the era of the trials.
4. How large are the harms? The USPSTF was criticized for ignoring or underestimating harms. In fact, the USPSTF considered the harms, but it was also influenced by evidence that many healthy women stated that they would be willing to take on these risks, as well as the morbidity associated with treatments, to avoid a breast cancer death.²⁶

What are the harms? Women who get 10 annual mammograms have about a 50% chance that at least one of them is a false positive result; many of these false positive results necessitate a biopsy. Of women who are found to have invasive cancer, about 30 must undergo major surgery, or surgery plus radiation or tamoxifen, to prevent one death from breast cancer. In addition, screening identifies many women with ductal carcinoma in situ, and many of these women also undergo surgery, with uncertain benefit. In sum, many women experience immediate morbidity from treatment; without screening, most of them would not have had consequences of their breast cancer (and no morbidity from mastectomy) for many years, if ever.

Clinical Breast Examination

The USPSTF could not determine the benefits of clinical breast examination (CBE) alone or the incremental benefit of adding CBE to mammography (grade I recommendation). No screening trial has examined the benefits of CBE alone (without accompanying mammography). Four of the eight trials of screening used mammography alone, and four used mammography plus CBE. In the trials that used both methods, CBE detected 40% to 69% of breast cancers. It is not clear from the trials whether CBE contributed to the reduction in breast cancer mortality observed in some of the trials.

Breast Self-examination

A randomized trial from China failed to show a reduction in breast cancer mortality or an improvement in tumor stage at presentation in women receiving instruction in breast self-examination.²⁷ Results from a Russian trial were similar.²⁸ In both trials, women who had been instructed in breast self-examination were more likely to seek medical advice for benign breast lesions.

Genetic Risk Assessment

In women whose family history suggests an increased risk of deleterious BRCA1 or BRCA2 mutations, the USPSTF recommends referral for genetic counseling and evaluation for BRCA testing (grade B recommendation). However, the USPSTF recommends against routine testing for breast cancer susceptibility genes (i.e., BRCA1 or BRCA2) or routine referral for genetic counseling in women whose family history does not suggest an increased risk of deleterious mutations in these genes (grade D recommendation). Such screening and counseling have few or no benefits and could have important adverse ethical, legal, social, and medical consequences.

Cancer Screening Measures That Are Not Recommended

The USPSTF recommended against screening for bladder, ovarian, pancreatic, and testicular cancers. In each case, the deciding factor was that screening and treatment caused serious, immediate harms, whereas evidence of a benefit was inconclusive. As with mammography for breast cancer, screening for these cancers is aimed at detection of early invasive disease, and treatment has substantial morbidity. This degree of morbidity is in contrast to that associated with screening for colonic polyps or cervical dysplasia, for which treatment is relatively safe and is aimed at preserving, rather than removing, the involved organ.

Prostate Cancer Screening

The USPSTF concluded that evidence was insufficient to recommend for or against prostate cancer screening. This conclusion was based on the following considerations: (1) there are no completed randomized, controlled trials of screening, although studies are ongoing in the United States²⁹ and in Europe³⁰; (2) although prostate cancer is a major cause of cancer death in men, many cases are clinically indolent (in autopsy studies, the prevalence of histologic prostate cancer in men older than 50 years is about 30%, but only 3% of men die of prostate cancer)³¹; (3) the value of treatment for the localized cancers targeted by screening is unknown; the one randomized, controlled trial of radical prostatectomy, which found no improvement in the 15-year survival rates of patients undergoing surgery, has been criticized for methodological problems³² (another randomized, controlled trial comparing expectant management with radical prostatectomy for the treatment of localized cancer is under way)³³; (4) aggressive treatments for localized disease are associated with significant morbidity; and (5) mortality from prostate cancer has not declined in the United States despite 15 years of widespread use of PSA testing.

Lung Cancer Screening

The USPSTF concluded that evidence was insufficient to recommend for or against screening asymptomatic patients for lung cancer with low-dose CT, chest x-ray, sputum cytology, or a combination of these tests. Although there is fair evidence that screening with these measures can result in detection of lung cancer at an earlier stage, there is poor evidence that any screening strategy for lung cancer decreases mortality. Moreover, the invasive nature of diagnostic testing and the possibility of a high number of false positive tests in certain populations raises the potential for significant harms from screening.

Noncancer Screening

Selected screening tests for diseases other than cancer are recommended for all adults, or for groups defined by age and sex. These diseases include abdominal aortic aneurysm in older men, depression, obesity, and osteoporosis [see Table 10].

Table 10 Recommended Preventive Noncancer Screening*

Condition Screening Measure Comments Abdominal aortic aneurysm Abdominal palpation, ultrasonography Men 65 to 70 yr of age who have ever smoked should be screened one time by ultrasonography Depression Standardized questionnaire In most trials, screening alone had nonsignificant effects on treatment rates and on clinical outcome; however, larger benefits were observed in studies in which the communication of screening results was coordinated with effective follow-up and treatment; in such settings, 110 patients would need to be screened to produce one additional remission after 6 mo of treatment Obesity Measurement of body mass index (BMI) Screening can identify obesity (BMI ≥ 30 kg/m2); programs that combined diet and physical activity produced modest weight loss (6.4 lb on average for 1 yr or more); most trials did not report the proportion of subjects who lost weight Osteoporosis Dual-energy x-ray absorptiometry Women older than 65 yr and high-risk women 50 yr of age and older should be screened; alendronate reduces the risk of fracture over 3–5 yr, but the longer-term benefit of treatment is unclear *“B” recommendations, United States Preventive Services Task Force.

Behavioral-Counseling Interventions

Unhealthy behaviors have a huge impact on mortality and morbidity. Tobacco use remains the leading preventable cause of death in the United States, contributing to more than 440,000 deaths each year. Misuse of alcohol is responsible for 100,000 more deaths. Although tobacco use has decreased, alcohol abuse, obesity, and diabetes have increased in recent years, bringing new attention to the need to eat, drink, and exercise sensibly.

The evidence base supporting brief counseling by primary care physicians has grown substantially in the past 10 years. To date, however, efficacy has been proved only for counseling on tobacco cessation and alcohol use [see Table 11]. Evidence to support counseling on diet, exercise, and other behaviors (e.g., use of sunscreens, seat-belt use) is limited. In many instances, follow-up in the available studies was too short to confirm that behavior change is sustained long enough to reduce the risk of developing disease or injury.

Table 11 Selected Recommendations for Counseling and Patient Education

Counseling Topic USPSTF Grade* Tobacco use B Alcohol use/driving after drinking B Healthy diet I Physical activity I Seat-belt use I Regular dental care I Avoidance of sun exposure/use of protective clothing I Adequate calcium intake (women) I Use of sunscreens I *See Table 6. USPSTF—United States Preventive Services Task Force

Smoking Cessation

There is strong evidence that smoking bans, increasing the price of tobacco products, and public-information campaigns can discourage people from starting to smoke and encourage them to stop. Smoking cessation rapidly decreases the risk of stroke and heart disease and slowly decreases the risk of lung cancer [see CE:III Reducing Risk of Injury and Disease]. In patients with peripheral vascular disease, smoking cessation reduces the risk of limb amputation and recurrent stroke.

Brief counseling by clinicians can help smokers take action. Counseling by physicians becomes increasingly important as more patients become motivated to quit. Because many patients have tried and failed before, brief messages should emphasize that repeated efforts often bring success.

Alcohol Use

Screening and counseling of alcohol use in primary care is aimed at drinkers who are at risk for harm from alcohol consumption that exceeds daily, weekly, or per-occasion norms (i.e., risky or hazardous drinking) [see 13:III Alcohol Abuse and Dependency]. Unlike harmful drinking and alcohol abuse or dependence, risky drinking behavior has not yet resulted in physical, social, or psychological harm to the drinker, and such drinkers do not meet diagnostic criteria for alcohol dependence.³⁴ In contrast to persons who engage in risky drinking, alcohol-abusing and alcohol-dependent drinkers may require intense addiction treatment and are unlikely to respond to brief advice from a physician.

Self-administered questionnaires or brief interviews can be used to assess average quantity or frequency and binge use. In the United States, about 8% to 18% of patients screen positive for binge drinking. CAGE is a four-item screening questionnaire to detect alcohol abuse and dependence. Its name derives from the topics of the four questions: Have you ever felt you ought to Cut down on drinking? Have peopleAnnoyed you by criticizing your drinking? Have you ever felt bad or Guilty about your drinking? Have you ever had a drink in the morning to steady your nerves or get rid of a hangover (Eye-opener)? In contrast, the Alcohol Use Disorders Identification Test (AUDIT), a 10-item instrument, is designed to identify risky and harmful use. In several controlled trials conducted in primary care settings, it was found that brief, multicontact behavioral-counseling interventions reduced risky and harmful alcohol use. About one in 10 risky drinkers reduced their alcohol use to sensible levels for up to 1 year.³⁵

Reminder Systems

The USPSTF has created patient pocket guides that are based on its guidelines and that clinicians can use as reminder systems to promote patients' involvement in their own preventive care. These pocket guides are available on the Internet. There is one for all adults (http://www.ahrq.gov/ppip/adguide), one for adults older than 50 years (http://www.ahrq.gov/ppip/50plus/index.html), and one for women (http://www.ahrq.gov/ppip/healthywom.htm).

References

1. Kochanek KD, Smith BD: Deaths: Preliminary Data for 2002. National Center for Health Statistics, Hyattsville, Maryland, 2004http://www.cdc.gov/nchs/data/nvsr/nvsr52/nvsr52_13.pdf
2. McGinnis M: Actual causes of death in the United States. JAMA 270:2207, 1993
3. Woodwell DA, Cherry DK: National Ambulatory Medical Care Survey: 2002 Summary. Advance data from vital and health statistics; no. 346. National Center for Health Statistics, Hyattsville, Maryland, 2004 http://www.cdc.gov/nchs/data/ad/ad346.pdf
4. Frame PS, Carlson SJ: A critical review of periodic health screening using specific criteria. J Fam Pract 2:29, 1975
5. Guide to Clinical Preventive Services: An Assessment of the Effectiveness of 169 Interventions, 1st ed. US Preventive Services Task Force. Williams & Wilkins, Baltimore, 1989
6. Harris R, Helfand M, Woolf SH et al: Current methods of the third US Preventive Services Task Force: a review of the process. Am J Prev Med 20:21, 2001
7. Recommended adult immunization schedule—United States, October 2004–September 2005. MMWR Morb Mortal Wkly Rep 53:Q1, 2004http://www.cdc.gov/nip/recs/adult-schedule.pdf
8. Guzick D: Efficacy of screening for cervical cancer: a review. Am J Public Health 68:125, 1978
9. McCrory DC, Matcher DB, Bastian L: Evaluation of Cervical Cytology: Evidence Report Number 5, Summary Agency for Health Care Policy and Research. Agency for Health Care Policy and Research, Rockville, Maryland, 1999
10. Nanda K, McCrory DC, Myers E et al: Accuracy of the Papanicolaou test in screening for and follow-up of cervical cytologic abnormalities: a systematic review. Ann Intern Med 132:810, 2000
11. Holowaty P, Miller AB, Rohan T et al: Natural history of dysplasia of the uterine cervix. J Natl Cancer Inst 91:252, 1999
12. Mandel JS, Church TR, Ederer F et al: Colorectal cancer mortality: effectiveness of biennial screening for fecal occult blood. J Natl Cancer Inst 91:434, 1999
13. Kronborg O, Fenger C, Olsen J et al: Randomised study of screening for colorectal cancer with faecal-occult-blood test. Lancet 348:1467, 1996
14. Hardcastle J, Chamberlain J, Robinson M et al: Randomised controlled trial of faecal-occult-blood screening for colorectal cancer. Lancet 348:1472, 1996
15. Single flexible sigmoidoscopy screening to prevent colorectal cancer: baseline findings of a UK multicentre randomised trial. UK Flexible Sigmoidoscopy Screening Trial Investigators. Lancet 359:1291, 2002
16. Screening for colorectal cancer: recommendation and rationale. US Preventive Services Task Force. Ann Intern Med 137:129, 2002
17. Pignone M, Rich M, Teutsch SM et al: Screening for colorectal cancer in adults at average risk: a summary of the evidence for the U.S. Preventive Services Task Force. Ann Intern Med 137:132, 2002
18. van Dam J, Cotton P, Johnson CD et al: AGA future trends report: CT colonography. Gastroenterology 127:970, 2004
19. Cancer Facts and Figures. American Cancer Society. American Cancer Society, Atlanta, 2004
20. Gøtzsche PC, Olsen O: Is screening for breast cancer with mammography justifiable? Lancet 355:129, 2000
21. Humphrey LL, Helfand M, Chan BK et al: Breast cancer screening: a summary of the evidence for the U.S. Preventive Services Task Force. Ann Intern Med 137:347, 2002
22. Green BB, Taplin SH: Breast cancer screening controversies. J Am Board Fam Pract 16:233, 2003
23. Woloshin S, Schwartz LM, Byram SJ et al: Women's understanding of the mammography screening debate. Arch Intern Med 160:1434, 2000
24. Baines CJ: Mammography screening: are women really giving informed consent? J Natl Cancer Inst 95:1508, 2003
25. Berry D: Commentary: screening mammography: a decision analysis. Int J Epidemiol 33:68, 2004
26. Schwartz LM, Woloshin S, Sox HC et al: US women's attitudes to false positive mammography results and detection of ductal carcinoma in situ: cross sectional survey. BMJ 320:1635, 2000
27. Thomas DB, Gao DL, Ray RM et al: Randomized trial of breast self-examination in Shanghai: final results. J Natl Cancer Inst 94:1445, 2002
28. Semiglazov VF, Manikhas AG, Moiseenko VM et al: [Results of a prospective randomized investigation [Russia (St. Petersburg)/WHO] to evaluate the significance of self-examination for the early detection of breast cancer]. Voprosy Onkologii 49:434, 2003
29. Gohagan JK, Prorok PC, Kramer BS et al: Prostate cancer screening in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial of the National Cancer Institute. J Urol 151:1283, 1994
30. Schroder FH, Kranse R, Rietbergen J et al: The European randomized study of screening for prostate cancer (ERSPC): an update. Eur Urol 35:539, 1999
31. Coley CM, Barry MJ, Fleming C et al: Early detection of prostate cancer: part I: prior probability and effectiveness of tests. Ann Intern Med 126:394, 1997
32. Graversen PH, Corle DK, Nielsen KT et al: Radical prostatectomy versus expectant primary treatment in stages I and II prostatic cancer: a fifteen-year follow-up. Urology 36:493, 1990
33. Wilt TJ, Brawer MK: The prostate cancer intervention versus observation trial (PIVOT). Oncology 8:1133, 1997
34. Diagnostic and Statistical Manual of Mental Disorders, 4th ed. American Psychiatric Association, Washington, DC, 1994
35. Whitlock EP, Polen MR, Green CA et al: Behavioral counseling interventions in primary care to reduce risky/harmful alcohol use by adults: a summary of the evidence for the U.S. Preventive Services Task Force. Ann Intern Med 140:557, 2004
36. Scholes D, Stergachis A, Heidrich FE et al: Prevention of pelvic inflammatory disease by screening for cervical chlamydial infection. N Engl J Med 334:1362, 1996
37. Kretsinger K, Broder KR, Cortese MM et al: Preventing tetanus, diphtheria, and pertussis among adults: use of tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccine: recommendations of the Advisory Committee on Immunization Practices (ACIP) and recommendation of ACIP, supported by the Healthcare Infection Control Practices Advisory Committee (HICPAC), for use of Tdap among health-care personnel. MMWR Recomm Rep 55:1, 2006

Editors: Dale, David C.; Federman, Daniel D.