Figure 105.1. Lead-time bias.

Source: Reprinted with permission from Welch et al. Overstating the evidence from lung cancer screening: The International Early Lung Cancer Action Program (I-ELCAP) Study. Arch Intern Med. 2007;167:2289–2895. © 2008 American Medical Association. All rights reserved.

    In the United States there are several sources for physicians to obtain up-to-date practice guidelines on evidence-supported health screening information. The United States Preventative Services Task Force (USPSTF) under the auspices of the Agency for Healthcare Research and Quality provides regularly updated reviews of the evidence to support a number of preventative services and grades this evidence with recommendations A–D and I (see box 105.1 and table 105.1). The American College of Physicians (ACP) also provides guidelines and consensus statements of screening and preventative services based on detailed reviews of the literature. In addition, screening recommendations are produced by various subspecialty professional societies (such as the American Gastroenterological Association recommendations on colorectal cancer screening as endorsed by the American Cancer Society [ACS] or the US Centers for Disease Control and Prevention [CDC] recommendations on HIV screening).

    This chapter reviews current health screening recommendations for cancer and cardiovascular disease, lifestyle issues including substance use, and common infectious diseases.

Box 105.1 UNITED STATES PREVENTATIVE SERVICES TASK FORCE (USPSTF) RATINGS OF STRENGTH OF RECOMMENDATIONS

CANCER SCREENING

According to the ACS it is estimated that 585,720 people will die from cancer-related mortality in 2014; cancer is the second most common cause of death in the United States. Lung, breast, cervical, prostate, and colorectal cancers account for nearly 50% of cancer deaths. Importantly, mortality of breast, colon, cervical, and prostate cancer has decreased—screening is likely responsible for at least a portion of this decline (although mortality from lung cancer has decreased, this is largely due to a decreased prevalence of smoking; see figures 105.3 and 105.4).

BREAST CANCER

Mammography remains the standard of care for breast cancer screening, with a maximal benefit that increases with age. Evidence supports a small but clinically significant mortality reduction from screening for breast cancer, particularly among women 50 years of age and older. For women between the ages of 40 and 50, while the relative risk reduction from mammography is similar the absolute benefit from screening is much smaller. In one analysis, 1904 women age 39 to 49 would have to be screened to prevent one death as compared to 1339 women age 50 to 69. Published guidelines reflect this debate. The ACS recommends mammography every 1–2 years, whereas the ACP recently reviewed the literature and updated their own clinical practice guidelines, recommending that any decision to screen women 40–49 years of age take into account the risk of false-positive results and an individual’s unique risk profile. Similarly the USPSTF also recently revised its recommendations for women between the ages of 40–49, calling for an assessment of the individual patient’s risk profile and an understanding of the potential benefits and harms of screening.

    In an effort to improve the test characteristics of mammography, several large trials have examined the role of magnetic resonance imaging (MRI) as a screening modality. These studies confirm that high-risk women (defined as a cumulative lifetime risk of ≥15%, including those with inherited predispositionsofBRCA-1 and BRCA-2) benefit from the increased sensitivity of MRI screening. Sensitivity of MRI to detect invasive cancer was significantly improved compared to that for mammography, 79.5% versus 33%. In light of these data, the ACS currently recommends MRI screening for high-risk women. The Gail Model (available online at http://www.acs.org) is one of several prospectively validated models for calculating lifetime breast cancer risk and can facilitate shared decision making between physician and patient. Because mammography can still detect breast cancers that are missed by MRI, high-risk women should be screened with both modalities.

CERVICAL CANCER

The introduction of cervical cancer screening with the Papanicolaou (Pap) test has led to a dramatic reduction in the incidence of invasive of cervical cancer. Recently revised guidelines for Pap testing recommend starting to screen women at the age of first sexual activity or 21 years, whichever is first. Cytology-only screening is recommended for women age 20 to 29 years, which may be performed every 3 years. Over 99% of cervical cancer may be attributed to infection with human papilloma virus (HPV), which is the highest attributable risk for any common malignancy. In light of this association there has been considerable interest in the use of viral probes as a standalone or adjuvant screening tool. HPV assays demonstrate a significantly higher sensitivity than Pap testing. For women over the age of 30 years, cytology-based testing in conjunction with HPV testing is recommended every 5 years. When used in conjunction with Pap tests, the additional sensitivity of HPV assays can provide a useful tool with which to triage those with abnormal cytology for colposcopy. Because the majority of HPV infections resolve without intervention, HPV probes may prove useful as standalone screening tests once a woman is of sufficient age that HPV detection likely reflects persistent infection.

PROSTATE CANCER

The benefit from prostate cancer screening is controversial. Since the advent of prostate specific antigen (PSA) for screening, prostate cancer mortality in the United States has declined, although this may be in part to overdetection bias discussed above. There was a dramatic increase in incidence of prostate cancer in the early 1990s shortly after PSA testing became available, the majority of which was localized disease. After 11 years of follow-up, the European Randomized Study of Screening of Prostate Cancer showed a small absolute reduction in prostate cancer mortality, although 1055 men would need to be screened and 37 men treated over that time interval to avoid one prostate cancer death. The ACS recommends consideration of screening starting at age 50 (or at age 40 for high-risk men including African Americans and those with a family history of prostate cancer) but only after a discussion of the risks and benefits. The American Society of Clinical Oncologists (ASCO) also recommends a tailored approach, factoring a man’s preferences and life expectancy. In July 2012 the USPSTF revised their recommendations, issuing a “D” recommendation for PSA-based prostate cancer screening of men at any age. In its final recommendation statement published May 2012, the USPSTF concludes that “there is moderate certainty that the benefits of PSA-based screening for prostate cancer do not outweigh the harms.” In an effort to improve the test characteristics of the PSA, some have advocated using free PSA values or PSA velocity, although the utility of these strategies remains unclear. Velocity may be useful to identify those with lower absolute PSA values who may have clinically significant cancer (e.g., ≥0.35 ng/mL/year if total PSA <4 ng/mL); similarly, in older patients with PSA values >4 ng/mL, a velocity >1.25 ng/mL/year may help to exclude those with clinically indolent cancers. However, clinical decision making based on PSA velocity has not yet demonstrated a mortality benefit in a prospective, randomized trial.

COLORECTAL CANCER

Routine screening for colorectal cancer (CRC) at age 50 (or earlier with a high-risk personal or family history) may be performed by several different strategies. Fecal occult blood testing (FOBT) was the first test employed for screening and remains the only CRC screening technique with a proven mortality benefit in randomized controlled trials. An extensive literature including well-performed case-control studies support alternative screening strategies, including FOBT coupled with flexible sigmoidoscopy every 5 years or colonoscopy every 10 years. Computed tomographic (CT) colonography (so-called virtual colonoscopy) has attracted significant attention in recent studies. Although it appears to have a similar specificity for larger adenomas and polyps as compared to optical colonoscopy, its ability to detect smaller polyps <1 cm is unclear.

CONTROVERSIES IN SCREENING LUNG CANCER

Lung cancer has long been considered a potential target for cancer screening. It is the most common cause of cancer-related mortality in the United States, with an estimated 215,020 new cases and 161,840 deaths in 2008. Unfortunately, early studies of screening high-risk patients with chest radiology and sputum cytology failed to demonstrate a mortality benefit despite detection of an increased number of malignant lesions. The International Early Lung Cancer Action Program (I-ELCAP) study showed that the majority of asymptomatic lung cancers identified by low-dose spiral CT were early-stage disease. In 2011, the National Lung Screening Trial demonstrated that annual CT scan screening of former or current heavy smokers resulted in a 20% relative reduction in mortality. However, the absolute benefit was less than 1%, and screening was associated with a high rate of false-positive results that could lead to unnecessary invasive procedures.

CARDIOVASCULAR SCREENING

HYPERTENSION

The Joint National Commission on the Prevention, Detection, Evaluation and Treatment of High Blood Pressure (JNC7) defines stage I hypertension as systolic blood pressure >140 mm Hg and/or a diastolic pressure >90 mm Hg. Most recent estimates indicate that over one-quarter of Americans have hypertension, a leading cause of cardiovascular morbidity and mortality. JNC7 recommends screening all adults for high blood pressure, a recommendation also endorsed by the USPSTF and AHA. Although the optimal screening interval is unclear, the JNC7 recommends screening all adults with an initial blood pressure of <120/80 mm Hg every 2 years, and annually if prehypertensive (120–139/80–90 mm Hg).The JNC8 guidelines has markedly changed the blood pressure goals and the approach to treatment. This is discussed in more detail in Chapter 84.

ABDOMINAL AORTIC ANEURYSMS

Abdominal aortic aneurysms (AAA) are common, with an estimated prevalence of 8% among elderly men. These aneurysms pose considerable risk to affected individuals, as rupture is associated with a mortality rate as high as 90% in selected populations. Although open repair of these aneurysms carries an operative mortality of approximately 4%, newer endovascular repair techniques have also strengthened the argument in favor of early detection. Because abdominal vascular ultrasonography demonstrates favorable test characteristics of high sensitivity and specificity, and surgical repair of AAAs ≥5.5 cm decreases AAA-specific mortality, the USPSTF has issued a grade B recommendation for one-time screening for AAA by ultrasonography for current or former male smokers aged 65–75 years. Coverage for this screening benefit is variable, although as of 2014 Medicare does provide coverage for men who have smoked more than 100 cigarettes and men and women with a family history of AAA.

CHOLESTEROL/LIPID SCREENING

Epidemiological studies have convincingly demonstrated that high levels of low-density lipoprotein (LDL) cholesterol are atherogenic and that elevated levels increase the risk of both first and recurrent cardiovascular events. In addition, clinical trials have confirmed that lowering cholesterol by pharmacologic therapy, especially with HMG-CoA reductase inhibitors, decreases coronary heart disease (CHD) incidence and mortality. The National Cholesterol Education Program (NCEP) and Adult Treatment Panel III (ATP III) sponsored by the National Heart Lung and Blood Institute last updated their guidelines in 2004. The ATP III recommendations do not define the age at which to begin screening patients, although the Framingham Risk Score used to calculate an individual’s 10-year risk can be applied for men and women ≥20 years of age. The American College of Cardiology (ACC) and American Heart Association (AHA), cholesterol guidelines developed in conjunction with the National Heart, Lung, and Blood Institute (NHLBI) have now updated the ATP III guidelines (alluded to above). The guidelines represent a departure from ATPIII because they abandon specific target levels of LDL cholesterol (Figure 105.5). Instead, the new guidelines focus on defining groups for whom LDL lowering is proven to be most beneficial. According to the guideline, in these patient groups atherosclerotic cardiovascular disease(ASCVD) risk reduction “clearly outweighs the risk of adverse events.” The groups are:

    1. Individuals with clinical ASCVD

    2. Individuals with primary elevations of LDL–C >190 mg/dL

    3. Diabetes patients aged 40 to 75 years with LDL–C 70 to189 mg/dL and without clinical ASCVD

    4. Individuals without clinical ASCVD or diabetes with LDL–C 70 to189 mg/dL and estimated 10-year ASCVD risk >7.5%.

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