Screening and Prevention of Disease¶
Chapter 6 | Part 1: The Profession of Medicine · Part 1 – The Profession of Medicine · Chapter 6
Key Clinical Points¶
- Screening requires a latent stage, effective treatment, and an acceptable test (WHO 1968 Principles).
- Lead time bias creates a false appearance of improved survival by moving the date of diagnosis earlier.
- Length time bias favors the detection of slowly progressing diseases, skewing survival statistics.
- Overdiagnosis is significant in breast cancer (15–40%) and prostate cancer (15–37%).
- Cost-effectiveness threshold for screening is $50,000–100,000 per quality-adjusted life-year (QALY) saved.
- Lung cancer screening via low-dose CT reduces mortality by 20% in adults 50–80 with a 20-pack-year history who currently smoke or quit within 15 years.
- Colorectal cancer screening: FOBT saves ~3 lives/1000; Colonoscopy saves ~20–24 lives/1000 over 25 years.
- Shared decision-making is essential for prostate and colon cancer due to complex benefit-to-harm ratios.
- Smoking cessation is a primary preventive measure, with significant impact on life expectancy.
- Age is the primary factor for determining screening recommendations; 'sunset' screening is applied when life expectancy is limited.
DEFINITION & OVERVIEW¶
• Core Concept: Screening and prevention are proactively administered to healthy individuals rather than in response to symptoms. • Primary Goal: Prevent disease or detect it early enough that intervention is more effective. • Methodologies: ◦ Biochemical (e.g., cholesterol, glucose) ◦ Physiologic (e.g., blood pressure, growth curves) ◦ Radiologic (e.g., mammogram, bone densitometry) ◦ Cytologic (e.g., Pap smear) ◦ Omics (Germline genomic data, polygenic risk scores, proteomics, metabolomics) ◦ Imaging (e.g., Coronary CT for statin therapy decisions) • Emerging Technologies: ◦ New imaging modalities to detect changes at cellular and subcellular levels. ◦ Germline genomic data and polygenic risk scores for risk stratification. ◦ Omics data and circulating DNA/mutations in stool/blood for early detection.
World Health Organization Principles¶
• WHO 1968 Principles: The basic principles of screening populations for disease include: ◦ Condition must be an important health problem. ◦ There must be a treatment available. ◦ Facilities for diagnosis and treatment must be available. ◦ There must be a latent stage of the disease. ◦ There must be a test or examination for the condition. ◦ The test must be acceptable to the population. ◦ The natural history of the disease must be adequately understood. ◦ There must be an agreed policy on whom to treat. ◦ Cost of finding a case must be balanced in relation to overall medical expenditure.
EPIDEMIOLOGY¶
• Leading Causes of Mortality (US): Heart diseases, malignant neoplasms, chronic obstructive pulmonary disease, accidents, and cerebrovascular diseases. • Global Health Burden: Malaria, malnutrition, AIDS, tuberculosis, and violence.
Lifetime Cumulative Risk¶
• Risk Statistics (Table 6-2): ◦ Breast cancer for women: 10% ◦ Colon cancer: 6% ◦ Cervical cancer for women: 2% (unscreened, no HPV vaccine) ◦ Domestic violence for women: Up to 15% ◦ Hip fracture for white women: 16%
ETIOLOGY & PATHOPHYSIOLOGY¶
• Requirement: Natural history of disease must be understood for screening to be effective. • Latent Phase: A long preclinical phase where early treatment increases the chance of cure is a hallmark of many cancers. • Clinical Examples: ◦ Polypectomy prevents progression to colon cancer. ◦ Early identification of hypertension or hyperlipidemia allows therapeutic interventions. ◦ Lung cancer: Historically challenging because most tumors are not curable by the time they are detected on chest x-ray. ◦ Prostate cancer: Often indolent; mortality often caused by competing morbidities (e.g., coronary artery disease).
Latent Phase & Natural History¶
• Duration: Depends on the resolution of the screening test. • Prostate Cancer: Early detection may not lead to a difference in mortality rate due to its indolent nature; uncertainty about natural history leads to controversy regarding treatment.
CLINICAL FEATURES¶
• Target Population: Asymptomatic individuals. • Detection: Abnormalities identified on screening tests (e.g., elevated PSA, abnormal mammogram). • Complications of Screening: ◦ Incidentalomas or adverse events. ◦ Overdiagnosis: Identifying disease that would not have presented clinically in the patient's lifetime.
Screening Targets¶
• Diseases/Conditions: ◦ Cardiovascular disease ◦ Diabetes ◦ Cancer (Breast, Colon, Cervical, Lung, Prostate) ◦ Infections (HIV, Hepatitis C, Chlamydia, Gonorrhea) ◦ Mental Health (Depression, Anxiety) ◦ Substance Use (Alcohol, Tobacco) ◦ Violence (Domestic, Intimate Partner)
DIFFERENTIAL DIAGNOSIS¶
• Distinction: Screening findings must be distinguished from incidentalomas. • False-Positives: Occur with nearly all screening tests. • Mimickers: Benign conditions identified on imaging or labs.
False-Positive Results¶
• Mammography: Abnormality identified that is not malignant, requiring biopsy or follow-up. • Chest CT: Identification of non-malignant abnormalities. • Pap Smears: Identifies a wide range of potentially premalignant states; only a small percentage progress to invasive cancer. • Risk Link: Risk of overdiagnosis is tied to the risk of false-positive tests.
INVESTIGATIONS & DIAGNOSIS¶
• Evidence Standards: ◦ Gold Standard: Randomized controlled trials (RCTs) with mortality outcomes. ◦ Alternative: Observational studies (case-control) used when RCTs are not feasible (e.g., colonoscopy). ◦ Ecologic data used for cervical cancer screening to demonstrate mortality decline. • Primary Endpoints: Must be disease incidence or mortality, NOT length of disease survival. • Biases: ◦ Lead time bias: Screening identifies a case before it would have presented clinically, creating a false appearance of improved survival. ◦ Length time bias: Screening is more likely to identify slowly progressing diseases than rapidly progressing ones.
USPSTF Recommended Screening Tests (Table 6-4)¶
• Abdominal aortic aneurysm: Ultrasound in men 65–75 who have ever smoked (Once). • Alcohol misuse: Alcohol Use Disorders Identification Test (AUDIT) for all adults. • Breast cancer: Mammography with or without clinical breast examination; women 40–75 (Every 2 years). • Cervical cancer: ◦ Pap smear: Women 21–65 (Every 3 years). ◦ Pap smear and/or HPV testing: Women 30–65 (Every 5 years if HPV negative). • Chlamydia/gonorrhea: Nucleic acid amplification test on urine or cervical swab; sexually active women <25. • Colorectal cancer: ◦ Fecal occult blood testing: 45–75 (Every year). ◦ Fecal immunochemical-DNA: 45–75 (Every 1–3 years). ◦ Sigmoidoscopy: 45–75 (Every 5 years). ◦ Colonoscopy (or occult blood combined with sigmoidoscopy): 45–75 (Every 10 years). • Depression/anxiety: Screening questions for all adults. • Diabetes: Fasting blood glucose or HgbA1c; overweight, obese, or hypertensive adults (Every 3 years). • Hepatitis C: Anti-HCV antibody followed by confirmatory PCR; ages 18–79 (Once). • HIV: Reactive immunoassay or rapid HIV followed by confirmatory test; ages 15–65 (At least once). • Hyperlipidemia: Cholesterol; ages 40–75. • Hypertension: Blood pressure; all adults (Periodically). • Intimate partner violence: Screening questions for women of childbearing age. • Lung cancer: Low-dose CT; adults 50–80 with a 20-pack-year smoking history who currently smoke or quit within 15 years (Yearly). • Obesity: Body mass index; all adults. • Osteoporosis: DEXA; women >65 or >60 with risk factors.
Life Expectancy Gains (Table 6-3)¶
- Mammography (Women 40–50) → 0–5 days
- Mammography (Women 50–70) → 1 month
- Smoking cessation (35-year-old) → 3–5 years
- Exercise (40-year-old man, 30 min, 3x/week) → 9 months–2 years Note: These are average population gains, not individual guarantees.
MANAGEMENT & TREATMENT¶
• Intervention Types: Counseling, vaccinations, medications, and surgery. • Shared Decision-Making: Essential when benefit-to-harm ratio is uncertain (e.g., prostate cancer). • Implementation Strategies: ◦ EHR reminder systems ◦ Standing orders for nurses/staff ◦ Age-specific flow sheets ◦ Use of age categories to guide implementation. • Clinical Focus: For patients with advanced disease and limited life expectancy, focus shifts from screening to conditions affecting quality/length of life. • Timing: Benefit for many tests does not accrue until 5–10 years of follow-up. • Age Limit: Fewer data support continuing screening past age 75.
Preventive Interventions (Table 6-5)¶
- Adult Immunization: ◦ COVID-19 (>18) ◦ Tetanus-diphtheria (>18, Every 10 years) ◦ Varicella (Susceptibles only, >18, Two doses) ◦ MMR (Women, childbearing age, One dose) ◦ Pneumococcal (>64, 20 valent option or 15/23) ◦ Influenza (>18, Yearly) ◦ HPV (Up to age 27, if not done prior) ◦ Zoster (>60, Once)
- Chemoprevention: ◦ Aspirin: Cardiovascular disease, aged 40–59 with ≥10% 10-year risk. ◦ Folic acid: Neural tube defects; women planning or capable of pregnancy. ◦ Tamoxifen/raloxifene: Breast cancer, high-risk women. ◦ Vitamin D: Fracture/falls, >64 at increased risk for falls.
Preventive Counseling (Table 6-6)¶
- Alcohol and drug use
- Genetic counseling (BRCA1/2) for high-risk women
- Nutrition and diet
- Sexually transmitted infections
- Sun exposure
- Tobacco use
PROGNOSIS & COMPLICATIONS¶
• Harms of Screening: ◦ Side effects from medications/vaccines ◦ False-positive results ◦ Overdiagnosis ◦ Anxiety ◦ Radiation exposure (Mammography, Chest CT) • Cost-Effectiveness: Target is $50,000–100,000 per quality-adjusted year of life saved. • Lung Cancer Impact: Low-dose CT reduces mortality by 20% in eligible individuals. • Colorectal Cancer Impact: ◦ FOBT: ~3 lives/1000 ◦ Colonoscopy: ~20–24 lives/1000 over 25 years.
Harms and Biases¶
• Overdiagnosis Rates: ◦ Breast cancer: 15–40% may never present clinically. ◦ Prostate cancer: 15–37% may never present clinically. • Lead Time Bias: Moves date of diagnosis earlier, creating false perception of improved survival. • Length Time Bias: Favors detection of slow-progressing disease.
SPECIAL CONSIDERATIONS¶
• Age as Risk Factor: Primary factor for determining screening recommendations. • Risk Factors: Specific tests based on smoking, family history, etc. • Family History: Colorectal cancer; start screening 10 years before the age of the youngest affected relative. • Pregnancy: ◦ Contraindicated: MMR, Varicella ◦ HPV vaccine: Up to age 27 • Elderly: 'Sunset' screening for advanced diseases/limited life expectancy.
Age-Specific Mortality and Prevention (Table 6-7)¶
- Age 15–24: ◦ Risks: Accident, Homicide, Suicide, Malignancy, Heart disease. ◦ Interventions: Seat belts/helmets; diet/exercise; alcohol awareness; vaccinations (tetanus, diphtheria, hepatitis B, MMR, rubella, varicella, meningitis, HPV, COVID-19); gun safety; substance abuse; domestic violence; depression/suicide screening; Pap smear (>21); skin/breast/testicular exams; UV protection; BMI measurement; tobacco cessation; STD prevention (Chlamydia, Gonorrhea, Hep B, Syphilis); Hep C (18–79); HIV; Influenza.
- Age 25–44: ◦ Risks: Accident, Malignancy, Heart disease, Suicide, Homicide, HIV. ◦ Interventions: Smoking cessation; family history assessment; cardiac risk factors (diabetes, hyperlipidemia); alcohol/liver health; mammography at age 40.
- Age 45–64: ◦ Risks: Malignancy, Heart disease, Accident, Diabetes, Cerebrovascular, COPD, Liver disease, Suicide. ◦ Interventions: Prostate cancer (PSA/DRE) at 50; Colorectal screening at 45/50; update vaccinations at 50; Pneumococcal for smokers at 50; Zoster at 60; Mammography by 50; Lung cancer (50–80 if 20-pack-year history).
- Age ≥65: ◦ Risks: Heart disease, Malignancy, Cerebrovascular, COPD, Alzheimer’s, Influenza/Pneumonia, Diabetes, Kidney disease, Accidents, Septicemia. ◦ Interventions: AAA ultrasound (men 65–75 who smoked); pulmonary function testing; osteoporosis screening; influenza/pneumococcal vaccination; vision/hearing/fall prevention; elder abuse screening.
KEY PEARLS & CLINICAL TRAPS¶
• Safety First: Screening must be low risk to have an acceptable benefit-to-harm ratio. • Bias Awareness: Lead time and length time bias are critical for interpreting survival data correctly. • Overdiagnosis: Significant concern in breast and prostate cancer. • Cost-Effectiveness: Target is $50,000–100,000 per quality-adjusted year of life saved. • Shared Decision-Making: Essential for prostate and colon cancer. • Lung Cancer Criteria: 20-pack-year history + current smoker or quit <15 years. • Family History Rule: Start colorectal screening 10 years before the youngest relative's diagnosis age. • Sunset Screening: Appropriate for patients with advanced disease/limited life expectancy.
Clinical Pearls¶
• WHO 1968 Principles are the foundation of screening. • Omics data (genomics, proteomics, metabolomics) are emerging for risk prediction. • Vaccinations are effective with limited side effects. • Smoking cessation is the single greatest preventive health care measure. • EHR systems assist with adherence to routine screening.
Reference Tables¶
TABLE 6-1 Principles of Screening The condition should be an important health problem. There should be a treatment for…¶
Harrison's 22e, p.37
| 6 | Screening and Prevention of Disease Gary J. Martin |
|---|---|
TABLE 6-1 Principles of Screening
- The condition should be an important health problem.
- There should be a treatment for the condition.
- Facilities for diagnosis and treatment should be available.
- There should be a latent stage of the disease.
- There should be a test or examination for the condition.
- The test should be acceptable to the population.
- The natural history of the disease should be adequately understood.
- There should be an agreed policy on whom to treat.
- The cost of finding a case should be balanced in relation to overall medical
expenditure.
TABLE 6-2 Lifetime Cumulative Risk Breast cancer for women Colon cancer Cervical cancer for women a Domestic violence…¶
Harrison's 22e, p.37
| Breast cancer for women | 10% |
|---|---|
| Cervical cancer for womena | 2% |
| Hip fracture for white women | 16% |
TABLE 6-3 Estimated Average Increase in Life Expectancy for a Population¶
Harrison's 22e, p.38
| SCREENING OR PREVENTIVE INTERVENTION | AVERAGE INCREASE |
|---|---|
| Mammography: | |
| Women, 40–50 years | 0–5 days |
| Women, 50–70 years | 1 month |
| Getting a 35-year-old smoker to quit | 3–5 years |
TABLE 6-4 Screening Tests Recommended by the U.S. Preventive Services Task Force for Average-Risk Adults DISEASE…¶
Harrison's 22e, p.39
| DISEASE | TEST | POPULATION | FREQUENCY | CHAPTER |
|---|---|---|---|---|
| Abdominal aortic aneurysm | Ultrasound | Men 65–75 who have ever smoked | Once | |
| Alcohol Use Disorders Identification Test | All adults | Unknown | ||
| Breast cancer | Mammography with or without clinical breast examination |
Women (40?) 50–75 | Every 2 years | 84 |
| Pap smear Pap smear and/or HPV testing |
Women 21–65 Women 30–65 |
Every 3 years Every 5 years if HPV negative |
||
| Chlamydia/gonorrhea | Nucleic acid amplification test on urine or cervical swab |
Sexually active women <25 | Unknown | 194 |
| Fecal occult blood testing Fecal immunochemical-DNA Sigmoidoscopy Colonoscopy (or occult blood testing combined with sigmoidoscopy) |
45–75 45–75 45–75 45–75 |
Every year Every 1–3 years Every 5 years Every 10 years |
||
| Depression+anxiety | Screening questions | All adults | Periodically | |
| Fasting blood glucose or HgbA1c | Adults overweight, obese, or with hypertension |
Every 3 years | ||
| Hepatitis C | Anti-HCV antibody followed by confirmatory PCR |
18–79 | Once | 350 |
| Reactive immunoassay or rapid HIV followed by confirmatory test |
15–65 | At least once | ||
| Hyperlipidemia | Cholesterol | 40–75 | Unknown | 419 |
| Blood pressure | All adults | Periodically | ||
| Intimate partner violence | Screening questions | Women of childbearing age | Unknown | |
| Low-dose computed tomography | Adults 50–80 years who have a 20-pack-year smoking history and currently smoke or have quit within the past 15 years |
Yearly | ||
| Obesity | Body mass index | All adults | Unknown | 414 |
| DEXA | Women >65 or >60 with risk factors | Unknown |
TABLE 6-5 Preventive Interventions Recommended for Average-Risk Adults INTERVENTION Adult immunization¶
Harrison's 22e, p.40
| INTERVENTION | DISEASE | POPULATION | FREQUENCY | CHAPTER |
|---|---|---|---|---|
| Adult immunization | 127, 129 | |||
| COVID-19 Tetanus-diphtheria |
>18 >18 |
Every 10 years | ||
| Varicella | Susceptibles only, >18 | Two doses | ||
| Measles-mumps-rubella | Women, childbearing age | One dose | ||
| Pneumococcal | >64 | 20 valent option or 15/23 | ||
| Influenza | >18 | Yearly | ||
| Human papillomavirus | Up to age 27 | If not done prior | ||
| Zoster | >60 | Once | ||
| Chemoprevention | ||||
| Aspirin | Cardiovascular disease | Aged 40–59 years with a ≥10% 10-year cardiovascular disease risk (bleeding risk may = benefit for some groups) |
||
| Folic acid | Neural tube defects in baby | Women planning or capable of pregnancy | ||
| Tamoxifen/raloxifene | Breast cancer | Women at high risk for breast cancer | ||
| Vitamin D | Fracture/falls | >64 at increased risk for falls |
TABLE 6-6 Preventive Counseling Recommended by the U.S. Preventive Services Task Force¶
Harrison's 22e, p.40
| TOPIC | CHAPTER REFERENCE |
|---|---|
| Alcohol and drug use | 464, 467, 468 |
| Nutrition and diet | 343, 344 |
| Sun exposure | 64 |
TABLE 6-7 Age-Specific Causes of Mortality and Corresponding Preventive Options¶
Harrison's 22e, p.41
| 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) • Assess and update vaccination status (tetanus, diphtheria, hepatitis B, MMR, rubella, varicella, meningitis, HPV, COVID-19) • 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 after age 21 (4) • Discuss skin, breast awareness, and testicular self-examinations (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 and gonorrhea screening and contraceptive counseling for sexually active females, discuss STD prevention • Hepatitis B, and syphilis testing if there is high-risk sexual behavior(s) or any prior history of sexually transmitted disease • Hepatitis C screening starting at age 18 to 79 • HIV testing • Continue annual influenza vaccination |
| 1. Accident 2. Malignancy 3. Heart disease 4. Suicide 5. Homicide 6. HIV |
||
| 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 examination at age 50 (or possibly earlier in African Americans or patients with family history) (1) • Begin colorectal cancer screening at age 45 or 50 with fecal occult blood testing, stool DNA testing, flexible sigmoidoscopy, or colonoscopy (1) • Reassess and update vaccination status at age 50 and vaccinate all smokers against Streptococcus pneumoniae at age 50 (6) • Consider screening for coronary disease in higher-risk patients (2,5) • Zoster vaccination at age 60 • Begin mammography screening by age 50 • Lung cancer screening at age 50–80 years if a 20-pack-year smoking history and currently smoke or have quit within the past 15 years, yearly |
| 1. Heart disease 2. Malignancy 3. Cerebrovascular disease 4. Chronic lower respiratory disease 5. Alzheimer’s disease 6. Influenza and pneumonia 7. Diabetes mellitus 8. Kidney disease 9. Accidents 10. Septicemia |