SCREENING: DEFINITION“The PRESUMPTIVE identification of UNRECOGNIZEDdisease or defect by the application of tests, exams orother procedures which can be applied RAPIDLY to sort outapparently well persons who PROBABLY have a diseasefrom those who PROBABLY do not”* Key Elements: disease/disorder/defect screening test population *Commission on Chronic Illness, 1957
Screening Definition: Presumptive identification of an unrecognized disease or defect by the application of tests, examinations, or other procedures. Classifies asymptomatic people as likely or unlikely to have a disease or defect. Usually not diagnostic. Scr eeni ng 3
ScreeningPurpose: Delay onset of symptomatic or clinical disease. Improve survival. Scr eeni ng 4
ScreeningFor screening to be successful you need a: Suitable disease Suitable test Suitable screening program Scr eeni ng 5
Suitable Disease Has serious consequences Is progressive Disease treatment must be effective at an earlier stage Prevalence of the detectable pre-clinical phase must be high Examples of suitable diseases: breast cancer, cervical cancer, hypertension Scr eeni ng 7
Natural History of Disease 20 30 40 50 60 70 Years A B C D Biological Disease Symptoms Death Onset Detectable Develop By Screening Scr eeni ng 8
Natural History of Disease Total pre-clinical phase = A to C (Age 30 to Age 60) = 30 years Detectable pre-clinical phase (DPCP) = B to C (Age 45 to Age 60) = 15 years Scr eeni ng 9
Natural History of Disease DPCP varies with the test, the disease, and the individual Lead Time: Duration of time by which the diagnosis is advanced as a result of screening. B to C (Age 45 to Age 60) = 15 years Scr eeni ng 10
Suitable Test Ideally, its inexpensive, easy to administer, has minimal discomfort has high level of validity and reliability Valid Test: Does what its supposed to do, that is, correctly classify people with pre- clinical disease as positive and people without pre-clinical disease as negative Scr eeni ng 11
Suitable Test Reliable Test: Gives you same results on repetition Validity is more important than reliability Scr eeni ng 12
Suitable Test Disease Status (Truth) Yes No Total Positive a b a+bScreening Negative c d c+dTest Result Total a+c b+d a + b + c+ d Scr eeni ng 13
Suitable TestMeasures of test validitySensitivity - enables you to pick up the cases of disease Sensitivity = a / a + c = those that test positive / all with disease Scr eeni ng 14
Issues in Screening Disease-Disease/disorder should be an important public healthproblem High prevalence Serious outcome-Early Detection in asymptomatic (pre-clinical)individuals is possible-Early detection and treatment can affect the course ofdisease (or affect the public health problem?)
Criteria for Evaluating a Screening Test•Validity: provide a good indication of who does anddoes not have disease -Sensitivity of the test -Specificity of the test•Reliability: (precision): gives consistent results whengiven to same person under the same conditions•Yield: Amount of disease detected in the population,relative to the effort -Prevalence of disease/predictive value
Validity of Screening Test (Accuracy)- Sensitivity: Is the test detecting true cases ofdisease? (Ideal is 100%: 100% of cases aredetected)-Specificity: Is the test excluding those withoutdisease? (Ideal is 100%: 100% of non-cases arenegative)
Screening for Glaucoma using IOP True Cases of Glaucoma Yes No IOP > 22: Yes 50 100 No 50 1900 (total) 100 2000Sensitivity = 50% (50/100) FalseNegative=50%Specificity = 95% (1900/2000) False
Where do we set the cut-off for a screening test? Consider: -The impact of high number of false positives: anxiety, cost of further testing -Importance of not missing a case: seriousness of disease, likelihood of re-screening
Yield from a Screening Test for Disease X Predictive Value Screening Test XX X X X X Negatives Positives
Yield from the Screening Test: Predictive Value•Relationship between Sensitivity, Specificity, andPrevalence of Disease Prevalence is low, even a highly specific test willgive large numbers of False Positives•Predictive Value of a Positive Test (PPV): Likelihoodthat a person with a positive test has the disease•Predictive Value of a Negative Test (NPV): Likelihoodthat a person with a negative test does not have thedisease
Screening for Glaucoma using IOP True Cases of Glaucoma Yes No IOP > 22: Yes 50 100 No 50 1900 (total) 100 2000Specificity = 95% (1900/2000) FalsePositive=5%Positive Predictive Value =33%
How Good does a Screening Test have to be?-Seriousness of disease, consequences of high falsepositivity rate: -Rapid HIV test should have >90% sensitivity, 99.9%specificity -Screen for nearsighted children proposes 80%sensitivity, >95% specificity -Pre-natal genetic questionnaire could be 99%sensitive, 80% specific
Principles for Screening Programs1. Condition should be an important health problem2. There should be a recognizable early or latent stage3. There should be an accepted treatment for persons with condition4. The screening test is valid, reliable, with acceptable yield5. The test should be acceptable to the population to be screened6. The cost of screening and case finding should be economically balanced in relation to medical care as a whole
Lead Time Bias screen-detectable clinically evident death 5 years clinically evident death 2 years
Lead Time Bias Because of lead-time bias, it is necessary to look at disease-specific and age- specific death rates in screened and unscreened groups when assessing a screening intervention. Time from diagnosis to death does not tell you if a screening test is effective
Screening Generally Is to seek about certain problem in certain high risk gp.
Validity of Screening Test Validity of test determined by ability to correctly categorise subjects to test-positive or test- negative Disease status Test Positive Negative TotalPositive result a b a+bNegative c d c+d Total a+c b+d
Validity of Screening Test cont... Sensitivity = ability of test to give a positive result when disease is present = a / a+c Specificity= ability of test to give a negative result when disease is absent = d / b+d
Validity of Screening Test cont... Predictive value is determined by sensitivity & specificity and also by the prevalence of preclinical diseas Positive predictive value = probability that a person with a positive test actually has the disease = a / a+b Negative predictive value = probability that a person with a negative test is truly disease-free = d / c+d
What is a Pap Smear? “Papanicolaou test” - 1941 Dr. Babes & Dr. Papanikolaou > 50% decrease in rates of cervical cancer in developed countries over last 30 yrs due to widespread screening A sample cervix cells from transformation zone. junction of endocervix and ectocervix Use of spatula +/- cytobrush, broom stick 2 types – conventional, liquid-based Send for cytologic interpretation
Screening Guidelines Start at age 21 (regardless of age of first intercourse) Age 21-29 screen every 2 years Age 30 + screen every 3 years if… Negative cytology x3 previous Paps NIELM and negative HR HPV test in 1 year No history of high grade lesions Annual screening if… Immunocompromised (ie. HIV, transplant pts) History of CIN II, III or cancer Exposure to DES in utero Stop screening at 65 or 70 yrs if … 3 prior consecutive normal Paps No history of abnormal screening in last 10 yrs Stop screening if hysterectomy for benign disease with no history of abnormal Pap smears
CRITERIA FOR SCREENINGDisease: Must be serious enough Must be widespread enough Must be fairly reliably diagnosable Must be treatable Must be affordable Hopefully legally defensible
Criteria for Screening Test 1. Simple & quick 2. Capable of being performed by paramedics 3. Inexpensive 4. Acceptable to population 5. Accurate 6. Repeatable 7. Sensitive 8. Specific
Secondary Prevention ofCa.Cx. Key Point is to detect precancerous lesions –BY - A good screening method - PAP smear test is considered to be the gold standard – Has limitations ? Alternatives to Pap Smear – What are they?
Why screening for cervicalcancer? 1. Is relatively common in unscreened women. 2. Has a relatively good prognosis if found early stage in its natural course of disease. 3.Has a characteristic natural course that is a slow progression through a premalignant stage.
Why screening for cervicalcancer? Cont… 4. A premalignant stage can be detected by noninvasive means (the Pap smear , cervicography&VIA). 5. There are effective treatment modalities to eradicate premalignant lesions and early invasive cervical cancer.
Screening by Pap. Cx. Smeara. Importance: unscreened female have ten fold risk > screened femaleb. To whom : - Every sexually active female (18-35 y) - Specially, high risk group.c. When: - Annually up to the age of 35y - No need to extend screening > 35y if smear is N. - At each pregnancy - If new risk factors appear after 35y. d- If + ve smear colposcopy
Alternatives to Cytology Visual Inspection of the cervix: Unaided: Downstaging. Aided with acetic acid: VIA: Naked eye Aided with acetic a and magnification( VIAM) Cervicography Colposcopy Speculoscopy Automated pap smear HPV DNA test Infrared Spectroscopy & Laser Fluorescence
Limitations of Pap Smear• Complex laboratory test• Requires trained cytotechnician for reading and pathologist for review• Continuous monitoring needed to maintain high- quality results• Reports often take minimum 1-2 weeks to obtain• Follow-up of women is difficult• Usually available only in large cities in many countries
Comparison between :VIA and Cytology Sensitivity(%) Specificity (%) Cytology 47--62 60-95 VIA 76-84 79-83
Breast• Population - women, age 20 + Breast self-examination Monthly, starting at age 20 Clinical breast examination Every three years, age 20-39 Annual, starting at age 40 * Mammography Annually, starting at age 40 * Beginning at age 40, annual clinical breast examination should be performed prior to mammography. Most other affluent countries recommend mammography every other year between ages 50 and 70.
Levels of Prevention Disease Onset Clinical Diagnosis No Disease Asymptomatic Clinical Course DiseasePrimary Secondary TertiaryRemove Risk Early Detection ReduceFactors and Treatment ComplicationsFletcher RF, Fletcher SW, Wagner EH. Clinical Epidemiology: The Essentials, 3rd ed. Williams andWilkins, Baltimore, 1996.