Cancer prevention and early detection

1. Cancer prevention and early detection C. Sauvaget MDScreening Group (SCR)

2. Prevention aims to reduce the frequency of new invasive cancers

3. Prevention is achieved by • Modulating exposure of individuals to cancer risk factors by • Awareness • Elimination of risk factors • Supplementation • Vaccination • Legislation • Early detection ad treatment of potentially malignant precancerous lesions (e.g. CIN, polyps)

4. Evaluation of prevention of cancer Trends in: • the prevalence of risk factors • incidence of cancer • mortality

5. Pre-clinical phase Clinical phase Onset of symptoms and/or signs Early detection Onset of disease Exposure D1 Cure B A C Primary prevention Secondary prevention Tertiary prevention Natural history of cancer and levels of prevention D2 Disability D3 Death

6. Time trends in age-standardized cancer incidence rate of breast in 13 cancer registries in Asia, females Hirabayashi and Zhang, Jpn J Clin Oncol 2009;39(6)411–412

7. Early detection approaches 1. Screening: Systematic, routine application of a suitable early detection test at specified intervals in a systematically invited asymptomatic population. 2. Early clinical diagnosis: Searching for precancerous or early invasive cancer in symptomatic or asymptomatic individuals in opportunistic settings. Improved awareness and access to health services promote early clinical diagnosis.

8. Population Screened + Sick Clinical early diagnosis target Screening target Cancer early detection options • Screening programs • Clinical early diagnosis

9. Early detection is associated with: • Benefits/harms • Costs to Individual and the Health Services It is important to establish that benefits of early detection, particularly screening, outweigh harms and it is cost-effective in reducing incidence/mortality.

10. Screening Presumptive identification of unrecognised disease by tests which can be applied rapidly Involves application of a simple, inexpensive test to a large number of persons to classify them as likely (screen positive) or unlikely (screen negative) to have the disease which is the object of screen It is the whole system to improve health: identification of risk and intervention

11. Objective of screening To achieve reduction in incidence and/ or mortality from the disease in question among the persons screened at a reasonable cost

12. ScreeningRequirements • Suitable disease • Suitable test • Suitable screening settings

13. Screening Requirements • Suitable disease • a) Important problem • b) Can be detected in preclinical stage • c) Effective treatment available • d) End result improved by early diagnosis

14. ScreeningRequirements • A suitable screening test 2.1 Adequate validity Sensitivity Specificity 2.2 Acceptability and cost

15. 2.1 Accuracy of diagnostic tool = Validity SENSITIVITY:likelihood that the test will detect disease when it is present SPECIFICITY:likelihood that the test is negative when the disease is absent POSITIVE PREDICTIVE VALUE:likelihood that a positive test has detected the disease of interest

16. Ideal situation for a screening test No overlap of distributions among healthy and diseased Cut-off Value A Negative Test Results Number of People Disease Free Positive Test Results Disease Affected Screening Test The test is 100% sensitive and 100% specific. The distribution of the screening test results among the subjects with the disease is completely separated from the distribution among the subjects without the disease.

17. B Number of People Disease Free Positive Test Results Negative Test Results False Positive Disease Affected False Negative Screening Test Moving the cut-off value to the right (increasing the screening test value) decreases sensitivity (detection of disease) but increases specificity (exclusion of healthy). More false negative will be missed at screening. Real situation for a screening test Overlap of distributions among healthy and diseased Cut-off Value The screening test tends to give higher values for subjects with the disease than those without the disease. Moving the cut-off value to the left (lowering the screening test value) increases sensitivity (detection of disease) and decreases specificity (exclusion of healthy).

18. 2.2 Acceptability and cost • In addition to adequate validity, a screening test should be: • Low cost • Convenient • Simple • As painless as possible • Does not cause complications

19. Screening Requirements • 3. Suitable programme settings • Adequate infrastructure for diagnosis and treatment in health services • Adequate trained manpower • Adequate financial resources

20. Successful cervical cancer prevention key elements Link Screening and Treatment Effectiveness of Treatment Screening Coverage

21. Evaluation of screeningprogrammes Process measures Outcome measures

22. Evaluation of screening Programmes Outcome Early outcome Stage distribution Case fatality and survival Final outcome Reduction in incidence (if precancerous lesions are detected); mortality (if invasive disease is detected)

23. Mortality rates from invasive cervical cancerand screening coverage rate, Mexico, 1979-2004 Courtesy Dr Eduardo Lazcano

24. Effectiveness of cervical cancer screening in Taiwan Chen et al, Br J Cancer 2009

25. Suitable cancers for screening • Cervical cancer • Breast cancer • Colorectal cancer • Oral cancer

26. Screening methods Colorectal cancer • Faecal occult blood tests (FOBT) • Sigmoidoscopy • Colonoscopy Oral cancer • Visual inspection Cervical Cancer • Pap smear • Liquid based cytology • HVP DNA testing • Visual screening Breast cancer • Mammography • Clinical breast examination

27. Organised and opportunistic screening programmes exist for • Cervical cancer • Breast cancer • Colorectal cancer