Cancer epidemiology, prevention and screening

1. Cancer epidemiology, prevention and screening R. Sankaranarayanan MDHead, Early Detection and Prevention Section (EDP) Head, Screening Group (SCR)

2. Cancer epidemiology • Distribution – burden, pattern • Determinants – causes, risk factors • Application – prevention, control

3. Cancer epidemiology studies • Descriptive studies • Observational studies • Experimental studies

4. Major causes of cancer • Tobacco use • Alcohol • Infection – HBV, HCV, HPV, EBV, Helicobacter pylori, liver fluke, among others • Dietary factors • Physical activity (lack of!) • Radiation • Chemical exposures • Genetic factors (list incomplete . . !)

5. Breast cancer risk factors • Estrogen exposure: early menarche (<12), late menopause (>55), never breast fed, hormone therapy • Late child beating: >30 years • Breast density • Obesity after menopause • Physical inactivity • Alcohol consumption • Radiation exposure • Genetic alterations: BRCA1, BRCA2 genes • Family history

6. 11 million New Cases 7 millionDeaths 25 millionLiving with Cancer Cancer – worldwide burden

7. WPRO Females 823,000,000 population 1.229,000 cases 778,000 deaths Males 858,000,000 population 1.782,000 cases 1.299,000 deaths Stomach Lung Liver Colon/Rectum Oesophagus Breast Leukaemia Cervix uteri Pancreas Non-Hodgkin lymphoma Brain nervous system Bladder Prostate Nasopharynx Ovary etc. Kidney etc. Incidence Mortality (Thousands) Population (2000): 1.681,000,000

8. Population (2000): 1,535,000,000 Females 749,000,000 population 660,000 cases 408,000 deaths Males 786,000,000 population 605,000 cases 442,000 deaths Cervix uteri Breast Oral cavity Lung Colon/Rectum Oesophagus Other pharynx Stomach Liver Larynx Leukaemia Non-Hodgkin lymphoma Ovary etc. Brain nervous system Prostate Bladder Incidence Mortality (Thousands) SEARO

9. Population (2000): 480,000,000 Females 234,000,000 population 187,000 cases 119,000 deaths Males 246,000,000 population 181,000 cases 134,000 deaths Breast Bladder Lung Oral cavity Colon/Rectum Stomach Oesophagus Leukaemia Non-Hodgkin lymphoma Cervix uteri Liver Brain nervous system Larynx Thyroid Ovary etc. Prostate Incidence Mortality (Thousands) EMRO

10. AFRO Population (2000): 640,000,000 Females 321,000,000 population 271,000 cases 204,000 deaths Males 319,000,000 Population 244,000 cases 196,000 deaths Cervix uteri Kaposi sarcoma Breast Liver Prostate Non-Hodgkin lymphoma Stomach Oesophagus Colon/Rectum Oral cavity Lung Leukaemia Bladder Ovary etc. Melanoma of skin Larynx Incidence Mortality (Thousands)

11. Population (2000): 874,000,000 Females 450,000,000 population 1.392,000 cases 783,000 deaths Males 424,000,000 population 1.560,000 cases 1.004,000 deaths Lung Breast Colon/Rectum Prostate Stomach Bladder Kidney etc. Corpus uteri Pancreas Leukaemia Non-Hodgkin lymphoma Ovary etc. Cervix uteri Melanoma of skin Oral cavity Liver Incidence Mortality (Thousands) EURO

12. Population (2000): 831,000,000 Females 420,000,000 Population 1.120,000 cases 512,000 deaths Males 411,000,000 population 1.180,000 cases 551,000 deaths Prostate Breast Lung Colon/Rectum Stomach Bladder Non-Hodgkin lymphoma Cervix uteri Melanoma of skin Corpus uteri Leukaemia Kidney etc. Pancreas Ovary etc. Brain nervous system Oral cavity Incidence Mortality (Thousands) PAHO

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

14. 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)

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

16. 4.0000 Early research on health effects of smoking Report of the US Surgeon General 3.5000 Broadcast of tobacco Uptake by women advertising phased out 3.0000 Commencement of Quit Campaigns Tobacco Taxation World War II 2.5000 Introductionof Annual amount of tobacco dutied per adult over 15 years ( kg) manufactured Workplace smoking bans introduced Depression cigarettes 2.0000 New health warnings 1.5000 1.0000 0.5000 0.0000 1903 1906 1909 1912 1915 1918 1921 1924 1927 1930 1933 1936 1939 1942 1945 1948 1951 1954 1957 1960 1963 1966 1969 1972 1975 1978 1981 1984 1987 1990 1993 1996 Year Adult per capita consumption of tobacco products in the 20th Century in Australia

17. Trends in lung cancer mortality and smoking prevalence in Australia 1940-2004

18. Trends in incidence of lung cancer in Asia

19. Impact of Hepatitis B vaccination on liver cancer incidence: Taiwan • Vaccination for infants born to HBsAg carriers during 1984-86 • Vaccination extended for all infants aged <12 months in 1986, 1-4 year old infants in 1987 • 5-9 year old infants during 1988-90, 10-19 years 1989-91 and to adults 20 years and above during 1990-93 • 64 liver cancers among vaccinated subjects in 377 709 304 Pyrs Vs. 444 cancers among unvaccinated subjects in 78496 406 Pyrs • 69% reduction in liver cancer among vaccinated cohort Chang et al., JNCI. 2009;101:1348-1355

20. Time trends in age-standardized cancer incidence rate of breast in 13 cancer registries in Asia, females

21. Singapore:Indian Singapore: Chinese Time Singapore: Malay Singapore: Mortality Years Trends in cervical cancer incidence in Singapore, 1960-2000 D.M. Parkin, S. Whelan, J. Ferlay and H. Storm. Cancer Incidence in Five Continents, Vol. I to VII. IARC CancerBase No. 7, Lyon, 2005

22. Adjusted death rate/100 000 women Cervical cancer mortality rates in Chile 1985-1999 Courtesy Dr Catterina Ferreccio Cancer Unit/ Health Ministry/M. Prieto

23. 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 precancer or early invasive cancer in symptomatic or asymptomatic individuals in opportunistic settings. Improved awareness and access to health services promote early clinical diagnosis.

24. Early detection is associated with: • Benefits/?harm • 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.

25. 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

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

27. 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

28. Age 20 30 40 50 60 Birth Death Cancer begins symptoms exposure screening Cells exfoliate • Interval Age Duration • Total pre-clinical phase (TPCP) 30 to 55 25 years • 2. Detectable pre-clinical phase (DPCP) 45 to 55 10 years

29. Short Natural History Preclinical Phase Clinical Phase Long Natural History Preclinical Phase Clinical Phase Short and long natural histories of disease: relationship of length of preclinical phase

30. Screening Requirements 2. Suitable test a) Affordable and easy to apply b) Valid: sensitivity specificity positive predictive value c) Safe and acceptable

31. 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

32. Possible normal limit A Number of People Disease Free Positive Teat Results Disease Affected Teat value Possible normal limit B Number of People Disease Free Positive Teat Results Disease Affected Teat value A, Ideal distribution of test results in disease-free and affected individual. B, The inevitable tradeoff of sensitivity and specificity. Moving the possible normal limits to the left increases sensitivity and decreases specificity, whereas moving the possible normal limit to the right increases specificity and decreases sensitivity. (adapted from Friedman GD: Epidemiology and patient care. In Laufer RS, Hrieger A (eds): Primer of Epidemiology. New York, McGraw-Hill, 1974; with permission)

33. Screening Requirements 3. Suitable programme settings a) Adequate infrastructure for diagnosis and treatment in health services b) Adequate trained manpower c) Adequate financial resources

34. Evaluation of screeningProgramme Process measures Outcome measures

35. Outcome evaluation of screening Programmes Early outcome Stage distribution Case fatality and survival Final outcome Reduction in incidence (if precancerous lesions are detected); mortality (if invasive disease is detected); quality of life; cost- effectiveness

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

37. 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

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