Cancer epidemiology, prevention and screening Epidemiology-Lausanne Cancer epidemiology, prevention and screening R. Sankaranarayanan MD Head, Early Detection and Prevention Section (EDP) Head, Screening Group (SCR)

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

Cancer epidemiology studies Descriptive studies Observational studies Experimental studies

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 . . !)

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

Cancer – worldwide burden 7 million Deaths 11 million New Cases 25 million Living with Cancer

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

SEARO Population (2000): 1,535,000,000 Females Males Epidemiology-Lausanne SEARO 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 Males 786,000,000 population 605,000 cases 442,000 deaths Females 749,000,000 population 660,000 cases 408,000 deaths Incidence Mortality (Thousands) Population (2000): 1,535,000,000

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

AFRO Population (2000): 640,000,000 Females Males Epidemiology-Lausanne 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 Males 319,000,000 Population 244,000 cases 196,000 deaths Females 321,000,000 population 271,000 cases 204,000 deaths (Thousands) Population (2000): 640,000,000 Incidence Mortality

EURO Population (2000): 874,000,000 Females Males Epidemiology-Lausanne 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 Males 424,000,000 population 1.560,000 cases 1.004,000 deaths Females 450,000,000 population 1.392,000 cases 783,000 deaths (Thousands) Population (2000): 874,000,000 Incidence Mortality :: Regional Office for Europe

PAHO Population (2000): 831,000,000 Females Males Epidemiology-Lausanne PAHO Males 411,000,000 population 1.180,000 cases 551,000 deaths Females 420,000,000 Population 1.120,000 cases 512,000 deaths (Thousands) 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 Population (2000): 831,000,000 Incidence Mortality

Prevention aims to reduce the frequency of new invasive cancers

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)

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

Adult per capita consumption of tobacco Epidemiology-Lausanne Adult per capita consumption of tobacco products in the 20th Century in Australia Year 0.0000 0.5000 1.0000 1.5000 2.0000 2.5000 3.0000 3.5000 4.0000 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 Annual amount of tobacco dutied per adult over 15 years ( kg) Depression World War II Uptake by women Early research on health effects of smoking Report of the US Surgeon General Broadcast of tobacco advertising phased out Commencement of Quit Campaigns Tobacco Taxation Workplace smoking bans introduced New health warnings Introduction of manufactured cigarettes Almost all of the major changes in tobacco consumption in Australia have come about as a result of government action, even the increases. Free distribution of cigarettes to the troops in WWII. The declines have come about because governments were persuaded to act by NGOs who could demonstrate strong public support.

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

Trends in incidence of lung cancer in Asia

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

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

Trends in cervical cancer incidence in Singapore, 1960-2000 Epidemiology-Lausanne Trends in cervical cancer incidence in Singapore, 1960-2000 Singapore: Chinese Singapore:Indian Singapore: Malay Singapore: Mortality Years Time 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

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

Early detection approaches Epidemiology-Lausanne 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.

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.

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

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

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

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

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

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

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

Disease Affected Positive Teat Results Free Possible normal limit Number of People Teat value A Disease Affected Positive Teat Results Free Possible normal limit Teat value Number of People B 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)

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

Evaluation of screening Programme Process measures Outcome measures

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

Suitable cancers for screening Cervical cancer Breast cancer Colorectal cancer Oral cancer

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

Organised and opportunistic screening programmes exist for Cervical cancer Breast cancer Colorectal cancer