1. Cancer prevention and early detection
Lausanne-March-2011
Cancer prevention and early detection
C. Sauvaget MD Screening Group (SCR)

2. Prevention aims to reduce mortality from cancer
Lausanne-March-2011
Prevention aims to reduce mortality from cancer

3. Burden of cancer in less-developed countries(2008)
Lausanne-March-2011
Men
Women

4. Natural history of cancer and levels of prevention
Lausanne-March-2011
Natural history of cancer and levels of prevention
Pre-clinical phase
Clinical phase
Exposure
Onset of disease
Early detection
Onset of symptoms and/or signs
D1 Cure A B C
D2 Disability
Primary prevention
Secondary prevention
Tertiary prevention
D3 Death

5. Early detection approaches
Lausanne-March-2011
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.

6. Cancer early detection options
Lausanne-March-2011
Cancer early detection options
Screening programs
Clinical early diagnosis
Screened +
Confirmed +
Population
Screening target
Clinical early diagnosis target

7. Early detection is associated with:
Lausanne-March-2011
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.

8. Screening Requirements
Lausanne-March-2011
Screening Requirements
Suitable disease
Suitable test
Suitable screening settings

9. Screening Requirements-1
Lausanne-March-2011
Screening Requirements-1
Suitable disease
a) Important problem
b) Can be detected in preclinical stage
c) Effective treatment available
d) End result improved by early diagnosis

10. Screening Requirements-2
Lausanne-March-2011
Screening Requirements-2
2. A suitable screening test
2.1 Adequate validity
Sensitivity
Specificity
2.2 Acceptability and cost

11. 2.2 Acceptability and cost
Lausanne-March-2011
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

12. Screening Requirements-3
Lausanne-March-2011
Screening Requirements-3
3. Suitable programme settings
Adequate infrastructure for diagnosis and treatment in health services
Adequate trained manpower
Adequate financial resources

13. Successful cancer prevention programme
Lausanne-March-2011
Successful cancer prevention programme
Key elements
Link Screening
and Treatment
Effectiveness
of Treatment
Screening
Coverage
Surveillance
and monitoring

14. Evaluation of screening programmes
Lausanne-March-2011
Evaluation of screening programmes
Process measures
Outcome measures

15. Evaluation of screening Programmes Outcome
Lausanne-March-2011
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)

16. Lausanne-March-2011
Mortality rates from invasive cervical cancer and screening coverage rate, Mexico,
Courtesy Dr Eduardo Lazcano

17. Suitable cancers for early detection in LMIC
Lausanne-March-2011
Oral cancer
Visual inspection by trained health workers
Health education to prompt symptomatic high-risk individuals
Cervical cancer
Visual inspection methods and HPV-DNA testing as alternatives of Pap smear
Health education on risk factors, symptoms and signs of cervical carcinoma
See-and-treat approach by trained health workers and physicians
Breast cancer
Health education to improve awareness and to motivate high-risk women to demand early detection
Clinical breast examination and mammography may then be used

18. Screening for oral cancer
Lausanne-March-2011
Screening for oral cancer

19. Study design TRIVANDRUM ORAL CANCER SCREENING STUDY (TOCS)
Lausanne-March-2011
Study design
Randomized 13 Panchayaths In Trivandrum District, India
Intervention
N=7 Panchayaths
participants
Control
N=6 Panchayaths
participants
Door-to-door identification and interview of eligible subjects (> 34 years, no debilitating disease)
Consent form, Individual questionnaire, Education on tobacco and alcohol health effects
Oral Visual Inspection by trained health worker
Screen-positives referred for inference investigations
Treatment given for precancers and cancer cases
Follow-up for oral cancer incidence and mortality
Usual care

20. Overall survival from oral cancer in the study groups
TRIVANDRUM ORAL CANCER SCREENING STUDY (TOCS)
Lausanne-March-2011
Overall survival from oral cancer in the study groups

21. Lausanne-March-2011
Cost-effectiveness of Visual Screening for Oral Cancer in India Results from the Trivandrum Oral Cancer Screening Study (TOCS) ( )
Intervention group
Control group
Person-years of observation
No. of oral cancers/deaths
205/77
158/87
Mortality rate (per 100,000)
16.4
20.7
Rate Ratio: 0.79 ( ) 95% CI
Mortality rate among tobacco and/or alcohol users (high-risk individuals)
29.9
45.4
Rate Ratio: 0.66 ( ) 95% CI
Cost per cancer detected (intervention compared to control)
All individuals
High-risk individuals -
$ 6,228
$ 9,394
Cost per life year saved*
$ 457
$ 156
* GDP per Capita for India (2004) $ 2900
Sankaranarayanan et al., 2005: Lancet 365: Subramanian et al., 2009: Bull WHO 87:

22. Screening for cervical cancer
Lausanne-March-2011
Screening for cervical cancer
Source: R. Sankaranarayanan, Ramani S. Wesley. A practical manual on visual screening for cervical neoplasia (IARC Technical Publication No. 41)

23. Study design 131 746 Women aged 30-59 yrs in 52 clusters
Lausanne-March-2011
Comparative efficacy of visual inspection with acetic acid, HPV testing and conventional cytology in cervical cancer screening: a randomized intervention trial in Osmanabad District, Maharashtra State, India
Study design
Women aged yrs in 52 clusters
Cytology 13 clusters (N = )
HPV 13 clusters (N = )
VIA 13 clusters (N = )
Control 13 clusters (N = )
Diagnosis and treatment of screen-positive women
Follow-up for cervical cancer incidence and mortality (passive and active)
Follow-up for cervical cancer incidence and mortality (passive and active)
Health education, routine existing care
Sankaranarayanan et al., N Engl J Med 2009;360:

24. Person years of follow-up
Lausanne-March-2011
Comparative efficacy of visual inspection with acetic acid, HPV testing and conventional cytology in cervical cancer screening: a randomized intervention trial in Osmanabad District, Maharashtra State, India
Hazard ratios of incidence of stage II+ cervical cancer and cervical cancer mortality with control group as the reference
Group
Cases
Person years of follow-up
Hazard ratio* (95% CI)
Stage II+ cervical cancer incidence
Control 82
247,895
1.00
HPV 39
268,185
0.47 ( )
Cytology 58
250,523
0.75 ( )
VIA 86
267,326
1.04 ( )
Cervical cancer mortality 64
248,175 34
268,674
0.52 ( ) 54
251,144
0.89 ( ) 56
267,917
0.86 ( )
CI: confidence interval
* Age-adjusted
Sankaranarayanan et al., N Engl J Med 2009;360:
In collaboration with TMC, Mumbai and NDMCH, Barshi, India
Study

25. Age-Standardized Incidence rate (per 100 000)
Lausanne-March-2011
Comparative efficacy of visual inspection with acetic acid, HPV testing and conventional cytology in cervical cancer screening: a randomized intervention trial in Osmanabad District, Maharashtra State, India
Cervical cancer incidence rates among screen-negative women by study group ( )
Group
Number of women
Cancer cases
Age-Standardized Incidence rate (per )
HPV
24 380 8
3.7
Cytology
23 762 22
15.5
VIA
23 032 25
16.0
Sankaranarayanan et al., N Engl J Med 2009;360:

26. The new HPV DNA test for low-resource settings - CareHPV
Lausanne-March-2011
The new HPV DNA test for low-resource settings - CareHPV
Hybrid capture 2
CareHPV

27. New algorithms for cervix screening
Developing countries
New algorithms for cervix screening
Lausanne-March-2011
- ve
Repeat test 5 or 10 years later?
CareHPV test
+ ve
VIA
+ ve
- ve
Cryotherapy
LEEP

28. Screening for breast cancer
Lausanne-March-2011
Screening for breast cancer
NORMAL BREAST
Normal female breasts: Note similar size and shape, nipples at the same level, normal nipple, areola and skin

29. Study design Trivandrum Breast Cancer Screening Study (TBCS)
Lausanne-March-2011
Study design
275 clusters women aged years
142 clusters women Control group
133 clusters women CBE once in 3 years x 3 rounds
133 clusters women CBE once in 3 years x 3 rounds
CBE +ve
Triple Diagnosis
Breast cancer cases
Breast cancer deaths

30. Performance characteristics of clinical breast examination
Trivandrum Breast Cancer Screening Study (TBCS)
Lausanne-March-2011
Performance characteristics of clinical breast examination
Test characteristics
Values
(95% CI)
Number of women screened
50 366
Number of women screened positive
2 880
Screen-positivity rate (per 100 women screened)
5.7
(5.5 – 5.9)
Breast cancer detection rate (per 10,000 women screened) 6
(4 – 8)
Screen detected cancers (true positive cancers) 30
Interval cancers (false negative cancers) 29
False positive rate (per 100)
Sensitivity (%)
50.8
(37.5 – 64.1)
Specificity (%)
94.3
(94.1 – 94.5)
PPV (%)
1.0
(0.7 – 1.5)
NPV (%)
99.9
(99.9 – 100.0)
CI: confidence interval; PPV: positive predictive value; NPV: negative predictive value
unpublished data
submitted
In collaboration with RCC, Trivandrum, India

31. First round of screening: intermediate outcome (2006-2009)
Trivandrum Breast Cancer Screening Study (TBCS)
Lausanne-March-2011
First round of screening: intermediate outcome ( )
Control
Intervention
p-value
Number %
Breast cancers cases 63 80
Size of tumor ≤ 2cm 4
(6.3) 15
(18.8)
0.030
Early stage breast cancers (0-IIA) 16
(25.4) 35
(43.8)
0.023
Negative axillary lymph nodes 22
(35.5) 40
(50.0)
0.084
ER positive breast cancers 23
(36.5) 28
(35.0)
0.852
Received conservative surgery 3
(4.8) 14
(17.5)
0.020
Deaths 6
(9.5)
(3.8)
0.158
unpublished data
* ER: estrogen receptors
submitted
In collaboration with RCC, Trivandrum, India

32. Non-suitable cancers for early detection in LMIC
Lausanne-March-2011
Digestive tract cancer
Endoscopy is not cost-effective nor feasible
Liver cancer
High fatality rate and ineffective treatment
Primary prevention
Lung cancer
Chest radiography and sputum cytology are ineffective
CT scan screening is not feasible
Tobacco control
Prostate cancer
PSA testing with considerable over-diagnosis
Early detection not recommended for developing countries
Ovarian cancer
Efficacy of α-fetoprotein and ultrasound is not yet known
Screening is not feasible

33. Thank you for your kind attention!
Lausanne-March-2011
Thank you for your kind attention!