1. Screening for oral cancer: Experience in developing countries
K. Ramadas MD, DNB
Additional Professor
Division of Head and Neck Oncology
Regional Cancer Centre
Trivandrum
India

2. Screening requirements
Suitable disease
Important problem
Can be detected in preclinical stage
Effective treatment available
End result improved by early diagnosis

3. Screening requirements
Suitable test
Cheap and easy to apply
Valid:
Sensitivity
Specificity
Positive predictive value
Safe and acceptable

4. Screening requirements
3. Suitable programme settings
Adequate infrastructure for Dx and Rx in health services
Adequate trained manpower
Adequate financial resources

5. OUTCOME EVALUATION OF SCREENING PROGRAMME
Early outcome
Stage distribution
Case fatality and survival
Final outcome
Reduction in incidence (if precancerous lesions are detected and treated)
Reduction in mortality (if early invasive disease is detected and treated)

6. Oral Cancer Burden Incidence Deaths World 274,000 127,200
More developed countries 91, ,600
Less developed countries 183, ,600
India 83, ,000
Ferlay J et al., GLOBOCAN 2002, IARC Press, 2004

9. Screening for oral cancer
Oral cancer is a major health problem
Oral cancer incidence on the increase
Survival rates remain unchanged
Easily accessible sites
Long premalignant and early invasive phase
Better Rx outcomes in early stages

10. Screening Tools for oral cancer
Visual inspection
Self Examination
Toluidine blue
Fluorescence imaging
Exfoliate cytology/Brush biopsy
Saliva Examination

11. Oral Visual Inspection
Sensitivity 58 – 94 %
Specificity %
Most widely evaluated test
Warnakulasuriya KAAS et al., Bull WHO 1984; 62:
Mehta FS et al., Cancer Detect Prev 1986; 9:
Mathew B et al., Br J Cancer 1997; 76:
Ramadas K et al., Oral oncol 2003; 39:

12. Toludine Blue Test Tested only in a few specified clinical settings
High false negative and false positive rates

13. Oral Cytology Lesion has to be seen before the sample collection
Yield is poor
Interpretation highly subjective
High false negative rates

14. Analysis of Saliva Increased levels 4 mRNA from the following genes
Interleukin1 beta
Ornithine decarboxylase antizyme1
Spermidine/spermine N1-acetyl transferase
Interleukin8

15. Oral cancer screening – Cuban experience
Screening programme in 1984
Annual oral inspection to all subjects aged 15 yrs and above in the assigned population of by each dentist.
In practice only opportunistic examination of subjects carried out
21% of males and 31% females underwent screening in any given year up to 1990
No evidence of any reduction in incidence or mortality from oral cancer
Fernandez L et al., Epidemiology 1995; 6:

16. Case Control study from Cuba
33 % reduction in the frequency of advanced oral cancer in screened subjects.
The protection increased to 59% in subjects who had two or more screening examinations
Protection lasts for 3 years
Sankaranarayanan et al., Oral Oncol 2002; 38:

17. TRIVANDRUM ORAL CANCER SCREENING STUDY (TOCS) Only randomized controlled clinical trial in a community setting COLLABORATIVE PROJECT OF INTERNATIONAL AGENCY FOR RESEARCH ON CANCER, LYON & REGIONAL CANCER CENTRE TRIVANDRUM & SUPPORTED BY ASSOCIATION FOR INTERNATIONAL CANCER RESEARCH (AICR),U.K

18. Objective
To evaluate the efficacy of oral cancer screening by visual inspection of the oral cavity in detecting early stages of oral cancer and in reducing mortality
To study the determinants of population compliance for intervention
To evaluate the cost effectiveness of intervention
Sankaranarayanan R, Ramadas K et al., Lancet 2005; 365:

19. Materials and Methods
13 Panchayaths randomized to intervention (N=7) and control (N=6) groups
Between , 3 rounds of screening, at 3-year intervals completed
Screening carried out in subjects 35 years or older by trained health workers
96,517 subjects in the intervention group and 95,356 subjects in the control groups
Ramadas K et al., Oral oncol 2003; 39:
(Continued…..)

20. (Continued…..)
Materials and Methods
Information on socio demographic factors and habits collected for both intervention and control cohorts
Education on the harmful aspects of tobacco/alcohol use for the intervention and control cohorts
3 rounds of oral visual inspection at 3-year intervals provided to eligible individuals in the intervention group by trained health workers
Screen positive cases referred for physician confirmation/ biopsy
Precancer cases were advised, cessation of habits, medication or surgical excision
Oral cancer cases were treated by radiation and/or surgery ± chemotherapy according to the stage at diagnosis

21. Map Showing Study Clusters
INDIA
TRIVANDRUM CITY
Kerala
Indian Ocean
Bay of Bengal
Arabian Sea
Vakkom
Kadakavoor
Kizhuvilam
Azhoor
Mangalapuram
Andoorkonam
Pothencode
Kazhakuttam
Sreekariyam
Attipra
Kadinamkulam
Chirayinkil
Anjuthengu
Intervention Clusters
Control Clusters

22. Trivandrum Oral Cancer Screening Study Design
Randomized 13 Panchayaths In Trivandrum District, India
Intervention
N = 7 panchayaths
Control
N = 6 panchayaths
Door-to-door identification and interview of eligible subjects (> age 34, 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

23. Screen positivity
White, red, nodular lesions suggestive of leukoplakia or eythroplakia
Oral submucous fibrosis
Suspicious ulcer or growth

24. Referral investigations
Clinical examination by dentist or clinical oncologist
Histological examination

25. Monitoring and Evaluation
Process measures
Participation in screening
Screen (test) positivity
Compliance with referral for reference investigators
Intermediate outcomes
Detection rates of precancers and cancer
Programme sensitivity
Positive predictive value of screening test to detect both precancers and invasive cancer
Stage distribution of cancers
Survival
Case fatality rate
Final outcome
Reduction in mortality from oral cancer

26. Sources of data Study database Population based cancer registry
Mortality registration offices
Death records from churches/mosques
Active follow-up by home visits and telephone inquiries

27. Screening history

28. Compliance with screening and referral

29. Stage Distribution of Oral Cancers
Intervention
Control
p < 0.05

30. Overall survival from oral cancer in the study groups20 40 60 80
100
Months
Intervention screen detected
Intervention Interval cancer
Intervention non-responders
Control group
Survival (%)
Time to death or end of follow-up (in months)
Kaplan-Meier survival estimates, by oral cancer type 25 50 75

31. Oral cancer incidence and mortality rates
PYOs=Person-years of observation

32. Oral cancer incidence and mortality rates by sex
PYOs=Person-years of observation

33. Conclusions Good participation rates for screening (~ 90%)
Moderate compliance to referral (~62%)
Significant detection of oral cancer at early stages (I & II) by visual inspection (41.2% vs. 23.2%)

34. Conclusions
Significant reduction in oral cancer mortality among high-risk individuals, particularly among males
Potential to prevent 37,000 oral cancer deaths world-wide
Sankaranarayanan R, Ramadas K et al., Lancet 2005; 365:

35. EPILOGUE
Oral visual screening reduces mortality among high-risk subjects
Can be integrated into existing health services

36. Thank you