1. ACCP Evidence base: Implications for policy and practice R. Sankaranarayanan MD Head, Screening Group World Health Organization (WHO) International Agency for Research on Cancer (IARC) Lyon, France http://screening.iarc.fr

2. ACCP Evidence Base  Test characteristics  Efficacy of treatment of CIN  Effectiveness of reducing disease burden  Cost effectiveness issues  Acceptability of participation determinants

3.  Reduced frequency of screening: one or twice a life time  Reducing the number of visits and improving adherence to treatment  screen and treat (1 or 2 visits)*  screen, see (colposcopy), and treat (1 to 2 visits) (with a posteriori histological confirmation)** ALTERNATIVE PROGRAMMATIC APPROACHES: *RTCOG/ JHPIEGO Lancet, 2003; 361: 814-20 ** Sankaranarayanan et al., Int J Cancer, 2004; 109: 461-7 * Denny et al., 2005 JAMA 294: 2173-81

4. Accuracy of screening tests in developing countries: range in sensitivity and specificity TestSensitivitySpecificity Cytology31-78%91-99% HPV testing61-90%62-94% VIA50-96%44-97% VILI44-93%75-85%

5. RESULTS OF TREATMENT OF CIN TreatmentTotal numberCured (%) Cryotherapy562477 (85%) LEEP422357 (85%) O SMANABAD RCT OF C ERVICAL S CREENING, I NDIA Study

6. Women SAFETY, ACCEPTABILITY, AND FEASIBILITY OF A SINGLE-VISIT APPROACH TO CERVICAL CANCER PREVENTION IN RURAL THAILAND Acceptability of Cryotherapy Treatment Lancet 2003; 361:814-820

7. RANDOMISED CONTROLLED TRIAL OF SCREEN AND TREAT APPROACH FOR CERVICAL CANCER PREVENTION IN SOUTH AFRICA CharacteristicHPV test & Treat (N=2163) VIA & Treat (N=2227) Delayed Evaluation (N=2165) 6 months post randomization Evaluated women CIN 2+ prevalence 1879 15 (0.80%) 1929 43 (2.23%) 1859 3.55% CIN 2 prevalence 12 months post randomization 25 (1.42%) 54 (2.91%) 93 (5.41%) Denny et al., JAMA 2005; 294: 2173-81 Study

8. Cluster Randomised Controlled Trial of VIA Screening, Dindigul District, India Christian Fellowship Community Health Centre (CFCHC), Ambillikai, India PSG Institute of Medical Sciences and Research (PSGIMSR), Coimbatore, India Cancer Institute (WIA), Chennai, India World Health Organization-International Agency for Research Cancer (WHO-IARC), Lyon, France Supported by the Bill & Melinda Gates Foundation through the ACCP

9. Study design Study CLUSTER RANDOMISED TRIAL OF VISUAL SCREENING FOR CERVICAL CANCER IN RURAL SOUTH INDIA: DINDIGUL DISTRICT CERVICAL SCREENING STUDY, TAMIL NADU, INDIA 113 Village clusters 79 372 eligible women aged 30-59 years Allocated to single round VIA screening by nurses, 57 clusters, 48 225 women Colposcopy/directed biopsy for screen +ve women Cryotherapy/LEEP/conization for CIN Follow-up of women for cervical cancer incidence and deaths Comparison of cervical cancer incidence and deaths in the VIA and Control Groups Diagnosis & treatment of invasive cancer Allocated to usual care control group health education, 56 clusters, 30167 women

10. Interim results Study CLUSTER RANDOMISED TRIAL OF VISUAL SCREENING FOR CERVICAL CANCER IN RURAL SOUTH INDIA: DINDIGUL DISTRICT CERVICAL SCREENING STUDY, TAMIL NADU, INDIA VIA Group, 48 225 women  32 340 (67%) received VIA screening  3 088 (9.5%) women screened positive  1 882 (5.8%) had CIN 1 lesions  278 (8.6%) had biopsy  239 (0.7%) had CIN 2 & 3 lesions  75% with CIN received treatment  Follow-up for cervical cancer incidence and mortality continuing Control Group, 30 167 women  Follow-up for cervical cancer incidence and mortality continuing An interim analysis of final outcomes at the end of 2006

11. Cost-Effectiveness of Cervical Cancer Screening in Five Developing Countries The most cost-effective strategies were those that required the fewest visits, resulting in improved follow-up testing and treatment. Screening women once in their lifetime, at age 35, with a one- or two-visit screening strategy involving visual inspection of the cervix with acetic acid or DNA testing for human papillomavirus (HPV) in cervical cell samples, reduced the lifetime risk of cancer by approximately 25 - 36 %, and cost less than $500 per year of life saved. Relative cancer risk declined by an additional 40 % with two screenings (at ages 35 and 40), resulting in a cost per year of life saved that was less than each country's per capita gross domestic product — a very cost-effective result, according to the Commission on Macroeconomics and Health. Goldie et al., 2005 N Engl J Med 353; 20: 2158-68

12. Comparative efficacy of visual inspection with acetic acid, HPV testing and conventional cytology in cervical cancer screening: a randomized intervention trial in Maharashtra State, India Tata Memorial Centre (TMC), Mumbai, India Nargis Dutt Memorial Cancer Hospital (NCMCH), Barshi, India International Agency for Research Cancer (WHO-IARC), Lyon, France Supported by the Bill & Melinda Gates Foundation through the ACCP

13. Primary Objectives  To evaluate the reduction in cervical cancer incidence and mortality associated with a single round of screening with visual inspection with acetic acid (VIA) or cytology or HPV testing, as compared to a control group with no screening  To evaluate the cost-effectiveness (CE) of the above three approaches O SMANABAD RCT OF C ERVICAL S CREENING, I NDIA Study

14. FLOW CHART OF THE STUDY DESIGN AND FINDINGS Eligible population 52 PHCs (n=142,701) Randomization Cytology arm (13 PHCs) VIA arm (13 PHCs) Control arm (13 PHCs) HPV arm (13 PHCs) Screening coverage 71.9% (positivity rate: 14.0%) Screening coverage 72.9% (positivity rate: 7.0%) Screening coverage 69.5% (positivity rate: 10.3%) Compliance with colposcopy in the field 98.5% Compliance with colposcopy at NDMCH 87.1% Compliance with colposcopy at NDMCH 88.2% Detection rates CIN 2-3 0.7% Condyloma/ CIN 1 5.6% cancer0.3% CIN 2-3 1.0% Condyloma/ CIN 1 2.0% cancer0.3% CIN 2-3 0.9% Condyloma/ CIN 1 2.3% cancer0.2% Collaboration with Tata Memorial Centre, Mumbai and NDMCH, Barshi O SMANABAD RCT OF C ERVICAL S CREENING, I NDIA Study

15. Stage of disease by group and detection mode