ACCP Evidence base: Implications for policy and practice

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. ALTERNATIVE PROGRAMMATIC APPROACHES: • 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)** *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. Test Sensitivity Specificity Cytology 31-78% 91-99% HPV testing 61-90% 62-94% VIA 50-96% 44-97% VILI 44-93% 75-85% Accuracy of screening tests in developing countries: range in sensitivity and specificity

5. OSMANABAD RCT OF CERVICAL SCREENING, INDIA Study RESULTS OF TREATMENT OF CIN

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

7. Characteristic HPV 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% Study CIN 2 prevalence 12 months post randomization 25 (1.42%) 54 (2.91%) 93 (5.41%) RANDOMISED CONTROLLED TRIAL OF SCREEN AND TREAT APPROACH FOR CERVICAL CANCER PREVENTION IN SOUTH AFRICA Denny et al., JAMA 2005; 294: 2173-81

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. CLUSTER RANDOMISED TRIAL OF VISUAL SCREENING FOR CERVICAL CANCER IN RURAL SOUTH INDIA: DINDIGUL DISTRICT CERVICAL SCREENING STUDY, TAMIL NADU, INDIA Study Study design 113 Village clusters 79 372 eligible women aged 30-59 years Allocated to usual care control group health education, 56 clusters, 30167 women 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 Diagnosis & treatment of invasive cancer Diagnosis & treatment of invasive cancer Follow-up of women for cervical cancer incidence and deaths Comparison of cervical cancer incidence and deaths in the VIA and Control Groups

10. CLUSTER RANDOMISED TRIAL OF VISUAL SCREENING FOR CERVICAL CANCER IN RURAL SOUTH INDIA: DINDIGUL DISTRICT CERVICAL SCREENING STUDY, TAMIL NADU, INDIA Study Interim results 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 requiredthe fewest visits, resulting in improved follow-up testing andtreatment. Screening women once in their lifetime, at age35, with a one- or two-visit screening strategyinvolving visual inspection of the cervix with acetic acid orDNA testing for human papillomavirus (HPV) in cervical cellsamples, reduced the lifetime risk of cancer by approximately25 - 36 %, and cost less than $500 per year of life saved.Relative cancer risk declined by an additional 40 % withtwo screenings (at ages 35 and 40), resulting in a costper year of life saved that was less than each country's percapita gross domestic product — a very cost-effectiveresult, 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, IndiaInternational Agency for Research Cancer (WHO-IARC), Lyon, France Supported by the Bill & Melinda Gates Foundation through the ACCP

13. OSMANABAD RCT OF CERVICAL SCREENING, INDIA Study 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

14. OSMANABAD RCT OF CERVICAL SCREENING, INDIA Study Eligible population52 PHCs(n=142,701) Randomization VIA arm(13 PHCs) Cytology arm(13 PHCs) HPV arm(13 PHCs) Control arm(13 PHCs) Screening coverage71.9%(positivity rate: 14.0%) Screening coverage72.9%(positivity rate: 7.0%) Screening coverage69.5%(positivity rate: 10.3%) Compliance with colposcopy in the field98.5% Compliance with colposcopy at NDMCH87.1% Compliance with colposcopy at NDMCH88.2% Detection rates Detection rates Detection rates Condyloma/ CIN 15.6% CIN 2-30.7% cancer0.3% Condyloma/ CIN 12.0% CIN 2-31.0% cancer0.3% Condyloma/ CIN 12.3% CIN 2-30.9% cancer0.2% FLOW CHART OF THE STUDY DESIGN AND FINDINGS Collaboration with Tata Memorial Centre, Mumbai and NDMCH, Barshi

15. Stage of disease by group and detection mode