IARC’s Cervical Screening Progamme - Cairo IARC’s CERVICAL CANCER SCREENING PROGRAMME R. Sankaranarayanan MD Screening Group World Health Organization International Agency for Research on Cancer, Lyon, France

IARC’s CERVICAL CANCER SCREENING PROGRAMME OBJECTIVE To guide public health policies on cervical cancer control in different regional, national and sub-national settings

IARC’s CERVICAL CANCER SCREENING PROGRAMME Evaluates the role of cytology and various non-cytology based screening in the early detection and prevention of cervical neoplasia world-wide

IARC’s CERVICAL CANCER SCREENING PROGRAMME SCREENING TESTS EVALUATED Conventional cervical cytology Unaided visual inspection (“downstaging”) Naked eye visual inspection with 3-5% acetic acid (VIA) Visual inspection with acetic acid using low-level (2-4X) magnification (VIAM) Visual inspection with Lugol’s iodine (VILI) HPV testing

SCREENING APPROACHES EVALUATED IARC’s CERVICAL CANCER SCREENING PROGRAMME SCREENING APPROACHES EVALUATED Low-intensity screening (“once a life-time”) Screen, triage, treat approaches with aposteriori histology (1- or 2-visit approach)

LEEP by mid-level clinicians IARC’s CERVICAL CANCER SCREENING PROGRAMME EVALUATION OF TREATMENT OF CERVICAL PRECANCERS Cryotherapy by nurses LEEP by mid-level clinicians LEEP (LLETZ) Cryotherapy

IARC’s CERVICAL CANCER SCREENING PROGRAMME STUDY DESIGNS Cross-sectional studies Follow-up (cohort) studies Non-randomised controlled trials Cluster-randomised controlled trials Randomised trials Demonstration programmes

IARC’s CERVICAL CANCER SCREENING PROGRAMME OUTCOMES STUDIED Accuracy Reproducibility Detection rates of CIN/Ca Cure rates of CIN Side-effects and complications of Rx of CIN Stage-distribution Reduction in incidence/mortality Determinants of participation

IARC’s CERVICAL CANCER SCREENING PROGRAMME STUDY LOCATIONS Vientiane Bangkok Singapore Trivandrum Emakulam Kannur Mumbai Barshi/ Osmanabad Hyderabad Coimbatore Ambillikai Calcutta Bhaktapur Banepa Barathpur New Delhi Jaipur Dar es Salaam Luanda Brazzaville Ibadan Ouagadougou Niamey Bamako Nouakchott Dakar Conakry Lima Bogota Randomised control trials Cross-sectional studies Training facilities Planned projected

COLLABORATING INSTITUTIONS: AFRICA, EUROPE AND SOUTH AMERICA IARC’s CERVICAL CANCER SCREENING PROGRAMME COLLABORATING INSTITUTIONS: AFRICA, EUROPE AND SOUTH AMERICA Maternity Hospital, Luanda, and MOH, Angola University Hospital, Ouagadougou, Burkina Faso University Hospital, Brazzaville, Republic of Congo University Hospital, Conakry, and MOH, Guinea Hospital Point G, Bamako, Mali University Hospital, Nouakchoutt, Mauritannia Medical College, Ibadan, Nigeria University Hospital, Niamey, Niger Ocean Road Cancer Institute, Dar es Salaam, Tanzania Regional Office of the WHO, Arican Region (AFRO) Hospital Edouard Herriot, Lyon, France Centre Leon Berard, Lyon, France University Hospital, Grenoble, France INCTR, Brussels, Belgium Health Economics Research Centre, University of Oxford National Cancer Institute, Lima, Peru National Cancer Institute, Bogota, Columbia

COLLABORATING INSTITUTIONS: INDIA IARC’s CERVICAL CANCER SCREENING PROGRAMME COLLABORATING INSTITUTIONS: INDIA Tata Memorial Centre, Mumbai, Nargis Dutt Memorial Cancer Hospital, Barshi Christian Fellowship Community Health Centre, Ambillikai Regional Cancer Centre, Trivandrum Chittaranjan National Cancer Institute, Kolkata Cancer Foundation of India, Kolkata Cancer Institute (WIA), Chennai All India Institute of Medical Sciences, New Delhi Bhagwan Mahaveer Cancer Hospital & Research Centre, Jaipur PSG Institute of Medical Sciences and Research, Coimbatore Christian Medical College, Vellore Malabar Cancer Care Society, Kannur MNJ Cancer Institute, Hyderabad Institute for Rural Health Studies, Hyderabad

IARC’s CERVICAL CANCER SCREENING PROGRAMME COLLABORATING INSTITUTIONS BP Koirala Memorial Cancer Hospital, Bharatpur, Chitwan, Nepal Bhakthapur Cancer Care Centre, Bhakthapur, Nepal Nepal Network for Cancer Treatment & Research, Banepa, Nepal University Hospital, Vientiane, Laos National Cancer Institute, Bangkok, Thailand

IARC’s CERVICAL CANCER SCREENING PROGRAMME 300,000 women in 11 countries 38 Institutions in 5 continents 436 investigators and workers

IARC’s CERVICAL CANCER SCREENING PROGRAMME CROSS-SECTIONAL STUDIES OF ACCURACY TO DETECT CIN 2-3 LESIONS 56,939 women 22,633 with cytology 18,085 with HPV testing/HCII 54,918 tested with VIA 16,900 withVIAM 49,080 with VILI 56,939 had colposcopy 9590 had biopsy 3369 CIN 1   1063 CIN 2 & 3 269 Cx Cancers

IARC’s CERVICAL CANCER SCREENING PROGRAMME ACCURACY OF SCREENING TESTS Int J Cancer 2004; 110-907-13; J Med Screening 2004; 11:77-84; Int J Cancer 2004 (in press); Cancer Detect Prev 2004 (in press)

Cancer Institute (WIA), Chennai, India 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

Flow chart of the design and preliminary results of the study DINDIGUL RCT OF VIA SCREENING, INDIA Flow chart of the design and preliminary results of the study Assessed for eligibility (n= 80,422) Excluded (n=2,030) Randomised 113 clusters (n= 78,392) Allocated to VIA screening 57 clusters (n= 48,225) 124,144 PYO Allocated to control group 56 clusters (n= 30,167) 90,172 PYO Received VIA screening (n= 30,577) Did not receive VIA screening (n= 17,648) 34 invasive cancers diagnosed CR: 37.7/100,000 PYO ASR: 43.1/100,000 PYO Screened positive n=2,939 (9.6%) CIN 1 n= 1,778 (5.8%) Treated n= 1,263 (71.0%) CIN 2-3 n= 222 (0.7%) n= 178 (80.2%) Screen detected invasive cancer n=69 (0.2%) n= 52 (75.4%) Clinically detected invasive cancer n=28 97 invasive cancers diagnosed CR: 78.1/100,000 PYO ASR: 92.4/100,000 PYO Sankaranarayanan et al., Int J Cancer: 109, 461-467 (2004) PYO: person years of observation; CR: crude incidence rate; ASR: age-standardized incidence rate; CIN: cervical intraepithelial neoplasia; Percentages refer to proportion of screened women (N=30,577) except for treatment where they refer to lesion detected

IARC’s Cervical Screening Progamme - Cairo 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

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% CIN 2-3 0.9% Condyloma/ CIN 1 2.3% cancer0.2%

STAGE DISTRIBUTION OF INVASIVE CANCER IN THE STUDY ARMS OSMANABAD RCT OF CERVICAL SCREENING, INDIA STAGE DISTRIBUTION OF INVASIVE CANCER IN THE STUDY ARMS VIA arm Cytology arm HPV arm Control arm Stage Number (%) I 52 (52.5) 61 (62.3) 50 (66.6) 10 (18.6) II 18 (18.2) 12 (11.2) 14 (18.7) 8 (14.9) III 24 (24.2) (24.5) (13.3) 33 (61.1) IV 5 (5.0) 1 (0.0) (1.3) 3 (5.6) Total 99 (100.0) 98 75 54 Study

OVERTREATMENT IN SCREEN, SEE AND TREAT APPROACH: OSMANABAD AND DINDIGUL DISTRICT SCREENING PROJECTS, INDIA Disease status based on histology Number (%) Normal 1595 (36) CIN 1 2157 (49) CIN 2 & 3 629 (15) Total 4381 Supported by the ACCP through the Bill & Melinda Gates Foundation

HOW EFFECTIVE ARE THE TREATMENT OF PRECANCERS IN THE DEVELOPING WORLD? Cryotherapy: Data from Indian studies Lesion Total Cured at 1 year CIN 1 1264 90% (N=1137) CIN 2 & 3 234 79% (N=184) LEEP: Data from Indian studies Lesion Total Cured at 1 year CIN 1 296 96% (N=283) CIN 2 & 3 336 86% (N=288) Overall 1 cure rate in CIN = 89% (1892/2130) Supported by the ACCP through the Bill & Melinda Gates Foundation

300 women with CIN randomized IARC’s CERVICAL CANCER SCREENING PROGRAMME EFFICACY OF SINGLE- VS DOUBLE-FREEZE CRYOTHERAPY 300 women with CIN randomized Preliminary findings indicate same efficacy : 89% NED at 1-year

IARC’s CERVICAL CANCER SCREENING PROGRAMME TRAINING QUALITY ASSURANCE

IARC’s CERVICAL CANCER SCREENING PROGRAMME TRAINING MATERIALS

Contraceptive practice IARC’s CERVICAL CANCER SCREENING PROGRAMME DETERMINANTS OF PARTICIPATION IN SCREENING Low SES Low income Education Parity Contraceptive practice Sankaranarayanan et al., Cancer Detect Prev 2003; 27: 457-65

IARC’s CERVICAL CANCER SCREENING PROGRAMME COST EFFECTIVENESS STUDIES

Unit costs of intervention in Osmanabad district cervical cancer screening project

Costs per CIN 2/3 detected in Osmanabad district cervical cancer screening project

IARC’s CERVICAL CANCER SCREENING PROGRAMME TRAINING CENTRES Chittaranjan National Cancer Institute, Kolkata, India Regional Cancer Centre, Trivandrum, India University Hospital, Conakry, Guinea Maternity Hospital, Luanda, Angola Ocean Road Cancer Institute, Dar es Salaam, Tanzania Instututo de Enfermedades Neoplasicas, Lima Peru National Cancer Institute, Bogota Columbia

Awareness Test Recall Follow-up SCREENING VS EARLY CLINICAL DETECTION IARC’s CERVICAL CANCER SCREENING PROGRAMME SCREENING VS EARLY CLINICAL DETECTION Awareness Test Recall Follow-up

Cervix Cancer Screening Volume 10 Cervix Cancer Screening 2004 (in press)

IARC’s CERVICAL CANCER SCREENING PROGRAMME SUPPORTED BY The Bill & Melinda Gates Foundation through the ACCP WHO-AFRO International Network for Cancer Treatment and Research (INCTR) International Union Against Cancer (UICC) Association for International Cancer Research (AICR) Program for Appropriate Technology in Health (PATH)