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Cervix Cancer Control

Cervix Cancer Control. R. Sankaranarayanan MD Head, Screening Group World Health Organization (WHO) International Agency for Research on Cancer (IARC) Lyon, France http://screening.iarc.fr. 5-YEAR SURVIVAL FROM CERVICAL CANCER IN SELECTED DEVELOPING COUNTRIES (DURING 1992-2000).

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Cervix Cancer Control

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  1. Cervix Cancer Control R. Sankaranarayanan MD Head, Screening Group World Health Organization (WHO) International Agency for Research on Cancer (IARC) Lyon, France http://screening.iarc.fr

  2. 5-YEAR SURVIVAL FROM CERVICAL CANCER IN SELECTED DEVELOPING COUNTRIES (DURING 1992-2000)

  3. Several studies address the feasible options for screening/early diagnosis • Screening tests evaluated: • Downstaging or unaided visual inspection (VI) • Visual inspection with acetic acid (VIA) • Magnified VIA (VIAM) • Visual inspection with Lugol’s iodine (VILI) • HPV testing • Low-intensity cytology • Low-intensity screening linked with diagnosis/treatment

  4. ALTERNATIVE PROGRAMMATIC APPROACHES: REDUCED FREQUENCY OF SCREENING • Once a life-time • Twice a life-time • Once in 10 years • Once in 5 years

  5. ALTERNATIVE PROGRAMMATIC APPROACHES: • REDUCING THE NUMBER OF VISITS AND IMPROVING ADHERENCE TO TREATMENT • CONVENTIONAL APPROACH: SCREEN, DIAGNOSE, CONFIRM, AND TREAT New paradigms: • 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

  6. Effectiveness of treatment Link Screening and Treatment Screening Coverage SUCCESSFUL CERVICAL CANCER PREVENTION: KEY ELEMENTS

  7. Study ACCURACY OF SCREENING TESTS Test No. of women Sensitivity % Specificity % (study sites) (range in study sites) range in study sites) Cytology 22,633 (5) 58 (29 - 77) 95 (89 - 99) HPV testing 18,065 (4) 67 (46 - 81) 94 (92 - 95) VIA 54,981 (11) 77 (58 - 94) 86 (75 - 94) VIAM 16,900 (3) 64 (61 - 71) 87 (83 - 90) Int J Cancer 2004; 110-907-13; J Med Screening 2004; 11:77-84; Int J Cancer 2004; 112: 341-7 Cancer Detect Prev 2004; 28: 345-51

  8. 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

  9. Provinces with all districts engaged Expansion of SVA in Thailand Nong Khai Roi Et Amnat Charoen Yasothon New Province Nan Chiang Mai Uttaradit Surat Thani Phitsanulok Nakorn Sri Thammaraj

  10. 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

  11. Assessed for eligibility (n= 80,422) Excluded (n=2,030) Randomised 113 clusters (n= 78,392) Allocated to control group 56 clusters (n= 30,167) 90,172 PYO Allocated to VIA screening 57 clusters (n= 48,225) 124,144 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%) Screen detected invasive cancer n=69 (0.2%) Treated n= 52 (75.4%) Clinically detected invasive cancer n=28 CIN 1 n= 1,778 (5.8%) Treated n= 1,263 (71.0%) CIN 2-3 n= 222 (0.7%) Treated n= 178 (80.2%) 97 invasive cancers diagnosed CR: 78.1/100,000 PYO ASR: 92.4/100,000 PYO DINDIGUL RCT OF VIASCREENING, INDIA Flow chart of the design and preliminary results of the study 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

  12. DINDIGUL RCT OF CERVICAL SCREENING, INDIA PROPORTION OF VIA POSITIVE WOMEN BY 5-YEAR AGE GROUPS

  13. DINDIGUL RCT OF CERVICAL SCREENING, INDIA DETECTION RATE OF CIN AND INVASIVE CANCER BY 5-YEAR AGE GROUPS IN THE SCREENED ARM Sankaranarayanan et al., Int J Cancer 2004; 109: 461-7

  14. CIN grade Cure rate CIN 1 87.4% (795/910) CIN 2-3 lesions CIN 2 CIN 3 83.7% (87/104) 80.5% (62/77) 92.6% (25/27) All grades 87.0% (882/1014) Cure rates for CIN treated by nurses using double-freeze cryotherapy in the Dindigul District Cervical Screening study, India (Range of follow-up 6-48 months) Cure defined as clinical or histological absence of disease at last follow-up

  15. 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

  16. Eligible population52 PHCs(n=142,701) Study 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

  17. Study OSMANABAD RCT OF CERVICAL SCREENING, INDIA VIA Trends in test positivity and CIN 2-3 detection rates in Osmanabad screening trial, India Cytology HPV Collaboration with Tata Memorial Centre, Mumbai and NDMCH, Barshi

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

  19. Study COSTS PER CIN 2/3 DETECTEDINOSMANABAD DISTRICT CERVICAL CANCER SCREENING PROJECT Collaboration with Tata Memorial Centre, Mumbai and NDMCH, Barshi LeGood et al., Int J Cancer 2005 (in press)

  20. CIN grade Cure rate CIN 1 94.5% (156/165) CIN 2-3 lesions CIN 2 CIN 3 84.8% (66/76) 84.6% (44/52) 91.7% (22/24) All grades 92.1% (222/241) Cure rates for CIN treated by nurses using double-freeze cryotherapy in the Osmanabad District Cervical Screening study, India (at 1-year from treatment) Cure defined as clinical or histological absence of disease at last follow-up

  21. CIN grade Cure rate CIN 1 97.7% (86/88) CIN 2-3 lesions CIN 2 CIN 3 93.7% (179/191) 97.8% (91/93) 89.8% (88/98) All grades 95.0% (265/279) Cure rates for CIN treated by LEEP by doctors in the Osmanabad District Cervical Screening study, India (at 1-year from treatment) Cure defined as clinical or histological absence of disease at last follow-up

  22. Characteristic Control Group (N=30378) VIA –ve women (N=23024) Cytology -ve women (N=23745) HPV –ve women (N=24347) Cervical Cancer (Cx Ca) cases (2002-04) 55 7 6 3 Study Person-years 86577 65618 67673 69389 Cx Ca incidence rate 63.5/100,000 10.7/100,000 8.9/100,000 4.3/100,000 RR of Cx Ca incidence 1.0 0.17 0.14 0.07 Osmanabad District Randomised Controlled Cervical Screening Study, India: Cervical Cancer Incidence in Screen Negative Women in the Intervention groups and Control Group Women during 2002-2004 after Completion of Single Round of Screening (2000-2003)

  23. Characteristic Control Group (N=30378) VIA Group (N=34149) Cytology Group (N=32316) HPV Group (N=34515) Cervical cancer cases (2004-05) 39 17 14 21 Study Person-years 45567 51224 48474 51773 Cx Ca incidence rate 85.6/100,000 33.2/100,000 28.9/100,000 40.1/100,000 RR of Cx Ca incidence 1.0 0.39 0.34 0.47 Osmanabad District Randomised Controlled Cervical Screening Study, India: Cervical Cancer Incidence in Study Groups during 2004-2005 after Completion of Single Round of Screening (2000-2003)

  24. CIN grade Cure rate CIN 1 87.4% (795/910) CIN 2-3 lesions CIN 2 CIN 3 83.7% (87/104) 80.5% (62/77) 92.6% (25/27) All grades 87.0% (882/1014) Cure rates for CIN treated by nurses using double-freeze cryotherapy in the Dindigul District Cervical Screening study, India (Range of follow-up 6-48 months) Cure defined as clinical or histological absence of disease at last follow-up

  25. 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

  26. How to optimize the performance of control programmes?

  27. COST EFFECTIVENESS OF CERVICAL CANCER SCREENING • Coverage • Appropriate test • Alternative programmatic approaches • Diagnosis/ treatment of screening positive women

  28. Breast cancer early detection • Mammography • Ultrasonography • Core biopsy/FNAC • CBE • BSE • Awareness

  29. Thanks to The Bill & Melinda Gates Foundation and International Network for Cancer Treatment and Research (INCTR)

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