ACCP Evidence base: ACCP Evidence base: Implications for policy and Implications for policy and

practicepractice

R. Sankaranarayanan MDR. Sankaranarayanan MDHead, Screening Group

World Health Organization (WHO)International Agency for Research on Cancer (IARC)

Lyon, Francehttp://screening.iarc.fr

ACCP Evidence Base

Test characteristics

Efficacy of treatment of CIN

Effectiveness of reducing disease burden

Cost effectiveness issues

Acceptability of participation determinants

Reduced frequency of screening: one or twice Reduced frequency of screening: one or twice a life timea life time

Reducing the number of visits and improving Reducing the number of visits and improving adherence to treatmentadherence 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: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

Accuracy of screening tests in developing countries: range in sensitivity and specificity

Test Sensitivity Specificity

Cytology 31-78% 91-99%

HPV testing 61-90% 62-94%

VIA 50-96% 44-97%

VILI 44-93% 75-85%

RESULTS OF TREATMENT OF CIN

Treatment Total number Cured (%)

Cryotherapy 562 477 (85%)

LEEP 422 357 (85%)

OOSMANABAD SMANABAD RCTRCT OF OF CCERVICAL ERVICAL SSCREENING, CREENING, IINDIANDIA StudyStudy

630

501

127

2

0

100

200

300

400

500

600

700 Treatment Offered

Accepted Immediate Treatment

Postponed Treatment

Refused Treatment

Women

SAFETY, ACCEPTABILITY, AND FEASIBILITY OF A SAFETY, ACCEPTABILITY, AND FEASIBILITY OF A SINGLE-VISIT APPROACH TO CERVICAL CANCER SINGLE-VISIT APPROACH TO CERVICAL CANCER

PREVENTION IN RURAL THAILANDPREVENTION IN RURAL THAILAND

Acceptability of Cryotherapy TreatmentAcceptability of Cryotherapy Treatment

Lancet 2003; 361:814-820

RANDOMISED CONTROLLED TRIAL OF SCREEN RANDOMISED CONTROLLED TRIAL OF SCREEN AND TREAT APPROACH FOR CERVICAL CANCER AND TREAT APPROACH FOR CERVICAL CANCER

PREVENTION IN SOUTH AFRICA PREVENTION IN SOUTH AFRICA

Characteristic HPV test & Treat(N=2163)

VIA & Treat(N=2227)

Delayed Evaluation(N=2165)

6 months post randomization

Evaluated womenCIN 2+

prevalence

  

187915 (0.80%)

  

192943 (2.23%)

  

18593.55%

 

CIN 2 prevalence 12 months post randomization

 

  

25 (1.42%) 

  

54 (2.91%) 

  

93 (5.41%)

Denny et al., JAMA 2005; 294: 2173-81

StudyStudy

Cluster Randomised Controlled Cluster Randomised Controlled

Trial of VIA Screening, Trial of VIA Screening,

Dindigul District, IndiaDindigul 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 ACCPSupported by the Bill & Melinda Gates Foundation through the ACCP

Study designStudy design

StudyStudyCLUSTER RANDOMISED TRIAL OF VISUAL SCREENING FOR CERVICAL CANCER IN RURAL SOUTH INDIA: DINDIGUL DISTRICT CERVICAL SCREENING STUDY, TAMIL NADU, INDIA

113 Village clusters79 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

Diagnosis & treatment of invasive cancer

Allocated to usual care control group health education, 56 clusters, 30167 women

Interim resultsInterim resultsStudyStudy

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

Cost-Effectiveness of Cervical Cancer Cost-Effectiveness of Cervical Cancer

Screening in Five Developing CountriesScreening 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

Comparative efficacy of visual inspection Comparative efficacy of visual inspection

with acetic acidwith acetic acid, HPV testing and , HPV testing and

conventional cytology in cervical cancer conventional cytology in cervical cancer

screening: a randomized intervention screening: a randomized intervention

trial in Maharashtra State, Indiatrial 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 ACCPSupported by the Bill & Melinda Gates Foundation through the ACCP

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

OOSMANABAD SMANABAD RCTRCT OF OF CCERVICAL ERVICAL SSCREENING, CREENING, IINDIANDIA StudyStudy

FLOW CHART OF THE STUDY DESIGN AND FINDINGSFLOW CHART OF THE STUDY DESIGN AND FINDINGS

Eligible population52 PHCs

(n=142,701)

Eligible population52 PHCs

(n=142,701)

RandomizationRandomization

Cytology arm(13 PHCs)

Cytology arm(13 PHCs)

VIA arm(13 PHCs)VIA arm

(13 PHCs)Control arm(13 PHCs)

Control arm(13 PHCs)

HPV arm(13 PHCs)HPV arm(13 PHCs)

Screening coverage71.9%

(positivity rate: 14.0%)

Screening coverage71.9%

(positivity rate: 14.0%)

Screening coverage72.9%

(positivity rate: 7.0%)

Screening coverage72.9%

(positivity rate: 7.0%)

Screening coverage69.5%

(positivity rate: 10.3%)

Screening coverage69.5%

(positivity rate: 10.3%)

Compliance with colposcopy in the field

98.5%

Compliance with colposcopy in the field

98.5%

Compliance with colposcopy at NDMCH

87.1%

Compliance with colposcopy at NDMCH

87.1%

Compliance with colposcopy at NDMCH

88.2%

Compliance with colposcopy at NDMCH

88.2%

Detection ratesDetection rates Detection ratesDetection rates Detection ratesDetection rates

CIN 2-30.7%

CIN 2-30.7%

Condyloma/ CIN 15.6%

Condyloma/ CIN 15.6%

cancer0.3%

cancer0.3%

CIN 2-31.0%

CIN 2-31.0%

Condyloma/ CIN 12.0%

Condyloma/ CIN 12.0%

cancer0.3%

cancer0.3%

CIN 2-30.9%

CIN 2-30.9%

Condyloma/ CIN 12.3%

Condyloma/ CIN 12.3%

cancer0.2%

cancer0.2%

Collaboration with Tata Memorial Centre, Mumbai and NDMCH, Barshi

OOSMANABAD SMANABAD RCTRCT OF OF CCERVICAL ERVICAL SSCREENING, CREENING, IINDIANDIA StudyStudy

Stage of disease by group and Stage of disease by group and

detection modedetection mode Group Detection mode Stage 1A (%) Stage 1B (%) Stage 2+ (%) Unknown stage (%) Total

Control Symptomatic 3 (5) 13 (22) 39 (66) 4 (7) 59

HPV Screening 36 (47) 21 (27) 10 (13) 10 (13) 77

Symptomatic 1 (4) 5 (21) 14 (58) 4 (17) 24

Total 37 (36) 26 (26) 24 (24) 14 (14) 101

Cytology Screening 40 (48) 20 (24) 7 (9) 16 (19) 83

Symptomatic 1 (2) 4 (9) 35 (80) 4 (9) 44

Total 41 (32) 24 (19) 42 (33) 20 (16) 127

VIA Screening 33 (41) 16 (20) 30 (37) 2 (2) 81

Symptomatic 1 (2) 8 (20) 26 (63) 6 (15) 41

Total 34 (28) 24 (20) 56 (46) 8 (6) 122