the Copenhagen Self-Sampling Initiative (CSi)

Transcription

1 Early experiences and preliminary data from the Copenhagen Self-Sampling Initiative (CSi) targeting screening non-responders Jesper Bonde Copenhagen University Hospital, Hvidovre

2 DISCLOSURE STATEMENT Jesper Bonde, PhD, Dipl.Med.Sci Senior Researcher Molecular Pathology Dept. Pathology & Clinical Research Centre Copenhagen University Hospital, Hvidovre, Denmark BD Diagnostics Genomica Hologic/Gen-Probe Qiagen Roche Diagnostics Roche Pharma

3 Why self-sampling?

4 Rationale The most efficient way to improve screening efficacy is to raise attendance rate Self sampling offers itself to molecular HPV testing, but can not be done using cytology The aim of self sampling is to get more women to go for a regular screening test

5 the Copenhagen Self-Sampling Initiative (CSi) Pilot implementation by mandate of the Regional Health Care Authorities to generate experience for near future roll out of self-sampling as a general offer to screening non-responders

6 Who are these screening non-attenders? The CSi Pilot

7 % of all non-responders registered The Non-responders 30% 25% 20% Age distribution non-responders (N=54,585) 15% 10% 5% 10% 24% 24% 25% 17% 0% yrs yrs yrs yrs 60+ yrs Age groups

8 Definition of Non-responder data retrieval from nationwide registry in April Alive and resident in the Capital Region - Eligible for screening (23-65 years) - Has not formally dismissed screening participation - No cervical cytological sample registered in nationwide Pathology Registry (Patobank) the last 4 years (<50 years) or last 6 years (> 50 years) N 2014 = 54,586

9 Who are the non-attenders? Non-Danish emigrants EU and non-eu Socio-economic group: low income, little or no education besides primary school, Regular women..difficult to reach..

10 Choice of self-sampling device The CSi Pilot

11 Definition: All self sampling devices requiring liquids distributed to private homes were deselected for safety reasons Innovation: Radio Frequency Induced Device (chip) in each brush for easy, secure identification The CSi Pilot RFID chip embedded

12 A new approach to Communications

13 The Invitation Package Info sheet Reply form Invitation

14 Innovative Communication

15 The pilot study design

16 Study design and strategy April 2014: Data retrieval of non-responders N max = 54,585 Invitation letter & Info material Letter with prestamped envelope Phone AIM Webpage / mobile application Yes, thank you No, thank you Register based 5000 returned brushes for analysis follow up (Opt-in) (opt-out) Brush received No brush returned Return to Screening HPV negative on CLART & Onclarity HPV positive on Clart and/or Onclarity Referral to GP for ordinary screening test Cytology test CLART & Onclarity test

17 Response rates

18 Response to invitation Did not No thank you 4% 3% Hysterectomized, pregnant or other 20% returned the brush 31% Accepted the invitation 62% Did not react to invitation 62%

19 Response by method 100% 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% 3% 34% 62% phone and web page and mobile app letter > 150 days after first invitation

20 % of all invited in age group How many got screened? 35% 30% 25% 20% 1% 9% 1% 11% 2% 10% 2% 11% 1% 7% 1% 0% 2% 0% 3% 2% 1% 6% 15% 10% 16% 17% 20% 21% 21% 20% 22% 22% 20% 5% 0% Age groups Gik til egen læge efter at have modtaget en HPV Hjemmetest (N=248) Gik til egen læge efter HPV Hjemmetest invitation (N=1515) Returnerede HPV Hjemmetest (N=4,774) Total PRELIMINARY DATA

21 How many got screened? Conclusion: 20% of invited women returned a self sampling brush 6% went to own GP after Self sampling invitation 1% went to own GP after receiving self sampling brush = 27% of all invited Additionally, 6% of all identified non-responder women went to GP before self sampling invitation

22 Test protocol & Sample Quality

23 Question: Can women supply samples of sufficient cellularity for analysis Cellularity analysis: Use the C t values of BD Onclarity HPV assay as a proxy end-point marker to assess the amount of human material in a sample

24 Cellularity in SurePath LBC and self-samples Routine SurePath screening samples (81% (84% primary screening, 19% 16% follow up samples) Age Average HBB Ct Value Average HBB Ct St.Dev ,19 1, ,40 1, ,93 1, ,73 1,41 HPV Self-sampling Age Average HBB Ct Value Average HBB Ct St.Dev ,41 1, ,91 1, ,34 1, ,08 1,50 N=998 Sample size: 10 ml N=1202 Sample size: 3 ml Insufficient samples 0.4% Inadequate cytologies 0.7% PRELIMINARY DATA

25 HPV Prevalence & Follow-up results

26 HPV prevalence HPV Self sampling HPV positive HPV Negative Total % 85% 100% VIPER % 84.5% 100% PRELIMINARY DATA VIPER-4 : Study of BD Onclarity performance on un-selected, routine screening samples (SurePath), 84% primary screening, 16% follow-up samples

27 Genotype Frequency (%) HPV Genotype Distribution 25 CSi VIPER HPV 16 HPV18 HPV 31 HPV 45 HPV 51 HPV 52 HPV 33/58 HPV 56/59/66 HPV 35/39/68 VIPER-4 : Unselected screening samples (SurePath), 84% primary screening, 16% follow-up samples

28 Follow-up cytology 80% of all self sampling HPV positive women returned for recommended follow up HPV status Normal ASCUS LSIL HSIL ASCH AGC Carcinoma Total HPV status Normal ASCUS LSIL HSIL ASCH AGC Carcinoma Total Negative Negative 34% 1% <1% 0 <1% <1% 0 36% Positive Positive 37% 6% 4% 12.5% 2.5% <1% <1% 63% Total Total 71% 7% 4.6% 12.5% 2.8% <1% <1% 100% ASCUS 29% In the HORIZON Study 4% of all women 30 years of age going for primary screening were HPV positive, ASCUS* (CLART HPV2) *Rebolj et al, forthcoming

29 Follow-up histology 5 CIN1 CIN2 30 CIN3 CX CA CIN1 CIN2 CIN3 CX CA 29% 16% 50% 5% 39,3 year (27-65) 43,5 year (27-64) 38,4 year (27-56) 50,2 year (39-59) Total number of CIN2: 72 *Lam et al, forthcoming

30 So what was the screening history of the participants? Non-attenders screening history and participation rate S1 (n=10,092) S2 (n=2,564) S3 (n=10,974) Total (N=23,630) Agreed to participate (n=7,353) 40% 34% 23% 31% Returned home tests (n=4,594) 65% 60% 60% 62% HPV positive test results (n=706) 15% 13% 17% 15% Cytology follow up (n=512) 77% 71% 66% 73% S1: women who have not been screened the last invitation round. S2: women who have not been screened the last two rounds. S3: women who have not been screened in the last three or more rounds.

31 Early conclusions & perspectives

32 Early conclusions OPT-IN strategy is a cost reductive, viable alternative to OPT-out strategies (11% loss of brushes vs. 78% loss if opt-out strategy) Self-sampling with an opt-in strategy was well accepted among screening non-participants no matter the age or screening history 20% returned Brushes Web-page and mobile-communication platforms were well accepted and provides a smooth and cheap communication link to the users

33 Early experiences Dry brush, BD CBD medium, and HPV Onclarity HPV test together constitutes a robust protocol for obtaining and analysing self-samples Very low number of insufficient samples

34 Early conclusions Self sampling responders in our uptake area has approx. same HPV prevalence as the ordinarily screened women Yet, self-sampling HPV positive women at followed-up has a higher proportion of cytology abnormalities detected, than women in ordinary, routine screening The pilot detected 5 cancers, 72 CIN2 and got more than 6500 screened out of women invited.

35 Acknowledgement Dept. Pathology & Clinical Research Centre, Copenhagen University Hospital, Hvidovre Copenhagen Danish Cancer Society Elise Christensen, Louise Thomsen Susanne Krüger Kjær Janni Lam, Ditte Ejegod, Helle Pedersen, Sarah Preisler, Carsten Rygaard, Matejka Rebolj & Jesper Bonde Center for Epidemiology and Screening, Copenhagen University Elsebeth Lynge

36 Thank you for your attention