HPV testing via self-sampling: today s performance and future perspectives in developed and developing countries

Transcription

1 6th Hellenic HPV Meeting Thessaloniki, HPV testing via self-sampling: today s performance and future perspectives in developed and developing countries Andreas M. Kaufmann Gynäkologische Tumor Immunologie Gynäkologie Charité Campus Benjamin Franklin Berlin, Germany andreas.kaufmann@charite.de GTI@CBF AMK

2 Background HPV DNA-based testing: has shown consistently higher sensitivity in screening algorithms for cervical dysplasia than cytology is robust and can be performed on different materials is being introduced as primary screening in several countries potentially any HPV DNA test can be performed on self-sampled material may need some processing (solubilization, concentration) HPV mrna-based tests maybe more demanding for RNA stabilization HPV E6/E7 protein testing may have higher specificity

3 Specificity of HPV Test DNA test RNA test E6/E7 protein test AMK

4 Background Self-sampling methods have to be: Secure Acceptable Representative sampling Reasonable pricing Clinically validated (Sensitivity, Specificity)

5 Background Self-Sampling devices studied: Swabs (cotton/dacron) Brushes (Rovers, Cytobrush) Conical cytobrush Digene cervical sampler Tampons Lavage applicators (Delphi Screener)

6 Absolute Sensitivity and Specificity Self vs clinician collected sample (Meta-analysis of 36 studies) cutof f Arbyn M et al., Lancet Oncology 2014;15:172

7 Pooled Relative Sensitivity and Specificity Self-sampling related to comparator clinician-obtained sample Arbyn M et al., Lancet Oncology 2014;15:172

8 Arbyn M et al., 2014

9 Arbyn M et al., Lancet Oncology 2014;15:172

10 Comparison self vs clinician Relative values according to HPV test type Arbyn M et al., Lancet Oncology 2014;15:172

11 Comparison by Sampling Method and HPV Test System Arbyn M et al., Lancet Oncology 2014;15:172

12 Conclusion: todays performance PCR-based HPV tests generally showed similar sensitivity on both self-sampled and clinician-sampled material Signal-based assays (like HCII) should use clinician-sampled material Self-sampling to reach women not participating in regular screening programme Self-sampling and PCR-based HPV tests suitable after careful assessing feasibility, logistics, compliance, and cost

13 Why Combine Self-Sampling and HPV Test? high resource countries low resource countries overloaded gynecologists Cytology needs trained technologists Sensitivity is higher with HPV test no gynecologists Few labs, no personnel Sample quality worse Participation rates for cytology can be low Once in a lifetime screen Access to women (non-attenders) Home-based sampling Remote villages Religious/cultural barriers Logistics for samples / result submission Travel time Use for Epidemiology and Monitoring See-and-treat approaches

14 Use of self-sampling Þ High resource settings: Reach non-attenders of screening programmes Low resource settings Epidemiology

15 Accuracy and Acceptability 1) Unsupervised HPV self-sampling by cotton swab vs clinician Digene cervical sampler Sensitivity for CIN2+ Self-sampled 81% (95%CI 60-92) Clinician 100% (95% CI ) Cytology 81% (95% CI 60-92) Specificity for CIN2+ Self-sampled 82% Clinician 85% Cytology >95% Generally well accepted (99%), instructions easy to follow Szarewski et al., 2007, 2011

16 Accuracy and Acceptability 2) Randomised trial in non-attenders for cervical screening 3000 persistent non-attenders, randomised 1:1 to additional invitation vs self-sampling kit. Response to invitation: 10.2% responded 4.5% attended cytological screening Response to self-sampler: 6.4% self-sampling at home 4.1% attended cytological screening Conclusion: 1) women prepared to participate in cytology also do so by self-sampling 2) Women who persistently not attend are likely also not to participate in self-sampling Szarewski et al., 2007, 2011

17 Use of self-sampling High resource settings Low resource settings =>reach all women with acceptable effort and cost Epidemiology

18 A flavour of the challenges

19 Gravitt et al., IJC, 2011

20 Adequate screening approach!? Easy to use, culturally acceptable and comfortable sampling, independent of gynecologist visit Easy to use, affordable, little resources needed for analysis Widely available, applicable, acceptable, diagnostic method for cervical cancer Krings et al., EUROGIN 2013

21 Analysis with Arbor Vita E6 oncoprotein test Lateral flow immuno assay test Detection of HPV 16 and 18 on separate test lines. Running up to 9 samples in <3 hours (hands on time appx. 2 hours) Women (25 to 65 years) living in rural China (n = 7,543) self-collected a cervicovaginal specimen by swab Sensitivity for detection of CIN3+ is 53.5%, for cervical cancer 100% Specificity for CIN3+ detection is 98.9% PPV for CIN3+ detection is 40.8% NPV for CIN3+ detection is 99.37% Zhao et al., Cancer Prev Res., 2013

22 Use of self-sampling High resource settings Low resource settings Epidemiology =>sample reliably and easily obtained

23 Self-sampling and HPV Test in Germany for Epidemiology Pretest HPV Prevalence Study Inclusion criteria Women 20 to 30 years of age both samples obtained non pregnant Two samplings per patient home-based self-sampling by cervicovaginal lavage Office-based clinician-taken cervical smear (Cytobrush) Questionnaire for risk factors and anamnestics Recruting Low prevalence (LP): screening population, n=109 High prevalence (HP): referral clinic Charité, n= 56 Multiplexed Genotyping: GP5+/6+ BS-PCR, Luminex read out

24 Self-sampling set Pretest HPV Prevalence Study Main Study

25 HPV Detection LP/HP Pretest HPV Prevalence Study (LP n=89, HP n=48) HPVpos = smear and/or lavage HPV-DNA detectable LP: Sensitivity self-sampled lavage: 0,84% Sensitivity clinician-obtained smear: 0,84% HP: Sensitivity self-sampled lavage: 0,9% Sensitivity clinician-obtained smear: 0,9%

26 Evaluation of Self-sampling Pretest HPV Prevalence Study (all n=140, HP n=58) If the result of the HPV test is equally reliable in selfsampling or gynecologist taken samples, which method for sampling would you prefer? Self-sampling: 41% 45% Gynecologist: 45% 43% undecided: 14% 12% 30

27 Main Study: German-wide representative study HPV-DNA prevalence (prevaccination) - Sampling 2010/ participants (20-25 years), from registries, 512 nonvaccinated, 223 vaccinated - representativly selected - recruting letter, if consent - Self-sampling-set via mail - Questionnaire (risk factors, vaccination status, sexuality) - vaginal lavage for HPV genotyping by MPG Number of persons

28 HPV Prevalence: cross-sectional (20-25 years) Deleré and Rmschmidt et al., BMC 2014

29 HPV Prevalence in non-vaccinated women years of age in Germany (2011) 30% Anteil der einzelnen HPV-Typen an allen identifizierten HPV-Typen (n=407) bei 235 Personen 25% 20% p o si ti v e s ( % ) 15% 10% 5% 0% HPV genotyp Deleré and Remschmidt et al., BMC 2014

30 Reduced Prevalence of Vaccine HPV and Related Types (2011) despite low (40%) vaccination coverage p os iti vi ty ( % )

31 Summary Self-sampling in conjunction with HPV testing is feasible and effective Slightly reduced sensitivity and specificity (less targeted smear, also vaginal infections) Differences in willingness in women prepared for sampling in clinic vs non-attenders Differences in high/low resource countries to be overcome with adequate sampling methods and tests Usefull for screening but also for epidemiology

32 Thank you & Acknowledgements Yvonne Deleré Cornelius Remschmidt Melanie Schmitt Michaela Fesenfeld Kiel: Ingke Hagemann Karin Unmack Amrei Krings Ursula Schiller Bianca Mandt Renate Noske-Reimers Achim Schneider Kofi Effah Sr. Edgitha Gorges Wolfgang Siebert