Cervical cytology or the molecular model: which is the best way forward?

Transcription

1 Cervical cytology or the molecular model: which is the best way forward? Pekka Nieminen, M.D. Chief Physician, Associate Professor Dept. of Obstetrics & Gynaecology Helsinki University Central Hospital Finland

2 Conflict of interest None

3 Organised cervical cancer screening programme in Finland -conventional Pap as the screening test Target population 1.3 million women ~ 260,000 women invited (98%) >180,000 screened (72%) Follow-up cytology (intensive screening) recommended: 5.4% Referral to colposcopy: 1.1% CIN2+ cases treated: 0.4% of screened women 3000 CIN treatments per year

4 Trends in incidence of cervical cancer in selected countries: age-standardised rate (W) per 100,000 (Globocan 2015)

5 Cervical cancer incidence trends by age in Finland Pap-screening has reached its performance limits in Finland Is not effective among younger women Ca incidence increasing among younger women, <40 years of age

6 Pap-screening is not without problems! Sasieni & Cuzick, BMJ 2009

7 Screening with cytology is clearly not enough! We have had over 50 years to make it perform, globally. Pap-smear is not very sensitive New methods? HPV-test? Primary prevention with vaccines

8 HPV primary screening Pap-test has good specificity but poor sensitivity HPV-test instead of Pap-smear? Results from the Finnish randomised trial started 2003, ongoing with cytology triage of HPV+ women women ja follow up years Meta-analyses of randomised prospective trials in Europe

9 HPV vs. cytology screening 1st screening round, 5 y F-U. Leinonen et al BMJ 2012;345:e7789 Colposcopy referral (HPV+ and/or LSIL+ in screening) HR 1.72 ( ) for CIN 1 HR 1.52 ( ) for CIN 2 HR 1.81 ( ) for CIN 3 or AIS HR 1.21 ( ) for ICC Need for intensive screening (HPV+ and cyt or ASC-US vs. ASC-US) HR 2.66 ( ) for CIN 1 HR 4.45 ( ) for CIN 2 HR 2.97 ( ) for CIN 3 or AIS HR NA for ICC Negative/normal findings HR 1.18 ( ) for CIN 1 HR 0.65 ( ) for CIN 2 HR 0.32 ( ) for CIN 3 or AIS HR 2.50 ( ) for ICC

10 DRR of CIN2+ and CIN3+ identified by hrhpv testing versus cytology in the first screening round. Marc Arbyn, Guglielmo Ronco, Ahti Anttila, Chris J.L.M. Meijer, Mario Poljak, Gina Ogilvie, George Koliopou... Vaccine Volume 30, Supplement F88 - F99

11 Relative detection rate of CIN3+ and cervical cancer, observed in the second screening round Less cancer with HPV screening! Marc Arbyn, Guglielmo Ronco, Ahti Anttila, Chris J.L.M. Meijer, Mario Poljak, Gina Ogilvie, George Koliopou... Vaccine Volume 30, Supplement F88 - F99

12 Cost-efficiency Based on mathematical modelling and simulation done by the THL HPV-expert group 2011 in Finland 2-4 CIN 3 treatments needed to prevent one cervical cancer Very low NNT

13 Present practice 34,0 MEUR 135 ICC 797 LY 2297 EH 1375 QALY EUR/QALYG 14,1 LEH/ES 6705 EUR/QALYG 6,8 LEH/ES EUR/QALYG 10,5 LEH/ES Organised only 30:5:60 14,4 MEUR 187 ICC 948 LY 1562 EH 1507 QALY EUR/QALYG 17,4 LEH/ES 25:5:60 15,8 MEUR 157 ICC 843 LY 1878 EH 1367 QALY 8451 EUR/QALYG 3,3 LEH/ES 22,26,30:5:60 17,4 MEUR 146 ICC 806 LY 2069 EH 1336 QALY 7000 EUR/QALYG 6,4 LEH/ES 25:5:65E:85 17,2 MEUR 112 ICC 615 LY 2041 EH 1107 QALY 5738 EUR/QALYG 9,1 LEH/ES 25:5:35HPV:5:65E:85 17,9 MEUR 98 ICC 509 LY 2169 EH 985 QALY 6564 EUR/QALYG 3,7 LEH/ES 30:5:65E:85 16,1 MEUR 143 ICC 720 LY 1725 EH 1248 QALY 30:5:70 16,2 MEUR 155 ICC 759 LY 1669 EH 1294 QALY EUR/QALYG 4,7 LEH/ES 30:5:85 18,1 MEUR 143 ICC 720 LY 1725 EH 1248 QALY

14 New screening recommendation by NIHW, Finland: years old women screened with 5 year intervals, HPV-test instead of Pap-test from 35 year old women Present practice 2008 Model population* New recomm Change Cancer cases % CIN treatments % Lost life years % Millions 41,0 34,0 17,9-47 % *Model population births girls /per year

15 Still possible difficulties Triage after HPV-screening to compensate the poorer specificity Cytology Molecular methods: genotyping, methylation, p16 etc. Today data and evidence from cytology triage, but not enough from molecular methods in routine screening HPV-vaccinated age cohorts: Requirements will change

16 Mille grazie!