The long term risk for CIN3+ in HC2 negative women and in HC2 positive women with a colposcopic diagnosis of CIN1 or less

Transcription

1 The long term risk for CIN3+ in HC2 negative women and in HC2 positive women with a colposcopic diagnosis of CIN1 or less - 6 years follow-up from an HPV-screening program in Wolfsburg, Germany Klinikum Wolfsburg Dies ist der Titel der Präsentation, die Eingabe erfolgt über den Folienmaster Dr. med. Alexander Luyten Oberarzt Frauenklinik Chefarzt Prof. Dr. KU Petry

2 QIAGEN would like to thank our speaker, Dr. Alexander Luyten, for his presentation. Disclaimer: QIAGEN is not affiliated with the Frauenklinik Wolfsburg. The views expressed herein are those of the speaker, and do not necessarily express the views of QIAGEN. For up-to-date licensing information and product-specific disclaimers for QIAGEN products, see the respective QIAGEN kit handbook or user manual. QIAGEN kit handbooks and user manuals are available at or can be requested from QIAGEN Technical Services or your local distributor.

3 Chances of primary HPV screening HPV testing defines the population at risk, there is almost no risk for CIN3+ in HPV negative women for 5 to 7 years Arbyn M, Vaccine 2012 High quality colposcopy should detect CIN2+ and prevent cervical cancer. The subsequent risk of CIN3+ in women with normal colposcopy should be low Rodriguez AC, JNCI 2008 Combining HPV testing and colposcopy as a one-time intervention should clear the screened population from CIN3+ with a low risk of subsequent lesions for many years 7th Diagnostic Days 27.Nov

4 Challenges: Is colposcopy in HPV screening programs more difficult? 1. The failure rate of Colposcopy may increase because of: Adenocarcinoma in situ will be associated with HC2-positive results but may be missed by cytology and colposcopy The low rate of CIN3+ among HPV+/cyto normal women may distract the colposcopist s attention (screening colposcopy effect?) Persisting HPV infections have an increased risk of progression to CIN3+. Therefore the risk of new lesions following a normal colposcopy should be increased in HPV screening compared to cytology screening with ASC-US or LSIL that may be explained by transient HPV infections or are even HPV negative 7th Diagnostic Days 27.Nov

5 Challenges: Is colposcopy in HPV screening programs more difficult? 2. Patient compliance with colposcopy in HPV+/Pap normal women may be poor 3. Risk of overtreatment in HPV+/Pap normal women. More unnecessary treatments in CIN2 that may have regressed spontaneously 7th Diagnostic Days 27.Nov

6 Long term risk stratification with primary HPV- and cytology co-testing Dillner J et al, BMJ th Diagnostic Days 27.Nov

7 Metaanalysis Which HPV Test can be used for screening? M. Arbyn, Vaccine th Diagnostic Days 27.Nov

8 WOLPHSCREEN = Wolfsburg Primary HPV Screening Pilot Project Women 30+ yrs, health insurance at Deutsche BKK Cytology + HPV-Test (HC2) Cytology negative HC2 negative Cytology positive HC2 negative HC2 positive Cytology negative HC2 positive Cytology positive Next Routine Screening after 5 yrs Repeat Cytology In 6 months Repeat Cytology 6 Mon and HPV-Test 12 Mon Transfer for colposcopy negative positive 7th Diagnostic Days 27.Nov

9 WOLPHSCREEN Private OBGYN: Participants N= 19,625 H P V -T e s t C y t o lo g y H P V -H R n e g P a p n e g H P V -H R n e g P a p p o s H P V -H R p o s P a p n e g H P V -H R p o s P a p p o s R o u t in e 5 y e a rs A S C -U S / L S IL O b s e rv a t io n H S I L c o lp o R e p e a t T e s t s C o lp o s c o p y 92.4% 1.3% 5.3% 1.0% % 0 % 8.9 % 41 % RISK OF CIN 3+ 7th Diagnostic Days 27.Nov

10 Quality control Central management of all project related data Invitation letters to non participants after 2 years Information letters to non attenders with a delay of 6+ months according to patient pathway Repeated searches for externally diagnosed CIN3+ cases in the regional tumor registry and Deutsche BKK s database 7th Diagnostic Days 27.Nov

11 Compliance with colposcopy 7th Diagnostic Days 27.Nov

12 Participants in colpo clinic between (=3.9%) n=712 Compliance 93,1% 7th Diagnostic Days 27.Nov

13 CIN3+ according to Pap smear results 7th Diagnostic Days 27.Nov

14 Cervical Cancer Incidence in Lower Saxony 2009 original tumour registry data 2012 Wolfsburg 7th Diagnostic Days 27.Nov

15 Overtreatment? 1,49% excisional therapy within 60 months Quality indicator fulfilled: 90.8% CIN2+ n= 273 7th Diagnostic Days 27.Nov

16 Colposcopy failure in detection of CIN3+ Definition colposcopy failure Definite failure: Occurence of CIN3 or cancer (CIN3+) within 15 months following a colposcopy classified as CIN1 or less Most likely failure: Occurence of ACIS or CIN3+ in type3 transformation zones more than 15 months following a colposcopy classification of CIN1 or less New lesion : Occurence of a new lesion on colposcopy, CIN3 on histology in type 1 or 2 transformation zones, more than 15 months after a normal colposcopy (CIN1 or less) Petry, KU, Gyn Oncol, 128: 282 (2013) 7th Diagnostic Days 27.Nov

17 WOLPHSCREEN 5 principles for colposcopy 1. Punch biopsies of minor and major changes in type 1 or 2 TZ 2. Endocervical curettage of type 3 TZ 3. Excisional treatment of any CIN3+ and of CIN2 with endocervical involvement 4. Excisional treatment of any HSIL+ cytology in type 3 TZ 5. Excisional treatment of any major changes in type 3 TZ Petry, KU, Gyn Oncol, 128: 282 (2013) 7th Diagnostic Days 27.Nov

18 Observed Colposcopy Failures Overall failure rate = 8 out of 171 = 4.7% Petry, KU, Gyn Oncol, 128: 282 (2013) 7th Diagnostic Days 27.Nov

19 Failure rate and screening results HC2 pos / Pap abnormal HC2 pos / Pap normal n= 76 n=95 correct failure correct failure Petry, KU, Gyn Oncol, 128: 282 (2013) 0% P= th Diagnostic Days 27.Nov %

20 Failure analysis No failure in cancer cases 5 failures in ECC / type 3 TZ 3 failures punch biopsies 7th Diagnostic Days 27.Nov

21 % Long term risks in women with </=CIN1 on colposcopy (n=460) CIN3 CIN overall risk true risk of new lesion 7th Diagnostic Days 27.Nov (n=460)

22 % Second HPV Screening after 5 years few HPV infections, no disease n= ( and women in Wolfsburg) 7th Diagnostic Days 27.Nov

23 HPV incidence and persistency after 5-6 years Inc idenc e P ers is tenc y S till HC 2 pos S till HP V neg HP V pos HC 2 neg without surgery HC 2 neg after treatment n= 3906, 2006 HC2 neg n= 160, 2006 HC2 pos 7th Diagnostic Days 27.Nov

24 Long term Risk for CIN % * * Risk groups 2006/2007 7th Diagnostic Days 27.Nov

25 Long term risk for CIN3+ during follow-up n 7th Diagnostic Days 27.Nov

26 WOLPHSCREEN = Wolfsburg Primary HPV Screening Pilot Project Women 30+ yrs, health insurance at Deutsche BKK Cytology + HPV-Test (HC2) Cytology negative HC2 negative Cytology positive HC2 negative HC2 positive Cytology negative HC2 positive Cytology positive Next Routine Screening after 5 yrs Repeat Cytology In 6 months Repeat Cytology 6 Mon and HPV-Test 12 Mon Transfer for colposcopy negative positive 7th Diagnostic Days 27.Nov

27 2. Round Feb 2011 Jul % 94.9% HPV-/Pap- 4,112 participants Risk of underlying CIN3+ 1st nd % 3.3% 0.2% HPV-/Pap+ HPV+/Pap- HPV+/Pap+ 0 % 0.7% 14% 7th Diagnostic Days 27.Nov

28 Conclusion HC2-Screening and colposcopy in an organized program with sufficient quality control reduced significantly the burden of CIN3+ HPV negative defines a long term zero risk for CIN3+ while a colpo diagnosis of </= CIN1 had a very low risk for CIN3+ during long term follow-up Our results fit in a concept that most CIN3 lesions develop before age 30 For colposcopy HPV screening offers specific challenges that are by far outweighed by the breathtaking reduction in cervical disease 7th Diagnostic Days 27.Nov

29 Thank you for attention Klinikum Wolfsburg K. Ulrich Petry Katrin Luyten Aileen Laksana Sarah Scherbring Antonella Sogari Bernd Braun Axel Reinecke-Lüthge Deutsche BKK Wolfsburg Stefan Lorenz Claudia Mauritz 34 niedergelassene Gynäkologen Externe Partner Universität Tübingen Thomas Iftner Barbara Holz Angelika Iftner QIAGEN (HC2) P16/Ki67 Dietmar Schmidt, Mannheim Rüdiger Ridder, Heidelberg Robert Koch Institut (RKI) Nina Buttmann 7th Diagnostic Days 27.Nov