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 06.03.2012 1 Dr. med. Alexander Luyten Oberarzt Frauenklinik Chefarzt Prof. Dr. KU Petry
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 www.qiagen.com or can be requested from QIAGEN Technical Services or your local distributor.
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.2013 2
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.2013 3
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.2013 4
Long term risk stratification with primary HPV- and cytology co-testing Dillner J et al, BMJ 2008 7th Diagnostic Days 27.Nov.2013 5
Metaanalysis Which HPV Test can be used for screening? M. Arbyn, Vaccine 2012 7th Diagnostic Days 27.Nov.2013 6 043
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.2013 7
WOLPHSCREEN 2006-2011 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% 0.00005 % 0 % 8.9 % 41 % RISK OF CIN 3+ 7th Diagnostic Days 27.Nov.2013 8
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.2013 9
Compliance with colposcopy 7th Diagnostic Days 27.Nov.2013 10
Participants in colpo clinic between 2006-12 (=3.9%) n=712 Compliance 93,1% 7th Diagnostic Days 27.Nov.2013 11 045
CIN3+ according to Pap smear results 7th Diagnostic Days 27.Nov.2013 12
Cervical Cancer Incidence in Lower Saxony 2009 original tumour registry data 2012 Wolfsburg 7th Diagnostic Days 27.Nov.2013 13
Overtreatment? 1,49% excisional therapy within 60 months Quality indicator fulfilled: 90.8% CIN2+ n= 273 7th Diagnostic Days 27.Nov.2013 14
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.2013 15
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.2013 16
Observed Colposcopy Failures Overall failure rate = 8 out of 171 = 4.7% Petry, KU, Gyn Oncol, 128: 282 (2013) 7th Diagnostic Days 27.Nov.2013 17
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= 0.021 7th Diagnostic Days 27.Nov.2013 18 8.4 %
Failure analysis No failure in cancer cases 5 failures in ECC / type 3 TZ 3 failures punch biopsies 7th Diagnostic Days 27.Nov.2013 19
% Long term risks in women with </=CIN1 on colposcopy (n=460) 8 7 6 5 4 3 CIN3 CIN2+ 2 1 0 overall risk true risk of new lesion 7th Diagnostic Days 27.Nov.2013 20 (n=460)
% Second HPV Screening after 5 years few HPV infections, no disease n= 19.625 (2006-2011 and 4.067 women 2011-2012 in Wolfsburg) 7th Diagnostic Days 27.Nov.2013 21
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.2013 22
Long term Risk for CIN3+ 2006-13 % * * Risk groups 2006/2007 7th Diagnostic Days 27.Nov.2013 23
Long term risk for CIN3+ during follow-up 2006-13 n 7th Diagnostic Days 27.Nov.2013 24
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.2013 25
2. Round Feb 2011 Jul 2012 0 % 94.9% HPV-/Pap- 4,112 participants Risk of underlying CIN3+ 1st 0.87 2nd 0.05 0.9% 3.3% 0.2% HPV-/Pap+ HPV+/Pap- HPV+/Pap+ 0 % 0.7% 14% 7th Diagnostic Days 27.Nov.2013 26
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.2013 27
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.2013 28