Strategies for non-invasive management of high-grade cervical intraepithelial neoplasia Citation for published version (APA): Koeneman, M. M. (2019). Strategies for non-invasive management of high-grade cervical intraepithelial neoplasia: prognostic biomarkers and immunotherapy. Maastricht University. https://doi.org/10.26481/dis.20190116mk Document status and date: Published: 01/01/2019 DOI: 10.26481/dis.20190116mk Document Version: Publisher's PDF, also known as Version of record Please check the document version of this publication: • A submitted manuscript is the version of the article upon submission and before peer-review. There can be important differences between the submitted version and the official published version of record. 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INTRAEPITHELIAL Aansluitend bent u van harte uitgenodigd voor een borrel in het Museum NEOPLASIA: aan het Vrijthof, Vrijthof 18. Margot Koeneman Giselbertstraat 18 PROGNOSTIC 6226 DS Maastricht [email protected] BIOMARKERS AND Paranimfen: Frouke Notten IMMUNOTHERAPY [email protected] MARGOT KOENEMAN MARGOT Janneke den Hartog [email protected] MARGOT KOENEMAN Strategies for non-invasive management of high-grade cervical intraepithelial neoplasia: prognostic biomarkers and immunotherapy Margot Maria Koeneman Strategies for non-invasive management of high-grade cervical intraepithelial neoplasia: prognostic biomarkers and immunotherapy Margot Maria Koeneman Strategies for non-invasive management of high-grade cervical intraepithelial neoplasia: prognostic biomarkers and immunotherapy PROEFSCHRIFT ter verkrijging van de graad van doctor aan de Universiteit Maastricht, op gezag van de Rector Magnificus, Prof. dr. Rianne M Letschert, volgens het besluit van het College van Decanen, © Copyright, M.M. Koeneman, Maastricht 2018 in het openbaar te verdedigen op woensdag 16 januari 2019 om 14:00 uur ISBN 978-94-6332-435-9 Graphic design by Loes Kema Printing by GVO drukkers & vormgevers, Ede, NL door All rights reserved. No part of this publication may be reproduced, stored in a retrieval system of any nature, or transmitted, in any form or by any means, electronic, mechanical, photocopying, recording or otherwise, without the prior permission in writing from the copyright owner. Margot Maria Koeneman Financial support for the publication of this thesis was provided by Stichting Olijf and geboren op 3 juni 1986 te Eindhoven Chipsoft. Strategies for non-invasive management of high-grade cervical intraepithelial neoplasia: prognostic biomarkers and immunotherapy PROEFSCHRIFT ter verkrijging van de graad van doctor aan de Universiteit Maastricht, op gezag van de Rector Magnificus, Prof. dr. Rianne M Letschert, volgens het besluit van het College van Decanen, © Copyright, M.M. Koeneman, Maastricht 2018 in het openbaar te verdedigen op woensdag 16 januari 2019 om 14:00 uur ISBN 978-94-6332-435-9 Graphic design by Loes Kema Printing by GVO drukkers & vormgevers, Ede, NL door All rights reserved. No part of this publication may be reproduced, stored in a retrieval system of any nature, or transmitted, in any form or by any means, electronic, mechanical, photocopying, recording or otherwise, without the prior permission in writing from the copyright owner. Margot Maria Koeneman Financial support for the publication of this thesis was provided by Stichting Olijf and geboren op 3 juni 1986 te Eindhoven Chipsoft. Promotores Prof. dr. RFPM Kruitwagen Prof. dr. HW Nijman (Universitair Medisch Centrum Groningen) Copromotor Dr. AJ Kruse Beoordelingscommissie Prof. dr. FCS Ramaekers (voorzitter) Dr. MIE van de Poelgeest (Leids Universitair Medisch Centrum) Prof. dr. EJM Speel Prof. dr. KK van de Vijver (UZ Gent) Prof. dr. GDEM van der Weijden Promotores Prof. dr. RFPM Kruitwagen Prof. dr. HW Nijman (Universitair Medisch Centrum Groningen) Copromotor Dr. AJ Kruse Beoordelingscommissie Prof. dr. FCS Ramaekers (voorzitter) Dr. MIE van de Poelgeest (Leids Universitair Medisch Centrum) Prof. dr. EJM Speel Prof. dr. KK van de Vijver (UZ Gent) Prof. dr. GDEM van der Weijden Table of contents Chapter 1 Introduction 9 Part 1 Assessment of clinical and molecular biomarkers as Part 2 Assessment of clinical applicability of imiquimod cream as a predictors for spontaneous regression of high-grade treatment modality for high-grade CIN CIN lesions Chapter 7 Physicians’ awareness, attitudes and experiences regarding 129 Chapter 2 Natural history of high-grade cervical intraepithelial 27 imiquimod treatment of vaginal and cervical intraepithelial neoplasia:a review of prognostic biomarkers neoplasia Expert Review of Molecular Diagnostics. 2015 Apr;15(4):527-46 Journal of Lower Genital Tract Disease. 2016 Jan;20(1):75-9 Chapter 3 A common epitope in HLA- DRB1*13/14 may protect against 65 Chapter 8 Treatment of cervical intraepithelial neoplasia: patients 151 HPV16 related high-grade cervical intraepithelial neoplasia preferences for surgery or immunotherapy with imiquimod Submitted Journal of Immunotherapy. 2017; 40:148-153 Chapter 4 Gain of chromosomal region 3q26 as a prognostic biomarker 79 Chapter 9a TOPical Imiquimod treatment of high-grade Cervical 165 for high-grade cervical intraepithelial neoplasia: literature intraepithelial neoplasia (TOPIC trial): study protocol for a overview and pilot study randomized controlled trial Pathology & Oncology Research. 2018 Oct 25 BMC Cancer. 2016 Feb 20;16:132 Chapter 5 A prediction model for spontaneous regression of cervical 97 Chapter 9b Preliminary stop of the TOPical Imiquimod treatment of high- 179 intraepithelial neoplasia grade 2, based on simple clinical grade Cervical intraepithelial neoplasia (TOPIC) trial. parameters BMC Cancer. 2017 Feb 7;17(1):110 Human Pathology. 2017 Jan;59:62-69 Chapter 10 Discussion 185 Chapter 6 Smoking status and parity are associated with spontaneous 113 regression of high-risk HPV-positive CIN2 Chapter 11 Valorisation 203 Submitted Chapter 12 Summary 211 Chapter 13 Nederlandstalige samenvatting 219 Abbreviations 227 Publications, presentations and awards 231 Dankwoord 237 Curriculum vitae 243 Table of contents Chapter 1 Introduction 9 Part 1 Assessment of clinical and molecular biomarkers as Part 2 Assessment of clinical applicability of imiquimod cream as a predictors for spontaneous regression of high-grade treatment modality for high-grade CIN CIN lesions Chapter 7 Physicians’ awareness, attitudes and experiences regarding 129 Chapter 2 Natural history of high-grade cervical intraepithelial 27 imiquimod treatment of vaginal and cervical intraepithelial neoplasia:a review of prognostic biomarkers neoplasia Expert Review of Molecular Diagnostics. 2015 Apr;15(4):527-46 Journal of Lower Genital Tract Disease. 2016 Jan;20(1):75-9 Chapter 3 A common epitope in HLA- DRB1*13/14 may protect against 65 Chapter 8 Treatment of cervical intraepithelial neoplasia: patients 151 HPV16 related high-grade cervical intraepithelial neoplasia preferences for surgery or immunotherapy with imiquimod Submitted Journal of Immunotherapy. 2017; 40:148-153 Chapter 4 Gain of chromosomal region 3q26 as a prognostic biomarker 79 Chapter 9a TOPical Imiquimod treatment of high-grade Cervical 165 for high-grade cervical intraepithelial neoplasia: literature intraepithelial neoplasia (TOPIC trial): study protocol for a overview and pilot study randomized controlled trial Pathology & Oncology Research. 2018 Oct 25 BMC Cancer. 2016 Feb 20;16:132 Chapter 5 A prediction model for spontaneous regression of cervical 97 Chapter 9b Preliminary stop of the TOPical Imiquimod treatment of high- 179 intraepithelial neoplasia grade 2,