Prevention of Cervical Cancer. Guideline of the DGGG and the DKG (S3 Level, AWMF Register Number 015/027OL, December 2017) – Part 2 on Triage, Treatment and Follow-up

Peter Hillemanns; Klaus Friese; Christian Dannecker; Stefanie Klug; Ulrike Seifert; Thomas Iftner; Juliane Hädicke; Thomas Löning; Lars Horn; Dietmar Schmidt; Hans Ikenberg; Manfred Steiner; Ulrich Freitag; Uwe Siebert; Gaby Sroczynski; Willi Sauerbrei; Matthias W. Beckmann; Marion Gebhardt; Michael Friedrich; Karsten Münstedt; Achim Schneider; Andreas Kaufmann; K. Ulrich Petry; Axel P. A. Schäfer; Michael Pawlita; Joachim Weis; Anja Mehnert; Mathias Fehr; Christoph Grimm; Olaf Reich; Marc Arbyn; Jos Kleijnen; Simone Wesselmann; Monika Nothacker; Markus Follmann; Thomas Langer; Matthias Jentschke

doi:10.1055/a-0828-7722

Geburtshilfe und Frauenheilkunde, Table of Contents

CC BY-NC-ND 4.0 · Geburtshilfe Frauenheilkd 2019; 79(02): 160-176
DOI: 10.1055/a-0828-7722

GebFra Science

Guideline/Leitlinie

Georg Thieme Verlag KG Stuttgart · New York

Prevention of Cervical Cancer. Guideline of the DGGG and the DKG (S3 Level, AWMF Register Number 015/027OL, December 2017) – Part 2 on Triage, Treatment and Follow-up

Article in several languages: English | deutsch

Authors

Peter Hillemanns

¹Klinik für Frauenheilkunde und Geburtshilfe, Medizinische Hochschule Hannover, Hannover, Germany
Klaus Friese

²Klinik Bad Trissl GmbH, Oberaudorf, Germany
Christian Dannecker

³Klinik und Poliklinik für Frauenheilkunde und Geburtshilfe, München, Germany
Stefanie Klug

⁴Lehrstuhl für Epidemiologie, Technische Universität München, München, Germany
Ulrike Seifert

⁵Tumorepidemiologie, Universitäts KrebsCentrum (UCC), Universitätsklinikum Carl Gustav Carus an der Technischen Universität Dresden, Dresden, Germany
Thomas Iftner

⁶Institut für Medizinische Virologie und Epidemiologie der Viruskrankheiten, Universitätsklinikum Tübingen, Tübingen, Germany
Juliane Hädicke

⁶Institut für Medizinische Virologie und Epidemiologie der Viruskrankheiten, Universitätsklinikum Tübingen, Tübingen, Germany
Thomas Löning

⁷Institut für Pathologie, Albertinen-Krankenhaus Hamburg, Hamburg, Germany
Lars Horn

⁸Institut für Pathologie, Universitätsklinikum Leipzig, Leipzig, Germany
Dietmar Schmidt

⁹Institut für Pathologie, Referenzzentrum für Gynäkopathologie, Mannheim, Germany
Hans Ikenberg

¹⁰CytoMol – MVZ für Zytologie und Molekularbiologie, Frankfurt, Germany
Manfred Steiner

¹¹Facharzt für Frauenheilkunde und Geburtshilfe, Ihringen, Germany
Ulrich Freitag

¹²Facharzt für Frauenheilkunde und Geburtshilfe, Wismar, Germany
Uwe Siebert

¹³Institute of Public Health, Medical Decision Making and Health Technology Assessment, Department of Public Health, Health Services Research and Health Technology Assessment, UMIT – University for Health Sciences, Medical Informatics and Technology, Hall i.T., Austria

³⁴Division of Health Technology Assessment and Bioinformatics, ONCOTYROL – Center for Personalized Cancer Medicine, Innsbruck, Austria
Gaby Sroczynski

¹³Institute of Public Health, Medical Decision Making and Health Technology Assessment, Department of Public Health, Health Services Research and Health Technology Assessment, UMIT – University for Health Sciences, Medical Informatics and Technology, Hall i.T., Austria
Willi Sauerbrei

¹⁴Institut für Med. Biometrie und Statistik (IMBI), Universitätsklinikum Freiburg, Freiburg, Germany
Matthias W. Beckmann

¹⁵Frauenklinik, Universitätsklinikum Erlangen, Erlangen, Germany
Marion Gebhardt

¹⁶Frauenselbsthilfe nach Krebs, Forchheim, Germany
Michael Friedrich

¹⁷Klinik für Frauenheilkunde und Geburtshilfe, Helios Klinikum Krefeld, Krefeld, Germany
Karsten Münstedt

¹⁸Frauenklinik, Ortenau Klinikum Offenburg-Gengenbach, Offenburg, Germany
Achim Schneider

¹⁹Medizinisches Versorgungszentrum im Fürstenberg-Karree, Berlin, Germany
Andreas Kaufmann

²⁰Klinik für Gynäkologie, Campus Benjamin Franklin, Charité – Universitätsmedizin Berlin, Berlin, Germany
K. Ulrich Petry

²¹Frauenklinik, Klinikum Wolfsburg, Wolfsburg, Germany
Axel P. A. Schäfer

²²Facharzt für Frauenheilkunde und Geburtshilfe, Berlin, Germany
Michael Pawlita

²³Deutsches Krebsforschungszentrum, Heidelberg, Germany
Joachim Weis

²⁴Klinik für Tumorbiologie, Klinik für Onkologische Rehabilitation – UKF Reha gGmbH, Freiburg, Germany
Anja Mehnert

²⁵Abteilung für Medizinische Psychologie und Medizinische Soziologie, Universitätsklinikum Leipzig, Leipzig, Germany
Mathias Fehr

²⁶Gynäkologie & Geburtshilfe in Frauenfeld, Spital Thurgau AG, Frauenfeld, Switzerland
Christoph Grimm

²⁷Privatklinik Döbling, Wien, Austria
Olaf Reich

²⁸Privatklinik Graz Ragnitz, Graz, Austria
Marc Arbyn

²⁹Cancer Center, Sciensano, Brüssel, Belgium
Jos Kleijnen

³⁰Kleijnen Systematic Reviews Ltd, York, United Kingdom
Simone Wesselmann

³¹Deutsche Krebsgesellschaft, Berlin, Germany
Monika Nothacker

³²AWMF-Institut für Medizinisches Wissensmanagement, Marburg, Germany
Markus Follmann

³³Leitlinienprogramm Onkologie, Deutsche Krebsgesellschaft, Berlin, Germany
Thomas Langer

³³Leitlinienprogramm Onkologie, Deutsche Krebsgesellschaft, Berlin, Germany
Matthias Jentschke

¹Klinik für Frauenheilkunde und Geburtshilfe, Medizinische Hochschule Hannover, Hannover, Germany

Abstract

Aims Annual opportunistic screening for cervical carcinoma has been done in Germany since 1971. The creation of this S3 guideline meets an important need, outlined in the National Cancer Plan, with regard to screening for cervical cancer, as this guideline aims to provide important information and support for planned organized screening for cervical cancer in Germany.

Methods With the financial support of German Cancer Aid, 21 professional societies developed evidence-based statements and recommendations (classified using the GRADE system) for the screening, management and treatment of precancerous conditions of the cervix. Two independent scientific institutes compiled systematic reviews for this guideline.

Recommendations The second part of this short summary deals with the triage, treatment and follow-up care of cervical dysplasia. With regard to those women who do not participate in screening, the guideline authors recommend sending out repeat invitation letters or an HPV self-collection kit. Colposcopy should be carried out for further investigation if cytology findings are Pap II-p and HPV test results are positive or if the results of an HPV 16 or HPV 18 screening test are positive. A single abnormal Pap smear should be triaged and investigated using HPV testing or p16/Ki67 dual staining.

Key words

cervical cancer - cervical intraepithelial neoplasia (CIN) - cervical precancerous condition - HPV

Full Text

References

References/Literatur
1 Balshem H, Helfand M, Schunemann HJ. et al. GRADE guidelines: 3. Rating the quality of evidence. J Clin Epidemiol 2011; 64: 401-406
2 Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften (AWMF) – Ständige Kommission Leitlinien. AWMF-Regelwerk „Leitlinien“. 2012. Online: http://www.awmf.org/leitlinien/awmf-regelwerk.html last access: 10.11.2015
3 Manos MM, Kinney WK, Hurley LB. et al. Identifying women with cervical neoplasia: using human papillomavirus DNA testing for equivocal Papanicolaou results. JAMA 1999; 281: 1605-1610
4 Bergeron C, Jeannel D, Poveda J. et al. Human papillomavirus testing in women with mild cytologic atypia. Obstet Gynecol 2000; 95 (6 Pt 1): 821-827
5 Lytwyn A, Sellors JW, Mahony JB. et al. Comparison of human papillomavirus DNA testing and repeat Papanicolaou test in women with low-grade cervical cytologic abnormalities: a randomized trial. HPV Effectiveness in Lowgrade Paps (HELP) Study No. 1 Group. CMAJ 2000; 163: 701-707
6 Shlay JC, Dunn T, Byers T. et al. Prediction of cervical intraepithelial neoplasia grade 2-3 using risk assessment and human papillomavirus testing in women with atypia on papanicolaou smears. Obstet Gynecol 2000; 96: 410-416
7 Morin C, Bairati I, Bouchard C. et al. Managing atypical squamous cells of undetermined significance in Papanicolaou smears. J Reprod Med 2001; 46: 799-805
8 Rebello G, Hallam N, Smart G. et al. Human papillomavirus testing and the management of women with mildly abnormal cervical smears: an observational study. BMJ 2001; 322: 893-894
9 Solomon D, Schiffman M, Tarone R. Comparison of three management strategies for patients with atypical squamous cells of undetermined significance: Baseline results from a randomized trial. J Natl Cancer Inst 2001; 93: 293-299
10 Kulasingam SL, Hughes JP, Kiviat NB. et al. Evaluation of human papillomavirus testing in primary screening for cervical abnormalities: comparison of sensitivity, specificity, and frequency of referral. JAMA 2002; 288: 1749-1757
11 Pretorius RG, Belinson JL, Burchette RJ. et al. Regardless of skill, performing more biopsies increases the sensitivity of colposcopy. J Low Genit Tract Dis 2011; 15: 180-188
12 Cuzick J, Szarewski A, Cubie H. et al. Management of women who test positive for high-risk types of human papillomavirus: the HART study. Lancet 2003; 362: 1871-1876
13 Guyot A, Karim S, Kyi MS. et al. Evaluation of adjunctive HPV testing by Hybrid Capture II in women with minor cytological abnormalities for the diagnosis of CIN2/3 and cost comparison with colposcopy. BMC Infect Dis 2003; 3: 23
14 Lonky NM, Felix JC, Naidu YM. et al. Triage of atypical squamous cells of undetermined significance with hybrid capture II: colposcopy and histologic human papillomavirus correlation. Obstet Gynecol 2003; 101: 481-489
15 Ordi J, Puig-Tintore LM, Torne A. et al. [Contribution of high risk human papillomavirus testing to the management of premalignant and malignant lesions of the uterine cervix]. Med Clin (Barc) 2003; 121: 441-445
16 Wensveen C, Kagie M, Veldhuizen R. et al. Detection of cervical intraepithelial neoplasia in women with atypical squamous or glandular cells of undetermined significance cytology: a prospective study. Acta Obstet Gynecol Scand 2003; 82: 883-889
17 Andersson S, Dillner L, Elfgren K. et al. A comparison of the human papillomavirus test and Papanicolaou smear as a second screening method for women with minor cytological abnormalities. Acta Obstet Gynecol Scand 2005; 84: 996-1000
18 Dalla Palma P, Pojer A, Girlando S. HPV triage of women with atypical squamous cells of undetermined significance: a 3-year experience in an Italian organized programme. Cytopathology 2005; 16: 22-26
19 Davis-Devine S, Day SJ, Freund GG. Test performance comparison of inform HPV and hybrid capture 2 high-risk HPV DNA tests using the SurePath liquid-based Pap test as the collection method. Am J Clin Pathol 2005; 124: 24-30
20 Giovannelli L, Capra G, Lama A. et al. Atypical squamous cells of undetermined significance-favour reactive compared to atypical squamous cells of undetermined significance-favour dysplasia: association with cervical intraepithelial lesions and human papillomavirus infection. J Clin Virol 2005; 33: 281-286
21 Nieh S, Chen SF, Chu TY. et al. Is p 16(INK4A) expression more useful than human papillomavirus test to determine the outcome of atypical squamous cells of undetermined significance-categorized Pap smear? A comparative analysis using abnormal cervical smears with follow-up biopsies. Gynecol Oncol 2005; 97: 35-40
22 Bergeron C, Cas F, Fagnani F. et al. [Assessment of human papillomavirus testing on liquid-based Cyto-screen system for women with atypical squamous cells of undetermined significance. Effect of age]. Gynecol Obstet Fertil 2006; 34: 312-316
23 Holladay EB, Logan S, Arnold J. et al. A comparison of the clinical utility of p 16(INK4a) immunolocalization with the presence of human papillomavirus by hybrid capture 2 for the detection of cervical dysplasia/neoplasia. Cancer 2006; 108: 451-461
24 Kelly D, Kincaid E, Fansler Z. et al. Detection of cervical high-grade squamous intraepithelial lesions from cytologic samples using a novel immunocytochemical assay (ProEx C). Cancer 2006; 108: 494-500
25 Kiatpongsan S, Niruthisard S, Mutirangura A. et al. Role of human papillomavirus DNA testing in management of women with atypical squamous cells of undetermined significance. Int J Gynecol Cancer 2006; 16: 262-265
26 Monsonego J, Pintos J, Semaille C. et al. Human papillomavirus testing improves the accuracy of colposcopy in detection of cervical intraepithelial neoplasia. Int J Gynecol Cancer 2006; 16: 591-598
27 Ronco G, Cuzick J, Segnan N. et al. HPV triage for low grade (L-SIL) cytology is appropriate for women over 35 in mass cervical cancer screening using liquid based cytology. Eur J Cancer 2007; 43: 476-480
28 De Francesco MA, Gargiulo F, Schreiber C. et al. Comparison of the AMPLICOR human papillomavirus test and the hybrid capture 2 assay for detection of high-risk human papillomavirus in women with abnormal PAP smear. J Virol Methods 2008; 147: 10-17
29 Monsonego J, Pollini G, Evrard MJ. et al. Detection of human papillomavirus genotypes among high-risk women: a comparison of hybrid capture and linear array tests. Sex Transm Dis 2008; 35: 521-527
30 Siddiqui MT, Hornaman K, Cohen C. et al. ProEx C immunocytochemistry and high-risk human papillomavirus DNA testing in papanicolaou tests with atypical squamous cell (ASC-US) cytology: correlation study with histologic biopsy. Arch Pathol Lab Med 2008; 132: 1648-1652
31 Szarewski A, Ambroisine L, Cadman L. et al. Comparison of predictors for high-grade cervical intraepithelial neoplasia in women with abnormal smears. Cancer Epidemiol Biomarkers Prev 2008; 17: 3033-3042
32 Cattani P, Zannoni GF, Ricci C. et al. Clinical performance of human papillomavirus E6 and E7 mRNA testing for high-grade lesions of the cervix. J Clin Microbiol 2009; 47: 3895-3901
33 Silverloo I, Andrae B, Wilander E. Value of high-risk HPV-DNA testing in the triage of ASCUS. Acta Obstet Gynecol Scand 2009; 88: 1006-1010
34 Del Mistro A, Frayle-Salamanca H, Trevisan R. et al. Triage of women with atypical squamous cells of undetermined significance (ASC-US): results of an Italian multicentric study. Gynecol Oncol 2010; 117: 77-81
35 Denton KJ, Bergeron C, Klement P. et al. The sensitivity and specificity of p 16(INK4a) cytology vs. HPV testing for detecting high-grade cervical disease in the triage of ASC-US and LSIL pap cytology results. Am J Clin Pathol 2010; 134: 12-21
36 Halfon P, Benmoura D, Agostini A. et al. Stepwise algorithm combining HPV high-risk DNA-based assays and RNA-based assay for high grade CIN in women with abnormal smears referred to colposcopy. Cancer Biomark 2010; 7: 133-139
37 Alameda F, Pijuan L, Lloveras B. et al. The value of p 16 in ASCUS cases: a retrospective study using frozen cytologic material. Diagn Cytopathol 2011; 39: 110-114
38 Belinson JL, Wu R, Belinson SE. et al. A population-based clinical trial comparing endocervical high-risk HPV testing using hybrid capture 2 and Cervista from the SHENCCAST II Study. Am J Clin Pathol 2011; 135: 790-795
39 Clad A, Reuschenbach M, Weinschenk J. et al. Performance of the Aptima high-risk human papillomavirus mRNA assay in a referral population in comparison with Hybrid Capture 2 and cytology. J Clin Microbiol 2011; 49: 1071-1076
40 Dufresne S, Sauthier P, Mayrand MH. et al. Human papillomavirus (HPV) DNA triage of women with atypical squamous cells of undetermined significance with Amplicor HPV and Hybrid Capture 2 assays for detection of high-grade lesions of the uterine cervix. J Clin Microbiol 2011; 49: 48-53
41 Monsonego J, Hudgens MG, Zerat L. et al. Evaluation of oncogenic human papillomavirus RNA and DNA tests with liquid-based cytology in primary cervical cancer screening: the FASE study. Int J Cancer 2011; 129: 691-701
42 Ratnam S, Coutlee F, Fontaine D. et al. Aptima HPV E6/E7 mRNA test is as sensitive as Hybrid Capture 2 Assay but more specific at detecting cervical precancer and cancer. J Clin Microbiol 2011; 49: 557-564
43 Schmidt D, Bergeron C, Denton KJ. et al. p 16/ki-67 dual-stain cytology in the triage of ASCUS and LSIL papanicolaou cytology: results from the European equivocal or mildly abnormal Papanicolaou cytology study. Cancer Cytopathol 2011; 119: 158-166
44 Stoler MH, Wright jr. TC, Sharma A. et al. High-risk human papillomavirus testing in women with ASC-US cytology: results from the ATHENA HPV study. Am J Clin Pathol 2011; 135: 468-475
45 Szarewski A, Mesher D, Cadman L. et al. Comparison of seven tests for high-grade cervical intraepithelial neoplasia in women with abnormal smears: the Predictors 2 study. J Clin Microbiol 2012; 50: 1867-1873
46 Alaghehbandan R, Fontaine D, Bentley J. et al. Performance of ProEx C and PreTect HPV-Proofer E6/E7 mRNA tests in comparison with the hybrid capture 2 HPV DNA test for triaging ASCUS and LSIL cytology. Diagn Cytopathol 2013; 41: 767-775
47 Oliveira A, Verdasca N, Pista A. Use of the NucliSENS EasyQ HPV assay in the management of cervical intraepithelial neoplasia. J Med Virol 2013; 85: 1235-1241
48 Denise Zielinski G, Snijders PJF, Rozendaal L. et al. High-risk HPV testing in women with borderline and mild dyskaryosis: long-term follow-up data and clinical relevance. J Pathol 2001; 195: 300-306
49 Chen HS, Su TH, Yang YC. et al. Human Papillomavirus Testing (Hybrid Capture Ii) to Detect High-Grade Cervical intraepithelial Neoplasia in Women with Mildly Abnormal Papanicolaou Results. Taiwanese Journal of Obstetrics and Gynecology 2005; 44: 252-257
50 Cuschieri KS, Graham C, Moore C. et al. Human Papillomavirus testing for the management of low-grade cervical abnormalities in the UK–Influence of age and testing strategy. J Clin Virol 2007; 38: 14-18
51 You K, Liang X, Qin F. et al. High-risk human papillomavirus DNA testing and high-grade cervical intraepithelial lesions. Aust N Z J Obstet Gynaecol 2007; 47: 141-144
52 Huang S, Erickson B, Tang N. et al. Clinical performance of Abbott RealTime High Risk HPV test for detection of high-grade cervical intraepithelial neoplasia in women with abnormal cytology. J Clin Virol 2009; 45 (Suppl. 01) S19-S23
53 Lee JK, Kim MK, Song SH. et al. Comparison of Human Papillomavirus Detection and Typing by Hybrid Capture 2, Linear Array, DNA Chip, and Cycle Sequencing in Cervical Swab Samples. Int J Gynecol Cancer 2009; 19: 266-272
54 Edgerton N, Cohen C, Siddiqui MT. Evaluation of CINtec PLUS^® testing as an adjunctive test in ASC-US diagnosed SurePath^® preparations. Diagn Cytopathol 2013; 41: 35-40
55 Wentzensen N, Schwartz L, Zuna RE. et al. Performance of p 16/Ki-67 immunostaining to detect cervical cancer precursors in a colposcopy referral population. Clin Cancer Res 2012; 18: 4154-4162
56 Loghavi S, Walts AE, Bose S. CINtec^® PLUS dual immunostain: a triage tool for cervical pap smears with atypical squamous cells of undetermined significance and low grade squamous intraepithelial lesion. Diagn Cytopathol 2013; 41: 582-587
57 Lee NW, Kim D, Park JT. et al. Is the human papillomavirus test in combination with the Papanicolaou test useful for management of patients with diagnoses of atypical squamous cells of undetermined significance/low-grade squamous intraepithelial lesions?. Arch Pathol Lab Med 2001; 125: 1453-1457
58 Pretorius RG, Peterson P, Novak S. et al. Comparison of two signal-amplification DNA tests for high-risk HPV as an aid to colposcopy. J Reprod Med 2002; 47: 290-296
59 Sherman ME, Schiffman M, Cox JT. et al. Effects of age and human papilloma viral load on colposcopy triage: data from the randomized Atypical Squamous Cells of Undetermined Significance/Low-Grade Squamous Intraepithelial Lesion Triage Study (ALTS). J Natl Cancer Inst 2002; 94: 102-107
60 Meyer JL, Hanlon DW, Andersen BT. et al. Evaluation of p 16INK4a expression in ThinPrep cervical specimens with the CINtec p 16INK4a assay: correlation with biopsy follow-up results. Cancer 2007; 111: 83-92
61 Castle PE, Fetterman B, Thomas Cox J. et al. The age-specific relationships of abnormal cytology and human papillomavirus DNA results to the risk of cervical precancer and cancer. Obstet Gynecol 2010; 116: 76-84
62 Halford JA, Batty T, Boost T. et al. Comparison of the sensitivity of conventional cytology and the ThinPrep Imaging System for 1,083 biopsy confirmed high-grade squamous lesions. Diagn Cytopathol 2010; 38: 318-326
63 Voss JS, Kipp BR, Campion MB. et al. Assessment of fluorescence in situ hybridization and hybrid capture 2 analyses of cervical cytology specimens diagnosed as low grade squamous intraepithelial lesion for the detection of high grade cervical intraepithelial neoplasia. Anal Quant Cytol Histol 2010; 32: 121-130
64 Wu R, Belinson SE, Du H. et al. Human papillomavirus messenger RNA assay for cervical cancer screening: the Shenzhen Cervical Cancer Screening Trial I. Int J Gynecol Cancer 2010; 20: 1411-1414
65 Heider A, Austin RM, Zhao C. HPV test results stratify risk for histopathologic follow-up findings of high-grade cervical intra-epithelial neoplasia in women with low-grade squamous intra-epithelial lesion Pap results. Acta Cytol 2011; 55: 48-53
66 Levi AW, Harigopal M, Hui P. et al. Use of high-risk human papillomavirus testing in patients with low-grade squamous intraepithelial lesions. Cancer Cytopathol 2011; 119: 228-234
67 Tsoumpou I, Valasoulis G, Founta C. et al. High-risk human papillomavirus DNA test and p 16(INK4a) in the triage of LSIL: a prospective diagnostic study. Gynecol Oncol 2011; 121: 49-53
68 Ziemke P, Marquardt K. [Immunocytochemistry of p 16(INK4a) and Ki-67 as adjunctive method for routine gynecological cytology of mild and moderate dysplasia]. Pathologe 2013; 34: 323-328
69 Waldstrom M, Christensen RK, Ornskov D. Evaluation of p 16(INK4a)/Ki-67 dual stain in comparison with an mRNA human papillomavirus test on liquid-based cytology samples with low-grade squamous intraepithelial lesion. Cancer Cytopathol 2013; 121: 136-145
70 Ronco G, Segnan N, Giorgi-Rossi P. et al. Human papillomavirus testing and liquid-based cytology: results at recruitment from the new technologies for cervical cancer randomized controlled trial. J Natl Cancer Inst 2006; 98: 765-774
71 Ronco G, Giorgi-Rossi P, Carozzi F. et al. Human papillomavirus testing and liquid-based cytology in primary screening of women younger than 35 years: results at recruitment for a randomised controlled trial. Lancet Oncol 2006; 7: 547-555
72 Carozzi F, Confortini M, Palma PD. et al. Use of p 16-INK4A overexpression to increase the specificity of human papillomavirus testing: a nested substudy of the NTCC randomised controlled trial. Lancet Oncol 2008; 9: 937-945
73 Carozzi F, Gillio-Tos A, Confortini M. et al. Risk of high-grade cervical intraepithelial neoplasia during follow-up in HPV-positive women according to baseline p 16-INK4A results: a prospective analysis of a nested substudy of the NTCC randomised controlled trial. Lancet Oncol 2013; 14: 168-176
74 Kitchener HC, Almonte M, Gilham C. et al. ARTISTIC: a randomised trial of human papillomavirus (HPV) testing in primary cervical screening. Health Technol Assess (Rockv) 2009; 13: 1-150 iii–iv
75 Naucler P, Ryd W, Törnberg S. et al. Efficacy of HPV DNA Testing With Cytology Triage and/or Repeat HPV DNA Testing in Primary Cervical Cancer Screening. J Natl Cancer Inst 2009; 101: 88-99
76 Rijkaart DC, Berkhof J, Rozendaal L. et al. Human papillomavirus testing for the detection of high-grade cervical intraepithelial neoplasia and cancer: Final results of the POBASCAM randomised controlled trial. Lancet Oncol 2012; 13: 78-88
77 Dijkstra MG, van Niekerk D, Rijkaart DC. et al. Primary hrHPV DNA Testing in Cervical Cancer Screening: How to Manage Screen-Positive Women? A POBASCAM Trial Substudy. Cancer Epidemiol Biomarkers Prev 2014; 23: 55-63
78 Leinonen MK, Anttila A, Malila N. et al. Type- and age-specific distribution of human papillomavirus in women attending cervical cancer screening in Finland. Br J Cancer 2013; 109: 2941-2950
79 Castle PE, Stoler MH, Wright jr. TC. et al. Performance of carcinogenic human papillomavirus (HPV) testing and HPV16 or HPV18 genotyping for cervical cancer screening of women aged 25 years and older: a subanalysis of the ATHENA study. Lancet Oncol 2011; 12: 880-890
80 Black ME, Yamada J, Mann V. A systematic literature review of the effectiveness of community-based strategies to increase cervical cancer screening. Can J Public Health 2002; 93: 386-393
81 Camilloni L, Ferroni E, Cendales BJ. et al. Methods to increase participation in organised screening programs: a systematic review. BMC Public Health 2013; 13: 464
82 Ferroni E, Camilloni L, Jimenez B. et al. How to increase uptake in oncologic screening: a systematic review of studies comparing population-based screening programs and spontaneous access. Prev Med 2012; 55: 587-596
83 Tseng DS, Cox E, Plane MB. et al. Efficacy of patient letter reminders on cervical cancer screening: a meta-analysis. J Gen Intern Med 2001; 16: 563-568
84 Stone EG, Morton SC, Hulscher ME. et al. Interventions that increase use of adult immunization and cancer screening services: A meta-analysis. Ann Intern Med 2002; 136: 641-651
85 Bais AG, van Kemenade FJ, Berkhof J. et al. Human papillomavirus testing on self-sampled cervicovaginal brushes: An effective alternative to protect nonresponders in cervical screening programs. Int J Cancer 2007; 120: 1505-1510
86 Gök M, Heideman DA, van Kemenade FJ. et al. HPV testing on self collected cervicovaginal lavage specimens as screening method for women who do not attend cervical screening: cohort study. BMJ 2010; 340: c1040
87 Castle PE, Rausa A, Walls T. et al. Comparative community outreach to increase cervical cancer screening in the Mississippi Delta. Prev Med 2011; 52: 452-455
88 Giorgi-Rossi P, Marsili LM, Camilloni L. et al. The effect of self-sampled HPV testing on participation to cervical cancer screening in Italy: a randomised controlled trial (ISRCTN96071600). Br J Cancer 2011; 104: 248-254
89 Lazcano-Ponce E, Lorincz AT, Cruz-Valdez A. et al. Self-collection of vaginal specimens for human papillomavirus testing in cervical cancer prevention (MARCH): A community-based randomised controlled trial. Lancet 2011; 378: 1868-1873
90 Szarewski A, Cadman L, Mesher D. et al. HPV self-sampling as an alternative strategy in non-attenders for cervical screening – a randomised controlled trial. Br J Cancer 2011; 104: 915-920
91 Virtanen A, Nieminen P, Luostarinen T. et al. Self-sample HPV tests as an intervention for nonattendees of cervical cancer screening in Finland: a randomized trial. Cancer Epidemiol Biomarkers Prev 2011; 20: 1960-1969
92 Gok M, van Kemenade FJ, Heideman DA. et al. Experience with high-risk human papillomavirus testing on vaginal brush-based self-samples of non-attendees of the cervical screening program. Int J Cancer 2012; 130: 1228-1235
93 Darlin L, Borgfeldt C, Forslund O. et al. Comparison of use of vaginal HPV self-sampling and offering flexible appointments as strategies to reach long-term non-attending women in organized cervical screening. J Clin Virol 2013; 58: 155-160
94 Sancho-Garnier H, Tamalet C, Halfon P. et al. HPV self-sampling or the Pap-smear: A randomized study among cervical screening nonattenders from lower socioeconomic groups in France. Int J Cancer 2013; 133: 2681-2687
95 Morrison EAB, Goldberg GL, Hagan RJ. et al. Self-administered home cervicovaginal lavage: A novel tool for the clinical-epidemiologic investigation of genital human papillomavirus infections. Am J Obstet Gynecol 1992; 167: 104-107
96 Hillemanns P, Kimmig R, Hüttemann U. et al. Screening for cervical neoplasia by self-assessment for human papillomavirus DNA. Lancet 1999; 354: 1970
97 Sellors JW, Lorincz AT, Mahony JB. et al. Comparison of self-collected vaginal, vulvar and urine samples with physician-collected cervical samples for human papillomavirus testing to detect high-grade squamous intraepithelial lesions. CMAJ 2000; 163: 513-518
98 Wright jr. TC, Denny L, Kuhn L. et al. HPV DNA testing of self-collected vaginal samples compared with cytologic screening to detect cervical cancer. JAMA 2000; 283: 81-86
99 Belinson J, Qiao YL, Pretorius R. et al. Shanxi province cervical cancer screening study: A cross-sectional comparative trial of multiple techniques to detect cervical neoplasia. Gynecol Oncol 2001; 83: 439-444
100 Lorenzato FR, Singer A, Ho L. et al. Human papillomavirus detection for cervical cancer prevention with polymerase chain reaction in self-collected samples. Am J Obstet Gynecol 2002; 186: 962-968
101 Nobbenhuis MAE, Helmerhorst TJM, Van den Brule AJC. et al. Primary screening for high risk HPV by home obtained cervicovaginal lavage is an alternative screening tool for unscreened women. J Clin Pathol 2002; 55: 435-439
102 Garcia F, Barker B, Santos C. et al. Cross-sectional study of patient- and physician-collected cervical cytology and human papillomavirus. Obstet Gynecol 2003; 102: 266-272
103 Salmerón J, Lazcano-Ponce E, Lorincz A. et al. Comparison of HPV-based assays with Papanicolaou smears for cervical cancer screening in Morelos State, Mexico. Cancer Causes Control 2003; 14: 505-512
104 Brink AATP, Meijer CJLM, Wiegerinck MAHM. et al. High concordance of results of testing for human papillomavirus in cervicovaginal samples collected by two methods, with comparison of a novel self-sampling device to a conventional endocervical brush. J Clin Microbiol 2006; 44: 2518-2523
105 Daponte A, Pournaras S, Mademtzis I. et al. Evaluation of HPV 16 PCR detection in self- compared with clinician-collected samples in women referred for colposcopy. Gynecol Oncol 2006; 103: 463-466
106 Girianelli VR, Thuler LCS, Szklo M. et al. Comparison of human papillomavirus DNA tests, liquid-based cytology and conventional cytology for the early detection of cervix uteri cancer. Eur J Cancer Prev 2006; 15: 504-510
107 Holanda jr. F, Castelo A, Veras TM. et al. Primary screening for cervical cancer through self sampling. Int J Gynaecol Obstet 2006; 95: 179-184
108 Seo SS, Song YS, Kim JW. et al. Good correlation of HPV DNA test between self-collected vaginal and clinician-collected cervical samples by the oligonucleotide microarray. Gynecol Oncol 2006; 102: 67-73
109 Szarewski A, Cadman L, Mallett S. et al. Human papillomavirus testing by self-sampling: Assessment of accuracy in an unsupervised clinical setting. J Med Screen 2007; 14: 34-42
110 Qiao YL, Sellors JW, Eder PS. et al. A new HPV-DNA test for cervical-cancer screening in developing regions: a cross-sectional study of clinical accuracy in rural China. Lancet Oncol 2008; 9: 929-936
111 Bhatla N, Dar L, Patro AR. et al. Can human papillomavirus DNA testing of self-collected vaginal samples compare with physician-collected cervical samples and cytology for cervical cancer screening in developing countries?. Cancer Epidemiol 2009; 33: 446-450
112 Balasubramanian A, Kulasingam SL, Baer A. et al. Accuracy and cost-effectiveness of cervical cancer screening by high-risk human papillomavirus DNA testing of self-collected vaginal samples. J Low Genit Tract Dis 2010; 14: 185-195
113 Gustavsson I, Sanner K, Lindell M. et al. Type-specific detection of high-risk human papillomavirus (HPV) in self-sampled cervicovaginal cells applied to FTA elute cartridge. J Clin Virol 2011; 51: 251-254
114 Taylor S, Wang C, Wright TC. et al. A comparison of human papillomavirus testing of clinician-collected and self-collected samples during follow-up after screen-and-treat. Int J Cancer 2011; 129: 879-886
115 Twu NF, Yen MS, Lau HY. et al. Type-specific human papillomavirus DNA testing with the genotyping array: A comparison of cervical and vaginal sampling. Eur J Obstet Gynecol Reprod Biol 2011; 156: 96-100
116 Wikström I, Lindell M, Sanner K. et al. Self-sampling and HPV testing or ordinary Pap-smear in women not regularly attending screening: A randomised study. Br J Cancer 2011; 105: 337-339
117 Belinson JL, Du H, Yang B. et al. Improved sensitivity of vaginal self-collection and high-risk human papillomavirus testing. Int J Cancer 2012; 130: 1855-1860
118 Dijkstra MG, Heideman DAM, van Kemenade FJ. et al. Brush-based self-sampling in combination with GP5+/6+-PCR-based hrHPV testing: High concordance with physician-taken cervical scrapes for HPV genotyping and detection of high-grade CIN. J Clin Virol 2012; 54: 147-151
119 Longatto-Filho A, Naud P, Derchain SFM. et al. Performance characteristics of Pap test, VIA, VILI, HR-HPV testing, cervicography, and colposcopy in diagnosis of significant cervical pathology. Virchows Archiv 2012; 460: 577-585
120 Van Baars R, Bosgraaf RP, Ter Harmsel BWA. et al. Dry storage and transport of a cervicovaginal self-sample by use of the Evalyn Brush, providing reliable human papillomavirus detection combined with comfort for women. J Clin Microbiol 2012; 50: 3937-3943
121 Zhao FH, Lewkowitz AK, Chen F. et al. Pooled analysis of a self-sampling HPV DNA test as a cervical cancer primary screening method. J Natl Cancer Inst 2012; 104: 178-188
122 Darlin L, Borgfeldt C, Forslund O. et al. Vaginal self-sampling without preservative for human papillomavirus testing shows good sensitivity. J Clin Virol 2013; 56: 52-56
123 Geraets DT, van Baars R, Alonso I. et al. Clinical evaluation of high-risk HPV detection on self-samples using the indicating FTA-elute solid-carrier cartridge. J Clin Virol 2013; 57: 125-129
124 Guan Y, Gravitt PE, Howard R. et al. Agreement for HPV genotyping detection between self-collected specimens on a FTA cartridge and clinician-collected specimens. J Virol Methods 2013; 189: 167-171
125 Jentschke M, Lange V, Soergel P. et al. Enzyme-linked immunosorbent assay for p 16INK4a – A new triage test for the detection of cervical intraepithelial neoplasia?. Acta Obstet Gynecol Scand 2013; 92: 160-164
126 Jentschke M, Soergel P, Hillemanns P. Evaluation of a multiplex real time PCR assay for the detection of human papillomavirus infections on self-collected cervicovaginal lavage samples. J Virol Methods 2013; 193: 131-134
127 Nieves L, Enerson CL, Belinson S. et al. Primary cervical cancer screening and triage using an mRNA human papillomavirus assay and visual inspection. Int J Gynecol Cancer 2013; 23: 513-518
128 World Health Organization. WHO Guidelines for Treatment of cervical intraepithelial Neoplasia 2 – 3 and Adenocarcinoma in situ: Cryotherapy, large Loop Excision of the Transformation Zone, and Cold Knife Conization. Geneva: World Health Organization; 2014
129 Massad LS, Einstein MH, Huh WK. et al. 2012 updated consensus guidelines for the management of abnormal cervical cancer screening tests and cancer precursors. J Low Genit Tract Dis 2013; 17 (5 Suppl. 1): S1-S27
130 Luesley D, Leeson S. Colposcopy and programme management Guidelines for the NHS Cervical Screening Programme. 2010; 2: [NHSCSP Publication No 20]. Online: https://www.gov.uk/government/uploads/system/uploads/attachment_data/file/436873/nhscsp20.pdf last access: 15.01.2016
131 Alonso I, Torné A, Puig-Tintoré LM. et al. Pre- and post-conization high-risk HPV testing predicts residual/recurrent disease in patients treated for CIN 2–3. Gynecol Oncol 2006; 103: 631-636
132 Melnikow J, McGahan C, Sawaya GF. et al. Cervical Intraepithelial Neoplasia Outcomes After Treatment: Long-term Follow-up From the British Columbia Cohort Study. J Natl Cancer Inst 2009; 101: 721-728
133 Strander B, Hällgren J, Sparén P. Effect of ageing on cervical or vaginal cancer in Swedish women previously treated for cervical intraepithelial neoplasia grade 3: population based cohort study of long term incidence and mortality. BMJ 2014; 348: f7361
134 Tropé A, Jonassen CM, Sjøborg KD. et al. Role of high-risk human papillomavirus (HPV) mRNA testing in the prediction of residual disease after conisation for high-grade cervical intraepithelial neoplasia. Gynecol Oncol 2011; 123: 257-262
135 Ryu A, Nam K, Kwak J. et al. Early human papillomavirus testing predicts residual/recurrent disease after LEEP. J Gynecol Oncol 2012; 23: 217-225
136 Verguts J, Bronselaer B, Donders G. et al. Prediction of recurrence after treatment for high-grade cervical intraepithelial neoplasia: the role of human papillomavirus testing and age at conisation. BJOG 2006; 113: 1303-1307
137 Kang WD, Oh MJ, Kim SM. et al. Significance of human papillomavirus genotyping with high-grade cervical intraepithelial neoplasia treated by a loop electrosurgical excision procedure. Am J Obstet Gynecol 2010; 203: 72.e1-72.e6
138 Cecchini S, Carozzi F, Confortini M. et al. Persistent human papilloma virus infection as an indicator of risk of recurrence of high-grade cervical intraepithelial neoplasia treated by the loop electrosurgical excision procedure. Tumori 2004; 90: 225-228
139 Ang C, Mukhopadhyay A, Burnley C. et al. Histological recurrence and depth of loop treatment of the cervix in women of reproductive age: incomplete excision versus adverse pregnancy outcome. BJOG 2011; 118: 685-692
140 Flannelly G, Bolger B, Fawzi H. et al. Follow up after LLETZ: could schedules be modified according to risk of recurrence?. BJOG 2001; 108: 1025-1030
141 Prato B, Ghelardi A, Gadducci A. et al. Correlation of recurrence rates and times with posttreatment human papillomavirus status in patients treated with loop electrosurgical excision procedure conization for cervical squamous intraepithelial lesions. Int J Gynecol Cancer 2008; 18: 90-94
142 Castle PE, Schiffman M, Herrero R. et al. A prospective study of age trends in cervical human papillomavirus acquisition and persistence in Guanacaste, Costa Rica. J Infect Dis 2005; 191: 1808-1816
143 Aerssens A, Claeys P, Garcia A. et al. Natural history and clearance of HPV after treatment of precancerous cervical lesions. Histopathology 2008; 52: 381-386
144 Sarian LO, Derchain SF, Pitta Dda R. et al. Factors associated with HPV persistence after treatment for high-grade cervical intra-epithelial neoplasia with large loop excision of the transformation zone (LLETZ). J Clin Virol 2004; 31: 270-274
145 Strander B, Andersson-Ellström A, Milsom I. et al. Long term risk of invasive cancer after treatment for cervical intraepithelial neoplasia grade 3: population based cohort study. BMJ 2007; 335: 1077
146 Jeong NH, Lee NW, Kim HJ. et al. High-risk human papillomavirus testing for monitoring patients treated for high-grade cervical intraepithelial neoplasia. J Obstet Gynaecol Res 2009; 35: 706-711
147 Chua KL, Hjerpe A. Human papillomavirus analysis as a prognostic marker following conization of the cervix uteri. Gynecol Oncol 1997; 66: 108-113
148 Houfflin Debarge V, Collinet P, Vinatier D. et al. Value of human papillomavirus testing after conization by loop electrosurgical excision for high-grade squamous intraepithelial lesions. Gynecol Oncol 2003; 90: 587-592
149 Chao A, Lin CT, Hsueh S. et al. Usefulness of human papillomavirus testing in the follow-up of patients with high-grade cervical intraepithelial neoplasia after conization. Am J Obstet Gynecol 2004; 190: 1046-1051
150 Fambrini M, Penna C, Pieralli A. et al. PCR detection rates of high risk human papillomavirus DNA in paired self-collected urine and cervical scrapes after laser CO2 conization for high-grade cervical intraepithelial neoplasia. Gynecol Oncol 2008; 109: 59-64
151 Aerssens A, Claeys P, Beerens E. et al. Prediction of recurrent disease by cytology and HPV testing after treatment of cervical intraepithelial neoplasia. Cytopathology 2009; 20: 27-35
152 Torné A, Fusté P, Rodriguez-Carunchio L. et al. Intraoperative post-conisation human papillomavirus testing for early detection of treatment failure in patients with cervical intraepithelial neoplasia: a pilot study. BJOG 2013; 120: 392-399
153 Persson M, Brismar Wendel S, Ljungblad L. et al. High-risk human papillomavirus E6/E7 mRNA and L1 DNA as markers of residual/recurrent cervical intraepithelial neoplasia. Oncol Rep 2012; 28: 346-352
154 Tinelli A, Guido M, Zizza A. et al. The mRNA-HPV test utilization in the follow up of HPV related cervical lesions. Curr Pharm Des 2013; 19: 1458-1465
155 Kreimer AR, Guido RS, Solomon D. et al. Human papillomavirus testing following loop electrosurgical excision procedure identifies women at risk for posttreatment cervical intraepithelial neoplasia grade 2 or 3 disease. Cancer Epidemiol Biomarkers Prev 2006; 15: 908-914
156 Brismar S, Johansson B, Borjesson M. et al. Follow-up after treatment of cervical intraepithelial neoplasia by human papillomavirus genotyping. Am J Obstet Gynecol 2009; 201: 17.e1-17.e8
157 Heymans J, Benoy IH, Poppe W. et al. Type-specific HPV geno-typing improves detection of recurrent high-grade cervical neoplasia after conisation. International journal of cancer. Int J Cancer 2011; 129: 903-909
158 Sroczynski G, Siebert U. Evidence Report: Decision Analysis to evaluate Benefits, Harms and Cost-effectiveness of different cervical Cancer Screening Strategies to inform the S3 clinical Guideline “Prevention of Cervical Cancer” in the Context of the German Health Care System. Hall i.T., Austria: UMIT – University for Health Sciences, Medical Informatics and Technology; 2015