Association between p16/Ki-67 dual stain cytology results prior to and 6 months after LLETZ treatment for CIN and the follow-up regimen three years after treatment: a retrospective cohort study.

Cervical intra-epithelial neoplasia Conization Dual stain cytology LLETZ Recurrence

Journal

Archives of gynecology and obstetrics
ISSN: 1432-0711
Titre abrégé: Arch Gynecol Obstet
Pays: Germany
ID NLM: 8710213

Informations de publication

Date de publication:
28 May 2024
Historique:
received: 20 02 2024
accepted: 12 05 2024
medline: 29 5 2024
pubmed: 29 5 2024
entrez: 28 5 2024
Statut: aheadofprint

Résumé

Investigate the association between p16/Ki-67 dual stain cytology test (DST) results, obtained prior to- and 6 months after LLETZ surgery for treatment of CIN, and the follow-up regimen three years after treatment. Secondary analysis of a prospective cohort study. Cervical cytology samples were obtained just prior to- and 6 months after LLETZ and underwent conventional liquid-based cytology (LBC) and p16/Ki-67 dual staining, as well as high-risk HPV genotyping. Clinical management after the LLETZ was according to Belgian national guidelines, with clinicians being blinded to DST results at both time points. Case records were reviewed in 01/2023 to document the follow-up regimen on average three years afterwards: women had either been advised to return to routine screening (i.e., three-annual LBC testing according to the Belgian guideline at that time), or were still subject to more frequent posttreatment surveillance (i.e., more frequent visits because of persistent hrHPV infection or absence of cytological regression). The follow-up regimen was recorded in 79/110 women originally recruited (72%). The need for continued intense posttreatment surveillance was associated with hrHPV infection 6 months after treatment (79.3% vs. 18.0%, p < 0.001), a positive DST result at baseline and follow-up (41.4% vs. 84.0%, p < 0.001-55.2% vs. 16.0%, p < 0.001), and persistent cytological anomalies at 6 months (at an ASCUS or worse threshold, 37.9% vs. 16.0%, p = 0.028). In multivariable logistic regression analysis, a positive DST at baseline (aOR 20.1, 95%CI 2.03-199.1) was independently associated with the need for intense post-treatment surveillance multiple years after treatment. This exploratory study suggests a possible role of dual-stain cytology in predicting treatment outcome multiple years after LLETZ surgery.

Identifiants

pubmed: 38806944
doi: 10.1007/s00404-024-07553-8
pii: 10.1007/s00404-024-07553-8
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Informations de copyright

© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.

Références

Soutter WP, De Barros LA, Fletcher A et al (1997) Invasive cervical cancer after conservative therapy for cervical intraepithelial neoplasia. Lancet 349(9057):978–980
doi: 10.1016/S0140-6736(96)08295-5 pubmed: 9100623
Perkins RB, Guido RS, Castle PE et al (2020) 2019 ASCCP risk-based management consensus guidelines for abnormal cervical cancer screening tests and cancer precursors. J Low Genit Tract Dis 24(2):102–131
doi: 10.1097/LGT.0000000000000525 pubmed: 32243307 pmcid: 7147428
Arbyn M, Ronco G, Anttila A et al (2012) Evidence regarding human papillomavirus testing in secondary prevention of cervical cancer. Vaccine. https://doi.org/10.1016/j.vaccine.2012.06.095
doi: 10.1016/j.vaccine.2012.06.095 pubmed: 23199969
Clarke MA, Unger ER, Zuna R et al (2020) A systematic review of tests for postcolposcopy and posttreatment surveillance. J Low Genit Tract Dis 24(2):148–156
doi: 10.1097/LGT.0000000000000526 pubmed: 32243310 pmcid: 7141755
Coupé VMH, Berkhof J, Verheijen RHM, Meijer CJLM (2007) Cost-effectiveness of human papillomavirus testing after treatment for cervical intraepithelial neoplasia. BJOG 114(4):416–424
doi: 10.1111/j.1471-0528.2007.01265.x pubmed: 17378816
Wentzensen N, Von Knebel DM (2007) Biomarkers in cervical cancer screening. Dis Markers 23(4):315–330
doi: 10.1155/2007/678793 pubmed: 17627065 pmcid: 3851733
Tjalma WAA (2017) Diagnostic performance of dual-staining cytology for cervical cancer screening: a systematic literature review. Eur J Obstet Gynecol Reprod Biol 210:275–280
doi: 10.1016/j.ejogrb.2017.01.009 pubmed: 28086168
Ikenberg H, Bergeron C, Schmidt D et al (2013) Screening for cervical cancer precursors with p16/Ki-67 dual-stained cytology: results of the PALMS study. J Natl Cancer Inst 105(20):1550–1557
doi: 10.1093/jnci/djt235 pubmed: 24096620 pmcid: 3814411
Wentzensen N, Clarke MA, Bremer R et al (2019) Clinical evaluation of human papillomavirus screening with p16/Ki-67 dual stain triage in a large organized cervical cancer screening program. JAMA Intern Med 179(7):881
doi: 10.1001/jamainternmed.2019.0306 pubmed: 31081870
Packet B, Poppe W, Vanherck M, Weynand B (2023) p16/Ki-67 dual stain, PAP cytology and HR-HPV test results prior to and 6 months after a LLETZ procedure: a prospective observational cohort study. Arch Gynecol Obstet 307(2):519–524
doi: 10.1007/s00404-022-06801-z pubmed: 36197541
Palmer AG, Tucker S, Warren R, Adams M (1993) Understanding women’s responses to treatment for cervical intra-epithelial neoplasia. Br J Clin Psychol 32(1):101–112
doi: 10.1111/j.2044-8260.1993.tb01033.x pubmed: 8467271
Miller SM, Tagai EK, Wen KY et al (2017) Predictors of adherence to follow-up recommendations after an abnormal Pap smear among underserved inner-city women. Patient Educ Couns 100(7):1353–1359
doi: 10.1016/j.pec.2017.01.020 pubmed: 28190541 pmcid: 5466500
Packet B, Poppe W, Weynand B, Vanherck M (2018) The use of p16/Ki-67 dual staining technology on cervical cytology of patients undergoing a LLETZ procedure. Eur J Obstet Gynecol Reprod Biol 228:191–196
doi: 10.1016/j.ejogrb.2018.06.025 pubmed: 30007246
Peeters E, Wentzensen N, Bergeron C, Arbyn M (2019) Meta-analysis of the accuracy of p16 or p16/Ki-67 immunocytochemistry versus HPV testing for the detection of CIN2+/CIN3+ in triage of women with minor abnormal cytology. Cancer Cytopathol 127(3):169–180
doi: 10.1002/cncy.22103 pubmed: 30811902
Hoda RS, Loukeris K, Abdul-Karim FW (2013) Gynecologic cytology on conventional and liquid-based preparations: A comprehensive review of similarities and differences. Diagn Cytopathol 41(3):257–278
doi: 10.1002/dc.22842 pubmed: 22508662
Solomon D, Davey D, Kurman R et al (2002) The 2001 Bethesda System: terminology for reporting results of cervical cytology. JAMA 287(16):2114–2119
doi: 10.1001/jama.287.16.2114 pubmed: 11966386
Cuvelier CA, Bogers JPM, Bourgain C et al (2009) Belgian consensus guidelines for follow-up of women with cervical cytological abnormalities. Acta Clin Belg 64(2):136–143
doi: 10.1179/acb.2009.023 pubmed: 19432026
Quaas J, Reich O, Frey Tirri B, Küppers V (2013) Explanation and use of the colposcopy terminology of the IFCPC (International Federation for Cervical Pathology and Colposcopy) Rio 2011. Geburtshilfe Frauenheilkd 73(9):904–907
doi: 10.1055/s-0033-1350824 pubmed: 24771940 pmcid: 3859163
Grant SW, Hickey GL, Head SJ (2019) Statistical primer: multivariable regression considerations and pitfalls. Eur J Cardiothorac Surg 55(2):179–185
doi: 10.1093/ejcts/ezy403 pubmed: 30596979
Hoffman SR, Le T, Lockhart A et al (2017) Patterns of persistent HPV infection after treatment for cervical intraepithelial neoplasia (CIN): A systematic review. Int J Cancer 141(1):8–23
doi: 10.1002/ijc.30623 pubmed: 28124442 pmcid: 5606195
Fernández-Montolí ME, Tous S, Medina G, Castellarnau M, García-Tejedor A, de Sanjosé S (2020) Long-term predictors of residual or recurrent cervical intraepithelial neoplasia 2–3 after treatment with a large loop excision of the transformation zone: a retrospective study. BJOG 127(3):377–387
doi: 10.1111/1471-0528.15996 pubmed: 31631477
Ding T, Li L, Duan R, Chen Y, Yang B, Xi M (2023) Risk factors analysis of recurrent disease after treatment with a loop electrosurgical excision procedure for high-grade cervical intraepithelial neoplasia. Int J Gynecol Obstet 160(2):538–547
doi: 10.1002/ijgo.14340
de Mello Silva MV, Coutinho IC, de Andrade HS, Fittipaldi HM Jr, Katz L (2014) Factors associated with the persistence/recurrence of CIN2/3 in women submitted to loop electrosurgical excision procedure in a teaching hospital in northeastern Brazil: a case-control study. J Low Genit Tract Dis 18(4):286–290
doi: 10.1097/LGT.0000000000000014 pubmed: 24633169
Clarke MA, Cheung LC, Castle PE et al (2019) Five-year risk of cervical precancer following p16/Ki-67 dual-stain triage of HPV-positive women. JAMA Oncol 5(2):181–186
doi: 10.1001/jamaoncol.2018.4270 pubmed: 30325982
Gustafson LW, Tranberg M, Christensen PN et al (2023) Clinical utility of p16/Ki67 dual-stain cytology for detection of cervical intraepithelial neoplasia grade two or worse in women with a transformation zone type 3: a cross-sectional study. BJOG 130(2):202–209
doi: 10.1111/1471-0528.17248 pubmed: 35686564
Polman NJ, Uijterwaal MH, Witte BI et al (2017) Good performance of p16/ki-67 dual-stained cytology for surveillance of women treated for high-grade CIN. Int J Cancer 140(2):423–430
doi: 10.1002/ijc.30449 pubmed: 27677098
Baak JPA, Kruse AJ, Robboy SJ, Janssen EAM, Van Diermen B, Skaland I (2006) Dynamic behavioural interpretation of cervical intraepithelial neoplasia with molecular biomarkers. J Clin Pathol 59(10):1017–1028
doi: 10.1136/jcp.2005.027839 pubmed: 16679355 pmcid: 1861745
Wang X, Kattan MW (2020) Cohort studies: design, analysis, and reporting. Chest 158(1):S72–S78
doi: 10.1016/j.chest.2020.03.014 pubmed: 32658655
Talari K, Goyal M (2020) Retrospective studies-utility and caveats. J Royal Coll Physicians Edinb 50(4):398–402
doi: 10.4997/jrcpe.2020.409

Auteurs

Bram Packet (B)

Department of Obstetrics and Gynecology, University Hospitals of Leuven (UZ Leuven), Herestraat 49, 3000, Louvain, Belgium. bram.packet@kuleuven.be.
Department of Development and Regeneration, Unit Woman and Child, Catholic University of Leuven (KU Leuven), Herestraat 49, 3000, Louvain, Belgium. bram.packet@kuleuven.be.

Janneke Goyens (J)

Department of Obstetrics and Gynecology, University Hospitals of Leuven (UZ Leuven), Herestraat 49, 3000, Louvain, Belgium.

Birgit Weynand (B)

Department of Pathology, University Hospitals of Leuven (UZ Leuven), Herestraat 49, 3000, Louvain, Belgium.
Department of Imaging and Pathology, Catholic University of Leuven (KU Leuven), Herestraat 49, 3000, Louvain, Belgium.

Willy Poppe (W)

Department of Obstetrics and Gynecology, University Hospitals of Leuven (UZ Leuven), Herestraat 49, 3000, Louvain, Belgium.
Department of Development and Regeneration, Unit Woman and Child, Catholic University of Leuven (KU Leuven), Herestraat 49, 3000, Louvain, Belgium.

Kobe Dewilde (K)

Department of Obstetrics and Gynecology, University Hospitals of Leuven (UZ Leuven), Herestraat 49, 3000, Louvain, Belgium.
Department of Development and Regeneration, Unit Woman and Child, Catholic University of Leuven (KU Leuven), Herestraat 49, 3000, Louvain, Belgium.

Classifications MeSH