Good performance of p16/ki-67 dual-stained cytology for surveillance of women treated for high-grade CIN

Nicole J Polman, Margot H Uijterwaal, Birgit I Witte, Johannes Berkhof, Folkert J van Kemenade, JWM Spruijt, W Marchien van Baal, Peppino G C M Graziosi, Dorenda K E van Dijken, René H M Verheijen, Theo J M Helmerhorst, Renske D M Steenbergen, Daniëlle A M Heideman, Ruediger Ridder, Peter J F Snijders, Chris J L M Meijer

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Women treated for high-grade cervical intraepithelial neoplasia (CIN) are at risk of recurrent CIN Grade 2 or worse (rCIN2+). Currently, posttreatment monitoring is performed using cytology or cytology/high-risk (hr)HPV cotesting. This study aimed to evaluate the performance of p16/Ki-67 dual-stained cytology (p16/Ki-67) for posttreatment monitoring. Three hundred and twenty-three women treated for high-grade CIN in the SIMONATH study underwent close surveillance by cytology, hrHPV and DNA methylation marker testing up to 12 months posttreatment. Histological endpoints were ascertained by colposcopy with biopsy at 6 and/or 12 months. p16/Ki-67 dual-staining was performed on residual liquid-based cytology samples obtained at, or shortly before biopsy collection. Clinical performance estimates of cytology, hrHPV, p16/Ki-67 testing and combinations thereof for the detection of rCIN2+ were determined and compared to each other. Sensitivity of p16/Ki-67 for rCIN2+ (69.2%) was nonsignificantly lower than that of cytology (82.1%; ratio 0.84, 95% CI: 0.71-1.01), but significantly lower than that of hrHPV testing (84.6%; ratio 0.82, 95% CI: 0.68-0.99). Specificity of p16/Ki-67 for rCIN2+ (90.4%) was significantly higher compared to both cytology (70.8%; ratio 1.28, 95% CI: 1.19-1.37) and hrHPV testing (76.2%; ratio 1.19, 95% CI: 1.12-1.26). Overall, hrHPV testing showed very high sensitivity, along with a good specificity. When considering cotesting, combined p16/Ki-67/hrHPV testing showed rCIN2+ sensitivity comparable to cytology/hrHPV cotesting (87.2% vs. 89.7%; ratio 0.97, 95% CI: 0.92-1.03), but with significantly increased specificity (74.2% vs. 58.1%; ratio 1.28, 95% CI: 1.19-1.38). Thus, when considered in combination with hrHPV, p16/Ki-67 might be an attractive approach for surveillance of women treated for high-grade CIN.

Original languageEnglish
Pages (from-to)423-430
Number of pages8
JournalInternational Journal of Cancer
Volume140
Issue number2
DOIs
Publication statusPublished - 15 Jan 2017

Cite this

Polman, Nicole J ; Uijterwaal, Margot H ; Witte, Birgit I ; Berkhof, Johannes ; van Kemenade, Folkert J ; Spruijt, JWM ; van Baal, W Marchien ; Graziosi, Peppino G C M ; van Dijken, Dorenda K E ; Verheijen, René H M ; Helmerhorst, Theo J M ; Steenbergen, Renske D M ; Heideman, Daniëlle A M ; Ridder, Ruediger ; Snijders, Peter J F ; Meijer, Chris J L M. / Good performance of p16/ki-67 dual-stained cytology for surveillance of women treated for high-grade CIN. In: International Journal of Cancer. 2017 ; Vol. 140, No. 2. pp. 423-430.
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title = "Good performance of p16/ki-67 dual-stained cytology for surveillance of women treated for high-grade CIN",
abstract = "Women treated for high-grade cervical intraepithelial neoplasia (CIN) are at risk of recurrent CIN Grade 2 or worse (rCIN2+). Currently, posttreatment monitoring is performed using cytology or cytology/high-risk (hr)HPV cotesting. This study aimed to evaluate the performance of p16/Ki-67 dual-stained cytology (p16/Ki-67) for posttreatment monitoring. Three hundred and twenty-three women treated for high-grade CIN in the SIMONATH study underwent close surveillance by cytology, hrHPV and DNA methylation marker testing up to 12 months posttreatment. Histological endpoints were ascertained by colposcopy with biopsy at 6 and/or 12 months. p16/Ki-67 dual-staining was performed on residual liquid-based cytology samples obtained at, or shortly before biopsy collection. Clinical performance estimates of cytology, hrHPV, p16/Ki-67 testing and combinations thereof for the detection of rCIN2+ were determined and compared to each other. Sensitivity of p16/Ki-67 for rCIN2+ (69.2{\%}) was nonsignificantly lower than that of cytology (82.1{\%}; ratio 0.84, 95{\%} CI: 0.71-1.01), but significantly lower than that of hrHPV testing (84.6{\%}; ratio 0.82, 95{\%} CI: 0.68-0.99). Specificity of p16/Ki-67 for rCIN2+ (90.4{\%}) was significantly higher compared to both cytology (70.8{\%}; ratio 1.28, 95{\%} CI: 1.19-1.37) and hrHPV testing (76.2{\%}; ratio 1.19, 95{\%} CI: 1.12-1.26). Overall, hrHPV testing showed very high sensitivity, along with a good specificity. When considering cotesting, combined p16/Ki-67/hrHPV testing showed rCIN2+ sensitivity comparable to cytology/hrHPV cotesting (87.2{\%} vs. 89.7{\%}; ratio 0.97, 95{\%} CI: 0.92-1.03), but with significantly increased specificity (74.2{\%} vs. 58.1{\%}; ratio 1.28, 95{\%} CI: 1.19-1.38). Thus, when considered in combination with hrHPV, p16/Ki-67 might be an attractive approach for surveillance of women treated for high-grade CIN.",
author = "Polman, {Nicole J} and Uijterwaal, {Margot H} and Witte, {Birgit I} and Johannes Berkhof and {van Kemenade}, {Folkert J} and JWM Spruijt and {van Baal}, {W Marchien} and Graziosi, {Peppino G C M} and {van Dijken}, {Dorenda K E} and Verheijen, {Ren{\'e} H M} and Helmerhorst, {Theo J M} and Steenbergen, {Renske D M} and Heideman, {Dani{\"e}lle A M} and Ruediger Ridder and Snijders, {Peter J F} and Meijer, {Chris J L M}",
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year = "2017",
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language = "English",
volume = "140",
pages = "423--430",
journal = "International Journal of Cancer",
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Good performance of p16/ki-67 dual-stained cytology for surveillance of women treated for high-grade CIN. / Polman, Nicole J; Uijterwaal, Margot H; Witte, Birgit I; Berkhof, Johannes; van Kemenade, Folkert J; Spruijt, JWM; van Baal, W Marchien; Graziosi, Peppino G C M; van Dijken, Dorenda K E; Verheijen, René H M; Helmerhorst, Theo J M; Steenbergen, Renske D M; Heideman, Daniëlle A M; Ridder, Ruediger; Snijders, Peter J F; Meijer, Chris J L M.

In: International Journal of Cancer, Vol. 140, No. 2, 15.01.2017, p. 423-430.

Research output: Contribution to journalArticleAcademicpeer-review

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T1 - Good performance of p16/ki-67 dual-stained cytology for surveillance of women treated for high-grade CIN

AU - Polman, Nicole J

AU - Uijterwaal, Margot H

AU - Witte, Birgit I

AU - Berkhof, Johannes

AU - van Kemenade, Folkert J

AU - Spruijt, JWM

AU - van Baal, W Marchien

AU - Graziosi, Peppino G C M

AU - van Dijken, Dorenda K E

AU - Verheijen, René H M

AU - Helmerhorst, Theo J M

AU - Steenbergen, Renske D M

AU - Heideman, Daniëlle A M

AU - Ridder, Ruediger

AU - Snijders, Peter J F

AU - Meijer, Chris J L M

N1 - © 2016 UICC.

PY - 2017/1/15

Y1 - 2017/1/15

N2 - Women treated for high-grade cervical intraepithelial neoplasia (CIN) are at risk of recurrent CIN Grade 2 or worse (rCIN2+). Currently, posttreatment monitoring is performed using cytology or cytology/high-risk (hr)HPV cotesting. This study aimed to evaluate the performance of p16/Ki-67 dual-stained cytology (p16/Ki-67) for posttreatment monitoring. Three hundred and twenty-three women treated for high-grade CIN in the SIMONATH study underwent close surveillance by cytology, hrHPV and DNA methylation marker testing up to 12 months posttreatment. Histological endpoints were ascertained by colposcopy with biopsy at 6 and/or 12 months. p16/Ki-67 dual-staining was performed on residual liquid-based cytology samples obtained at, or shortly before biopsy collection. Clinical performance estimates of cytology, hrHPV, p16/Ki-67 testing and combinations thereof for the detection of rCIN2+ were determined and compared to each other. Sensitivity of p16/Ki-67 for rCIN2+ (69.2%) was nonsignificantly lower than that of cytology (82.1%; ratio 0.84, 95% CI: 0.71-1.01), but significantly lower than that of hrHPV testing (84.6%; ratio 0.82, 95% CI: 0.68-0.99). Specificity of p16/Ki-67 for rCIN2+ (90.4%) was significantly higher compared to both cytology (70.8%; ratio 1.28, 95% CI: 1.19-1.37) and hrHPV testing (76.2%; ratio 1.19, 95% CI: 1.12-1.26). Overall, hrHPV testing showed very high sensitivity, along with a good specificity. When considering cotesting, combined p16/Ki-67/hrHPV testing showed rCIN2+ sensitivity comparable to cytology/hrHPV cotesting (87.2% vs. 89.7%; ratio 0.97, 95% CI: 0.92-1.03), but with significantly increased specificity (74.2% vs. 58.1%; ratio 1.28, 95% CI: 1.19-1.38). Thus, when considered in combination with hrHPV, p16/Ki-67 might be an attractive approach for surveillance of women treated for high-grade CIN.

AB - Women treated for high-grade cervical intraepithelial neoplasia (CIN) are at risk of recurrent CIN Grade 2 or worse (rCIN2+). Currently, posttreatment monitoring is performed using cytology or cytology/high-risk (hr)HPV cotesting. This study aimed to evaluate the performance of p16/Ki-67 dual-stained cytology (p16/Ki-67) for posttreatment monitoring. Three hundred and twenty-three women treated for high-grade CIN in the SIMONATH study underwent close surveillance by cytology, hrHPV and DNA methylation marker testing up to 12 months posttreatment. Histological endpoints were ascertained by colposcopy with biopsy at 6 and/or 12 months. p16/Ki-67 dual-staining was performed on residual liquid-based cytology samples obtained at, or shortly before biopsy collection. Clinical performance estimates of cytology, hrHPV, p16/Ki-67 testing and combinations thereof for the detection of rCIN2+ were determined and compared to each other. Sensitivity of p16/Ki-67 for rCIN2+ (69.2%) was nonsignificantly lower than that of cytology (82.1%; ratio 0.84, 95% CI: 0.71-1.01), but significantly lower than that of hrHPV testing (84.6%; ratio 0.82, 95% CI: 0.68-0.99). Specificity of p16/Ki-67 for rCIN2+ (90.4%) was significantly higher compared to both cytology (70.8%; ratio 1.28, 95% CI: 1.19-1.37) and hrHPV testing (76.2%; ratio 1.19, 95% CI: 1.12-1.26). Overall, hrHPV testing showed very high sensitivity, along with a good specificity. When considering cotesting, combined p16/Ki-67/hrHPV testing showed rCIN2+ sensitivity comparable to cytology/hrHPV cotesting (87.2% vs. 89.7%; ratio 0.97, 95% CI: 0.92-1.03), but with significantly increased specificity (74.2% vs. 58.1%; ratio 1.28, 95% CI: 1.19-1.38). Thus, when considered in combination with hrHPV, p16/Ki-67 might be an attractive approach for surveillance of women treated for high-grade CIN.

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