Good performance of p16/ki-67 dual-stained cytology for surveillance of women treated for high-grade CIN.
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.
Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands.
Nicole J
NJ
Polman
Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands.
Margot H
MH
Uijterwaal
Department of Epidemiology and Biostatistics, VU University Medical Center, Amsterdam, The Netherlands.
Birgit I
BI
Witte
Department of Epidemiology and Biostatistics, VU University Medical Center, Amsterdam, The Netherlands.
Johannes
J
Berkhof
Department of Pathology, Erasmus MC University Medical Center, Rotterdam, The Netherlands.
Folkert J
FJ
van Kemenade
Department of Obstetrics and Gynecology, VU University Medical Center, Amsterdam, The Netherlands.
Johan W M
JW
Spruijt
Department of Obstetrics and Gynecology, Flevo Hospital, Almere, The Netherlands.
W Marchien
WM
van Baal
Department of Obstetrics and Gynecology, Sint Antonius Hospital, Nieuwegein, The Netherlands.
Peppino G C M
PG
Graziosi
Department of Obstetrics and Gynecology, Onze Lieve Vrouwen Gasthuis West, Amsterdam, The Netherlands.
Dorenda K E
DK
van Dijken
Department of Gynaecological Oncology, Division of Surgical Oncology, UMC Utrecht Cancer Center, Utrecht, The Netherlands.
René H M
RH
Verheijen
Department of Obstetrics and Gynecology, Erasmus MC University Medical Center, Rotterdam, The Netherlands.
Theo J M
TJ
Helmerhorst
Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands.
Renske D M
RD
Steenbergen
Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands.
Daniëlle A M
DA
Heideman
Roche mtm Laboratories AG, Mannheim, Germany.|Ventana Medical Systems, Inc., Tucson, Arizona.
Ruediger
R
Ridder
Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands.
Peter J F
PJ
Snijders
Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands.
Chris J L M
CJ
Meijer
D000328:Adult; D003127:Colposcopy / Q000379:methods; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000378:metabolism*; D003581:Cytodiagnosis / Q000379:methods; D055088:Early Detection of Cancer / Q000379:methods; D005260:Female; D006801:Humans; D019394:Ki-67 Antigen / Q000378:metabolism*; D008875:Middle Aged; D027383:Papillomaviridae; D030361:Papillomavirus Infections / Q000378:metabolism / Q000473:pathology; D011247:Pregnancy; D011446:Prospective Studies; D012680:Sensitivity and Specificity; D002583:Uterine Cervical Neoplasms / Q000378:metabolism* / Q000473:pathology* / Q000821:virology; D055815:Young Adult; D002578:Uterine Cervical Dysplasia / Q000378:metabolism* / Q000473:pathology* / Q000821:virology
D019941:Cyclin-Dependent Kinase Inhibitor p16; D019394:Ki-67 Antigen
cervical cytology; human papillomavirus; p16/Ki-67 dual-stained cytology; posttreatment; recurrent cervical intraepithelial neoplasia