Usefulness of p16/Ki67 immunostaining in the triage of women referred to colposcopy

Authors

  • Jaume Ordi MD, PhD,

    Corresponding author
    1. Department of Pathology, CRESIB (Centre de Recerca en Salut Internacional de Barcelona)-Hospital Clínic, University of Barcelona, Barcelona, Spain
    • Corresponding author: Jaume Ordi, MD, PhD, Department of Pathology, CRESIB-Hospital Clínic, Barcelona, Spain, C/Villarroel 170, 08036-Barcelona, Spain; Fax: (011) 34 93 2275717; jordi@clinic.ub.es

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  • Amaia Sagasta MD,

    1. Department of Pathology, CRESIB (Centre de Recerca en Salut Internacional de Barcelona)-Hospital Clínic, University of Barcelona, Barcelona, Spain
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  • Meritxell Munmany MD,

    1. Institut Clinic of Gynecology, Obstetrics and Neonatology, Hospital Clínic-Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain
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  • Leonardo Rodríguez-Carunchio MD,

    1. Department of Pathology, CRESIB (Centre de Recerca en Salut Internacional de Barcelona)-Hospital Clínic, University of Barcelona, Barcelona, Spain
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  • Aureli Torné MD, PhD,

    1. Institut Clinic of Gynecology, Obstetrics and Neonatology, Hospital Clínic-Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain
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  • Marta del Pino MD, PhD

    1. Institut Clinic of Gynecology, Obstetrics and Neonatology, Hospital Clínic-Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain
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Errata

This article is corrected by:

  1. Errata: Erratum: Ordi J, Sagasta A, Munmany M, Rodríguez-Carunchio L, Torné A and del Pino M. Usefulness of p16/Ki67 immunostaining in the triage of women referred to colposcopy. Cancer Cytopathology. 2014;122:227-35. Volume 125, Issue 9, 733, Article first published online: 18 July 2017

  • Presented in part at the United States and Canadian Academy of Pathology Annual Meeting, Vancouver, BC, Canada, March 19-21, 2012.

  • The authors are grateful to Lorena Marimon, Nadia Abu-Ligha, Roser Esteve, Silvia Alòs, Francisco Manuel Pérez, and Naiara Vega for their help with the evaluation of the p16/Ki67 dual-stained slides. We thank Donna Pringle for the English revision of the manuscript.

Abstract

BACKGROUND

This study compared the performance of p16/Ki67 dual-staining and human papillomavirus (HPV) testing in women referred to colposcopy and sought to determine the usefulness of a morphological evaluation of the double-stained cells.

METHODS

This prospective study included 1123 women (mean age, 35.8 ± 10.9 years) referred to colposcopy from October 2009 to November 2012 due to positive HPV testing or abnormal cytology results (atypical squamous cells of unknown significance, or worse abnormalities). Liquid-based cytology specimens (PreservCyt, Hologic) were used for HPV detection (Hybrid Capture 2 [HC2]; Qiagen) and p16/Ki67 dual-staining (CINtec Plus; Roche-mtm Laboratories). All women underwent histological study. After completion of the study, 18 patients were classified as having cervical cancer (CC), 378 had a high-grade squamous intraepithelial lesion (HSIL), 304 had a low-grade squamous intraepithelial lesion, and 423 were negative.

RESULTS

The sensitivity and specificity of p16/Ki67 dual-staining for HSIL/CC were 90.9% (95% confidence interval [CI] = 87.9-93.9) and 72.1 (95% CI = 68.7-75.4), respectively. For HC2, the figures were, respectively, 96.0% (95% CI = 93.9-98.0) and 41.4 (95% CI = 37.7-45.0). The values were high both in women < 30 and ≥ 30 years old (86.9% and 63.3% versus 92.3% and 77.8%, respectively). The addition of a morphological evaluation of the dual-stain–positive cells with establishment of HSIL features as the threshold for a positive reaction increased the specificity (93.5%) but decreased the sensitivity (84.1%).

CONCLUSIONS

Use of the molecular markers p16 and Ki67 has higher specificity than HC2 tests for HSIL or CC, which may support p16/Ki67 dual-staining use in the triage of patients referred for abnormal screening results. Morphological evaluation of p16/Ki67-positive cells may have some benefits in women younger than 30 years or with low-grade squamous intraepithelial lesion. Cancer (Cancer Cytopathol) 20141;22:227–235. © 2013 American Cancer Society.

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