Screening for cervical cancer precursors with p16/Ki-67 dual-stained cytology: results of the PALMS study.

Abstract

BACKGROUND:

Pap cytology is known to be more specific but less sensitive than testing for human papillomavirus (HPV) for the detection of high-grade cervical intraepithelial neoplasia (CIN2+). We assessed whether p16/Ki-67 dual-stained cytology, a biomarker combination indicative of transforming HPV infections, can provide high sensitivity for CIN2+ in screening while maintaining high specificity. Results were compared with Pap cytology and HPV testing.

METHODS:

A total of 27,349 women 18 years or older attending routine cervical cancer screening were prospectively enrolled in five European countries. Pap cytology, p16/Ki-67 immunostaining, and HPV testing were performed on all women. Positive test results triggered colposcopy referral, except for women younger than 30 years with only positive HPV test results. Presence of CIN2+ on adjudicated histology was used as the reference standard. Two-sided bias-corrected McNemar P values were determined.

RESULTS:

The p16/Ki-67 dual-stained cytology positivity rates were comparable with the prevalence of abnormal Pap cytology results and less than 50% of the positivity rates observed for HPV testing. In women of all ages, dual-stained cytology was more sensitive than Pap cytology (86.7% vs 68.5%; P < .001) for detecting CIN2+, with comparable specificity (95.2% vs 95.4%; P = .15). The relative performance of the tests was similar in both groups of women: younger than age 30 and 30 years or older. HPV testing in women 30 years or older was more sensitive than dual-stained cytology (93.3% vs 84.7%; P = .03) but less specific (93.0% vs 96.2%; P < .001).

CONCLUSIONS:

The p16/Ki-67 dual-stained cytology combines superior sensitivity and noninferior specificity over Pap cytology for detecting CIN2+. It suggests a potential role of dual-stained cytology in screening, especially in younger women where HPV testing has its limitations.

• Authors: Hans Ikenberg, Christine Bergeron, Dietmar Schmidt, Henrik Griesser, Francisco Alameda, Claudio Angeloni, Johannes Bogers, Roger Dachez, Karin Denton, Jalil Hariri, Thomas Keller, Magnus von Knebel Doeberitz, Heinrich H Neumann, Luis M Puig-Tintore, Mario Sideri, Susanne Rehm, Ruediger Ridder, PALMS Study Group
• Journal: Journal of the National Cancer Institute (J Natl Cancer Inst) Vol. 105 Issue 20 Pg. 1550-7 (Oct 16 2013) ISSN: 1460-2105 [Electronic] United States
• PMID: 24096620 (Publication Type: Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)

Chemical References

• Biomarkers, Tumor
• CDKN2A protein, human
• Cyclin-Dependent Kinase Inhibitor p16
• Ki-67 Antigen
• Neoplasm Proteins

Topics

• Adult
• Aged
• Biomarkers, Tumor (analysis)
• Cell Transformation, Neoplastic (chemistry)
• Colposcopy
• Cyclin-Dependent Kinase Inhibitor p16
• Cytopathogenic Effect, Viral
• Early Detection of Cancer (methods)
• Europe
• Female
• Humans
• Ki-67 Antigen (analysis)
• Mass Screening (methods)
• Middle Aged
• Neoplasm Grading
• Neoplasm Proteins (analysis)
• Papillomaviridae (isolation & purification)
• Papillomavirus Infections (diagnosis, virology)
• Prospective Studies
• Referral and Consultation
• Sensitivity and Specificity
• Uterine Cervical Neoplasms (chemistry, diagnosis, pathology)
• Vaginal Smears
• Uterine Cervical Dysplasia (chemistry, diagnosis, pathology)