Dual-Stained Cytology Has Greater Sensitivity and Comparable Specificity vs Pap Cytology for High-Grade Cervical Intraepithelial Neoplasia


Key Points

  • Prevalence rates of high-grade cervical intraepithelial neoplasia (CIN2+) were similar with dual-stained cytology and Pap cytology.
  • Dual-stained cytology had significantly better sensitivity and comparable specificity compared with Pap cytology.
  • In women aged ≥ 30 years, HPV testing was more sensitive but less specific than dual-stained cytology.

Pap cytology is more specific but less sensitive than human papillomavirus (HPV) testing for the detection of high-grade cervical intraepithelial neoplasia (CIN2+). In the pan-European PALMS study, reported in the Journal of the National Cancer Institute, Hans Ikenberg, MD, of CytoMol in Frankfurt, Germany, and colleagues assessed the specificity and sensitivity of p16/Ki-67 dual-stained cytology, a biomarker combination indicative of transforming HPV infections, in CIN2+ screening. They found that dual-stained cytology was more sensitive than Pap cytology and had comparable specificity.

Study Details

The study enrolled a total of 27,349 women aged ≥ 18 years attending routine cervical cancer screening in five European countries. Pap cytology, p16/Ki-67 immunostaining, and HPV testing were performed on all women. Women with positive test results were referred for colposcopy, except those aged < 30 years with positive HPV test results only. Assessment of the diagnostic performance characteristics of the tests was based on 181 cases of biopsy-confirmed CIN2+ (including 100 cases of CIN3+) using histopathologic reference standard hematoxylin-and-eosin staining.

Prevalence and Performance

Among 27,248 subjects with all three tests performed, the prevalence of positive test results for CIN2+ was 5.4% for dual-stained cytology, 5.2% for atypical squamous cells of undetermined significance or worse, and 10.7%  for HPV testing. Positivity rates were higher in women 18 to 29 years of age (8.3%, 8.9%, and 20.2%) compared with women 30 years or older (4.1%, 4.2%, and 7.5%).

In women of all ages, dual-stained cytology was more sensitive than Pap cytology (86.7% vs 68.5%, P < .001) for detecting CIN2+ and had comparable specificity (95.2% vs 95.4%, P = .15). For dual-stained cytology vs Pap cytology, sensitivities were 89.4% vs 71.9% in women aged 18 to 29 years and 84.7% vs 65.9% in those aged 30 to 65 years, and specificities were 92.0% vs 92.6% and 96.2% vs 96.3%, respectively. HPV testing in women aged ≥ 30 years was more sensitive than dual-stained cytology (93.3% vs 84.7%, P = .03) but less specific (93.0% vs 96.2%, P < .001).

The investigators concluded, “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.”

Ruediger Ridder, PhD, of Ventana Medical Systems, Inc, a member of the Roche group, Tucson, Arizona, is the corresponding author for the Journal of the National Cancer Institute article.

The study was supported by Roche mtm laboratories.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.