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.