Triaging Atypical Squamous Cells-Cannot Exclude High-Grade Squamous Intraepithelial Lesion With p16/Ki67 Dual Stain.

OBJECTIVES: The management of women with Pap cytology results categorized as "atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesion" (ASC-H) can often be challenging. We assessed the performance of p16/Ki67 dual-stained cytology as a potential triage tool for the detection of biopsy-confirmed high-grade squamous intraepithelial lesions (HSILs) in women with ASC-H.

MATERIALS AND METHODS: Women with ASC-H were followed for a period of 36 months by repeat cytology and colposcopy. p16/Ki67 dual staining was performed retrospectively on the initial Pap cytology slide with ASC-H interpretation. Results were compared with the final histological diagnosis and/or cytological follow-up for at least 1 year. All outcomes were defined as clinically significant at the threshold of HSIL (cervical intraepithelial neoplasia grade 2 or worse).

RESULTS: One hundred sixty-nine cases fulfilled all conditions to be included in the study group. The rate of histologically confirmed HSIL was 57.4%, low-grade squamous intraepithelial lesion was diagnosed in 17.7% of the patients and normal histology or follow-up in 24.9% of the patients. Overall sensitivity and specificity of p16/Ki67 dual stain were 95% and 72%, respectively. Overall positive likelihood ratio of p16/Ki67 in detection of HSIL was 3.41, considerably increasing pretest probability from 57% to posttest probability of 82%.

CONCLUSIONS: A substantial subset of patients with ASC-H interpretations is associated with an appreciable risk of clinically significant cervical disease. p16/Ki67 dual stain can provide additional valuable information that may lead to higher-quality management of women with ASC-H, especially when initial colposcopy or biopsy results do not show HSIL lesions.