Triage of women with ASCUS and LSIL cytology -: Use of qualitative assessment of p16INK4a positive cells to identify patients with high-grade ceivical intraepithelial neoplasia

BACKGROUND. The identification of a small percentage of high-grade cervical intraepithelial neoplasias (HGCIN) among patients with minor cytological abnormalities (atypical squamous cells of undetermined significance [ASCUS] and/or low-grade squamous intraepithelial lesions [LSIL] group) is a major problem in cytology-based cervical cancer screening. The authors investigated the efficacy of p16(INK4a) as a biomarker to identify samples of patients with HGCIN among those with an ASCUS or LSIL result in Papanicolaou cytology. METHODS. Consecutive liquid-based cytology specimens of 137 ASCUS and 88 LSIL results were selected from gynecologists who adopted a triage regimen with biopsy under colposcopy 2 months later, independent of the p16(INK4a), result. p16(INK4a) stained slides were prepared and independently read by 2 observers, who used a recently described score to categorize p16(INK4a) stained squamous cells. The endpoint of the study was detection of a biopsy-confirmed HGCIN. RESULTS. The overall sensitivity and specificity of p16(INK4a) positive cells with a nuclear score > 2 for diagnosis of HGCIN in ASCUS and LSIL cases combined was 96% and 83%, respectively. The sensitivity and specificity in the ASCUS group was 95% and 84%, and 100% and 81% in the LSIL group, respectively. Two observers had a high concordance in assessing p16(INK4a) stained cells (K value of 0.841). CONCLUSIONS. These data suggested that the use of p16(INK4a) as a biomarker combined with nuclear scoring of p16(INK4a) positive cells in cervical cytology to triage ASCUS and/or LSIL cases allows identification of HGCIN with good sensitivity and specificity.