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Literature on Cervical Cancer

Triage of Women with ASUS and LSIL Cytology

Nicolas Wentzensen,Christine Bergeron,et. al.,

CANCER (CANCER CYTOPATHOLOGY) Volume 111 / Number 1 February 25, 2007


Use of Qualitative Assessment of p16INK4a  Positive Cells to Identify Patients With High-Grade Cervical 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 pro- blem in cytology-based cervical cancer screening. The authors investigated the efficacy of p16INK4a 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 p16INK4a result. p16INK4a stained slides were prepared and independently read by 2 observers, who used a recently described score to categorize p16INK4a stained squamous cells. The endpoint of the study was detection of a biopsy-confirmed HGCIN.

RESULTS. The overall sensitivity and specificity of p16INK4a positive cells with a nu- clear 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 p16INK4a stained cells (k value of 0.841).

CONCLUSIONS. These data suggested that the use of p16INK4a as a biomarker com- bined with nuclear scoring of p16INK4a positive cells in cervical cytology to triage ASCUS and/or LSIL cases allows identification of HGCIN with good sensitivity and specificity. Cancer (Cancer Cytopathol) 2007;111:58–66.