Role of P16(INK4a) expression in identifying CIN2 or more severe lesions among HPV-positive patients referred for colposcopy after abnormal cytology

Abstract

BACKGROUND p16 is strongly overexpressed in dysplastic cervical cells because of the transforming activity of the E7 oncogene of all high‐risk human papillomavirus (HR‐HPV) types and may be easily revealed by immunochemistry: p16 may, therefore, be considered a surrogate marker for the activated oncogene expression of HR‐HPV in dysplastic cervical cells. METHODS HPV and p16^INK4a testing were performed in a consecutive series of 283 patients with abnormal cytology referred to colposcopy assessment or follow‐up. Triage of patients to colposcopy by HPV or HPV and p16 testing was simulated, and the relative sensitivity, specificity, and positive predictive value (PPV) of HPV and p16 testing for > CIN2 lesions was determined as well as the cost balance of the two triage types. RESULTS Compared to current protocol, triage by HPV testing reduced the number of colposcopies by 44.2%, but also reduced the > CIN2 detection rate by 10.7%, and was associated with a cost of € 54.16 per assessed woman and of € 613.20 per > CIN2 detected. Compared with current protocol, triage by HPV and p16 testing combined reduced the number of colposcopies by 73.1%, but reduced > CIN2 detection rate by 21.5%, and was associated with a cost of € 54.73 per woman assessed and of € 704.09 per > CIN2 detected. CONCLUSIONS Triage by HPV and p16 improves considerably the PPV of diagnostic assessment, but decreases > CIN2 detection rate, and is associated with substantially higher costs. Further decrease of molecular immunochemistry testing due to technological progress may allow HPV and p16 testing to become a cost effective procedure in the future. Cancer (Cancer Cytopathol) 2006. © 2006 American Cancer Society.