Expression of p16/Ki-67 in ASC-US/LSIL or Normal Cytology with Presence of Oncogenic HPV DNA

Aim: To determine if positive dual staining of p16/Ki-67 in cytology samples from women with atypical squamous cells of undetermined significance (ASC-US), low-grade squamous intraepithelial lesion (LSIL) or normal cytological reports with presence of high-risk human papillomavirus (HPV), helps in predicting the risk of developing high-grade cervical lesions during one-year of follow-up after a normal initial colposcopy. Materials and Methods: One-hundred and sixty women with ASC-US, LSIL or otherwise normal cytology, but with the presence of high-risk HPV, were referred to the colposcopy Unit of our Hospital. Cytology and HPV testing were repeated and dual staining of p16/Ki-67 performed on a new cytological specimen, and subsequently patients were colposcopically assessed and prospectively followed-up for one year, after which the colposcopy was repeated. An optional intermediate colposcopical assessment after six months was also offered. Results: Out of 143/160 women with a normal initial colposcopy, 13 were ultimately lost to follow-up. Out of the remaining 130, nine developed histologically verified cervical intraepithelial neoplasia or higher grade (CIN2+) lesions during the one-year follow-up period. Two thirds of them (6/9) were initially p16/Ki-67-positive. Conclusion: Biomarker detection may identify women at higher risk of CIN2+, and these women may benefit from early colposcopic assessment. Women who test negatively for the biomarkers could eventually follow a less aggressive protocol.