P16^INK4a expression and progression risk of low-grade intraepithelial neoplasia of the cervix uteri

The aim of the study was to evaluate the immunohistochemical expression of p16^INK4a as a marker of progression risk in low-grade dysplastic lesions of the cervix uteri. p16^INK4a immunohistochemistry was performed on 32 CIN1 with proven spontaneous regression of the lesion in the follow-up (group A), 31 (group B) with progression to CIN3 and 33 (group C) that were randomly chosen irrespective of the natural history of the lesion. p16^INK4a staining pattern was scored as negative (less than 5% cells in the lower third of dysplastic epithelium stained), as focally positive (≤25%) and as diffuse positive (>25%). A diffuse staining pattern was detected in 43.8% of CIN1 of group A, 74.2% of group B and 56.3% of group C. No p16^INK4a staining was detected in 31.3% and 12.9% CIN1 lesions of groups A and B, respectively. Overall, 71.4% and 37.8% of p16^INK4a-negative and diffusely positive CIN1 had regressed at follow-up, whereas 28.6% and 62.2% negative and diffusely positive CIN1 were progressed to CIN3, respectively (P<0.05). All CIN3 lesions analyzed during follow-up of group B were diffusely stained for p16^INK4a. Although p16^INK4a may be expressed in low-grade squamous lesions that undergo spontaneous regression, in this study, CIN1 cases with diffuse p16^INK4a staining had a significantly higher tendency to progress to a high-grade lesion than p16^INK4a-negative cases. p16^INK4a may have the potential to support the interpretation of low-grade dysplastic lesions of the cervix uteri.