POSTTRANSCRIPTIONAL INDUCTION OF P21CIP1 PROTEIN IN CONDYLOMATA AND DYSPLASIAS IS INVERSELY RELATED TO HUMAN-PAPILLOMAVIRUS ACTIVITIES

Infections of the genital and oral epithelia by human papillomaviruses cause condylomata, papillomas, and squamous intraepithelial neoplasms , some of which can progress to invasive cancers. We describe an induc tion of p21cip1/WAF1/sdi1 protein in a fraction of the spinous cells i n benign lesions and in cervical intraepithelial neoplasia grades I an d II, The induction appears to be post-transcriptional and independent of p53. p21cip1 antigen-positive cells were sporadic in cervical intr aepithelial neoplasia III and rare and focal in carcinomas. In contras t, p21cip1 protein was below or at the threshold of detection in the d ifferentiated cells of normal squamous epithelia from different body s ites despite an up-regulation of p21cip1 RNA, In cervical intraepithel ial neoplasias from patients who were also positive for the human immu nodeficiency virus, there was an additional increase in p21cip1 RNA in the upper spinous cells without concomitant p21cip1 protein induction , A consistent inverse relationship was observed between the p21cip1 p rotein induction and abundant human papillomavirus DNA and RNAs, We pr opose that p21cip1 protein induction is a novel host response that inh ibits viral DNA replication and thus prevents elevated viral transcrip tion. This hypothesis can partly account for the heterogeneity and the differentiation-dependent viral activities commonly observed in benig n human papillomavirus lesions.