Virological and biological characteristics of cervical intraepithelial neoplasia grade i with marked koilocytotic atypia

Abstract

The aim of this study was to evaluate virologic and biological significance of marked koilocytotic atypia observed in some cases of grade I cervical intraepithelial neoplasia (CIN I). Thirty-one CIN I cervical biopsy specimens with marked koilocytotic atypia, defined by the presence of meganuclei in the superficial epithelial layers, were compared to 37 CIN I biopsy specimens with usual koilocytes for (1) the human papillomavirus (HPV) type and signal pattern as detected by nonisotopic in situ hybridization (ISH); (2) the proliferation index assessed by Ki 67 immunostaining and (3) the p53 labeling pattern. Interobserver agreement for meganuclei was excellent (k = 0.9). Twenty-five out of 68 biopsies (37%) were positive by ISH for the 6 of 11 HPV probe, 30 (44%) for the 16–18 probe, and 7 (10%) for the 31/33 HPV probe, 6 (9%) were negative for ISH. The presence of meganuclei was strongly related to high and intermediate risk HPV type (P = 0.0001). The sensitivity and specificity of meganuclei for the detection of high or intermediate risk HPV in CINI were 73 and 87%, respectively. Loss of p53 immunostaining in the lower third of the epithelium was also related to the presence of meganuclei (P < .05), but the MIB-1 index and ISH labeling pattern were not. In conclusion, marked koilocytotic atypia in CIN I is a reliable and sensitive marker for infection by high or intermediate-risk HPV, and might be a guide to therapy.