Altered expression of filaggrin in human papillomavirus (HPV) lesions of the uterine cervix.

A series of 64 punch biopsies collected from women prospectively followed-up for cervical Human papillomavirus (HPV) infections (with and without CIN), and 38 control biopsies (normal epithelia, and classical CIN) were analysed for expression of filaggrin (a histidine-rich protein constituent of keratohyalin granules) using the ABC technique and polyclonal antibody. HPV typing was completed using the in situ hybridization technique with DNA probes for HPV 6, 11, 16, 18 and 31. Three patterns of filaggrin distribution were differentiated: pattern I, all layers above the basal cells stained positive regularly; pattern II, all layers above the basal cells stained irregularly, and pattern III, scattered superficial cells stained positive. There was a significant difference between HPV-noCIN and HPV-CIN lesions in their filaggrin patterns, pattern I being present in the majority (77.7%) of HPV-noCIN lesions, as contrasted to HPV-CIN lesions, where pattern III was the predominant one (43.5%), followed by pattern II (32.6%). In HPV-CIN as well as in CIN lesions, pattern I was inversely related to the grade of CIN, being entirely absent in HPV-CIN III and CIN III. A significant difference exists between CIN and HPV-CIN lesions, concerning the presence of pattern III (4.3% and 43.5%, respectively, P less than 0.001). The difference was less dramatic with regard to pattern I (30.4% and 21.7%, respectively, P less than 0.05). In the lesions containing HPV 6, 11 or 31 DNA, filaggrin distribution was shown to be more close to that of the normal epithelium (I 36.7%, and II 34.7%), while in the HPV 16 and 18-infected cases, pattern III was the predominant one (46.7%). The assessment of filaggrin pattern in HPV lesions might be of help in evaluating the severity of the disturbance of keratinocyte differentiation induced by the progression of HPV infections.