ANALYSIS OF IGG REACTIVITY AGAINST HUMAN PAPILLOMAVIRUS TYPE-16 E7 INPATIENTS WITH CERVICAL INTRAEPITHELIAL NEOPLASIA INDICATES AN ASSOCIATION WITH CLEARANCE OF VIRAL-INFECTION - RESULTS OF A PROSPECTIVE-STUDY

IgG reactivity against the immunodominant region aa6-35 of Human Papil lomavirus (HPV) type-16 by was determined in a peptide-based ELISA in a cohort study of women with initial mild to moderate cervical dyskary osis. On the basis of HPV DNA patterns, as determined by PCR in cervic al smears prior to IgG testing, HPV-16-positive patients were grouped as having either a cleared, a fluctuating, or a persistent HPV-16 infe ction. In a cross-sectional study at the start of serological follow-u p, positive IgG reactivities were found more often in the total group of HPV-16-positive patients (20.0%) than in patients consistently type d as HPV-negative over a period of at least 12 months prior to testing (3.1%, p <0.04). The highest proportion of positive responders was fo und in patients with a cleared HPV-16 infection (29.4%). Also, IgG rea ctivities found in HPV-16 clearance patients were significantly higher than in patients with a persistent infection (p <0.008). In a subsequ ent longitudinal study over a period of up to 27 months, consistently positive reactivities were observed in patients with cleared viral inf ections who showed seroreactivity in the cross-sectional study, while mostly negative reactivities were found in patients with viral persist ence. HPV-16 E7-specific IgG subclass responses were determined in a s election of 19 CIN and 11 HPV-16-positive cervical carcinoma (CeCa) pa tients with positive E7-specific IgG responses. IgG(2) was predominant in the CIN patients, suggesting the presence of IFN gamma (ThI) at th e site of HPV infection. In the CeCa patients IgG(1) and IgG(2) were p roduced equally, possibly indicating a rise in Th2 cytokines. Our data suggest that HPV-16 E7 IgG reactivity in a subset of CIN patients wit h viral clearance may result from successful ThI responses. (C) 1996 W iley-Liss, Inc.