title: Neutralizing antibodies against oncogenic human papillomavirus as a possible determinant of the fate of low-grade cervical intraepithelial neoplasia.
abstract: To determine whether neutralizing antibodies (NAs) against HPV16 is responsible for a higher regression rate of low-grade cervical intraepithelial neoplasia (CIN1), we investigated an association between the presence of the NAs and the fate of the HPV16-related CIN1. All the women examined in this study had HPV16 positive cervix. The women were allocated into four groups by their cervical pathology, i.e., non-pathological (n:7), CIN1 (n:37), CIN2/3 (n:19), and cervical cancer (n:13). Their sera were tested for the presence of NAs against HPV16 by an in vitro assay using HPV16-pseudovirions. As for the CIN1 cases, clinical regression of the lesions were compared between NA-positive and NA-negative groups. Copy number of HPV16-DNA in smear samples was measured by quantitative PCR. The incidence of the presence of the NAs in the women with a non-pathological cervix (85.7%) was significantly higher than in the CIN1 cases (21.5%), the CIN2/3 cases (15.7%), and the cervical cancer cases (0%) (p<0.0001). The regression of the CIN1 lesion was closely associated with the presence of the N As (p=0.0002). The presence of the NAs was associated with low-level copy number of the viral DNA relative to the NA-negative group (p=0.05). The presence of the NAs against HPV16 was associated with a higher regression rate of HPV-related CIN1 lesions. The NAs seem to have a role in deterring HPV-related cervical lesions from progressing to CIN2/3 by inhibiting the infection with de novo replicated HPV. This study further suggests that HPV vaccine to induce the NAs may be effective in eliminating CIN lesions, especially in the NA-negative cases.
authors.affiliation: Department of Obstetrics and Gynecology, Faculty of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, 113-8655, Tokyo, Japan. kkawana-tky@umin.ac.jp
authors.forename: Kei
authors.initials: K
authors.lastname: Kawana
authors.forename: Toshiharu
authors.initials: T
authors.lastname: Yasugi
authors.forename: Tadahito
authors.initials: T
authors.lastname: Kanda
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Kawana
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Hirai
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Yoshikawa
authors.forename: Yuji
authors.initials: Y
authors.lastname: Taketani
mesh_terms: D000914:Antibodies, Viral / Q000276:immunology*; D004279:DNA, Viral; D005260:Female; D006801:Humans; D009500:Neutralization Tests; D009856:Oncogene Proteins, Viral / Q000276:immunology*; D027383:Papillomaviridae / Q000235:genetics / Q000276:immunology* / Q000302:isolation & purification; D019562:Viral Load; D002578:Uterine Cervical Dysplasia / Q000473:pathology* / Q000821:virology
chemical_list: D000914:Antibodies, Viral; D004279:DNA, Viral; D009856:Oncogene Proteins, Viral