Kawana Kei, Yasugi Toshiharu, Kanda Tadahito, Kawana Yukiko, Hirai Yasuo, Yoshikawa Hiroyuki, Taketani Yuji
Department of Obstetrics and Gynecology, Faculty of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, 113-8655, Tokyo, Japan.
Biochem Biophys Res Commun. 2002 Aug 9;296(1):102-5. doi: 10.1016/s0006-291x(02)00843-4.
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.
为了确定针对人乳头瘤病毒16型（HPV16）的中和抗体（NAs）是否导致低级别宫颈上皮内瘤变（CIN1）的较高消退率，我们研究了NAs的存在与HPV16相关CIN1转归之间的关联。本研究中所有接受检查的女性宫颈HPV16均呈阳性。根据宫颈病理情况将这些女性分为四组，即无病变组（n = 7）、CIN1组（n = 37）、CIN2/3组（n = 19）和宫颈癌组（n = 13）。通过使用HPV16假病毒的体外试验检测她们血清中针对HPV16的NAs。对于CIN1病例，比较了NA阳性组和NA阴性组病变的临床消退情况。通过定量PCR测定涂片样本中HPV16-DNA的拷贝数。宫颈无病变女性中NAs存在的发生率（85.7%）显著高于CIN1病例（21.5%）、CIN2/3病例（15.7%）和宫颈癌病例（0%）（p<0.0001）。CIN1病变的消退与NAs的存在密切相关（p = 0.0002）。与NA阴性组相比，NAs的存在与病毒DNA的低拷贝数相关（p = 0.05）。针对HPV16的NAs的存在与HPV相关CIN1病变的较高消退率相关。NAs似乎通过抑制新生复制HPV的感染，在阻止HPV相关宫颈病变进展为CIN2/3方面发挥作用。本研究进一步表明，诱导NAs的HPV疫苗可能对消除CIN病变有效，尤其是在NA阴性病例中。
