de Gruijl T D, Bontkes H J, Walboomers J M, Schiller J T, Stukart M J, Groot B S, Chabaud M M, Remmink A J, Verheijen R H, Helmerhorst T J, Meijer C J, Scheper R J
Department of Pathology, Free University Hospital, Amsterdam, The Netherlands.
J Natl Cancer Inst. 1997 May 7;89(9):630-8. doi: 10.1093/jnci/89.9.630.
Infection with cancer-linked human papillomavirus (HPV) types such as HPV type 16 (HPV16) is the most important risk factor in the development of cervical cancer. It has been shown that immunoglobulin G (IgG) antibody responses against HPV16 virus-like particles (VLPs) are specifically associated with genital HPV16 infection.
The aim of this study was to determine the temporal relationships between the presence of HPV16 VLP-specific IgGs, HPV16 infection patterns, and the course of premalignant cervical disease.
Plasma samples from 133 women who had been diagnosed originally with mild to moderate cervical dyskaryosis and enrolled in a prospective non-intervention cohort study conducted in Amsterdam, The Netherlands, from 1991 through 1996 were analyzed for the presence of HPV16 VLP-specific IgGs by use of an enzyme-linked immunosorbent assay. A detailed analysis was performed on 43 women with different HPV16 infection patterns during a follow-up period of 10-34 months. Progression or regression of cervical intraepithelial neoplasia (CIN) lesions was monitored by cytologic and colposcopic testing at intervals of 3-4 months. HPV typing in cervical smears was performed by use of a polymerase chain reaction-based assay. Statistical analysis of the serologic data was performed by use of the Mann-Whitney U test or 2 x 2 table analyses.
The presence of HPV16 VLP-specific IgGs in the plasma of the patients was found to be associated with the presence of HPV16 DNA in the cervical smear. Significantly higher proportions of patients with persistent HPV16 infections (i.e., who were polymerase chain reaction positive in three to 11 consecutive tests) than of patients with cleared HPV16 infections were found to be positive for the presence of HPV16 VLP-specific IgGs (18 [69.2%] of 26 versus nine [28.1%] of 32, respectively; P = .003). HPV16 VLP-specific IgGs were consistently detected in all women (n = 11) who were persistently HPV16 DNA positive during follow-up and whose disease ultimately progressed to CIN III (histologically diagnosed severe dysplasia or carcinoma in situ).
HPV16 VLP-specific IgG responses are present in the plasma of a majority of patients with persistent HPV16 infections and histologically confirmed high-grade lesions but only in a smaller subset of patients with cleared HPV16 infections and either normal cervical histology or low-grade CIN lesions.
These results suggest that HPV16 VLP-specific antibodies are not responsible for the clearance of virally induced CIN lesions but that they might, in patients with persistent HPV16 infections, be indicative of an increased cervical cancer risk.
感染与癌症相关的人乳头瘤病毒（HPV）类型，如16型HPV（HPV16），是宫颈癌发生的最重要风险因素。研究表明，针对HPV16病毒样颗粒（VLP）的免疫球蛋白G（IgG）抗体反应与生殖器HPV16感染存在特异性关联。
本研究旨在确定HPV16 VLP特异性IgG的存在、HPV16感染模式与宫颈癌前病变病程之间的时间关系。
对1991年至1996年在荷兰阿姆斯特丹进行的一项前瞻性非干预队列研究中最初被诊断为轻度至中度宫颈发育异常的133名女性的血浆样本，采用酶联免疫吸附测定法分析HPV16 VLP特异性IgG的存在情况。对43名在10 - 34个月随访期内具有不同HPV16感染模式的女性进行了详细分析。通过每隔3 - 4个月进行的细胞学和阴道镜检查监测宫颈上皮内瘤变（CIN）病变的进展或消退。采用基于聚合酶链反应的检测方法对宫颈涂片进行HPV分型。血清学数据的统计分析采用曼-惠特尼U检验或2×2表格分析。
发现患者血浆中HPV16 VLP特异性IgG的存在与宫颈涂片中HPV16 DNA的存在相关。与HPV16感染已清除的患者相比，持续HPV16感染（即连续3至11次检测聚合酶链反应呈阳性）的患者中，HPV16 VLP特异性IgG呈阳性的比例显著更高（分别为26例中的18例[69.2%]和32例中的9例[28.1%]；P = 0.003）。在随访期间持续HPV16 DNA阳性且疾病最终进展为CIN III（组织学诊断为重度发育异常或原位癌）的所有女性（n = 11）中均持续检测到HPV16 VLP特异性IgG。
大多数持续HPV16感染且组织学确诊为高级别病变的患者血浆中存在HPV16 VLP特异性IgG反应，但在HPV16感染已清除且宫颈组织学正常或为低级别CIN病变的患者中只有较小一部分存在该反应。
这些结果表明，HPV16 VLP特异性抗体并非病毒诱导的CIN病变清除的原因，但在持续HPV16感染的患者中，它们可能表明宫颈癌风险增加。
