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自然获得性抗体阳性妇女中 HPV-16/18 感染和相关宫颈异常的风险:基于两项大型临床试验对照臂的汇总分析。

Risk of HPV-16/18 Infections and Associated Cervical Abnormalities in Women Seropositive for Naturally Acquired Antibodies: Pooled Analysis Based on Control Arms of Two Large Clinical Trials.

机构信息

Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.

Cancer Epidemiology Research Program, Catalan Institute of Oncology, Institut d'Investigació Biomédica de Bellvitge, L'Hospitalet de Llobregat, Catalonia, Spain.

出版信息

J Infect Dis. 2018 Jun 5;218(1):84-94. doi: 10.1093/infdis/jiy112.

Abstract

BACKGROUND

Studies on the role of antibodies produced after infection with human papillomavirus 18 (HPV-18) and subsequent protection from HPV-18 infection have been conflicting, mainly due to inadequate sample size.

METHODS

We pooled data from the control arms of the Costa Rica Vaccine Trial and the PATRICIA trial. Using Poisson regression we compared the risk of newly detected 1-time HPV-18 infection, HPV-18 1-year persistent infection (12MPI), and HPV-18-associated atypical squamous cells of undetermined significance or greater (ASC-US+) lesions between HPV-18 seropositive and seronegative women.

RESULTS

High HPV-18 antibodies at enrollment was associated with reduced subsequent HPV-18 detection (P trend = 0.001; relative rate [RR] = 0.69; 95% confidence interval [CI], 0.47-1.01 for the third quartile; RR = 0.63; 95% CI, 0.43-0.94 for the fourth quartile, compared to seronegative). The risk of 12MPI showed a decreasing trend with increasing antibodies (P trend = 0.06; RR = 0.72; 95% CI, 0.29-1.77; RR = 0.42; 95% CI, 0.13-1.32 for the third and fourth quartiles, respectively). Lastly, we observed a significant decreased risk of HPV-18 ASC-US+ with increasing antibody (P trend = 0.01; RR = 0.46; 95% CI, 0.21-0.97 for the fourth quartile). We also observed a significant decreased risk of HPV-16 infection, 12MPI, and ASC-US+ with increasing HPV-16 antibody level.

CONCLUSIONS

High HPV-18 naturally acquired antibodies were associated with partial protection from future HPV-18 infections and associated lesions.

CLINICAL TRIALS REGISTRATION

NCT00128661 and NCT001226810.

摘要

背景

关于 HPV-18 感染后产生的抗体的作用及其对 HPV-18 感染的后续保护作用的研究结果一直存在争议,这主要是由于样本量不足所致。

方法

我们对 Costa Rica 疫苗试验和 PATRICIA 试验的对照组数据进行了汇总。使用泊松回归,我们比较了 HPV-18 血清阳性和血清阴性妇女中 HPV-18 新发 1 次感染、HPV-18 持续感染 1 年(12MPI)以及 HPV-18 相关的非典型意义不明确的鳞状细胞或更高级别病变(ASC-US+)的风险。

结果

较高的 HPV-18 抗体在入组时与后续 HPV-18 检测减少相关(趋势 P = 0.001;第 3 四分位和第 4 四分位的相对风险 [RR] 分别为 0.69[95%CI,0.47-1.01] 和 0.63[95%CI,0.43-0.94],与血清阴性相比)。12MPI 的风险随抗体的增加呈下降趋势(趋势 P = 0.06;第 3 四分位和第 4 四分位的 RR 分别为 0.72[95%CI,0.29-1.77] 和 0.42[95%CI,0.13-1.32])。最后,我们观察到 HPV-18 ASC-US+的风险随抗体的增加而显著降低(趋势 P = 0.01;第 4 四分位的 RR 为 0.46[95%CI,0.21-0.97])。我们还观察到 HPV-16 抗体水平的增加与 HPV-16 感染、12MPI 和 ASC-US+的风险降低相关。

结论

高水平的 HPV-18 自然获得抗体与未来 HPV-18 感染和相关病变的部分保护相关。

临床试验注册

NCT00128661 和 NCT001226810。

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