Correlation between cervical HPV DNA detection and HPV16 seroreactivity measured with L1-only and L1+L2 viral capsid antigens.
Correlation between cervical HPV DNA detection and HPV16 seroreactivity measured with L1-only and L1+L2 viral capsid antigens.
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DOI：
10.1099/jmm.0.001213
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发表时间：
2020-06
影响因子：
3
通讯作者：
A. Trevisan;J. Candeias;P. Thomann;L. Villa;E. Franco;H. Trottier
中科院分区：
文献类型：
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作者：
A. Trevisan;J. Candeias;P. Thomann;L. Villa;E. Franco;H. Trottier
导言。人乳头瘤病毒16型持续性感染是宫颈癌的主要致病因素。大多数HPV感染会在1-2年内自发清除。虽然不是所有受感染的妇女都会产生可检测到的HPV抗体，但大约60%-70%的血清转换并将其抗体保留在低水平。我们调查了宫颈HPV16DNA阳性是否与用两种不同的抗原配方测量的HPV16血清反应性有关。我们评估合并感染其他类型的HPV和HPV16病毒载量是否会影响相关性。我们使用了参加路德维希-麦吉尔队列的妇女的基线数据，这是一项关于HPV感染和宫颈肿瘤自然病史的纵向调查。这项研究从1993年到1997年(接种疫苗前)招募了2462名巴西妇女。酶联免疫吸附试验基于L1或L1+L2病毒样颗粒(VLP)。血清反应性用归一化吸光度比表示。用聚合酶链式反应方法检测HPV基因分型和病毒载量。皮尔逊的r被用来衡量区间标度变量之间的相关性。用受试者工作特征(ROC)曲线评价血清学检测HPV16DNA的准确性。我们通过线性回归分析了HPVDNA阳性与HPV16血清反应性之间的关系。L1+L2和仅L1-VLP检测HPV16的相关性较差(1：10和1：50的相关系数分别为0.43和0.44)。当血清稀释度为1：10时，L1+L2 VLP诊断准确率最高(ROC面积=0.73，95%CI：0.65~0.85)。HPV16DNA阳性与HPV16型血清反应性相关，不受混合感染或病毒载量的影响。在较小程度上，HPV16型血清反应性与其他Alpha-9型乳头瘤病毒感染有关。HPV16DNA阳性与HPV16型血清反应性密切相关。在检测感染HPV16或其他Alpha-9型HPV的妇女中，L1+L2 VLP比仅L1-VLP检测HPV16抗体的效果更好。本研究通过对VLP抗原组成对体液免疫应答的影响的研究，促进了我们对HPV16体液免疫应答的理解。
Introduction. Persistent human papillomavirus (HPV) type 16 infection is the main causal agent of cervical cancer. Most HPV infections clear spontaneously within 1-2 years. Although not all infected women develop detectable HPV antibodies, about 60-70 % seroconvert and retain their antibodies at low levels.Aim. We investigated if cervical HPV16 DNA positivity was associated with HPV16 seroreactivity measured with two different antigen formulations. We assessed if associations were influenced by co-infection with other HPV types and HPV16 viral load.Methodology. We used baseline data for women participating in the Ludwig-McGill cohort, a longitudinal investigation of the natural history of HPV infection and cervical neoplasia. The study enrolled 2462 Brazilian women from 1993 to 1997 (pre-vaccination). ELISA assays were based on L1-only or L1+L2 virus-like particles (VLPs). Seroreactivity was expressed as normalized absorbance ratios. HPV genotyping and viral load were evaluated by PCR protocols. Pearson's r was used to measure correlations between interval-scaled variables. Serological accuracy in HPV16 DNA detection was assessed using receiver operating characteristic (ROC) curves. We analysed the association between HPV DNA positivity and HPV16 seroreactivity by linear regression.Results. Correlations between L1+L2 and L1-only VLPs for detection of HPV16 were poor (r=0.43 and 0.44 for dilutions 1 : 10 and 1 : 50, respectively). The protocol with the best accuracy was L1+L2 VLPs at serum dilution 1 : 10 (ROC area=0.73, 95 % CI: 0.65-0.85). HPV16 DNA positivity was correlated with HPV16 seroreactivity and was not influenced by co-infection or viral load. To a lesser degree, HPV16 seroreactivity was correlated with infection by other Alpha-9 papillomavirus species.Conclusion. HPV16 DNA positivity and HPV16 seroreactivity are strongly correlated. L1+L2 VLPs perform better than L1-only VLPs for detecting IgG antibodies to HPV16 in women infected with HPV16 or other Alpha-9 HPV species. This study advances our understanding of humoral immune responses against HPV16 by providing insights about the influence of VLP antigen composition to measure humoral immune response against naturally acquired HPV infection.