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.

中文翻译：

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仅使用L1和L1 + L2病毒衣壳抗原检测到的宫颈HPV DNA检测与HPV16血清反应性之间的相关性。

介绍。持久性人乳头瘤病毒（HPV）16型感染是宫颈癌的主要病因。大多数HPV感染会在1-2年内自发清除。尽管并非所有受感染的妇女都会产生可检测到的HPV抗体，但约60–70％的血清会发生血清转化并保持其抗体水平较低。目标。我们调查了宫颈HPV16 DNA阳性是否与用两种不同抗原制剂测得的HPV16血清反应性相关。我们评估了协会是否受到与其他HPV类型和HPV16病毒载量的共感染的影响。方法。我们使用参加路德维希-麦吉尔队列研究的女性的基线数据，对HPV感染和宫颈癌的自然病程进行了纵向调查。该研究从1993年至1997年（疫苗接种前）招募了2462名巴西妇女。ELISA分析基于仅L1或L1 + L2病毒样颗粒（VLP）。血清反应性表示为归一化吸光度比。HPV基因分型和病毒载量通过PCR方案进行评估。皮尔逊（Pearson）r用于测量区间比例变量之间的相关性。使用接收器工作特征（ROC）曲线评估HPV16 DNA检测中的血清学准确性。我们通过线性回归分析了HPV DNA阳性与HPV16血清反应性之间的关联。结果。用于检测HPV16的L1 + L2和仅L1的VLP之间的相关性较差（稀释液1:10和1:50的r = 0.43和0.44）。最准确的方案是血清稀释度为1:10的L1 + L2 VLP（ROC面积= 0.73，95％CI：0.65-0.85）。HPV16 DNA阳性与HPV16血清反应性相关，不受合并感染或病毒载量的影响。在较小程度上，HPV16血清反应性与其他Alpha-9乳头瘤病毒种类的感染相关。结论。HPV16 DNA阳性与HPV16血清反应强烈相关。在感染HPV16或其他Alpha-9 HPV物种的女性中，L1 + L2 VLP的性能优于仅L1的VLP，可检测针对HPV16的IgG抗体。这项研究通过提供有关VLP抗原成分对测量针对自然获得性HPV感染的体液免疫反应的影响的见解，提高了我们对HPV16体液免疫反应的理解。