1 Infections and Cancer Epidemiology, German Cancer Research Center (DKFZ) , Im Neuenheimer Feld 242, 69120 Heidelberg , Germany.
2 Department of Gynaecology, Jena University Hospital , Am Klinikum 1, Haus F2, 07747 Jena , Germany.
Philos Trans R Soc Lond B Biol Sci. 2019 May 27;374(1773):20180295. doi: 10.1098/rstb.2018.0295.
Antibodies to the E6 and E7 oncoproteins of high-risk human papillomavirus (HPV) types are strongly associated with HPV-driven cancer, while antibodies against the capsid protein L1 are considered cumulative exposure markers. To test the hypothesis that L1 antibody levels are stable over time, whereas E6 and E7 levels undergo decay after cervical cancer (CxCa) treatment, we performed multiplex serology for HPV16 and 18 antigens E6, E7 and L1 in a post-treatment study of 184 patients with invasive CxCa that were characterized with a median follow-up time of 725 days, and 2-12 sera per patient. Antibody titers significantly decreased within the first six months for HPV16 E6 and E7 but not L1, and stabilized for the following 12 months on a high level, with few patients showing seroreversion. Of 67 patients seropositive for HPV16 E6 at diagnosis, 28 (41.8%) showed a decrease in antibody titers of at least 50% within the first 18 months. Similarly, of 50 HPV16 E7 seropositives, 33 (66.0%) showed decreasing antibody levels, whereas antibody decay was less frequent for HPV16 L1 (12 of 47, 25.5%). Using a power-law mathematical model to characterize antibody decay kinetics, the mean (±s.e.) durations to a 50% reduction in antibody titers within individual patients were estimated to be 56.9 (±26.1) and 56.3 (±19.0) days for HPV16 E6 and E7, respectively. In summary, HPV16 E6 and E7 antibodies undergo a slow but significant decrease in antibody titers within the first 6-18 months following CxCa treatment. However, larger studies are needed to confirm the utility of serology for prediction of disease progression and time to relapse based on antibody decay kinetics. This article is part of the theme issue 'Silent cancer agents: multi-disciplinary modelling of human DNA oncoviruses'.
针对高危型人乳头瘤病毒（HPV）的 E6 和 E7 癌蛋白的抗体与 HPV 驱动的癌症密切相关，而针对衣壳蛋白 L1 的抗体则被认为是累积暴露标志物。为了检验 HPV16 和 18 型的 E6、E7 和 L1 抗原的 L1 抗体水平随时间保持稳定，而 E6 和 E7 水平在宫颈癌（CxCa）治疗后下降的假说，我们对 184 例侵袭性 CxCa 患者进行了治疗后研究，采用多重血清学方法检测 HPV16 和 18 型的 E6、E7 和 L1 抗原。这些患者的中位随访时间为 725 天，每个患者有 2-12 份血清样本。HPV16 E6 和 E7 的抗体滴度在治疗后的前 6 个月内显著下降，但 L1 则没有，并且在接下来的 12 个月内稳定在高水平，很少有患者出现血清学逆转。在 184 例患者中，有 67 例 HPV16 E6 诊断时为血清阳性，其中 28 例（41.8%）在最初 18 个月内抗体滴度下降至少 50%。同样，在 50 例 HPV16 E7 血清阳性患者中，有 33 例（66.0%）出现抗体水平下降，而 HPV16 L1 则较少见（47 例中有 12 例，25.5%）。使用幂律数学模型来描述抗体衰减动力学，估计每个患者的抗体滴度下降 50%的平均（±s.e.）持续时间分别为 HPV16 E6 和 E7 的 56.9（±26.1）和 56.3（±19.0）天。总之，在宫颈癌治疗后的前 6-18 个月内，HPV16 E6 和 E7 抗体的抗体滴度会缓慢但显著下降。然而，需要更大的研究来证实血清学检测基于抗体衰减动力学预测疾病进展和复发时间的效用。本文是主题为“沉默的致癌因子：人类 DNA 致癌病毒的多学科建模”的一部分。
