Infections and Cancer Epidemiology, Infection, Inflammation and Cancer Research Program, German Cancer Research Center (DKFZ), Heidelberg, Germany.
The Wellcome Centre for Human Genetics, University of Oxford, Oxford, UK; Big Data Institute, Li Ka Shing Centre for Health Information and Discovery, University of Oxford, Oxford, UK.
EBioMedicine. 2020 Dec;62:103123. doi: 10.1016/j.ebiom.2020.103123. Epub 2020 Nov 25.
Antibodies against the HPV16 oncoprotein E6 are promising biomarkers for HPV16-driven oropharyngeal cancer (HPV16-OPC) due to their high sensitivity and specificity, and prospective manifestation. In previous studies, 0•7% of controls without HPV-associated malignancies were HPV16 E6 seropositive of which only a minority is expected to develop HPV16-driven cancer. We aimed to characterise HPV16 E6 antibodies in individuals without HPV-associated malignancies.
We analysed serum antibodies against HPV16 E6, E7, L1 and HPV18 L1 in a random sample (n = 9,695) of the prospective UK Biobank cohort (UKB). Excluding individuals with potentially HPV-associated malignancies (n = 192), we assessed risk factors for seropositivity by logistic regression.
In individuals without potentially HPV-associated malignancies (n = 9,503), the HPV16 E6 seroprevalence was 0•8%. Seropositivity against HPV16 E6 and all other HPV antigens was strongly associated with sexual behaviour. The seroprevalence of HPV16 E6, L1 and HPV18 L1 increased with the number of lifetime sex partners (p<0•005), and all HPV antibodies were associated with same-sex intercourse (OR 3•1, 95%CI 1•4-6•9; reference category: no same-sex intercourse). HPV16 E6 and L1 seropositivity were associated with young age (≤17 years) at sexual debut (OR 2•0, 95%CI 1•1-3•7) compared with individuals reporting sexual debut at age ≥20 years.
This is the first study characterising HPV16 E6 antibodies in the general UK population. Their strong association with sexual behaviour, and overlapping risk factor profiles with other HPV antibodies support their relevance for HPV16-OPC disease prediction. However, additional risk stratification will be required to identify individuals at highest risk to develop HPV16-OPC.
针对 HPV16 致癌蛋白 E6 的抗体是 HPV16 驱动型口咽癌（HPV16-OPC）有前景的生物标志物，因为它们具有高灵敏度和特异性以及前瞻性表现。在之前的研究中，0.7%没有 HPV 相关恶性肿瘤的对照者 HPV16 E6 血清呈阳性，其中只有少数人预计会发展为 HPV16 驱动的癌症。我们旨在描述没有 HPV 相关恶性肿瘤的个体中 HPV16 E6 抗体的特征。
我们分析了前瞻性英国生物库队列（UKB）的随机样本（n=9695）中针对 HPV16 E6、E7、L1 和 HPV18 L1 的血清抗体。排除有潜在 HPV 相关恶性肿瘤的个体（n=192），我们通过逻辑回归评估了血清阳性的危险因素。
在没有潜在 HPV 相关恶性肿瘤的个体（n=9503）中，HPV16 E6 的血清阳性率为 0.8%。针对 HPV16 E6 和所有其他 HPV 抗原的血清阳性与性行为强烈相关。HPV16 E6、L1 和 HPV18 L1 的血清阳性率随着终生性伴侣数量的增加而增加（p<0.005），所有 HPV 抗体均与同性性行为相关（OR 3.1，95%CI 1.4-6.9；参考类别：无同性性行为）。HPV16 E6 和 L1 血清阳性与性初潮时的年轻年龄（≤17 岁）相关（OR 2.0，95%CI 1.1-3.7），与报告 20 岁及以上性初潮的个体相比。
这是第一项描述英国普通人群中 HPV16 E6 抗体特征的研究。它们与性行为的强烈关联，以及与其他 HPV 抗体的重叠危险因素谱支持了它们对 HPV16-OPC 疾病预测的相关性。然而，需要进行额外的风险分层以确定发生 HPV16-OPC 的风险最高的个体。
