Background Human papillomavirus (HPV)16-E6 seropositivity accurately predicts oropharyngeal squamous cell carcinoma (OPSCC) risk decades before diagnosis; but the biomarker’s translational potential is unknown. To inform considerations for OPSCC screening, we described HPV16-E6 seroprevalence, predictors, and kinetics among cancer-free men. Methods In a cohort study in Brazil, Mexico, and United States, we calculated HPV16-E6 seropositivity [median fluorescence intensity (MFI) units > 1,000], measured by multiplex serology, in cancer-free men. HPV16-E6 seropositivity predictors were assessed using logistic regression, adjusting for country, age, sexual orientation, and lifetime number of partners. Among HPV16-E6 seropositive men, we retrieved all available retrospective serum samples and described temporal HPV16-E6 antibody patterns. Results Of 3,997 men, 14 had HPV16-E6 antibodies detected [seroprevalence = 0.35%; 95% confidence interval (95%CI)=0.19%-0.59%] (median MFI = 2,407; interquartile range = 1,325-5,986). Older age was associated with increased odds of HPV16-E6 seropositivity (50-84 years vs 18-29 years odds ratio = 16.61; 95%CI = 2.20-417.03). Serum from 11 of the 14 seropositive men retested positive; six men had MFI > 5,000, of whom two had MFI > 10,000. Seven men had ≥3 years follow-up; all were persistently seropositive for 3 years. One man was seropositive for nine years but seroreverted at his exit visit. Oral HPV16-DNA (prevalence = 1.13%) was associated with HPV16-E6 seropositivity (odds ratio = 16.87; 95%CI = 3.35-69.55). However, oral HPV16-DNA positivity was not persistent over follow-up, even when HPV16-E6 antibodies were persistently detected. Conclusion HPV16-E6 seropositivity is rare but generally stable once detected; thus, HPV16-E6 antibodies may be an informative biomarker of HPV-driven OPSCC. Few men seroreverted following HPV16-E6 seropositivity but remained close to the seropositivity cut-off; thus, cancer risk among these men is less clear.

中文翻译：

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在一项多中心纵向队列研究中，无癌男性 HPV16-E6 血清学的自然病程


背景 人瘤病毒 （HPV）16-E6 血清阳性可在诊断前几十年准确预测口咽鳞状细胞癌 （OPSCC） 风险;但这种生物标志物的转化潜力尚不清楚。为了告知 OPSCC 筛查的注意事项，我们描述了无癌男性的 HPV16-E6 血清阳性率、预测因子和动力学。方法 在巴西、墨西哥和美国的一项队列研究中，我们计算了无癌男性的 HPV16-E6 血清阳性 [中位荧光强度 （MFI） 单位 > 1,000]，通过多重血清学测量。使用 logistic 回归评估 HPV16-E6 血清阳性预测因子，调整国家、年龄、性取向和伴侣的终生数量。在 HPV16-E6 血清阳性男性中，我们检索了所有可用的回顾性血清样本并描述了颞部 HPV16-E6 抗体模式。结果 在 3,997 名男性中，14 名检测到 HPV16-E6 抗体 [血清阳性率 = 0.35%;95% 置信区间 （95%CI）=0.19%-0.59%] （中位 MFI = 2,407;四分位距 = 1,325-5,986）。年龄较大与 HPV16-E6 血清阳性几率增加相关 （50-84 岁 vs 18-29 岁比值比 = 16.61;95% CI = 2.20-417.03）。14 名血清阳性男性中有 11 名的血清再次检测呈阳性;6 名男性的 MFI > 5,000，其中 2 名的 MFI > 10,000。7 名男性进行了 ≥3 年的随访;所有患者均持续 3 年血清阳性。一名男子血清反应阳性 9 年，但在出院访视时被排除在外。口服 HPV16-DNA （患病率 = 1.13%） 与 HPV16-E6 血清阳性相关 （比值比 = 16.87;95% CI = 3.35-69.55）。然而，即使持续检测到 HPV16-E6 抗体，口服 HPV16-DNA 阳性在随访中也不是持续的。 结论 HPV16-E6 血清阳性罕见，但一旦检测到通常稳定;因此，HPV16-E6 抗体可能是 HPV 驱动的 OPSCC 的信息性生物标志物。很少有男性在 HPV16-E6 血清阳性后进行血清切除，但仍接近血清阳性临界值;因此，这些男性的癌症风险不太清楚。