Fakhry Carole, Qualliotine Jesse R, Zhang Zhe, Agrawal Nishant, Gaykalova Daria A, Bishop Justin A, Subramaniam Rathan M, Koch Wayne M, Chung Christine H, Eisele David W, Califano Joseph, Viscidi Raphael P
Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Cancer Prev Res (Phila). 2016 Feb;9(2):135-41. doi: 10.1158/1940-6207.CAPR-15-0299. Epub 2015 Dec 23.
Human papillomavirus (HPV) is responsible for increasing incidence of oropharyngeal cancer. At present, there are no biomarkers in the surveillance algorithm for HPV-positive oropharyngeal cancer (HPV-OPC). HPV16 E6 antibody precedes oropharyngeal cancer diagnosis. If HPV16 E6 indeed precedes primary diagnosis, it is similarly expected to precede disease recurrence and may have a potential role as a biomarker for surveillance of HPV-OPC. To determine whether HPV antibody titers have a potential role as early markers of disease recurrence or prognosis, a retrospective pilot study was designed to determine whether HPV16 early antibody titers E6, E7, E1, and E2 decrease after treatment of HPV16-positive OPC. Trends in pretreatment, early (≤6 months after treatment), and late posttreatment (>6 months after treatment) HPV16 antibody titers were examined. There were 43, 34, and 52 subjects with serum samples available for pretreatment, early, and late posttreatment intervals. Mean pretreatment antibody levels were higher than posttreatment antibody levels. Average antibody levels decreased significantly over time for E6 (Ptrend = 0.001) and E7 (Ptrend < 0.001). Six disease recurrences were observed during the follow-up period (median, 4.4 years). In univariate analysis, a log-unit increase in pretreatment E6 titer was significantly associated with increased risk of disease recurrence (HR, 5.42; 95% CI, 1.1-25.7; P = 0.03). Therefore, levels of antibodies to HPV16 early oncoproteins decline after therapy. Higher E6 titers at diagnosis are associated with significant increases in the risk of recurrence. These data support the prospective evaluation of HPV16 antibodies as markers of surveillance and for risk stratification at diagnosis.
人乳头瘤病毒（HPV）是导致口咽癌发病率上升的原因。目前，HPV阳性口咽癌（HPV-OPC）的监测算法中没有生物标志物。HPV16 E6抗体先于口咽癌诊断出现。如果HPV16 E6确实先于初次诊断出现，同样预计它会先于疾病复发出现，并且可能作为HPV-OPC监测的生物标志物发挥潜在作用。为了确定HPV抗体滴度是否具有作为疾病复发或预后早期标志物的潜在作用，设计了一项回顾性试点研究，以确定HPV16阳性OPC治疗后HPV16早期抗体滴度E6、E7、E1和E2是否下降。研究了治疗前、早期（治疗后≤6个月）和后期（治疗后>6个月）HPV16抗体滴度的变化趋势。分别有43、34和52名受试者的血清样本可用于治疗前、早期和后期时间段。治疗前抗体平均水平高于治疗后抗体水平。E6（Ptrend = 0.001）和E7（Ptrend < 0.001）的平均抗体水平随时间显著下降。随访期间观察到6例疾病复发（中位数为4.4年）。在单变量分析中，治疗前E6滴度每增加一个对数单位与疾病复发风险显著增加相关（HR，5.42；95%CI，1.1 - 25.7；P = 0.03）。因此，治疗后HPV16早期癌蛋白抗体水平下降。诊断时较高的E6滴度与复发风险显著增加相关。这些数据支持对HPV16抗体作为监测标志物和诊断时风险分层进行前瞻性评估。
