Department of Otorhinolaryngology, Head and Neck Surgery and Audiology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
Clin Otolaryngol. 2018 Oct;43(5):1242-1249. doi: 10.1111/coa.13136. Epub 2018 Jun 7.
The incidence of human papillomavirus-induced (HPV+) head and neck squamous cell carcinoma (HNSCC), that is, especially oropharyngeal cancers (OPSCC), is increasing, and a significant proportion of patients encounter disease progression. A simple and sensitive test to identify patients with progression is an unmet need.
To systematically review the literature and carry out a meta-analysis of studies, investigating circulating HPV-DNA as a biomarker for disease progression in patients with HNSCC.
A systematic review and meta-analysis.
PubMed, EMBASE and the Cochrane Library were systematically searched for articles published in English from January 1980 to November 2017. Search terms used were related to HPV, cancer sites, blood-based biomarkers and terms for specific use settings.
Articles reviewed and selected by authors and data on study design, demographic variables, location, HPV status, number of pre-treatment blood tests, number of post-treatment blood tests, blood HPV status and number of recurrences and length of follow-up were extracted. A meta-analysis of HPV-DNA as a diagnostic test for recurrence by means of a hierarchical summary receiver operating curve (HSROC) model was performed.
We identified 5 studies (n = 600 subjects) examining circulating HPV-DNA in patients with HNSCC. In these 5 studies (n = 411), patients had both pre- and post-treatment blood samples. The pooled sensitivity, in detecting a recurrence, was estimated to be 54% (95% CI: 32%-74%), while the pooled specificity was 98% (95% CI: 93%-99.4%). The pooled false-positive rate is 2% (95% CI: 0.6%-7%). The area under the curve (AUC) of the summary HSROC was 0.93. Positive predictive value was estimated to 93% and the negative predictive value to 94%.
Plasma HPV-DNA is a promising tool for surveillance in patients with HPV-related HNSCC, that is, OPSCC, and has a high specificity. By recent technical advances and by increasing follow-up blood samples, the sensitivity could likely be improved.
人乳头瘤病毒（HPV）诱导的（HPV+）头颈部鳞状细胞癌（HNSCC）的发病率正在上升，尤其是口咽癌（OPSCC），而且相当一部分患者会出现疾病进展。因此，需要一种简单而敏感的方法来识别进展的患者。
系统地回顾文献，并对研究进行荟萃分析，以探讨循环 HPV-DNA 作为 HNSCC 患者疾病进展的生物标志物。
系统评价和荟萃分析。
系统地检索了 1980 年 1 月至 2017 年 11 月期间发表的英文文献，使用的检索词与 HPV、癌症部位、基于血液的生物标志物以及特定用途设置的术语有关。
作者对文章进行了审查和选择，并提取了研究设计、人口统计学变量、位置、HPV 状态、治疗前血液检测次数、治疗后血液检测次数、血液 HPV 状态、复发次数和随访时间等数据。通过分层汇总受试者工作特征曲线（HSROC）模型对 HPV-DNA 作为复发的诊断试验进行了荟萃分析。
我们共确定了 5 项研究（n=600 例患者），均涉及 HNSCC 患者的循环 HPV-DNA。在这 5 项研究（n=411 例患者）中，所有患者均有治疗前后的血液样本。检测复发时的汇总敏感性估计为 54%（95%CI：32%-74%），而汇总特异性为 98%（95%CI：93%-99.4%）。汇总假阳性率为 2%（95%CI：0.6%-7%）。总结性 HSROC 的曲线下面积（AUC）为 0.93。阳性预测值估计为 93%，阴性预测值为 94%。
血浆 HPV-DNA 是监测 HPV 相关 HNSCC（即 OPSCC）患者的一种很有前途的工具，其特异性很高。通过最近的技术进步和增加随访的血液样本，敏感性可能会提高。
