Götz Carolin, Bischof Clara, Wolff Klaus-Dietrich, Kolk Andreas
Department of Oral and Maxillofacial Surgery, Technical University of Munich, Klinikum Rechts der Isar, D-81675 Munich, Germany.
Mol Clin Oncol. 2019 Jan;10(1):17-28. doi: 10.3892/mco.2018.1749. Epub 2018 Oct 22.
The current controversial discussion on the disease-specific survival of patients with human papillomavirus (HPV)-positive (+) and -negative (-) squamous cell carcinoma (SCC) of the head neck region was the motivation for the present meta-analysis. Different detection methods for HPV are available, though these often lack sensitivity. As a consequence, there may be false interpretation of HPV positivity. A bias concerning HPV status and therefore also survival rates is serving a non-durable relevance in the discussion of tailored therapies. A literature search was performed via the online database PubMed/NCBI, and data extraction and statistical analysis were conducted. A total of 139 studies published between 2004 and 2014 were evaluated in the present meta-analysis. The HPV detection methods, patient characteristics, tumor localizations and stages, as well as (neo-) adjuvant therapies and survival times were analyzed. The average incidence rates of HPV patients with oropharyngeal tumors were higher than those of patients with cancers of other regions of the head and neck. Upon evaluating the results of different detection methods no significant differences were identified. We have compared the HPV incidence rates of each detection method, when studies have used more than one. Regarding overall survival, the pooled adjusted hazard ratio (HR) for oropharyngeal SCC was 0.31 [95% confidence interval (CI)=0.27-0.36]. Unfortunately, only 3 equivalent studies were available on nonoropharyngeal tumors, for which the pooled adjusted HR was 1 (95% CI=0.73-1.36). Overall, the evaluation demonstrated that the survival rates reported in numerous studies were not evaluated multifactorially and important confounders were excluded from the statistics. The HPV detection methods used were often not sufficient in representing HPV positivity. In addition, oropharyngeal and oral SCCs were assessed together in the localization. The widely differing number of HPV patients in each of the various studies may be explained by insufficient detection methods and by a lack of localization distinction. The considerations of a tailored therapy according to HPV status should be rejected based on the present information. The previously published studies should be read critically and do not represent a basis for therapeutic decisions.
目前关于头颈部人乳头瘤病毒（HPV）阳性（+）和阴性（-）鳞状细胞癌（SCC）患者疾病特异性生存的争议性讨论，是进行本次荟萃分析的动机。HPV有多种检测方法，但这些方法往往缺乏敏感性。因此，可能会对HPV阳性产生错误解读。在讨论定制治疗时，HPV状态的偏差以及生存率的偏差都没有持久的相关性。通过在线数据库PubMed/NCBI进行了文献检索，并进行了数据提取和统计分析。本次荟萃分析共评估了2004年至2014年间发表的139项研究。分析了HPV检测方法、患者特征、肿瘤定位和分期，以及（新）辅助治疗和生存时间。口咽肿瘤患者中HPV的平均发病率高于头颈部其他区域癌症患者。在评估不同检测方法的结果时，未发现显著差异。当研究使用一种以上检测方法时，我们比较了每种检测方法的HPV发病率。关于总生存期，口咽SCC的合并调整风险比（HR）为0.31 [95%置信区间（CI）=0.27 - 0.36]。遗憾的是，关于非口咽肿瘤仅有3项等效研究，其合并调整HR为1（95% CI = 0.73 - 1.36）。总体而言，评估表明众多研究报告的生存率未进行多因素评估，重要的混杂因素被排除在统计之外。所使用的HPV检测方法通常不足以代表HPV阳性。此外，在定位方面口咽和口腔SCC被一起评估。各项研究中HPV患者数量差异很大，这可能是由于检测方法不足和缺乏定位区分所致。基于目前的信息，应摒弃根据HPV状态进行定制治疗的考量。此前发表的研究应谨慎解读，不能作为治疗决策的依据。
