Schroeder Lea, Boscolo-Rizzo Paolo, Dal Cin Elisa, Romeo Salvatore, Baboci Lorena, Dyckhoff Gerhard, Hess Jochen, Lucena-Porcel Carlota, Byl Anne, Becker Nikolaus, Alemany Laia, Castellsagué Xavier, Quer Miquel, León Xavier, Wiesenfarth Manuel, Pawlita Michael, Holzinger Dana
Division of Molecular Diagnostics of Oncogenic Infections, Infection, Inflammation and Cancer Program, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 242, 69120 Heidelberg, Germany.
Department of Neurosciences, ENT Clinic and Regional Center for Head and Neck Cancer, University of Padua, School of Medicine, Treviso Regional Hospital, Piazza Ospedale 1, 31100 Treviso, Italy.
Eur J Cancer. 2017 Mar;74:73-81. doi: 10.1016/j.ejca.2016.12.020. Epub 2017 Feb 10.
Patients with neck squamous cell carcinomas of unknown primary tumour (NSCCUP) present with lymph node metastasis without evidence for a primary tumour. Most patients undergo an aggressive multimodal treatment, which induces severe, potentially unnecessary toxicity. Primary tumours of NSCCUP can be hidden in the oropharynx. Human papillomavirus (HPV) is causally involved in a subgroup of oropharyngeal squamous cell carcinomas (OPSCC) associated with early lymph node metastasis and good prognosis. Detection of markers for HPV transformation in NSCCUP could allow focussing on the oropharynx in primary tumour search and could be of value for choice and extent of treatment. In a retrospective multicentre study (Germany, Italy and Spain), we analysed metastatic lymph nodes from 180 NSCCUP patients for the presence of HPV DNA, HPV E6*I mRNA and cellular p16 overexpression, a surrogate marker for HPV-induced transformation. HPV status, defined as positivity for viral mRNA with at least one additional marker, was correlated with clinical parameters and survival outcome. A substantial proportion (16%) of NSCCUP were HPV-driven, mainly by HPV16 (89%). HPV prevalence increased with year of diagnosis from 9% during 1998-2004 to 23% during 2005-2014 (p = 0.007). HPV-driven NSCCUP had significantly better overall and progression-free survival rates (p ≤ 0.008). Based on this survival benefit, it is contended that HPV RNA status should be included in NSCCUP diagnosis and in therapeutic decision-making. Deintensification of radiation in patients with HPV-driven NSCCUP, while concurrently concentrating on the oropharynx appears to be a promising therapeutic strategy, the efficacy of which should be assessed in prospective trials. To our knowledge, this is the largest study on HPV in NSCCUP.
不明原发肿瘤的颈部鳞状细胞癌（NSCCUP）患者表现为淋巴结转移但无原发肿瘤证据。大多数患者接受积极的多模式治疗，这会引发严重的、可能不必要的毒性。NSCCUP的原发肿瘤可能隐匿于口咽。人乳头瘤病毒（HPV）与口咽鳞状细胞癌（OPSCC）的一个亚组存在因果关系，该亚组与早期淋巴结转移及良好预后相关。检测NSCCUP中HPV转化标志物可使原发肿瘤搜索聚焦于口咽，且对治疗选择和范围具有价值。在一项回顾性多中心研究（德国、意大利和西班牙）中，我们分析了180例NSCCUP患者转移淋巴结中HPV DNA、HPV E6*I mRNA的存在情况以及细胞p16过表达（HPV诱导转化的替代标志物）。HPV状态定义为病毒mRNA阳性且至少有一项其他标志物阳性，将其与临床参数及生存结果进行关联分析。相当一部分（16%）NSCCUP由HPV驱动，主要是HPV16（89%）。HPV患病率随诊断年份增加，从1998 - 2004年期间的9%增至2005 - 2014年期间的23%（p = 0.007）。HPV驱动的NSCCUP总体生存率和无进展生存率显著更高（p≤0.008）。基于这种生存获益，有人认为HPV RNA状态应纳入NSCCUP诊断及治疗决策。对于HPV驱动的NSCCUP患者，在集中关注口咽的同时减少放疗强度似乎是一种有前景的治疗策略，其疗效应在前瞻性试验中评估。据我们所知，这是关于NSCCUP中HPV的最大规模研究。
