Department of Medical Oncology, Institut Gustave Roussy, Villejuif, France.
Department of Medical Oncology, Hotel Dieu de France University Hospital, Faculty of Medicine, Saint Joseph University, Beirut, Lebanon.
Head Neck. 2019 Oct;41(10):3700-3711. doi: 10.1002/hed.25858. Epub 2019 Jul 13.
Human papillomavirus (HPV)-related squamous cell carcinoma of unknown primary (SCCUP) is currently rising in incidence but lacks a validated management approach.
This paper reviews the clinical presentation, diagnosis, and treatment of HPV-related SCCUP.
The Medline/Pubmed database was searched by using the following keywords "CUP", "cancer of unknown primary", "HPV", "human papilloma virus", and "head and neck". The references of the publications of interest were also screened for relevant papers.
The clinical assessment of HPV-related SCCUP includes a complete clinical examination, an endoscopic evaluation with white-light and narrow band imaging, and radiologic assessment using morphologic and metabolic imaging. If the diagnosis remains unconfirmed, endoscopic examination under anesthesia with tonsillectomy ± base of tongue mucosectomy is performed. The therapeutic rationale aims to eradicate the involved lymph nodes and potential primary tumor with a sequence of chemoradiotherapy and neck dissection.
As a general approach, p16-negative SCCUP are truly HPV negative, whereas p16-positive specimens require confirmation with HPV in situ hybridization or polymerase chain reaction to confirm HPV infection. If a cervical metastasis is considered HPV positive, the primary lesion is likely in the oropharynx, and further diagnostic interventions such as tonsillectomy seems to be mandatory. Whether the optimal treatment is neck dissection followed by adjuvant radiotherapy or concomitant chemoradiotherapy (CRT) (in case of extranodal extension or advanced lymph node stages) or definitive CRT followed by neck dissection (in case of positive F-FDG-PET/CT) remains a matter of debate. Solid scientific evidence supporting treatment de-escalation in HPV-related SCCUP is lacking, and the results of ongoing trials are at the brink of reporting.
Currently, the treatment of patients with HPV-related SCCUP should not differ from the standard treatment of other SCCUP patients and is similarly based on the staging of the disease and general condition of the patient.
人乳头瘤病毒（HPV）相关的不明原发部位鳞状细胞癌（SCCUP）的发病率正在上升，但缺乏经过验证的治疗方法。
本文综述了 HPV 相关 SCCUP 的临床表现、诊断和治疗。
通过使用以下关键词在 Medline/Pubmed 数据库中进行搜索：“CUP”、“癌症的不明原发部位”、“HPV”、“人乳头瘤病毒”和“头颈部”。还对感兴趣的出版物的参考文献进行了筛选，以查找相关文献。
HPV 相关 SCCUP 的临床评估包括完整的临床检查、白光和窄带成像的内镜评估以及形态学和代谢成像的影像学评估。如果诊断仍未明确，则进行全身麻醉下的内镜检查，同时行扁桃体切除术和/或舌根黏膜切除术。治疗的基本原理旨在通过序贯放化疗和颈清扫术来根除受累的淋巴结和潜在的原发肿瘤。
作为一般方法，p16 阴性 SCCUP 确实为 HPV 阴性，而 p16 阳性的标本需要通过 HPV 原位杂交或聚合酶链反应进行确认以确定 HPV 感染。如果认为宫颈转移灶为 HPV 阳性，则原发灶可能位于口咽，进一步的诊断干预如扁桃体切除术似乎是必要的。最佳治疗方法是颈清扫术加辅助放疗，还是同期放化疗（如果存在结外侵犯或晚期淋巴结分期），或单纯放化疗加颈清扫术（如果正电子发射断层扫描/计算机体层摄影术（PET/CT）检查结果为阳性），这仍然存在争议。缺乏支持 HPV 相关 SCCUP 治疗降级的坚实科学证据，正在进行的试验结果即将公布。
目前，HPV 相关 SCCUP 患者的治疗不应与其他 SCCUP 患者的标准治疗方法有所不同，同样基于疾病的分期和患者的一般状况。
