Department of Neurosciences, Regional Center for Head and Neck Cancer, University of Padova, Azienda ULSS 2 Marca Trevigiana, Treviso, Italy.
Molecular Diagnostics of Oncogenic Infections, Infection, Inflammation and Cancer Program, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Head Neck. 2019 Nov;41(11):3833-3841. doi: 10.1002/hed.25915. Epub 2019 Aug 15.
To enforce the evidence for causality between high-risk human papillomavirus (hrHPV) infections and neck squamous cell carcinoma from unknown primary (NSCCUP) and provide biological basis for treatment de-intensification, we searched for TP53 mutations in association with HPV status.
TP53 mutations were searched for by amplification of exons 4 to 10.
Of the 70 NSCCUP, 27 (39%) harbored HPV infection. TP53 sequencing resulted in the identification of 19 patients harboring single mutations including 16 disruptive alterations (84%). The association of TP53 mutations and HPV could be evaluated in 48 NSCCUP including those with disruptive mutation in any exon (n = 16) and those without mutations but with complete sequence of exons 4 to 9 (n = 32): no disruptive mutations were found in the 17 HPV-driven NSCCUP but in 16 of the 31 non-HPV-driven NSCCUP (P = .0002).
In a fraction of cases, NSCCUP is an HPV-driven entity harboring wild-type TP53 gene or nondisruptive TP53 mutations. HPV-driven NSCCUP might benefit from treatment de-intensification.
为了从因果关系上证实高危型人乳头瘤病毒（hrHPV）感染与不明原发部位的颈部鳞状细胞癌（NSCCUP）之间的关系，并为治疗减量化提供生物学依据，我们对 HPV 状态相关的 TP53 突变进行了研究。
通过扩增外显子 4 到 10 来寻找 TP53 突变。
在 70 例 NSCCUP 中，27 例（39%）存在 HPV 感染。TP53 测序鉴定出 19 例患者携带单突变，其中 16 例为破坏性改变（84%）。可对 48 例 NSCCUP 中 TP53 突变与 HPV 的相关性进行评估，包括那些在外显子任何部位均存在破坏性突变的患者（n=16）和那些无突变但外显子 4 到 9 序列完整的患者（n=32）：在 17 例 HPV 驱动的 NSCCUP 中未发现破坏性突变，但在 31 例非 HPV 驱动的 NSCCUP 中发现了 16 例（P=0.0002）。
在一部分病例中，NSCCUP 是一种 HPV 驱动的实体，携带野生型 TP53 基因或非破坏性的 TP53 突变。HPV 驱动的 NSCCUP 可能受益于治疗减量化。
