Department of Otorhinolaryngology, Head and Neck Surgery, Justus-Liebig University Giessen, 35392 Giessen, Germany.
Department of Otorhinolaryngology, Head and Neck Surgery, Justus-Liebig University Giessen, 35392 Giessen, Germany.
Oral Oncol. 2019 Jun;93:59-65. doi: 10.1016/j.oraloncology.2019.04.013. Epub 2019 Apr 28.
Despite improved survival rates of patients with HPV-associated OPSCC, a subset has distant metastasis or develops local recurrence during follow-up. To investigate potential underlying genetic alterations, we analyzed patients with HPV-driven OPSCC who suffered from recurrence in comparison to matching pairs with successful tumor control.
We performed chromosomal copy number analyses and targeted next generation sequencing using a custom panel comprising genes that are frequently mutated in HPV-associated OPSCC.
Specific differences regarding chromosomal aberrations were not observed between both groups. In HPV-driven OPSCC from patients with recurrence we found higher mutation rates compared to patients with successful tumor control. Especially mutation rates of HRAS (p ≤ 0.05) PIK3R1, STK11 and TP63 (p ≤ 0.1 each) were statistically significant or trending towards significance. The respective genes can be linked to transcription factors and signaling pathways involved in cell cycle regulation, proliferation and survival. Additionally, combinations of alterations were observed on chromosomes 16 and 19, which might also influence outcome.
Patients with HPV-driven OPSCC who develop recurrence or have metastasis may be defined by genetic alterations that might be responsible for poor outcome after standard therapy. This might be of importance for stratification in future de-escalation and targeted therapy.
尽管 HPV 相关口咽鳞状细胞癌（OPSCC）患者的生存率有所提高，但仍有一部分患者在随访期间发生远处转移或局部复发。为了研究潜在的遗传改变，我们分析了 HPV 驱动的 OPSCC 患者中发生复发的患者与具有成功肿瘤控制的匹配患者的复发情况。
我们使用包含 HPV 相关 OPSCC 中常发生突变的基因的定制面板进行了染色体拷贝数分析和靶向下一代测序。
两组之间未观察到染色体异常的特定差异。在 HPV 驱动的 OPSCC 中，复发患者的突变率高于成功肿瘤控制的患者。特别是 HRAS（p≤0.05）、PIK3R1、STK11 和 TP63（p≤0.1 每个）的突变率具有统计学意义或有趋势意义。这些基因与参与细胞周期调控、增殖和存活的转录因子和信号通路有关。此外，还观察到染色体 16 和 19 上的改变组合，这也可能影响结果。
发生复发或转移的 HPV 驱动的 OPSCC 患者可能存在遗传改变，这些改变可能是标准治疗后预后不良的原因。这对于未来的降阶梯和靶向治疗分层可能很重要。
