人乳头瘤病毒感染与肺腺癌：免疫检查点抑制剂治疗的患者观察到特殊获益。
Human papillomavirus infection and lung adenocarcinoma: special benefit is observed in patients treated with immune checkpoint inhibitors.
机构信息
Foundation for Clinical and Applied Cancer Research (FICMAC), Bogotá, Colombia; Oncology Department, Clinica Colsanitas, Bogotá, Colombia; Molecular Oncology and Biology Systems Research Group (FOX-G), Universidad el Bosque, Bogotá, Colombia; Clinical and Traslational Oncology Group, Institute of Oncology, Clínica del Country, Bogotá, Colombia.
Foundation for Clinical and Applied Cancer Research (FICMAC), Bogotá, Colombia; Molecular Oncology and Biology Systems Research Group (FOX-G), Universidad el Bosque, Bogotá, Colombia.
出版信息
ESMO Open. 2022 Aug;7(4):100500. doi: 10.1016/j.esmoop.2022.100500. Epub 2022 Jun 23.
BACKGROUND
Human papilloma virus (HPV) has been associated with the development and modulation of response in a series of neoplasms. In the case of lung adenocarcinoma, its role in etiology and pathogenesis is still controversial. Considering that this infection brings foreign epitopes, it could be of prognostic significance in patients with lung adenocarcinoma treated with immunotherapy.
METHODS
In a retrospective cohort study we evaluated the presence of HPV genomic material in lung adenocarcinoma primary lesions with the INNO-LiPA platform. Viral replication was also evaluated by detecting the presence of oncoprotein E6/E7 messenger RNA (mRNA) by quantitative RT-PCR. To confirm possible hypotheses regarding viral oncogenesis, vascular endothelial growth factor (VEGF) and hypoxia-inducible factor 1 (HIF1) were evaluated with stromal fibrosis and immunoscore.
RESULTS
A total of 133 patients were included in the analysis, of whom 34 tested positive for HPV, reaching an estimated prevalence of 25.6% [95% confidence interval (CI) 18.2% to 32.9%]. E6/7 mRNA was identified in 28 out of the 34 previously positive cases (82.3%). In immune checkpoint inhibitor (ICI)-treated patients, the median overall survival reached 22.3 months [95% CI 19.4 months- not reached (NR)] for HPV-negative and was not reached in HPV-positive (HPV+) ones (95% CI 27.7-NR; P = 0.008). With regard to progression-free survival, HPV- patients reached a median of 9.2 months (95% CI 7.9-11.2 months) compared to 14.3 months (95% CI 13.8-16.4 months) when HPV was positive (P = 0.001). The overall response rate for HPV+ patients yielded 82.4% compared to 47.1% in negative ones. No differences regarding programmed death-ligand 1, VEGF, HIF1, stromal fibrosis, or immunoscore were identified.
CONCLUSIONS
In patients with HPV+ lung adenocarcinoma, a significant benefit in overall response and survival outcomes is observed.
背景
人乳头瘤病毒（HPV）与一系列肿瘤的发生和反应调节有关。在肺腺癌的情况下，其在病因学和发病机制中的作用仍存在争议。鉴于这种感染带来了外来表位，它可能对接受免疫治疗的肺腺癌患者的预后有意义。
方法
我们在一项回顾性队列研究中，使用 INNO-LiPA 平台评估了肺腺癌原发灶中 HPV 基因组物质的存在。通过定量 RT-PCR 检测致癌蛋白 E6/E7 信使 RNA（mRNA）的存在，也评估了病毒复制。为了证实关于病毒致癌的可能假说，我们评估了血管内皮生长因子（VEGF）和缺氧诱导因子 1（HIF1）与基质纤维化和免疫评分的关系。
结果
共纳入 133 例患者进行分析，其中 34 例 HPV 检测阳性，估计患病率为 25.6%（95%置信区间 18.2%至 32.9%）。在之前的 34 例阳性病例中，有 28 例检测到 E6/7 mRNA（82.3%）。在接受免疫检查点抑制剂（ICI）治疗的患者中，HPV 阴性患者的中位总生存期达到 22.3 个月（95%CI 19.4 个月-NR），而 HPV 阳性患者则未达到（95%CI 27.7-NR；P=0.008）。关于无进展生存期，HPV-患者达到 9.2 个月（95%CI 7.9-11.2 个月），而 HPV 阳性患者达到 14.3 个月（95%CI 13.8-16.4 个月）（P=0.001）。HPV+患者的总缓解率为 82.4%，而 HPV-患者为 47.1%。在程序性死亡配体 1、VEGF、HIF1、基质纤维化或免疫评分方面未发现差异。
结论
在 HPV+肺腺癌患者中，观察到总反应率和生存结果有显著改善。
Zotero 插件