Background: Despite advances in the management of head and neck squamous cell carcinoma (HNSCC), prognostic models and treatment strategies remain inadequate, particularly for HPV-positive oropharyngeal squamous cell carcinoma (OPSCC). The rising incidence of HPV-positive OPSCC highlights an urgent need for innovative therapeutic approaches. Ferroptosis, a regulated form of non-apoptotic cell death, has gained attention for its role in cancer progression, but its potential as a prognostic and therapeutic target in HPV-positive OPSCC remains largely unexplored. This study investigates the role of ferroptosis in HPV-positive OPSCC, aiming to identify prognostic markers and provide insights into potential therapeutic strategies that could improve patient outcomes. Methods: Thirteen ferroptosis gene expression signatures were retrieved from the literature, and their performance and association to the immune microenvironment were validated on a meta-analysis of 267 HPV-positive cases (Metanalysis-HPV267) and 286 samples from the BD2Decide project (BD2-HPV286). Results: Our analysis revealed that specific ferroptosis-related gene expression signatures, particularly FER3, FER4, FER6, and FER12, are significantly associated (p-value < 0.05) with high-risk patient groups and adverse tumor microenvironment features, including suppressed immune activity and enhanced stromal involvement. Elevated expression of CAV1, a ferroptosis suppressor, further delineates high-risk profiles. Conclusions: These findings highlight the prognostic significance of ferroptosis in stratifying patients and identifying those with poorer clinical outcomes. Targeting ferroptosis pathways represents a novel and promising approach to addressing the unmet need for effective prognostic and therapeutic strategies in HPV-positive OPSCC. Future research should focus on translating these findings into clinical applications to advance precision oncology and improve outcomes for this growing patient population.
背景：尽管头颈部鳞状细胞癌（HNSCC）的治疗管理已取得进展，但预后模型和治疗策略仍显不足，尤其对于人乳头瘤病毒（HPV）阳性口咽鳞状细胞癌（OPSCC）。HPV阳性OPSCC发病率不断上升，凸显了对创新治疗方法的迫切需求。铁死亡作为一种受调控的非凋亡性细胞死亡形式，因其在癌症进展中的作用而受到关注，但其作为HPV阳性OPSCC预后和治疗靶点的潜力在很大程度上尚未被探索。本研究旨在探讨铁死亡在HPV阳性OPSCC中的作用，以识别预后标志物，并为改善患者预后的潜在治疗策略提供见解。 方法：从文献中检索了13个铁死亡基因表达特征，并在包含267例HPV阳性病例的荟萃分析（Metanalysis-HPV267）及来自BD2Decide项目的286个样本（BD2-HPV286）中验证了其性能及其与免疫微环境的关联。 结果：分析显示，特定的铁死亡相关基因表达特征，尤其是FER3、FER4、FER6和FER12，与高风险患者群体及不良肿瘤微环境特征（包括免疫活性抑制和基质浸润增强）显著相关（p值<0.05）。铁死亡抑制因子CAV1的表达升高进一步界定了高风险特征。 结论：这些发现强调了铁死亡在患者分层和识别临床预后较差患者方面的预后意义。靶向铁死亡通路代表了一种新颖且有前景的方法，可应对HPV阳性OPSCC中有效预后和治疗策略的未满足需求。未来研究应侧重于将这些发现转化为临床应用，以推进精准肿瘤学并改善这一不断增长的患者群体的预后。
肿瘤(癌症)患者之家