Department of Otolaryngology-Head and Neck Surgery, University Hospitals, Cleveland, Ohio, USA.
University Hospitals Seidman Cancer Center, Cleveland, Ohio, USA.
J Immunother Cancer. 2021 Mar;9(3). doi: 10.1136/jitc-2020-001259.
Patients with human papillomavirus (HPV+) head and neck squamous cell carcinoma (HNSCC) have superior prognoses compared with patients with HPV- HNSCC and strategies for treatment de-escalation are under investigation for the HPV+ setting. However, the survival advantage associated with HPV is not universal, and a subset of patients with HPV+ HNSCC fail definitive treatment and progress with metastatic/recurrent disease. Currently, no biomarker is available to distinguish aggressive from indolent HPV+ HNSCC. Immune dysfunction facilitates tumorigenesis and is associated with poor treatment response; therefore, we hypothesized that diminished intratumoral immune cell functionality may be attractive biomarkers to identify patients with HPV+ HNSCC at risk for early disease-specific mortality.
This is a retrospective analysis of The Cancer Genome Atlas (TCGA) HPV+ HNSCC cohort.
Immunoglobulin J polypeptide (IGJ), uniquely expressed in plasma cells, showed a broad expression range in HPV+ HNSCC. Cox regression model, adjusting for clinical covariates, indicated that IGJ is an independent prognostic biomarker for disease-specific survival (DSS) and overall survival (OS). Patients with low IGJ had a 7.2-fold (p<0.001) increase in risk of disease-specific death with a median DSS of 13 months. Low IGJ showed an area under curve (AUC) of 0.89 with 91.0% sensitivity and 87.6% specificity to identify early disease-specific mortality (defined as DSS ≤12 months). Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed a global dampening of immune pathways in low IGJ tumors.
Our work showed that IGJ is a robust and independent prognostic biomarker for disease-specific mortality in HPV+ HNSCC. Patient with HPV+ HNSCC with limited adaptive immune functionality should not be candidates for treatment de-escalation modalities.
与 HPV- HNSCC 患者相比，HPV+头颈部鳞状细胞癌（HNSCC）患者的预后更好，并且正在研究 HPV+ 环境下的治疗降级策略。然而，与 HPV 相关的生存优势并非普遍存在，一部分 HPV+ HNSCC 患者无法接受确定性治疗，并进展为转移性/复发性疾病。目前，尚无生物标志物可区分侵袭性和惰性 HPV+ HNSCC。免疫功能障碍促进肿瘤发生，并与治疗反应差相关；因此，我们假设肿瘤内免疫细胞功能的减弱可能是识别 HPV+ HNSCC 患者发生疾病特异性死亡风险的有吸引力的生物标志物。
这是对癌症基因组图谱（TCGA）HPV+ HNSCC 队列的回顾性分析。
免疫球蛋白 J 多肽（IGJ），仅在浆细胞中表达，在 HPV+ HNSCC 中表现出广泛的表达范围。Cox 回归模型，调整临床协变量后，表明 IGJ 是疾病特异性生存（DSS）和总生存（OS）的独立预后生物标志物。IGJ 低的患者疾病特异性死亡风险增加 7.2 倍（p<0.001），中位 DSS 为 13 个月。IGJ 低值的曲线下面积（AUC）为 0.89，具有 91.0%的敏感性和 87.6%的特异性，可识别早期疾病特异性死亡率（定义为 DSS≤12 个月）。京都基因与基因组百科全书（KEGG）通路分析显示，IGJ 低值肿瘤中免疫通路普遍减弱。
我们的工作表明，IGJ 是 HPV+ HNSCC 患者疾病特异性死亡的稳健且独立的预后生物标志物。适应性免疫功能有限的 HPV+ HNSCC 患者不应成为治疗降级方式的候选者。
