肿瘤细胞治疗研究
英文原题：HPV viral load predicts immune exhaustion and prognosis in cervical neoplasia.
HPV viral load predicts immune exhaustion and prognosis in cervical neoplasia.
高HPV病毒载量是宫颈癌不良预后的独立预测因素，与免疫抑制性肿瘤微环境和增殖活性增强相关。将病毒载量纳入常规评估可能改善风险分层并指导个体化治疗策略，特别是对于可能从免疫增强治疗中获益的高病毒载量患者。
高危型人乳头瘤病毒（HPV）持续感染是宫颈癌的主要病因；然而，HPV病毒载量的预后作用及其与肿瘤免疫微环境的关联仍不完全清楚。本研究旨在系统评估宫颈癌患者中HPV病毒载量与疾病进展、预后及肿瘤免疫微环境的关联。
对278例宫颈肿瘤患者的回顾性队列进行了分析。对HPV病毒载量进行了定量并作log10转换。采用分段回归将患者分为低病毒载量组和高病毒载量组。比较了临床特征、复发、转移和生存情况。评估了免疫参数（CD3+、CD4+、CD8+、FOXP3+ T细胞、程序性死亡配体1 [PD-L1]表达）、血清肿瘤标志物（鳞状细胞癌抗原[SCC]、癌抗原125 [CA125]、CA199、癌胚抗原[CEA]）、Ki67、p16及性激素水平。
高HPV病毒载量（log 10 ≥5.6）与晚期疾病分期（p < 0.001）、淋巴结转移（28.3% vs. 13.5%，p = 0.002）和更高的复发率（27.4% vs. 13.0%，p = 0.002）显著相关。高病毒载量组的五年总生存（OS）（68.5% vs. 87.3%）和无复发生存（RFS）（59.3% vs. 82.1%）显示出预后更差的趋势，但差异无统计学意义（log-rank p = 0.38 和 p = 0.068）。多因素Cox分析证实高病毒载量是复发的独立预测因子（风险比[HR] 2.18，95%置信区间[CI] 1.32-3.61，p = 0.002）。高病毒载量与TIL（肿瘤浸润淋巴细胞）（TILs）减少相关（CD3 +：12.1% vs. 18.3%，p = 0.001）、PD-L1阳性率降低（36.4% vs. 63.2%，p = 0.045）以及Ki67表达升高（58.3% vs. 42.5%，p = 0.003）。将病毒载量与血清SCC联合可改善对高级别病变（曲线下面积[AUC] 0.78 vs. 0.73，p = 0.02）和复发（C指数0.71 vs. 0.65）的预测。机器学习模型将病毒载量列为最重要的预测因子。治疗后病毒载量下降与较低的复发风险显著相关（下降缓慢的比值比[OR] 4.12，p = 0.02）。在绝经前女性中，雌二醇水平与病毒载量（ρ = 0.31，p = 0.003）和疾病严重程度呈正相关。相关性网络揭示了一个将高病毒载量、低免疫浸润和高增殖联系在一起的聚类。病毒载量的预后效应在不同HPV型别中一致，且在晚期患者中更为明显（交互作用p = 0.09）。
OBJECTIVE: Persistent infection with high-risk human papillomavirus (HPV) is the primary cause of cervical cancer; however, the prognostic role of HPV viral load and its association with the tumor immune microenvironment remain incompletely understood. This study aimed to systematically evaluate the association between HPV viral load and disease progression, prognosis, and tumor immune microenvironment in patients with cervical cancer. METHODS: A retrospective cohort of 278 patients with cervical neoplasia was analyzed. HPV viral load was quantified and log 10 -transformed. Patients were categorized into low- and high-viral load groups using segmented regression. Clinical characteristics, recurrence, metastasis, and survival were compared. Immune parameters (CD3 + , CD4 + , CD8 + , FOXP3 + T cells, programmed death-ligand 1 [PD-L1] expression), serum tumor markers (squamous cell carcinoma antigen [SCC], cancer antigen 125 [CA125], CA199, carcinoembryonic antigen [CEA]), Ki67, p16, and sex hormone levels were assessed. RESULTS: High HPV viral load (log 10 ≥5.6) was significantly associated with advanced disease stage (p < 0.001), lymph node metastasis (28.3% vs. 13.5%, p = 0.002), and higher recurrence rates (27.4% vs. 13.0%, p = 0.002). Five-year overall survival (OS) (68.5% vs. 87.3%) and recurrence-free survival (RFS) (59.3% vs. 82.1%) showed a trend toward worse outcomes in the high viral load group, but the differences were not statistically significant (log-rank p = 0.38 and p = 0.068, respectively). Multivariable Cox analysis confirmed high viral load as an independent predictor of recurrence (hazard ratio [HR] 2.18, 95% confidence interval [CI] 1.32-3.61, p = 0.002). High viral load correlated with reduced tumor-infiltrating lymphocytes (TILs) (CD3 + : 12.1% vs. 18.3%, p = 0.001), lower PD-L1 positivity (36.4% vs. 63.2%, p = 0.045), and higher Ki67 expression (58.3% vs. 42.5%, p = 0.003). Combining viral load with serum SCC improved prediction of high-grade lesions (area under the curve [AUC] 0.78 vs. 0.73, p = 0.02) and recurrence (C-index 0.71 vs. 0.65). Machine learning models ranked viral load as the top predictor. Post-treatment viral load decline was significantly associated with lower recurrence risk (odds ratio [OR] 4.12 for slow decline, p = 0.02). In premenopausal women, estradiol levels correlated positively with viral load (ρ = 0.31, p = 0.003) and disease severity. A correlation network revealed a cluster linking high viral load, low immune infiltration, and high proliferation. The prognostic effect of viral load was consistent across HPV types and was more pronounced in advanced-stage patients (interaction p = 0.09). CONCLUSION: High HPV viral load is an independent predictor of poor prognosis in cervical cancer, associated with an immunosuppressive tumor microenvironment and enhanced proliferative activity. Incorporating viral load into routine assessment may improve risk stratification and guide personalized treatment strategies, particularly for patients with high viral load who may benefit from immune-enhancing therapies.
MEMBER ACCOUNT
登录成功会直接打开下一页。
