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利用单细胞外周免疫图谱对子宫颈癌前病变进行微创诊断。

Minimally invasive diagnosis of precancerous cervical lesions using single-cell peripheral immune atlas.

作者信息

Xu Junfen, Ji Qinghua, Kong Quanming, Lv Lijuan, Zhu Bo, Huang Xiufeng, Chen Zhengyun, Xu Ping, Li Xiao, Yin Weiwei, Wang Hui

机构信息

Department of Gynecologic Oncology, Women's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China; Zhejiang Key Laboratory of Precision Diagnosis and Therapy for Major Gynecological Diseases, Women's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China; Cancer Center, Zhejiang University, Hangzhou, Zhejiang, China.

Zhejiang Puluoting Health Technology Co Ltd, Hangzhou, Zhejiang, China.

出版信息

Cell Rep Med. 2025 Jun 17;6(6):102149. doi: 10.1016/j.xcrm.2025.102149. Epub 2025 May 23.

DOI:10.1016/j.xcrm.2025.102149
PMID:40412381
原文链接:
https://pmc.ncbi.nlm.nih.gov/articles/PMC12208321/
Abstract

Cervical cancer remains a major global health concern for women. Current screening methods are either invasive or lead to low participation and over-referral for colposcopy, particularly among high-risk human papillomavirus (HPV)-positive women. This study analyzes 613 participants with varying cervical lesions using mass cytometry by time-of-flight (CyTOF) to identify disease-specific peripheral immune signatures. A diagnostic model based on 23 immune features achieves ∼91% sensitivity and specificity for detecting precancerous and cancerous lesions. A separate model for HPV-positive women shows even higher accuracy (∼93% sensitivity, ∼95% specificity), especially in HPV16/18-positive cases (99% sensitivity, 100% specificity). In an independent validation cohort (n = 105), the model distinguishes cervical intraepithelial neoplasia (CIN) 2+ from ≤CIN1 with 86.5% sensitivity and 85.3% specificity (area under the curve [AUC] = 0.89). These findings support peripheral immune profiling as a minimally invasive and accurate biomarker strategy for early cervical cancer screening, particularly in HPV16/18-positive women.

摘要

宫颈癌仍然是全球女性主要的健康问题。目前的筛查方法要么具有侵入性,要么导致参与度低以及阴道镜检查转诊过多,尤其是在高危人乳头瘤病毒(HPV)阳性女性中。本研究使用飞行时间质谱流式细胞术(CyTOF)分析了613名患有不同宫颈病变的参与者,以识别疾病特异性外周免疫特征。基于23种免疫特征的诊断模型在检测癌前病变和癌性病变时,灵敏度和特异性达到了约91%。针对HPV阳性女性的单独模型显示出更高的准确性(约93%的灵敏度,约95%的特异性),尤其是在HPV16/18阳性病例中(99%的灵敏度,100%的特异性)。在一个独立验证队列(n = 105)中,该模型区分宫颈上皮内瘤变(CIN)2级及以上与CIN1级及以下的灵敏度为86.5%,特异性为85.3%(曲线下面积[AUC] = 0.89)。这些发现支持外周免疫谱分析作为一种微创且准确的生物标志物策略,用于早期宫颈癌筛查,尤其是在HPV16/18阳性女性中。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/08db/12208321/fc23a4608560/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/08db/12208321/8d046de4764c/fx1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/08db/12208321/93438d323e13/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/08db/12208321/57e70bd7ca28/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/08db/12208321/1750d70abddb/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/08db/12208321/e2a4304c3733/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/08db/12208321/293298632dd0/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/08db/12208321/fc23a4608560/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/08db/12208321/8d046de4764c/fx1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/08db/12208321/93438d323e13/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/08db/12208321/57e70bd7ca28/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/08db/12208321/1750d70abddb/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/08db/12208321/e2a4304c3733/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/08db/12208321/293298632dd0/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/08db/12208321/fc23a4608560/gr6.jpg

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本文引用的文献

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Characterization of immune phenotypes in peripheral blood of adult renal transplant recipients using mass cytometry (CyTOF).使用质谱流式细胞术(CyTOF)对成年肾移植受者外周血中的免疫表型进行表征。
Immunohorizons. 2025 Feb 18;9(4). doi: 10.1093/immhor/vlae013.
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Embracing more treatment choices for metastatic, recurrent, or persistent cervical cancer.为转移性、复发性或持续性宫颈癌提供更多治疗选择。
Lancet. 2024 Oct 26;404(10463):1618-1620. doi: 10.1016/S0140-6736(24)02196-2. Epub 2024 Oct 16.
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Causal attribution of human papillomavirus genotypes to invasive cervical cancer worldwide: a systematic analysis of the global literature.
全球范围内人乳头瘤病毒基因型与浸润性宫颈癌的因果关系归因:全球文献的系统分析。
Lancet. 2024 Aug 3;404(10451):435-444. doi: 10.1016/S0140-6736(24)01097-3.
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Cervical Cancer Evades the Host Immune System through the Inhibition of Type I Interferon and CXCL9 by LIF.LIF 通过抑制Ⅰ型干扰素和 CXCL9 来逃避宿主免疫系统对宫颈癌的作用。
Clin Cancer Res. 2024 Oct 1;30(19):4505-4516. doi: 10.1158/1078-0432.CCR-24-0385.
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Neoadjuvant Nivolumab Plus Chemotherapy Followed By Response-Adaptive Therapy for HPV+ Oropharyngeal Cancer: OPTIMA II Phase 2 Open-Label Nonrandomized Controlled Trial.新辅助纳武利尤单抗联合化疗后采用反应适应性疗法治疗人乳头瘤病毒阳性口咽癌:OPTIMA II期2期开放标签非随机对照试验
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Human Papillomavirus and Associated Cancers: A Review.人乳头瘤病毒及相关癌症:综述。
Viruses. 2024 Apr 26;16(5):680. doi: 10.3390/v16050680.
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Cancer Cell. 2024 May 13;42(5):759-779.e12. doi: 10.1016/j.ccell.2024.04.008.
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Human papillomavirus infection: Epidemiology, biology, host interactions, cancer development, prevention, and therapeutics.人乳头瘤病毒感染:流行病学、生物学、宿主相互作用、癌症发展、预防和治疗。
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Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries.2022 年全球癌症统计数据:全球 185 个国家和地区 36 种癌症的发病率和死亡率全球估计数。
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