鼻咽癌诊疗变革:生物标志物与鼻内镜手术协同推进早期治疗发展

doi:10.6040/j.issn.1673-3770.0.2024.542

摘要/Abstract

摘要： 鼻咽癌(nasopharyngeal carcinoma, NPC)的诊疗已进入“精准筛查-微创干预-功能保全”的新阶段。在筛查领域,EB病毒(epstein-barr virus, EBV)标志物检测技术通过CRISPR关联蛋白12a(CRISPR-associated protein 12a, CRISPR-Cas12a)无扩增检测、P85抗体及T细胞受体(T cell receptor, TCR)测序实现突破,敏感性与特异性分别达97.9%和99.3%,并可提前6~12个月预警疾病;microRNA多标志物联合检测与窄带成像(narrow band imaging, NBI)/高清染色内镜(I-scan virtual chromoendoscopy, I-scan)的协同应用,推动筛查从单一指标向多模态整合转型。治疗领域,内镜鼻咽切除术(endoscopic nasopharyngectomy, ENPG)凭借精准切除(切缘阴性率≥90%)与功能保留优势,使早期患者5年生存率达92.1%,生活质量显著优于传统放疗。然而,肿瘤异质性、基层技术普及不足及ENPG适应症局限仍是核心挑战。未来需聚焦多组学AI模型构建、手术-免疫协同策略(如PD-1抑制剂新辅助治疗)、便携设备研发及多中心循证研究,以突破筛查敏感性与治疗普惠性瓶颈。通过跨学科协作,NPC诊疗正从经验医学迈向精准医学,有望实现“早诊率>80%、功能保全率>90%”的防治目标。

关键词: 鼻咽癌, EB病毒, 内镜鼻咽切除术

Abstract: The diagnosis and treatment of nasopharyngeal carcinoma has entered a new era characterized by “precision screening, minimally invasive intervention, and preservation of function”. In the screening arena, breakthroughs in Epstein-Barr virus biomarker detection technologies-including CRISPR-associated protein 12a amplification-free assays, P85 antibody testing, and T-cell receptor sequencing-have achieved sensitivity and specificity of 97.9% and 99.3%, respectively, enabling disease prediction 6-12 months before clinical diagnosis. The synergistic application of multi-microRNA panels with narrow-band imaging(NBI)and I-scan virtual chromoendoscopy has shifted screening paradigms from single-marker approaches to multimodal integration.In therapeutics, endoscopic nasopharyngectomy(ENPG)demonstrates superior precision(negative margin rate ≥90%)and functional preservation, achieving a 5-year survival rate of 92.1% in early stage patients while significantly improving quality of life compared to conventional radiotherapy. However, challenges remain, including tumor heterogeneity, limited accessibility of advanced technologies in primary care settings, and restrictive eligibility criteria for ENPG. Future efforts should focus on:(1)multi-omics AI-driven risk stratification models;(2)synergy between surgery and immunotherapy(e.g., neoadjuvant PD-1 inhibitors);(3)portable diagnostic tools;(4)multicenter trials to validate long-term outcomes. Through interdisciplinary collaboration, the management of NPC is moving from empirical to precision medicine with the goal of achieving “early detection rates >80% and functional preservation rates >90%” and ultimately overcoming the global burden of this regionally prevalent malignancy.

Key words: Nasopharyngeal carcinoma, Epstein-Barr virus, Endoscopic nasopharyngectomy

中图分类号:

R739.6

覃德波,薛建成,杨文月,胡兵,陈涛,俞艳萍,孟庆国,孙焕吉,苗北平,卢永田. 鼻咽癌诊疗变革:生物标志物与鼻内镜手术协同推进早期治疗发展[J]. 山东大学耳鼻喉眼学报, 2025, 39(4): 85-92.

QIN Debo, XUE Jiancheng, YANG Wenyue, HU Bing, CHEN Tao, YU Yanping, MENG Qingguo, SUN Huanji, MIAO Beiping, LU Yongtian. Changing the diagnosis and treatment of nasopharyngeal cancer: biomarkers and nasal endoscopic surgery synergise to advance early treatment development[J]. Journal of Otolaryngology and Ophthalmology of Shandong University, 2025, 39(4): 85-92.

参考文献 45

[1]	杜云, 张超, 冯瑞梅, 等. 鼻咽癌的流行病学进展[J]. 广西医科大学学报, 2024, 41(9): 1237-1246. doi:10.16190/j.cnki.45-1211/r.2024.09.002 DU Yun, ZHANG Chao, FENG Ruimei, et al. Advances in epidemiology of nasopharyngeal carcinoma[J]. J Guangxi Med Univ, 2024, 41(9): 1237-1246. doi:10.16190/j.cnki.45-1211/r.2024.09.002
[2]	Jiang C, Chen JN, Xie SH, et al. Evaluation of circulating EBV microRNA BART2-5p in facilitating early detection and screening of nasopharyngeal carcinoma[J]. Int J Cancer, 2018, 143(12): 3209-3217. doi:10.1002/ijc.31642
[3]	Li Y, Wang K, Yin SK, et al. Expression of Epstein-Barr virus antibodies EA-IgG, Rta-IgG, and VCA-IgA in nasopharyngeal carcinoma and their use in a combined diagnostic assay[J]. Genet Mol Res, 2016, 15(1): GMRvol.15, 110.4238/gmr.15017368.18Mar.2016,. doi:10.4238/gmr.15017368
[4]	Zhang SS, Zhou Y, Liu ZH, et al. Immunosequencing identifies signatures of T cell responses for early detection of nasopharyngeal carcinoma[J]. Cancer Cell, 2025: S1535-6108(25)00168-0. doi:10.1016/j.ccell.2025.04.009
[5]	张改霞, 谢希翔, 何婉怡. 内镜NBI技术应用于鼻咽癌早期诊治中的价值[J]. 中国医疗器械信息, 2021, 27(16): 159-160. doi:10.15971/j.cnki.cmdi.2021.16.077 ZHANG Gaixia, XIE Xixiang, HE Wanyi. The value of endoscopic narrow band imaging in early diagnosis and treatment of nasopharyngeal carcinoma[J]. China Medical Device Information, 2021, 27(16): 159-160. doi:10.15971/j.cnki.cmdi.2021.16.077
[6]	倪凌达, 唐旭兰, 孟丽丽, 等. 电子鼻咽喉镜中I-scan各模式与白光模式的应用比较[J]. 山东大学耳鼻喉眼学报, 2025, 39(3): 19-25. doi:10.6040/j.issn.1673-3770.2023.515 NI Lingda, TANG Xulan, MENG Lili, et al. Comparison of different modes of I-scan and WL in the application of electronic nasopharyngoscope[J]. Journal of Otolaryngology and Ophthalmology of Shandong University, 2025, 39(3): 19-25. doi:10.6040/j.issn.1673-3770.2023.515
[7]	Liu YP, Lv X, Zou X, et al. Minimally invasive surgery alone compared with intensity-modulated radiotherapy for primary stage I nasopharyngeal carcinoma[J]. Cancer Commun, 2019, 39(1): 75. doi:10.1186/s40880-019-0415-3
[8]	宋鹏, 田丽娟. 下一代测序伴随诊断与抗肿瘤药物同步开发研究进展[J]. 中国新药杂志, 2023, 32(13): 1345-1350. doi:10.3969/j.issn.1003-3734.2023.13.009 SONG Peng, TIAN Lijuan. Research progress in the co-development of next-generation sequencing companion diagnosis and antitumor drugs[J]. Chinese Journal of New Drugs, 2023, 32(13): 1345-1350. doi:10.3969/j.issn.1003-3734.2023.13.009
[9]	Jacky Lam WK, Jiang PY, Allen Chan KC, et al. Sequencing-based counting and size profiling of plasma Epstein-Barr virus DNA enhance population screening of nasopharyngeal carcinoma[J]. Proc Natl Acad Sci USA, 2018, 115(22): E5115-E5124. doi:10.1073/pnas.1804184115
[10]	Wu XL, Tay JK, Goh CK, et al. Digital CRISPR-based method for the rapid detection and absolute quantification of nucleic acids[J]. Biomaterials, 2021, 274: 120876. doi:10.1016/j.biomaterials.2021.120876
[11]	Jiang CT, Zheng XH, Lin L, et al. CRISPR Cas12a-mediated amplification-free digital DNA assay improves the diagnosis and surveillance of Nasopharyngeal carcinoma[J]. Biosens Bioelectron, 2023, 237: 115546. doi:10.1016/j.bios.2023.115546
[12]	Pan YX, Huang Q, Xing S, et al. A novel serum protein biomarker for the late-stage diagnosis of nasopharyngeal carcinoma[J]. BMC Cancer, 2025, 25(1): 585. doi:10.1186/s12885-025-13958-8
[13]	Tan R, Phua SKA, Soong YL, et al. Clinical utility of Epstein-Barr virus DNA and other liquid biopsy markers in nasopharyngeal carcinoma[J]. Cancer Commun, 2020, 40(11): 564-585. doi:10.1002/cac2.12100
[14]	Li TD, Li FG, Guo XY, et al. Anti-Epstein-Barr virus BNLF2b for mass screening for nasopharyngeal cancer[J]. N Engl J Med, 2023, 389(9): 808-819. doi:10.1056/nejmoa2301496
[15]	李珂. P85-Ab鼻咽癌诊断试剂盒获批上市[N]. 福建日报, 2024-11-04(005)
[16]	李诗华, 周慧, 姚俊. miRNA在鼻咽癌中的研究进展[J]. 国际医药卫生导报, 2022, 28(8): 1168-1171. doi:10.3760/cma.j.issn.1007-1245.2022.08.032 LI Shihua, ZHOU Hui, YAO Jun. Research progress of miRNA in nasopharyngeal carcinoma[J]. Int J Med Health Guide, 2022, 28(8): 1168-1171. doi:10.3760/cma.j.issn.1007-1245.2022.08.032
[17]	李中华. 血清miR-93联合EB病毒相关免疫球蛋白对鼻咽癌患者调强放疗预后评估价值[J]. 临床军医杂志, 2019, 47(3): 308-310. doi:10.16680/j.1671-3826.2019.03.31
[18]	柳帅, 王振鹏, 张治文, 等. 血清CYFRA21-1、TSGF及miR-93检测在鼻咽癌早期诊断中的应用[J]. 分子诊断与治疗杂志, 2022, 14(4): 623-626. doi10.19930j.cnki.jmdt.2022.04.022 LIU Shuai, WANG Zhenpeng, ZHANG Zhiwen, et al. Application of serum CYFRA21-1, TSGF, and miR-93 detection in early diagnosis of nasopharyngeal carcinoma[J]. J Mol Diagn Ther, 2022, 14(4): 623-626. doi:10.19930/j.cnki.jmdt.2022.04.022
[19]	李伟利, 周烈伟. CYFRA21-1、Granulysin、miR-17-5p和miR-20a联合对早期鼻咽癌的诊断价值[J]. 解剖学研究, 2019, 41(4): 274-277, 281. doi:10.20021/j.cnki.1671-0770.2019.04.008 LI Weili, ZHOU Liewei. Diagnostic value of CYFRA21-1, Granulysin, miR-17-5p and miR-20a in early nasopharyngeal carcinoma[J]. Anatomy Research, 2019, 41(4): 274-277, 281. doi:10.20021/j.cnki.1671-0770.2019.04.008
[20]	陈琦, 崔哲卿, 黄维平. 血清中miR-140-3p、miR-192-5p、miR-223-3p联合检测对早期鼻咽癌的诊断价值[J]. 实用癌症杂志, 2023, 38(6): 917-921. doi:10.3969/j.issn.1001-5930.2023.06.013 CHEN Qi, CUI Zheqing, HUANG Weiping. Combined Value of miR-140-3p, miR-192-5p and miR-223-3p in Serum in the Diagnosis of Early Nasopharyngeal Carcinoma[J]. The Practical Journal of Cancer, 2023, 38(6): 917-921. doi:10.3969/j.issn.1001-5930.2023.06.013
[21]	魏晓, 陈鹏, 张艳. miR-10b、LMP1和Twist1联合检测在鼻咽癌早期诊断及复发诊断中的应用[J]. 分子诊断与治疗杂志, 2021, 13(9): 1537-1540. doi:10.19930/j.cnki.jmdt.2021.09.039 WEI Xiao, CHEN Peng, ZHANG Yan. Application of combined detection of miR-10b, LMP1, and Twist1 in early diagnosis and recurrence monitoring of nasopharyngeal carcinoma[J]. J Mol Diagn Ther, 2021, 13(9): 1537-1540. doi:10.19930/j.cnki.jmdt.2021.09.039
[22]	王皓颖, 赵一电, 梁垲, 等. HLA-F及miR-93在鼻咽癌中的表达及其对调强放疗预后评估的价值[J]. 右江医学, 2022, 50(1): 18-23 WANG Haoying, ZHAO Yidian, LIANG Kai, et al. Expression of HLA-F and miR-93 in nasopharyngeal carcinoma and their prognostic value for intensity-modulated radiotherapy[J]. Youjiang Med J, 2022, 50(1): 18-23. doi:10.3760/j.issn.1000-8030.2022.01.005
[23]	杨芝芝, 杨兵, 田彬, 等. 高通量互作蛋白组图谱研究揭示U6 snRNA在肿瘤细胞中多维度调控mRNA加工成熟过程[J]. 岭南现代临床外科, 2022, 22(1): 42-50. doi:10.3969/j.issn.1009-976X.2022.01.007 YANG Zhizhi, YANG Bing, TIAN Bin, et al. High-throughput interaction proteome mapping revealed that U6 snRNA multi-dimensionally regulates mRNA processing and maturation in tumor cells[J]. Lingnan Modern Clinics in Surgery, 2022, 22(1): 42-50. doi:10.3969/j.issn.1009-976X.2022.01.007
[24]	范一博, 张玉婷, 刘晓博. 局部晚期鼻咽癌患者血清外泌体miR-205表达与诱导化疗敏感性的临床研究[J]. 临床肿瘤学杂志, 2021, 26(2): 122-127 FAN Yibo, ZHANG Yuting, LIU Xiaobo. Clinical study of miR-205 expression in serum exosomes and induction of chemotherapy sensitivity in patients with locally advanced nasopharyngeal carcinoma[J]. Chinese Clinical Oncology, 2021, 26(2): 122-127
[25]	金雪玲, 黄小燕. 窄带成像早期诊断鼻咽癌的价值[J]. 实用临床医学, 2024, 25(4): 33-35+140. doi:10.13764/j.cnki.lcsy.2024.04.009 JIN Xueling, HUANG Xiaoyan. Value of narrow-band imaging in early diagnosis of nasopharyngeal carcinoma[J]. J Pract Clin Med, 2024, 25(4): 33-35+140. doi:10.13764/j.cnki.lcsy.2024.04.009
[26]	杨涌, 瞿申红, 袁弘, 等. 窄带成像技术在鼻咽癌放疗后复查中的诊断要点及效能分析[J]. 微创医学, 2022, 17(4): 513-517. doi:10.11864/j.issn.1673.2022.04.29 YANG Yong, QU Shenhong, YUAN Hong, et al. Diagnostic key points and efficacy analysis of narrow-band imaging in post-radiotherapy follow-up of nasopharyngeal carcinoma[J]. J Minim Invasive Med, 2022, 17(4): 513-517. doi:10.11864/j.issn.1673.2022.04.29
[27]	尚辉辉, 焦莉, 宋文先, 等. i-Scan染色对非糜烂性胃食管反流病诊断研究[J]. 临床军医杂志, 2017, 45(9): 968-970. doi:10.16680/j.1671-3826.2017.09.27
[28]	练键勤, 凌威, 赵以谦. 高清染色内镜(i-scan)技术在鼻咽癌早期诊断中的价值分析[J]. 当代医学, 2020, 26(12): 163-164. doi:10.3969/j.issn.1009-4393.2020.12.071 LIAN Jianqin, LING Wei, ZHAO Yiqian. Value of high-resolution stained endoscopic(i-scan)technique in early diagnosis of nasopharyngeal carcinoma[J]. Contemporary Medicine, 2020, 26(12): 163-164. doi:10.3969/j.issn.1009-4393.2020.12.071
[29]	吴双, 郎锦义, 李志琳, 等. 复发性鼻咽癌再次放疗182例临床分析[J]. 四川医学, 2000, 21(3): 199-201. doi:10.16252/j.cnki.issn1004-0501-2000.03.006 WU Shuang, LANG Jinyi, LI Zhilin, et al. Re-irradiation of recurrent nasopharyngeal carcinoma[J]. Sichuan Medical Journal, 2000, 21(3): 199-201. doi:10.16252/j.cnki.issn1004-0501-2000.03.006
[30]	司勇锋, 王培中, 陈世强, 等. 手术在早期鼻咽癌综合治疗中的作用研究[J]. 中国肿瘤临床, 2005, 32(3): 158-161. doi:10.3969/j.issn.1000-8179.2005.03.011 SI Yongfeng, WANG Peizhong, CHEN Shiqiang, et al. The study on the role of operation for synthetical therapy of the early nasopharyngeal carcinoma[J]. Chinese Journal of Clinical Oncology, 2005, 32(3): 158-161. doi:10.3969/j.issn.1000-8179.2005.03.011
[31]	King WW, Ku PK, Mok CO, et al. Nasopharyngectomy in the treatment of recurrent nasopharyngeal carcinoma: a twelve-year experience[J]. Head Neck, 2000, 22(3): 215-222. doi:10.1002/(sici)1097-0347(200005)22: 3<215: aid-hed2>3.0.co;2-b
[32]	邱前辉, 李娜, 张秋航, 等. 内镜手术治疗首诊局部晚期鼻咽癌的疗效分析[J]. 中华耳鼻咽喉头颈外科杂志, 2017, 52(5): 365-371. doi:10.3760/cma.j.issn.1673-0860.2017.05.009 QIU Qianhui, LI Na, ZHANG Qiuhang, et al. Clinical efficacy of endoscopic nasopharyngectomy for initially diagnosed advanced nasopharyngeal carcinoma[J]. Chinese Journal of Otorhinolaryngology Head and Neck Surgery, 2017, 52(5): 365-371. doi:10.3760/cma.j.issn.1673-0860.2017.05.009
[33]	Liu J, Yu HP, Sun XC, et al. Salvage endoscopic nasopharyngectomy for local recurrent or residual nasopharyngeal carcinoma: a 10-year experience[J]. Int J Clin Oncol, 2017, 22(5): 834-842. doi:10.1007/s10147-017-1143-9
[34]	孟庆国, 陈涛, 方黎, 等. 外侧入路和内镜腹侧入路咽旁段颈内动脉的解剖路图[J]. 临床耳鼻咽喉头颈外科杂志, 2024, 38(6): 477-484. doi:10.13201/j.issn.2096-7993.2024.06.005 MENG Qingguo, CHEN Tao, FANG Li, et al. An anatomical road map of the parapharyngeal internal carotid artery in lateral and endoscopic ventral approaches[J]. Journal of Clinical Otorhinolaryngology Head and Neck Surgery, 2024, 38(6): 477-484. doi:10.13201/j.issn.2096-7993.2024.06.005
[35]	文卫平, 陈明远, 许庚, 等. 经鼻内镜鼻咽癌救援性切除术[C] //中华医学会第十次全国耳鼻咽喉-头颈外科学术会议论文汇编(上).中国江苏南京.中华医学会耳鼻咽喉-头颈外科学分会, 2007: 1
[36]	周宇翔, 苗北平, 卢永田. 首诊鼻咽癌内镜手术的治疗进展[J]. 山东大学耳鼻喉眼学报, 2021, 35(6): 108-112. doi:10.6040/j.issn.1673-3770.0.2020.493 ZHOU Yuxiang, MIAO Beiping, LU Yongtian. Treatment progress of endoscopic surgery for first diagnosed nasopharyngeal carcinoma[J]. Journal of Otolaryngology and Ophthalmology of Shandong University, 2021, 35(6): 108-112. doi:10.6040/j.issn.1673-3770.0.2020.493
[37]	Emanuelli E, Albu S, Cazzador D, et al. Endoscopic surgery for recurrent undifferentiated nasopharyngeal carcinoma[J]. J Craniofac Surg, 2014, 25(3): 1003-1008. doi:10.1097/SCS.0000000000000698
[38]	Liu YP, Wen YH, Tang J, et al. Endoscopic surgery compared with intensity-modulated radiotherapy in resectable locally recurrent nasopharyngeal carcinoma: a multicentre, open-label, randomised, controlled, phase 3 trial[J]. Lancet Oncol, 2021, 22(3): 381-390. doi:10.1016/S1470-2045(20)30673-2
[39]	刘全, 孙希才, 于华鹏, 等. 鼻内镜下鼻咽癌切除术的手术分型[J]. 山东大学耳鼻喉眼学报, 2019, 33(2): 39-45. doi:10.6040/j.issn.1673-3770.1.2019.016 LIU Quan, SUN Xicai, YU Huapeng, et al. Types of endoscopic transnasal nasopharyngectomy for nasopharyngeal carcinoma[J]. Journal of Otolaryngology and Ophthalmology of Shandong University, 2019, 33(2): 39-45. doi:10.6040/j.issn.1673-3770.1.2019.016
[40]	Li WP, Zhang HK, Lu HY, et al. Clinical outcomes of salvage endoscopic nasopharyngectomy for patients with advanced recurrent nasopharyngeal carcinoma[J]. Front Oncol, 2021, 11: 716729. doi:10.3389/fonc.2021.716729
[41]	Huang Y, Qiu QH. Endoscopic surgery for early-stage nasopharyngeal carcinoma: a justified initial option[J]. Acta Otolaryngol, 2017, 137(11): 1194-1198. doi:10.1080/00016489.2017.1351041
[42]	翁敬锦, 高俊潇, 李敏, 等. 鼻内镜手术联合化疗与手术联合放疗对高发区早期鼻咽癌患者预后的影响[J]. 临床耳鼻咽喉头颈外科杂志, 2024, 38(6): 472-476, 484. doi:10.13201/j.issn.2096-7993.2024.06.004 WENG Jingjin, GAO Junxiao, LI Min, et al. Effect of endoscopic surgery combined with chemotherapy and radiotherapy on prognosis of early nasopharyngeal carcinoma patients in high incidence area[J]. Journal of Clinical Otorhinolaryngology Head and Neck Surgery, 2024, 38(6): 472-476, 484. doi:10.13201/j.issn.2096-7993.2024.06.004
[43]	Si YF, Lan GP, Deng ZX, et al. Influence of endoscopic sinus surgery on the quality of life of patients with early nasopharyngeal carcinoma and the analysis of prognosis-related factors[J]. Tumour Biol, 2017, 39(7): 1010428317707435. doi:10.1177/1010428317707435
[44]	Weng JJ, Wei JZ, Li M, et al. Effects of surgery combined with chemoradiotherapy on short- and long-term outcomes of early-stage nasopharyngeal carcinoma[J]. Cancer Manag Res, 2020, 12: 7813-7826. doi:10.2147/CMAR.S262567
[45]	Zhang BJ, Li YL, Weng JJ, et al. Efficacy and safety of endoscopic nasopharyngectomy combined with low-dose radiotherapy for primary T1-2 nasopharyngeal carcinoma[J]. Technol Cancer Res Treat, 2021, 20: 15330338211011975. doi:10.1177/15330338211011975

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