郝凤臣,李 妍

晚期宫颈癌的治疗是全球性的临床难题，传统治疗模式已遭遇瓶颈。本文系统综述了晚期宫颈癌治疗领域的最新进展与未来方向。文章首先阐明了传统疗法的局限性，随后重点阐述了以靶向治疗和免疫治疗为代表的前沿策略。在靶向治疗方面，详细梳理了抗血管生成药物、PARP抑制剂及抗体偶联药物（ADC）等关键药物的作用机制与临床应用。在免疫治疗方面，深入探讨了以免疫检查点抑制剂为核心的突破性疗法及其面临的挑战。最后，文章展望了未来的发展趋势，强调个体化精准医疗、对肿瘤微环境的深入理解以及靶向与免疫联合治疗，将是攻克晚期宫颈癌的核心研究方向。

晚期宫颈癌；靶向治疗；免疫治疗；抗体偶联药物；免疫检查点抑制剂；精准医疗；联合治疗

[1] Small W Jr,Bacon MA,Bajaj A,Chuang LT,Fisher BJ,Harkenrider MM,et al.Cervical cancer:A global health crisis.Cancer,123(13), 2404–2412. [2] Sung H,Ferlay J,Siegel RL,Laversanne M,Soerjomataram I,Jemal A,et al.Global Cancer Statistics 2020:GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries.CA:a cancer journal for clinicians,71(3),209–249. [3] Arbyn M,Weiderpass E,Bruni L,de SanjoséS,Saraiya M,Ferlay J,et al.Estimates of incidence and mortality of cervical cancer in 2018:a worldwide analysis.The Lancet.Global health,8(2),e191–e203. [4] Bogani G,Sopracordevole F,Di Donato V,Ciavattini A,Ghelardi A,Lopez S,et al.High-risk HPV-positive and-negative high-grade cervical dysplasia:Analysis of 5-year outcomes.Gynecologic oncology,161(1),173–178. [5] Arbyn M,Weiderpass E,Bruni L,de SanjoséS,Saraiya M,Ferlay J,et al.Estimates of incidence and mortality of cervical cancer in 2018:a worldwide analysis.The Lancet.Global health,8(2),e191–e203. [6] National Comprehensive Cancer Network.NCCN clinical practice guidelines in oncology:cervical cancer(version 3.2024)[EB/OL]. (2024-05-28)[2024-10-20]. [7] Cibula D,Rosaria Raspollini M,Planchamp F,et al.ESGO/ESTRO/ESP guidelines for the management of patients with cervical cancer-Update 2023[J].Radiother Oncol,2023,184:109682. [8] Li X,Zheng R,Li X,Shan H,Wu Q,Wang Y,et al.Trends of incidence rate and age at diagnosis for cervical cancer in China,from 2000 to 2014.Chinese journal of cancer research=Chung-kuo yen cheng yen chiu,29(6),477–486. [9] Chen W,Zheng R,Baade PD,Zhang S,Zeng H,Bray F,et al.Cancer statistics in China,2015.CA:a cancer journal for clinicians,66(2),115–132. [10] 孟令昊,胥秋艳,李科,等.1990~2019年中国女性宫颈癌疾病负担变化的分析[J].中国循证医学杂志,2021,21(06):648-653. [11] 张仲华,刘晨瑛,任会叶,等.2003―2018年间中国女性宫颈癌发病与死亡趋势研究[J].中华疾病控制杂志,2022,26(01):14-20. [12] Tewari,K.S.,Sill,M.W.,Long,H.J.,3rd,Penson,R.T.,Huang,H.,Ramondetta,L.M.,Landrum,L.M.,Oaknin,A.,Reid,T.J.,Leitao,M.M.,Michael,H.E.,&Monk,B.J.(2014).Improved survival with bevacizumab in advanced cervical cancer.The New England journal of medicine,370(8),734–743. [13] Eskander,R.N.,Sill,M.W.,Beffa,L.,Moore,R.G.,Hope,J.M.,Musa,F.B.,Mannel,R.S.,Shahin,M.S.,Cantuaria,G.H.,Girda,E.,Lokich,E.,Ka-vecansky,J.,Leath,C.A.,3rd,Gien,L.T.,Hinchcliff,E.M.,Lele,S.B.,Landrum,L.M.,Backes,F.,O'Cearbhaill,R.E.,Baghdadi,T.A,Aghajanian,C.(2025).Pembrolizumab plus chemotherapy in advanced or recurrent endometrial cancer:overall survival and exploratory analyses of the NRG GY018 phase 3 randomized trial.Nature medicine,31(5),1539–1546. [14] Schrevel,M.,Gorter,A.,Kolkman-Uljee,S.M.,Trimbos,J.B.,Fleuren,G.J.,&Jordanova,E.S.(2011).Molecular mechanisms of epidermal growth factor receptor overexpression in patients with cervical cancer.Modern pathology:an official journal of the United States and Canadian Academy of Pathology,Inc,24(5),720–728. [15] Peng,Y.,Wang,Y.,Zhou,C.,Mei,W.,&Zeng,C.(2022).PI3K/Akt/mTOR Pathway and Its Role in Cancer Therapeutics:Are We Making Headway.Frontiers in oncology,12,819128. [16] Buza N.(2025).The Rapidly Evolving Landscape of Human Epidermal Growth Factor Receptor 2(HER2)Testing in Endometrial Carcinoma and Other Gynecologic Malignancies.Archives of pathology&laboratory medicine,10.5858/arpa.2025-0046-RA.Advance online publication. [17] Wijenayake,N.,Ladino,D.,Patterson,K.,Rosim,M.,Rojas Rojas,M.,Davies,A.,&Young,K.(2025).Evaluating the broad societal value of pembrolizumab in women's cancer in Brazil.Journal of medical economics,28(1),1651–1668. [18] Okamoto,K.,Kikuchi,D.,Yamashita,S.,Kinowaki,K.,Suzuki,Y.,&Hoteya,S.(2025).Long-term survival after resolution of pulmonary metastasis in a patient with unresectable cervical esophageal carcinoma after nivolumab-induced immune-related adverse events.Clinical journal of gastroenterology,10.1007/s12328-025-02207-x.Advance online publication. [19] Takekuma,M.,Nishio,S.,Yamaguchi,S.,Yunokawa,M.,Nishio,H.,Nishino,K.,Kurosaki,A.,Minobe,S.,Villacampa,G.,Oaknin,A.,&Okam-oto,A.(2025).Atezolizumab,bevacizumab,and platinum chemotherapy in cervical cancer:results of Japanese population from BEATcc.Journal of gynecologic oncology,10.3802/jgo.2025.36.e116.Advance online publication. [20] Zhu,L.,Pu,J.,Tao,Y.,Shi,L.,Liu,S.,Zhang,X.,Liu,W.,Sun,M.,Yao,Y.,&Shi,L.(2025).A therapeutic multi-epitope protein vaccine targeting HPV16 E6 E7 elicits potent tumor regression and cytotoxic immune responses.Cancer biology&medicine,22(9),1102–1126. [21] Gutiérrez-Hoya,A.,Ortiz-Garrido,I.,Salazar-Valencia,I.,Romero-Hernández,C.,Valle-Mendiola,A.,Weiss-Steider,B.,&Soto-Cruz,I.(2024).Cervical Cancer Cells Use the CD95 and IL-2 Pathways to Promote Their Proliferation and Survival.Biomolecules,14(12),1543. [22] 杨长香.细胞因子诱导的杀伤细胞联合紫杉醇+顺铂化疗方案治疗宫颈癌的效果及近期预后观察[J].中国医学工程,2021, 29(08):71-73. [23] 石蕊,冯淑娴,马薇,等.免疫检查点抑制剂治疗复发/转移性宫颈癌的预后预测指标研究进展[J].中国医药导报,2025, 22(02):57-60+65. [24] 胡菁华,桑学梅,乔伟,等.PD-1抑制剂帕博利珠单抗用于宫颈癌治疗效果的影响因素研究[J].中国药师,2024,27(08):1375-1382. [25] 邓清华,方醒艺,陈祝明,等.免疫通路调控对宫颈癌肿瘤微环境影响的研究进展[J].妇儿健康导刊,2025,4(04):22-26. [26] 刘堃,卢善明,郑志坚,等.宫颈癌淋巴结转移患者PD-L1与TILs表达水平及其与预后的关系[J].检验医学与临床,2024,21(15):2186-2192. [27] 肖宇航,李芳.宫颈癌中RYR2基因突变与肿瘤突变负荷和免疫调节的关系及其预后价值[J].同济大学学报(医学版),2025, 46(02):193-199. [28] 王芳,平智广,袁佩.宫颈癌与微卫星不稳定性的相关性研究[J].第二军医大学学报,2012,33(09):991-995. [29] 王晓君,刘军秀.人工智能在妇科恶性肿瘤中的进展[J].中山大学学报(医学科学版),2025,46(01):21-29.

点击下载PDF