妊娠合并宫颈癌患者的管理

​妊娠合并宫颈癌患者的管理

宫颈癌是妊娠女性中最常见的恶性肿瘤之一，随着宫颈癌发病的年轻及女性首次生育年龄的推迟，妊娠合并宫颈癌也成为妇产科医师关注的问题。一般将妊娠期及产后6个月内发现的宫颈癌定义为妊娠合并宫颈癌，又称为妊娠相关性宫颈癌。延迟治疗至胎儿成熟还是立即终止妊娠接受治疗是患者和医生必须共同做出的困难选择。

妊娠期宫颈癌临床表现

妊娠期宫颈癌的临床表现与非妊娠期宫颈癌的临床表现基本相同。常表现为偶发性或性交后阴道流血。由于发生在妊娠期，常易误诊为先兆流产、前置胎盘、胎盘早剥、早产等，可能因为恐惧流产避免阴道检查而导致误诊。

妊娠期宫颈癌筛查

妊娠期宫颈癌的筛查可按照一般诊断程序进行，即细胞学、阴道镜、活组织检查，当怀疑有浸润性病变时可进行诊断性锥切。要特别注意，由于可能导致早产、胎膜早破、感染等发生，妊娠期宫颈活组织检查禁忌做宫颈诊刮检查。

1.如细胞学结果为ASCUS切HR-HPV阳性则需行阴道镜检查；

2.如细胞学结果为LSIL，可以待产后行阴道镜检查；

3.若细胞学结果提示ASC-H、HSIL或AGC-AIS，则需要行阴道镜检查：

1）若阴道镜结果为阴性或CIN I，一年后复查；

2）若阴道镜结果为CIN II，可待产后再治疗；

3）若阴道镜结果为CIN III，可暂不治疗，但需严密检测，每三个月进行一次阴道镜检查以及时发现病情变化；

4）如阴道镜结果提示浸润癌，需立即接受治疗。

图1. 妊娠期宫颈癌筛查与处理[1]

妊娠期宫颈癌治疗

目前对于妊娠合并宫颈癌患者的临床管理办法还没有统一定论。为妊娠合并宫颈癌患者制定治疗方案应综合考虑宫颈癌的分期及胎儿的孕周。

​

国际癌症、不孕与妊娠网络（the International Network on Cancer，Infertility and Pregnancy，INCIP）协会推荐：

1.IA1期患者无淋巴管浸润可行宫颈锥切术；

2.有淋巴管浸润的IA1期、IA2期和IB1期宫颈癌患者：

1）孕周＜22周者：行淋巴结分期手术，如淋巴结阳性则建议终止妊娠，如淋巴结阴性可行宫颈切除或待产后治疗；

2）孕周＞22周者：新辅助化疗或待产后治疗；

3.IB2期宫颈癌患者：

1）孕周＜22周者：可接受新辅助化疗；或行淋巴结分期手术，如淋巴结阳性则建议终止妊娠，如淋巴结阴性可行新辅助化疗或待产后治疗；

2）孕周＞22周者：新辅助化疗或待产后治疗；

4.IB3期宫颈癌患者：

1）孕周＜22周者：终止妊娠或接受新辅助化疗；

2）孕周＞22周者：新辅助化疗或待产后治疗；

5.II期及以上宫颈癌患者：不推荐继续妊娠。

图2.妊娠期宫颈癌治疗

备注：PLND：盆腔淋巴结清扫; NACT：新辅助化疗; AC：辅助化疗; TOP：终止妊娠; ST：单纯子宫颈切除术; DTAD：延迟至产后治疗[2]

​参考文献：

1. Korenaga TK, Tewari KS. Gynecologic cancer in pregnancy. Gynecol Oncol. 2020 Jun;157(3):799-809. doi: 10.1016/j.ygyno.2020.03.015. Epub 2020 Apr 5. PMID: 32268951; PMCID: PMC7380448.

2. Amant F, Berveiller P, Boere IA, Cardonick E, Fruscio R, Fumagalli M, Halaska MJ, Hasenburg A, Johansson ALV, Lambertini M, Lok CAR, Maggen C, Morice P, Peccatori F, Poortmans P, Van Calsteren K, Vandenbroucke T, van Gerwen M, van den Heuvel-Eibrink M, Zagouri F, Zapardiel I. Gynecologic cancers in pregnancy: guidelines based on a third international consensus meeting. Ann Oncol. 2019 Oct 1;30(10):1601-1612. doi: 10.1093/annonc/mdz228. PMID: 31435648.

李芳主任临床团队

上海市东方医院（同济大学附属东方医院）本部妇科设有普通妇科、宫颈疾病、妇科肿瘤、盆底重建、生殖外科、计划生育和妇科内镜。妇科以“创建诊疗特色鲜明的临床研究复合型学科”为目标，在医、教、研各方面实现跨越式发展，各亚专科逐渐形成明显特色。科室始终坚持以人为本，重点培养中青年技术骨干，增强团队的整体技术能力，优化医疗环境，提高医疗质量。开展新技术、新项目，倡导微笑服务，不断焕发新的活力，在竞争中发展壮大。

科室技术力量雄厚，病房4K腹腔镜、3D腹腔镜等国际一流的现代化新型手术设备，能完成各类妇科手术诊治，在妇科良、恶性肿瘤诊断、手术和综合治疗方面积累了丰富的临床经验。在妇科微创手术、腹腔镜/单孔腹腔镜、妇科盆底重建、妇科肿瘤保留子宫和生育功能的手术等方面具有鲜明特色。宫颈癌前病变及宫颈癌诊疗水平居国际领先地位。

目前妇科门诊：开设了宫颈疾病、普通妇科门诊、宫腔镜门诊，计划生育门诊，妇科肿瘤门诊。门诊开展阴道镜以及显微阴道镜检查，leep术，宫腔镜检查，无痛人流以及各类计划生育手术。

专家门诊 / 时间

周一全天、周二上午

周四下午妇科专家特需门诊

地址：上海市浦东新区即墨路150号，

上海市东方医院 北院。

周二下午妇科专家门诊，

地址：上海市浦东新区云台路1800号，

上海市东方医院 南院

周四上午线上门诊。

东方医院北院 / 周边交通

李芳教授临床科研团队

李芳主任团队开展临床和临床相关基础研究。

同济大学附属东方医院本部妇科是妇科学博士后和硕博士研究生培养点，医师规范化培训基地。主要研究方向：高危HPV整合相关致癌机制、三代转录组和宫单细胞测序揭示宫颈癌免疫微环境和宫颈癌免疫治疗新靶点。李芳教授以通讯作者身份在Nucleic Acids Research, J Exp Clin Cancer Res.等期刊上发表40余篇学术论文。累计影响因子251.4分，最高影响因子20.69分。主持国家自然基金、科技部重大项目、上海市科委、卫健委和上海市申康课题20余项。主编论著2部。获省部二等奖1项（2/7）。国家级 宫颈病专业精英奖 1项。获批发明专利3项，实用新型专利5项。知识产权转化1项：显微内镜在体病理诊断子宫颈病变。实验室依托同济大学附属东方医院转化医学研究中心，拥有具有完成国家级科研项目所必需的先进仪器设备和充足的科研经费。

发表论文 / 目录如下

1. Min Liu＃, Zhiqiang Han＃, Yong Zhi, Yetian Ruan, Guangxu Cao, Guangxue Wang, Xinxin Xu, Jianbing Mu, Jiuhong Kang, Fangping Dai, Xuejun Wen, Qingfeng Zhang*, Fang Li*. Long-read sequencing reveals oncogenic mechanism of HPV-human fusion transcripts in cervical cancer. Translational Research. (IF=10.17)

2. Zhi Y, Chen X, Cao G, Chen F, Seo HS, Li F. The effects of air pollutants exposure on the transmission and severity of invasive infection caused by an opportunistic pathogen Streptococcus pyogenes. Environ Pollut. 2022 Oct 1;310:119826. IF=9.98

3. Hu H, Yang M, Dong W, Yin B, Ding J, Huang B, Zheng Q, Li F, Han L. A Pyroptosis-Related Gene Panel for Predicting the Prognosis and Immune Microenvironment of Cervical Cancer. Front Oncol. 2022 Apr 29;12:873725. IF=5.7

4. Jianyi D, Haili G, Bo Y, Meiqin Y, Baoyou H, Haoran H, Fang L, Qingliang Z, Lingfei H. Myeloid-derived suppressor cells cross-talk with B10 cells by BAFF/BAFF-R pathway to promote immunosuppression in cervical cancer. Cancer Immunol Immunother. 2022 Jun 20. IF=6.3

5. Yang, M.＃, Hu, H.＃, Wu, S., Ding, J., Yin, B., Huang, B., Li, F.*, Guo, X.*, ＆ Han, L*. (2022). EIF4A3-regulated circ_0087429 can reverse EMT and inhibit the progression of cervical cancer via miR-5003-3p-dependent upregulation of OGN expression. Journal of experimental ＆ clinical cancer research : CR, 41(1), 165. IF=12.66

6. Yin Bo＃, Ding Jianyi＃, Hu Haoran＃, Yang Meiqin, Huang Baoyou, Dong Wei*, Li Fang*, Han Lingfei*. Overexpressed CMTM6 improves prognosis and associated with immune infiltrates of ovarian cancer. Front Mol Biosci.2021. IF=6.11

7. Le Fu＃, Wei Xia＃, Wei Shi, Guangxu Cao, Yetian Ruana, Xingyu Zhao, Min Liu, Sumei Niu, Fang Li*, Xin Gao*. Deep learning based cervical screening by the cross-modal integration of colposcopy, cytology, and HPV test. International Journal of Medical Informatics,159 (2022) 104675. IF=4.73

8. Xinxin Xu＃, Zhiqiang Han＃, Yetian Ruan, Min Liu, Guangxu Cao, Chao Li*, Fang Li*. HPV16-LINC00393 integration alters local 3D genome architecture in cervical cancer cells. Front Cell Infect Microbiol. 2021 Dec 7;11:785169. IF=6.07

9. Zhiyuan Huang＃, Fang Li*, Qinchuan Li*. Expression profile of RNA binding protein in cervical cancer using bioinformatics approach. Cancer Cell Int. 2021 Dec 4;21(1):647. IF=6.42

10. Li Y＃, Gong YX＃, Wang Q, Gao S, Zhang H, Xie F, Cong Q, Chen L, Zhou Q, Hong Z, Qiu L, Li F, Xie Y*, Sui L*. Optimizing the Detection of Occult Cervical Cancer: A Prospective Multicentre Study in China. Int J Womens Health. 2021 Oct 27;13:1005-1015. IF=2.59

11. Zhu J＃, Chen F, Luo L, Wu W, Dai J, Zhong J, Lin X, Chai C, Ding P, Liang L, Wang S, Ding X, Chen Y, Wang H, Qiu J, Wang F, Sun C, Zeng Y, Fang J, Jiang X, Liu P, Tang G, Qiu X, Zhang X, Ruan Y, Jiang S, Li J, Zhu S, Xu X, Li F, Liu Z, Cao G*, Chen D*. Single-cell atlas of domestic pig cerebral cortex and hypothalamus. Science Bulletin 2021, 66(14): 1448-1461. IF=20.57

12. Ruan Y＃, Liu M, Guo J, Zhao J, Niu S, Li Fang*, Evaluation of the accuracy of colposcopy in detecting high-grade squamous intraepithelial lesion and cervical cancer. Arch Gynecol Obstet. 2020 Aug;10.1007/s00404-020-05740-x. doi:10.1007/s00404-020-05740-x IF=2.49

13. Guo, Junhan＃, Fu Le＃, Zhao Junwei, Lei Lei, Zhan Qin, Liu Min, Ruan Yetian, Li Hui, Xu Jin, Li Nana, Wang Hanlin, Zhu Huiting, Han Zhiqiang, Li Fang*, The value of microendoscopy in the diagnosis of cervical precancerous lesions and cervical microinvasive carcinoma. Archives of Gynecology and Obstetrics. 2020 June 302. doi:10.1007/s00404-020-05565-8. IF=2.49

14. Wen Yu＃, Cai Long, Tailin Zhu, Huiting Zhu, Zhiqiang Han*, Fang Li*, High resolution multispectral endoscopy significantly improves the diagnostic accuracy of cervical intraepithelial lesions. Journal of obstetrics and gynaecology research, 2020 April, 46: 939-944. doi:10.1111/jog.14241. IF=1.69

15. Chao Li＃*, Hongfeng Ao＃, Guofang Chen, Fang Wang, Fang Li*. The Interaction of CDH20 With β-Catenin Inhibits Cervical Cancer Cell Migration and Invasion via TGF-β/Smad/SNAIL Mediated EMT. Front Oncol. 2020 Jan 9;9:1481. doi: 10.3389/fonc.2019.01481. IF=5.7

16. Junwei Zhao＃, Qin Zhan, Junhan Guo, Min Liu, Yetian Ruan, Tailin Zhu, Lingfei Han*, Fang Li*. Phylogeny and polymorphism in the E6 and E7 of human papillomavirus: alpha-9 (HPV16, 31, 33, 52, 58), alpha-5 (HPV51), alpha-6 (HPV53, 66), alpha-7 (HPV18, 39, 59, 68) and alpha-10 (HPV6, 44) in women from Shanghai. Infect Agent Cancer. 2019 Nov 21;14:38. doi: 10.1186/s13027-019-0250-9. IF=3.69

17. Junwei Zhao＃, Jiacheng Zhu, Junhan Guo, Tailin Zhu, Jixing Zhong, Min Liu, Yetian Ruan, Shujie Liao*, Fang Li*. Genetic variability and functional implication of HPV16 from cervical intraepithelial neoplasia in Shanghai women. J Med Virol. 2020 Mar;92(3):372-381. doi: 10.1002/jmv.25618. IF=20.69

18. Chao Li＃*, Yanfei Li＃, Lanxia Sui, Jian Wang, Fang Li*, Phenyllactic acid promotes cell migration and invasion in cervical cancer via IKK/NF-κB-mediated MMP-9 activation. Cancer Cell Int. 2019 Sep 23;19:241. doi: 10.1186/s12935-019-0965-0. IF=6.42

19. Huiyan Hu＃, Jingjing Zhao＃, Wen Yu, Junwei Zhao, Zhewei Wang, Lin Jin, Yunyun Yu, Lingfei Han, Lu Wang, Huiting Zhu*, Fang Li*, Human papillomavirus DNA, HPV L1 capsid protein and p16INK4a protein as markers to predict cervical lesion progression. Archives of Gynecology and Obstetrics. 2019 Jan, 299(1):141-149. IF=2.49

20. Junwei Zhao＃, Lu Wang＃, Hui Lin, Wen Yu, Xianghong Xu, Huiyan Hu, Laifang Zhu, Lingfei Han*, Fang Li*, Association of HLA-DRB1/DQB1 polymorphism with high-risk HPV infection and cervical intraepithelial neoplasia women from Shanghai. International Journal of Clinical and Experimental Pathology, 2018.2.15, 11(2):748-756.

21. Yahui Zhang＃, Lin Wang＃, Xiang Xu＃, Fang Li*, Qingsheng Wu*, Combined systems of different antibiotics with nano-CuO against Escherichia coli and the mechanisms involved. Nanomedicine (Lond), 2018 Feb; 13(3):339-351. IF=6.09

22. Xiaojie Huang＃, Chao Li＃, Fang Li, Junwei Zhao, Xiaoping Wan*, Kai Wang*, Cervicovaginal microbiota composition correlates with the acquisition of high- risk human papillomavirus types. International Journal of Cancer, 2018 Aug 1, 143(3):621-634. IF=7.31

23. Dongsheng Chen＃*, Sanjie Jiang, Xiaoyan Ma, Fang Li*, TFBSbank: a platform to dissect the big data of protein-DNA interaction in human and model species. Nucleic Acids Research, 2017.1.4, 45(D1): D151-D157. IF=19.6

24. Xiaohui Zhou＃*, Yanfeng Shi, Lijie Wang, Mei Liu, Fang Li*, Distribution Characteristics of Human Papillomavirus Infection: A Study Based on Data from Physical Examination. Asian Pacific Journal of Cancer Prevention, 2017 Jul 27, 18(7):1875-1879.

25. Junwei Zhao＃, Fang Fang＃, Yi Guo, Tailin Zhu, Yunyun Yu, Fanfei Kong, Lingfei Han, Dongsheng Chen*, Fang Li*, HPV16 integration probably contributes to cervical oncogenesis through interrupting tumor suppressor genes and inducing chromosome instability. Journal of Experimental ＆ Clinical Cancer Research, 2016.11.25, 35(1): 180-180. IF=12.66

26. Yunyun Yu＃, Lingfei Han＃, Wen Yu, Yankang Duan, Zhewei Wang, Huiyan Hu, Junwei Zhao, Suman Singh, Fanfei Kong, Lin Jin, Jing Sun*, Fang Li*, High risk factors associated with HPV persistence after loop electrosurgical excision procedure in patients with intraepithelial neoplasia. International Journal of Clinical and Experimental Pathology, 2017,10(2):1817-1824.

27. Yi Guo＃, Jiachang Hu, Liping Zhu, Jing Sun, Longxu Xie, Fanfei Kong, Lingfei Han, Fang Li*, Physical Status and Variant Analysis of Human Papillomavirus 16 in Women from Shanghai. Gynecologic and Obstetric Investigation, 2016.01.01, 81(1):61-70. IF=2.72

28. Suman Singh＃, Qian Zhou＃, Yunyun Yu, Xianghong Xu, Xiaojie Huang, Junwei Zhao, Lingfei Han, Kai Wang, Jing Sun*, Fang Li*, Distribution of HPV genotypes in Shanghai women. International Journal of Clinical and Experimental Pathology, 2015.01.01, 8(9): 11901-11908.

29. Lingfei Han＃*, Wei Wang＃, Jiahong Lu＃, Fanfei Kong, Ge Ma, Yiping Zhu, Dong Zhao, Jianlong Zhu, Wen Shuai, Qian Zhou, Ping Chen, Lei Ye, Jie Tao, Sarfraz Ahmad, Fang Li*, Jing Sun*, AAV-sBTLA facilitates HSP70 vaccine-triggered prophylactic antitumor immunity against a murine melanoma pulmonary metastasis model in vivo. Cancer Letters, 2014.11.28, 354(2):398-406. IF=9.75

30. Fang Li＃*, Yi Guo, Lingfei Han*, Yankang Duan, Fang Fang, Sumei Niu, Qiujie Ba, Huaishi Zhu, Fanfei Kong, Chao Lin, Xuejun Wen, In vitro and in vivo growth inhibition of drug-resistant ovarian carcinoma cells using a combination of cisplatin and a TRAIL-encoding retrovirus. Oncology Letters, 2012.12.01, 4(6): 1254-1258. IF=3.11

31. Fang Li＃*, Qiujie Ba＃, Sumei Niu, Yi Guo, Yankang Duan, Peng Zhao, Chao Lin*, Jing Sun*, In-situ forming biodegradable glycol chitosan-based hydrogels: Synthesis, characterization, and chondrocyte culture. Materials Science and Engineering: C, 2012.10.1, 32(7): 2017-2025. IF=8.45

32. Fang Li＃*, Jing Sun, Huaishi Zhu, Xuejun Wen, Chao Lin, Donglu Shi, Preparation and characterization novel polymer-coated magnetic nanoparticles as carriers for doxorubicin. Colloids and Surfaces B: Biointerfaces, 2011.11.1, 88(1): 58-62. IF=5.99

33. Xu Song＃*, Fang Li＃, Jingwei Ma, Nengqin Jia*, Jianming Xu, Hebai Shen*, Synthesis of fluorescent silica nanoparticles and their applications as fluorescence probes. Journal of Fluorescence, 2011.5.01, 21(3):1205-1212. IF=2.52

34. Fang Li＃*, Sumei Niu, Jing Sun, Huaishi Zhu, Qiujie Ba, Yi Guo, Donglu Shi, Efficient In Vitro TRAIL-Gene Delivery in Drug-Resistant A2780/DDP Ovarian Cancer Cell Line via Magnetofection. Journal of Nanomaterials, 2011.01.01. IF=3.79

35. Fang Li＃*, Pingping Su＃, Chao Lin, Hong Li, Jiajing Cheng, Donglu Shi, Ribosome display and selection of human anti-placental growth factor scFv derived from ovarian cancer patients. Protein and Peptide Letters, 2010.5.01, 17(5):585-590. IF=1.92

36. Lin, Chao＃*, Peng Zhao＃, Fang Li*, Fangfang Guo, Zhuoquan Li, Xuejun Wen, Thermosensitive in situ-forming dextran-pluronic hydrogels through Michael addition. Materials Science and Engineering: C, 2010.01.01, 30(8):1236-1244. IF=8.45

37. Fang Li＃*, Jianing Li, Xuejun Wen*, Shenghu Zhou, Xiaowen Tong, Pingping Su, Hong Li, Donglu Shi*, Anti-tumor activity of paclitaxel-loaded chitosan nanoparticles: An in vitro study. Materials Science and Engineering: C, 2009.01.01, 29(8):2392-2397. IF=8.45

38. Fang Li＃, Li Meng＃, Hui Xing, Jianfeng Zhou, Shixuan Wang, Lei Huang, Gang Xu, Huaishi Zhu, Yunping Lu, Ding Ma*, Essential role of c-Jun-NH2-terminal kinase on synergy induction of apoptosis by TRAIL plus ADM in ADM resistant MCF-7/ADM cells. Apoptosis, 2006.01.01, 11:1239-1246. IF=5.99

39. Fang Li＃, Li Meng＃, Jianfeng Zhou, Hui Xing, Shixuan Wang, Gang Xu, Huaishi Zhu,Beibei Wang, Gang Chen, Yunping Lu, Ding Ma*, Reversing chemoresistance in cisplatin-resistant human ovarian cancer cells: A role of c-Jun NH(2)-terminal kinase 1. Biochemical and Biophysical Research Communications, 2005.10.01, 335(4):1070-1077. IF=3.32

40. Lei Huang＃, Qilin Ao, Qinghua Zhang, Xiaokui Yang, Hui Xing, Fang Li, Gang Chen, Jianfeng Zhou, Shixuan Wang, Gang Xu, Li Meng, YunPing Lu, Ding Ma*, Hypoxia induced paclitaxel resistance in human ovarian cancers via hypoxia-inducible factor 1 alpha. Journal of Cancer Research and Clinical Oncology, 2010.3.01, 136(3):447-456. IF=4.32

41. 胡家昌(＃)，李芳，高危型HPV DNA与宿主基因整合及致癌机理的相关研究进展，现代妇产科进展，2015.5.01，（05）：384~386

42. 方芳，李芳，段燕康，宫颈病变患者人乳头瘤病毒感染分型研究，中国药房，2013.01.01，（34）：3241~3243

43. 韩凌斐，郭晓青，胡家昌，孔繁飞，何拉曼，李芳，朱建龙，孙静，宫颈癌患者外周血髓源性抑制细胞的比例及其临床意义，华中科技大学学报(医学版)，2015.01.01，（01）：32~36.

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