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中华妇幼临床医学杂志(电子版)

Chinese Journal of Obstetrics & Gynecology and Pediatrics(Electronic Edition) ›› 2023, Vol. 19 ›› Issue (05): 497 -504. doi: 10.3877/cma.j.issn.1673-5250.2023.05.001

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Current research status of treatment of cervical cancer

Minrong Ma, Cong Li, Qin Zhou†()   

  1. Department of Gynaecology and Obstetrics, First Affiliated Hospital of Chongqing Medical University, Chongqing 400000, China
  • Received:2023-04-17 Revised:2023-09-08 Published:2023-10-01
  • Corresponding author: Qin Zhou
  • Supported by:
    National Natural Science Foundation of China for Youths(81100399)
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According to the 2022 Global Cancer Statistics Report, the incidence of uterine cervical neoplasms ranks first among third major gynecological malignancies in the world, it is the fourth most common type of gynecological cancer in women, and is also the fourth leading cause of malignancy related death in women in the United States. According to International Federation of Obstetrics and Gynecology (FIGO), patients with advanced or recurrent cervical cancer have a poor prognosis and are the leading cause of death from uterine cervical neoplasms. The classical treatments of cervical cancer include radiotherapy, chemotherapy and surgery, etc.. However, the effectiveness of these treatments may not be good to some patients, especially those patients with advanced or recurrent uterine cervical neoplasms. Recent research have found that viral gene integration, cellular oxidative stress, vascular endothelial growth factor (VEGF), epidermal growth factor (EGFR), programmed cell death receptor (PD)-1 and other related signaling pathways play an important role in uterine cervical neoplasms occurrence and development. A variety of novel and emerging therapeutic strategies based on these signaling pathways have been developed and applied clinically, bringing hope for treatment of more patients with advanced or recurrent uterine cervical neoplasms. In addition, there are still a lot of researches on uterine cervical neoplasms stem cells (CCSC), exosome microRNA (miR)-651 and other potential therapeutic targets of uterine cervical neoplasms is under way. The authors intend to review the latest research progresses of 5 new therapeutic schemes of neoadjuvant chemotherapy (NACT), drug targeted therapy, immunotherapy, therapeutic vaccine and photodynamic therapy (PDT), and their potential therapeutic targets for uterine cervical neoplasms.

Key words: Uterine neoplasms, Neoadjuvant therapy, Immunosuppressive agents, Vaccination, Molecular targeted therapy, Immunotherapy, active, Photochemotherapy, Female
[1]
Xia C, Dong X, Li H, et al. Cancer statistics in China and United States, 2022: profiles, trends, and determinants[J]. Chin Med J (Engl), 2022, 135(5): 584-590. DOI: 10.1097/CM9.0000000000002108.
[2]
Sung H，Ferlay J, Siegel RL, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J]. CA Cancer J Clin, 2021, 71(3): 209-249. DOI: 10.3322/caac.21660.
[3]
Hu C, Liu T, Han C, et al. HPV E6/E7 promotes aerobic glycolysis in cervical cancer by regulating IGF2BP2 to stabilize m6A-MYC expression[J]. Int J Biol Sci, 2022, 18(2): 507-521. DOI: 10.7150/ijbs.67770.
[4]
Burmeister CA, Khan SF, Schäfer G, et al. Cervical cancer therapies: current challenges and future perspectives[J]. Tumour Virus Res, 2022, 13: 200238. DOI: 10.1016/j.tvr.2022.200238.
[5]
Bhatla N, Aoki D, Sharma DN, et al. Cancer of the cervix uteri: 2021 update[J]. Int J Gynaecol Obstet, 2021, 155 (Suppl 1): 28-44. DOI: 10.1002/ijgo.13865.
[6]
Bhatla N, Denny L. FIGO cancer report 2018[J]. Int J Gynecol Obstet, 2018, 143 (Suppl 2): 2-3. DOI: 10.1002/ijgo.12608.
[7]
丁文洁，李苒苒，闻先萍，等. 双侧子宫动脉灌注化疗在局部晚期宫颈癌治疗中的价值及安全性分析[J]. 皖南医学院学报，2021, 40(6): 564-566, 577. DOI: 10.3969/j.issn.1002-0217.2021.06.015.
[8]
Himiniuc LM, Toma BF, Popovici R, et al. Update on the use of nanocarriers and drug delivery systems and future directions in cervical cancer[J]. J Immunol Res, 2022, 2022: 1-11. DOI: 10.1155/2022/1636908.
[9]
Mutlu L, Tymon-Rosario J, Harold J, et al. Targeted treatment options for the management of metastatic/persistent and recurrent cervical cancer[J]. Expert Rev Anticancer Ther, 2022, 22(6): 633-645. DOI: 10.1080/14737140.2022.2075348.
[10]
Gopu P, Antony F, Cyriac S, et al. Updates on systemic therapy for cervical cancer[J]. Indian J Med Res, 2021, 154(2): 293-302. DOI: 10.4103/ijmr.IJMR_4454_20.
[11]
Sharma S, Deep A, Sharma AK. Current treatment for cervical cancer: an update[J]. Anticancer Agents Med Chem, 2020, 20(15): 1768-1779. DOI: 10.2174/1871520620666200224093301.
[12]
Rahmani AH, ABabiker AY, Alsahli MA, et al. Prognostic significance of vascular endothelial growth factor (VEGF) and Her-2 protein in the genesis of cervical carcinoma[J]. Open Access Maced J Med Sci, 2018, 6(2): 263-268. DOI: 10.3889/oamjms.2018.089.
[13]
Garcia J, Hurwitz HI, Sandler AB, et al. Bevacizumab (Avastin®) in cancer treatment: a review of 15 years of clinical experience and future outlook[J]. Cancer Treat Rev, 2020, 86: 102017. DOI: 10.1016/j.ctrv.2020.102017.
[14]
Tewari KS, Sill MW, Penson RT, et al. Bevacizumab for advanced cervical cancer: final overall survival and adverse event analysis of a randomised, controlled, open-label, phase 3 trial (Gynecologic Oncology Group 240)[J]. Lancet, 2017, 390(10103): 1654-1663. DOI: 10.1016/S0140-6736(17)31607-0.
[15]
de Aguiar RB, de Moraes JZ. Exploring the immunological mechanisms underlying the anti-vascular endothelial growth factor activity in tumors[J]. Front Immunol, 2019, 10: 1023. DOI: 10.3389/fimmu.2019.01023.
[16]
Li S, Ma YM, Zheng PS, et al. GDF15 promotes the proliferation of cervical cancer cells by phosphorylating AKT1 and Erk1/2 through the receptor ErbB2[J]. J Exp Clin Cancer Res, 2018, 37(1): 80. DOI: 10.1186/s13046-018-0744-0.
[17]
Liu Y, An Q, Zhao X. A pan-HER-targeted approach for recurrent or late-stage cervical cancer therapy: mechanisms, recent advances, and clinical prospects[J].Eur Rev Med Pharmacol Sci, 2020, 24(8): 4123-4131. DOI: 10.26355/eurrev_202004_20992.
[18]
Benson R, Pathy S, Kumar L, et al. Locally advanced cervical cancer-neoadjuvant chemotherapy followed by concurrent chemoradiation and targeted therapy as maintenance: a phase Ⅱ study[J]. J Cancer Res Ther, 2019, 15(6): 1359-1364. DOI: 10.4103/jcrt.JCRT_39_18.
[19]
李璐，黄建鸣，冯梅，等. 放射诱导的EGFR核转位阻断可增加人宫颈癌细胞放射敏感度[J]. 肿瘤防治研究，2020, 47(1): 25-31. DOI: 10.3971/j.issn.1000-8578.2020.19.0807.
[20]
高颜凤，温坚，庄茜茹. 贝伐珠单抗联合同步放化疗治疗局部晚期宫颈癌的效果观察[J]. 中国肿瘤临床与康复，2022, 29(6): 713-716. DOI: 10.13455/j.cnki.cjcor.2022.06.19.
[21]
Liu X, Zhang X, Liu C, et al. Immune and inflammation: related factor alterations as biomarkers for predicting prognosis and responsiveness to PD-1 monoclonal antibodies in cervical cancer [J].Discov Oncol, 2022, 13(1): 96. DOI: 10.1007/s12672-022-00560-8.
[22]
Han X, Chang WW, Xia X. Immune checkpoint inhibitors in advanced and recurrent/metastatic cervical cancer[J]. Front Oncol, 2022, 12: 996495. DOI: 10.3389/fonc.2022.996495.
[23]
刘恒，侯宇川. 膀胱癌新型灌注药物的研究进展[J/OL]. 中华腔镜泌尿外科杂志(电子版)，2023，17(5)：445-451. DOI：10.3877/cma.j.issn.1674-3253.2023.05.004.
[24]
D′Oria O, Corrado G, Laganà AS, et al. New advances in cervical cancer: from bench to bedside[J]. Int J Environ Res Public Heath, 2022, 19(12): 7094. DOI: 10.3390/ijerph19127094.
[25]
Stevanovi S, Helman SR, Wunderlich JR, et al. A phase Ⅱ study of tumor-infiltrating lymphocyte therapy for human papillomavirus-associated epithelial cancers[J]. Clin Cancer Res, 2019, 25(5): 1486-1493. DOI: 10.1158/1078-0432.CCR-18-2722.
[26]
Huang H，Nie CP, Liu XF, et al. Phase Ⅰ study of adjuvant immunotherapy with autologous tumor-infiltrating lymphocytes in locally advanced cervical cancer[J]. J Clin Invest, 2022, 132(15): e157726. DOI: 10.1172/JCI157726.
[27]
Son J, George GC, Nardo M, et al. Adoptive cell therapy in gynecologic cancers: a systematic review and Meta-analysis[J]. Gynecol Oncol, 2022, 165(3): 664-670. DOI: 10.1016/j.ygyno.2022.03.013.
[28]
Xu Q, Wang J, Sun Y, et al. Efficacy andsafety of sintilimab plus anlotinib for PD-L1-positive recurrent or metastatic cervical cancer: a multicenter, single-arm, prospective phaseⅡtrial[J]. J Clin Oncol, 2022, 40(16): 1795-1805. DOI: 10.1200/JCO.21.02091.
[29]
Ota N, Yoshimoto Y，Darwis NDM, et al. High tumor mutational burden predicts worse prognosis for cervical cancer treated with radiotherapy[J]. Jpn J Radiol, 2022, 40(5): 534-541. DOI: 10.1007/s11604-021-01230-5.
[30]
Liang Y, Yu M, Zhou C, et al. Variation of PD-L1 expression in locally advanced cervical cancer following neoadjuvant chemotherapy[J]. Diagn Pathol, 2020, 15(1): 67. DOI: 10.1186/s13000-020-00977-1.
[31]
Feng CH, Mell LK, Sharabi AB, et al. Immunotherapy with radiotherapy and chemoradiotherapy for cervical cancer[J]. Semin Radiat Oncol, 2020, 30(4): 273-280. DOI: 10.1016/j.semradonc.2020.05.003.
[32]
Wang R, Pan W, Jin L, et al. Human papillomavirus vaccine against cervical cancer: opportunity and challenge[J]. Cancer Lett, 2020, 471: 88-102. DOI: 10.1016/j.canlet.2019.11.039.
[33]
Rahangdale L, Mungo C, O′Connor S, et al. Human papillomavirus vaccination and cervical cancer risk[J]. BMJ, 2022, 379: e070115. DOI: 10.1136/bmj-2022-070115.
[34]
Alhashimi M, Elkashif A, Sayedahmed EE, et al. Nonhuman adenoviral vector-based platforms and their utility in designing next generation of vaccines for infectious diseases[J]. Viruses, 2021, 13(8): 1493. DOI: 10.3390/v13081493.
[35]
Wang WC，Sayedahmed EE, Mittal SK. Significance of preexisting vector immunity and activation of innate responses for adenoviral vector-based therapy[J]. Viruses, 2022, 14(12): 2727. DOI: 10.3390/v14122727.
[36]
Haghighi D, Yazdani S, Farzanehpour M, et al. Combined extract of heated TC1, a heat-killed preparation of Lactobacillus casei and alpha-galactosyl ceramide in a mouse model of cervical cancer[J]. Infect Agents Cancer, 2022, 17(1): 51. DOI: 10.1186/s13027-022-00464-w.
[37]
Xie L, Li Y. Advances in vaccinia virus-based vaccine vectors, with applications in flavivirus vaccine development[J]. Vaccine, 2022, 40(49): 7022-7031. DOI: 10.1016/j.vaccine.2022.10.047.
[38]
Hollenberg RK, Krieger DR, Samuels R, et al. Safety and immunogenicity of VGX-3100 formulations in a healthy young adult population[J]. Hum Vaccin Immunother, 2020, 16(6): 1404-1412. DOI: 10.1080/21645515.2019.1695459.
[39]
Tang J, Li M, Zhao C, et al. Therapeutic DNA vaccines against HPV-related malignancies: promising leads from clinical trials[J]. Viruses, 2022, 14(2): 239. DOI: 10.3390/v14020239.
[40]
Zhang Y, Lin S, Wang XY, et al.Nanovaccines for cancer immunotherapy[J]. Wiley Interdiscip Rev Nanomed Nanobiotechnol, 2019, 11(5): e1559. DOI: 10.1002/wnan.1559.
[41]
Peng S, Tan M, Li YD, et al. PD-1 blockade synergizes with intratumoral vaccination of a therapeutic HPV protein vaccine and elicits regression of tumor in a preclinical model[J]. Cancer Immunol Immunother, 2021, 70(4): 1049-1062. DOI: 10.1007/s00262-020-02754-x.
[42]
Einstein MH, Roden RBS, Ferrall L, et al. Safety run-in of intramuscular pNGVL4a-Sig/E7(detox)/HSP70 DNA and TA-CIN protein vaccination as treatment for HPV16＋ ASC-US, ASC-H, or LSIL/CIN1[J]. Cancer Prev Res (Phila), 2023, 16(4): 219-227. DOI: 10.1158/1940-6207.CAPR-22-0413.
[43]
Tseng SH, Cheng MA, Farmer E, et al. Albumin and interferon-β fusion protein serves as an effective vaccine adjuvant to enhance antigen-specific CD8＋ T cell-mediated antitumor immunity[J]. J Immunother Cancer, 2022, 10(4): e004342. DOI: 10.1136/jitc-2021-004342.
[44]
Dhandapani H, Seetharaman A, Jayakumar H, et al. Autologous cervical tumor lysate pulsed dendritic cell stimulation followed by cisplatin treatment abrogates FOXP3＋ cells in vitro[J]. J Gynecol Oncol, 2021, 32(4): e59. DOI: 10.3802/jgo.2021.32.e59.
[45]
Hou YJ, Yang XX, Liu RQ, et al. Pathological mechanism of photodynamic therapy and photothermal therapy based on nanoparticles[J]. Int J Nanomedicine, 2020, 15: 6827-6838. DOI: 10.2147/IJN.S269321.
[46]
Unanyan A, Pivazyan L, Davydova J, et al. Efficacy of photodynamic therapy in women with HSIL, LSIL and early stage squamous cervical cancer: a systematic review and Meta-analysis[J]. Photodiagn Photodyn Ther, 2021, 36: 102530. DOI: 10.1016/j.pdpdt.2021.102530.
[47]
Zafari J, Zadehmodarres S, Javani Jouni F, et al. Investigation into the effect of photodynamic therapy and cisplatin on the cervical cancer cell line (A2780)[J]. J Lasers Med Sci, 2020, 11(Suppl 1): S85-S91. DOI: 10.34172/jlms.2020.S14.
[48]
Vendette ACF, Piva HL, Muehlmann LA, et al. Clinical treatment of intra-epithelia cervical neoplasia with photodynamic therapy[J]. Int J Hyperth, 2020, 37(3): 50-58. DOI: 10.1080/02656736.2020.1804077.
[49]
Niu J, Cheng M, Hong Z, et al. The effect of 5-aminolaevulinic acid Photodynamic therapy versus CO2 laser in the treatment of cervical low-grade squamous intraepithelial lesions with high-risk HPV infection: a non-randomized, controlled pilot study[J]. Photodiagn Photodyn Ther, 2021, 36: 102548. DOI: 10.1016/j.pdpdt.2021.102548.
[50]
Wang L, Liu X, Zhang J, et al. Evaluation of the efficacy and safety of 5-aminolevulinic acid-mediated photodynamic therapy in women with high-risk HPV persistent infection after cervicalconization[J]. Photodiagn Photodyn Ther, 2022, 40: 103144. DOI: 10.1016/j.pdpdt.2022.103144.
[51]
Razlog R, Kruger CA, Abrahamse H. Enhancement of conventional and photodynamic therapy for treatment of cervical cancer with cannabidiol[J]. Integr Cancer Ther, 2022, 21: 15347354221092706. DOI: 10.1177/15347354221092706.
[52]
Hu Z. Therapeuti cantibody-like immunoconjugates against tissue factor with the potential to treat angiogenesis-dependent as well as macrophage-associated human diseases[J]. Antibodies, 2018, 7(1): 8. DOI: 10.3390/antib7010008.
[53]
Yin X, Lu Y, Zou M, et al. Synthesis and characterization of salinomycin-loaded high-density lipoprotein and its effects on cervical cancer cells and cervical cancer stem cells[J]. Int J Nanomed, 2021, 16: 6367-6382. DOI: 10.2147/IJN.S326089.
[54]
Zhu X, Long L, Xiao H, et al. Cancer-derived exosomal miR-651 as a diagnostic marker restrains cisplatin resistance and directly targets ATG3 for cervical cancer[J]. Dis Markers, 2021, 2021: 1544784. DOI: 10.1155/2021/1544784.
[55]
Gao C, Wu P, Yu L, et al. The application of CRISPR/Cas9 system in cervical carcinogenesis[J]. Cancer Gene Ther, 2022, 29(5): 466-474. DOI: 10.1038/s41417-021-00366-w.
[56]
Nile A, Nile SH, Shin J, et al. Quercetin-3-glucoside extracted from apple pomace induces cell cycle arrest and apoptosis by increasing intracellular ROS levels[J]. Int J Mol Sci, 2021, 22(19): 10749. DOI: 10.3390/ijms221910749.
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