|
宫颈癌筛查方法研究进展
|
Abstract:
宫颈癌是我国最常见的妇科恶性肿瘤,也是一种病因明确且可预防的癌症。宫颈癌筛查在宫颈癌防控中发挥重要作用,随着医疗技术的进步,宫颈癌筛查方法也不断更新发展。宫颈细胞学检查、人乳头瘤病毒检测、阴道镜检查等均为宫颈癌筛查的重要方法,为临床明确病情提供重要参考依据。本文将对目前宫颈癌筛查方法研究进展进行归纳总结,以期为临床工作者的宫颈癌筛查工作提供帮助。
Cervical cancer is the most common gynecological malignant tumor in China, and it is also a kind of cancer with clear etiology and can be prevented. Cervical cancer screening plays an important role in the prevention and control of cervical cancer, and with the advancement of medical technology, cervical cancer screening methods are constantly updated and developed. Cervical cytology, human papillomavirus test, colposcopy, etc. are crucial methods for cervical cancer screening, which provide significant references for clinical clarification of the disease. This article will summarize the current research progress of cervical cancer screening methods, in order to provide help for clinical workers in cervical cancer screening.
[1] | Bray, F., Laversanne, M., Sung, H., Ferlay, J., Siegel, R.L., Soerjomataram, I., et al. (2024) Global Cancer Statistics 2022: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA: A Cancer Journal for Clinicians, 74, 229-263. https://doi.org/10.3322/caac.21834 |
[2] | Han, B., Zheng, R., Zeng, H., Wang, S., Sun, K., Chen, R., et al. (2024) Cancer Incidence and Mortality in China, 2022. Journal of the National Cancer Center, 4, 47-53. https://doi.org/10.1016/j.jncc.2024.01.006 |
[3] | Quinn, M., Benedet, J., Odicino, F., Maisonneuve, P., Beller, U., Creasman, W., et al. (2006) Carcinoma of the Cervix Uteri. International Journal of Gynecology & Obstetrics, 95, S43-S103. https://doi.org/10.1016/s0020-7292(06)60030-1 |
[4] | Khakwani, M., Parveen, R. and Azhar, M. (2022) Comparison of PAP Smear and Liquid Based Cytology as a Screening Method for Cervical Carcinoma. Pakistan Journal of Medical Sciences, 38, 1827-1831. https://doi.org/10.12669/pjms.38.7.5742 |
[5] | Kaban, I., Bacanakgil, B.H. and Koca, S. (2021) The Comparison of Two Methods in Cervical Smear Screening—Which Method Is Better for Smear Adequacy Rates? Ginekologia Polska, 92, 335-338. https://doi.org/10.5603/gp.a2020.0185 |
[6] | Monsonego, J., Autillo-Touati, A., Bergeron, C., Dachez, R., Liaras, J., Saurel, J., et al. (2001) Liquid-Based Cytology for Primary Cervical Cancer Screening: A Multi-Centre Study. British Journal of Cancer, 84, 360-366. https://doi.org/10.1054/bjoc.2000.1588 |
[7] | Hashmi, A.A., Naz, S., Ahmed, O., Yaqeen, S.R., Irfan, M., Asif, M.G., et al. (2020) Comparison of Liquid-Based Cytology and Conventional Papanicolaou Smear for Cervical Cancer Screening: An Experience from Pakistan. Cureus, 12, e12293. https://doi.org/10.7759/cureus.12293 |
[8] | 中国优生科学协会阴道镜和子宫颈病理学分会, 中华医学会妇科肿瘤学分会, 中国抗癌协会妇科肿瘤专业委员会, 等. 中国子宫颈癌筛查指南(一) [J]. 现代妇产科进展, 2023, 32(7): 481-487. |
[9] | Fontham, E.T.H., Wolf, A.M.D., Church, T.R., Etzioni, R., Flowers, C.R., Herzig, A., et al. (2020) Cervical Cancer Screening for Individuals at Average Risk: 2020 Guideline Update from the American Cancer Society. CA: A Cancer Journal for Clinicians, 70, 321-346. https://doi.org/10.3322/caac.21628 |
[10] | Holmström, O., Linder, N., Kaingu, H., Mbuuko, N., Mbete, J., Kinyua, F., et al. (2021) Point-of-Care Digital Cytology with Artificial Intelligence for Cervical Cancer Screening in a Resource-Limited Setting. JAMA Network Open, 4, e211740. https://doi.org/10.1001/jamanetworkopen.2021.1740 |
[11] | Wang, C., Liou, Y., Lin, Y., Chang, C., Chu, P., Lee, Y., et al. (2021) Artificial Intelligence-Assisted Fast Screening Cervical High Grade Squamous Intraepithelial Lesion and Squamous Cell Carcinoma Diagnosis and Treatment Planning. Scientific Reports, 11, Article No. 16244. https://doi.org/10.1038/s41598-021-95545-y |
[12] | Bao, H., Sun, X., Zhang, Y., Pang, B., Li, H., Zhou, L., et al. (2020) The Artificial Intelligence‐assisted Cytology Diagnostic System in Large‐Scale Cervical Cancer Screening: A Population‐based Cohort Study of 0.7 Million Women. Cancer Medicine, 9, 6896-6906. https://doi.org/10.1002/cam4.3296 |
[13] | Wang, J., Yu, Y., Tan, Y., Wan, H., Zheng, N., He, Z., et al. (2024) Artificial Intelligence Enables Precision Diagnosis of Cervical Cytology Grades and Cervical Cancer. Nature Communications, 15, Article No. 4369. https://doi.org/10.1038/s41467-024-48705-3 |
[14] | Kurita, Y., Meguro, S., Kosugi, I., Enomoto, Y., Kawasaki, H., Kano, T., et al. (2024) Enhancing Cervical Cancer Cytology Screening via Artificial Intelligence Innovation. Scientific Reports, 14, Article No. 19535. https://doi.org/10.1038/s41598-024-70670-6 |
[15] | Yang, W., Jin, X., Huang, L., Jiang, S., Xu, J., Fu, Y., et al. (2024) Clinical Evaluation of an Artificial Intelligence-Assisted Cytological System among Screening Strategies for a Cervical Cancer High-Risk Population. BMC Cancer, 24, Article No. 776. https://doi.org/10.1186/s12885-024-12532-y |
[16] | Guo, Y., Peng, Q., Wang, Y., Li, L., Yi, X., Yan, B., et al. (2021) The Application of DNA Ploidy Analysis in Large-Scale Population Screening for Cervical Cancer. Acta Cytologica, 65, 385-392. https://doi.org/10.1159/000518052 |
[17] | 李秀萍, 党小雨, 陈燕, 等. DNA倍体分析在50岁以上女性宫颈癌筛查中的意义[J]. 诊断病理学杂志, 2023, 30(8): 802-803, 806. |
[18] | 关春艳, 董格红, 陈柯霖, 等. HPV阳性女性中宫颈液基细胞学、DNA倍体分析及P16/Ki-67双染检测对宫颈癌前病变的分流效果研究[J]. 标记免疫分析与临床, 2024, 31(6): 1157-1161. |
[19] | 刘燕翔, 戴欣, 郑玉双, 等. DNA倍体分析、液基细胞学检测对宫颈高危型HPV感染患者分流的应用分析[J]. 标记免疫分析与临床, 2024, 31(8): 1427-1430, 1447. |
[20] | Vink, F.J., Meijer, C.J.L.M., Hesselink, A.T., Floore, A.N., Lissenberg-Witte, B.I., Bonde, J.H., et al. (2023) FAM19A4/miR124-2 Methylation Testing and Human Papillomavirus (HPV) 16/18 Genotyping in HPV-Positive Women under the Age of 30 Years. Clinical Infectious Diseases, 76, e827-e834. https://doi.org/10.1093/cid/ciac433 |
[21] | Kaliff, M., Lillsunde Larsson, G., Helenius, G., Karlsson, M.G. and Bergengren, L. (2022) Full Genotyping and FAM19A4/miR124-2 Methylation Analysis in High-Risk Human Papillomavirus-Positive Samples from Women over 30 Years Participating in Cervical Cancer Screening in Örebro, Sweden. PLOS ONE, 17, e0274825. https://doi.org/10.1371/journal.pone.0274825 |
[22] | Vink, F.J., Lissenberg-Witte, B.I., Meijer, C.J.L.M., Berkhof, J., van Kemenade, F.J., Siebers, A.G., et al. (2021) FAM19A4/miR124-2 Methylation Analysis as a Triage Test for HPV-Positive Women: Cross-Sectional and Longitudinal Data from a Dutch Screening Cohort. Clinical Microbiology and Infection, 27, 125.e1-125.e6. https://doi.org/10.1016/j.cmi.2020.03.018 |
[23] | Salta, S., Maia‐Moço, L., Estevão‐Pereira, H., Sequeira, J.P., Vieira, R., Bartosch, C., et al. (2021) Performance of DNA Methylation‐Based Biomarkers in the Cervical Cancer Screening Program of Northern Portugal: A Feasibility Study. International Journal of Cancer, 149, 1916-1925. https://doi.org/10.1002/ijc.33778 |
[24] | Leffers, M., Herbst, J., Kropidlowski, J., Prieske, K., Bohnen, A.L., Peine, S., et al. (2022) Combined Liquid Biopsy Methylation Analysis of CADM1 and MAL in Cervical Cancer Patients. Cancers, 14, Article 3954. https://doi.org/10.3390/cancers14163954 |
[25] | Molano, M., Machalek, D.A., Tan, G., Garland, S., Balgovind, P., Haqshenas, G., et al. (2024) Performance of CADM1, MAL and miR124-2 Methylation as Triage Markers for Early Detection of Cervical Cancer in Self-Collected and Clinician-Collected Samples: An Exploratory Observational Study in Papua New Guinea. BMJ Open, 14, e081282. https://doi.org/10.1136/bmjopen-2023-081282 |
[26] | Chen, X., Jin, X., Kong, L., Liou, Y., Liu, P., Dong, Z., et al. (2024) Triage Performance of PAX1m/JAM3m in Opportunistic Cervical Cancer Screening of Non-16/18 Human Papillomavirus-Positive Women: A Multicenter Prospective Study in China. Clinical Epigenetics, 16, Article No. 108. https://doi.org/10.1186/s13148-024-01731-w |
[27] | Herzog, C., Sundström, K., Jones, A., Evans, I., Barrett, J.E., Wang, J., et al. (2022) DNA Methylation-Based Detection and Prediction of Cervical Intraepithelial Neoplasia Grade 3 and Invasive Cervical Cancer with the WID™-qCIN Test. Clinical Epigenetics, 14, Article No. 150. https://doi.org/10.1186/s13148-022-01353-0 |
[28] | Chan, K.K.L., et al. (2025) PAX1/SOX1 DNA Methylation versus Cytology and HPV16/18 Genotyping for the Triage of High-Risk HPV-Positive Women in Cervical Cancer Screening: Retrospective Analysis of Archival Samples. BJOG: An International Journal of Obstetrics and Gynaecology, 132, 197-204. https://doi.org/10.1111/1471-0528.17965 |
[29] | Sha, Y., Liu, Y., Yang, X., Wang, J., Zhang, R. and Shen, F. (2024) Exploring the Diagnostic Potential of EPB41L3 Methylation in Cervical Cancer and Precancerous Lesions: A Systematic Review and Meta-Analysis. Gynecologic and Obstetric Investigation, 89, 1-10. https://doi.org/10.1159/000535563 |
[30] | Salta, S., Lobo, J., Magalhães, B., Henrique, R. and Jerónimo, C. (2023) DNA Methylation as a Triage Marker for Colposcopy Referral in HPV-Based Cervical Cancer Screening: A Systematic Review and Meta-Analysis. Clinical Epigenetics, 15, Article No. 125. https://doi.org/10.1186/s13148-023-01537-2 |
[31] | 陈飞, 王华庆, 赵方辉. 中国子宫颈癌三级规范化防治蓝皮书[M]. 北京: 人民卫生出版社, 2023. |
[32] | 中国中西医结合学会检验医学专业委员会, 中华医学会检验医学分会, 中国医师协会检验医师分会, 等. 子宫颈癌PAX1联合JAM3双基因甲基化检测流程、报告及临床应用专家共识[J]. 中华检验医学杂志, 2025, 48(2): 192-200. |
[33] | Reuschenbach, M., Seiz, M., Doeberitz, C.v.K., Vinokurova, S., Duwe, A., Ridder, R., et al. (2011) Evaluation of Cervical Cone Biopsies for Coexpression of P16INK4a and Ki‐67 in Epithelial Cells. International Journal of Cancer, 130, 388-394. https://doi.org/10.1002/ijc.26017 |
[34] | Bergeron, C., Ikenberg, H., Sideri, M., Denton, K., Bogers, J., Schmidt, D., et al. (2015) Prospective Evaluation of p16/Ki‐67 Dual‐stained Cytology for Managing Women with Abnormal Papanicolaou Cytology: PALMS Study Results. Cancer Cytopathology, 123, 373-381. https://doi.org/10.1002/cncy.21542 |
[35] | Wright, T.C., Stoler, M.H., Ranger‐Moore, J., Fang, Q., Volkir, P., Safaeian, M., et al. (2021) Clinical Validation of p16/Ki‐67 Dual‐Stained Cytology Triage of HPV‐Positive Women: Results from the impact Trial. International Journal of Cancer, 150, 461-471. https://doi.org/10.1002/ijc.33812 |
[36] | Uijterwaal, M.H., Polman, N.J., Witte, B.I., van Kemenade, F.J., Rijkaart, D., Berkhof, J., et al. (2014) Triaging HPV‐Positive Women with Normal Cytology by p16/Ki‐67 Dual‐Stained Cytology Testing: Baseline and Longitudinal Data. International Journal of Cancer, 136, 2361-2368. https://doi.org/10.1002/ijc.29290 |
[37] | Zhang, J., Zhao, Y., Dai, Y., Dang, L., Ma, L., Yang, C., et al. (2021) Effectiveness of High-Risk Human Papillomavirus Testing for Cervical Cancer Screening in China: A Multicenter, Open-Label, Randomized Clinical Trial. JAMA Oncology, 7, 263-270. https://doi.org/10.1001/jamaoncol.2020.6575 |
[38] | McBride, E., Tatar, O., Rosberger, Z., Rockliffe, L., Marlow, L.A.V., Moss-Morris, R., et al. (2020) Emotional Response to Testing Positive for Human Papillomavirus at Cervical Cancer Screening: A Mixed Method Systematic Review with Meta-Analysis. Health Psychology Review, 15, 395-429. https://doi.org/10.1080/17437199.2020.1762106 |
[39] | Tjalma, W.A.A. and Depuydt, C.E. (2013) Cervical Cancer Screening: Which HPV Test Should Be Used—l1 or E6/E7? European Journal of Obstetrics & Gynecology and Reproductive Biology, 170, 45-46. https://doi.org/10.1016/j.ejogrb.2013.06.027 |
[40] | Cuschieri, K. and Wentzensen, N. (2008) Human Papillomavirus mRNA and P16 Detection as Biomarkers for the Improved Diagnosis of Cervical Neoplasia. Cancer Epidemiology, Biomarkers & Prevention, 17, 2536-2545. https://doi.org/10.1158/1055-9965.epi-08-0306 |
[41] | Arbyn, M., Simon, M., de Sanjosé, S., Clarke, M.A., Poljak, M., Rezhake, R., et al. (2022) Accuracy and Effectiveness of HPV mRNA Testing in Cervical Cancer Screening: A Systematic Review and Meta-Analysis. The Lancet Oncology, 23, 950-960. https://doi.org/10.1016/s1470-2045(22)00294-7 |
[42] | Granados, R., Duarte, J.A., Luján, D.R., Gutierrez‐Pecharromán, A.M., Solís, I., Molpeceres, L., et al. (2024) RNA Extended Interventional Nucleic Acid Longitudinal Study: Clinical Performance of Aptima Messenger RNA HPV Testing in Cervical Cancer Screening with a 9‐Year Follow‐Up. Cancer Cytopathology, 132, 757-767. https://doi.org/10.1002/cncy.22895 |
[43] | Singini, M.G., Singh, E., Bradshaw, D., Ramaliba, T., Chen, W.C., Motlhale, M., et al. (2022) Usefulness of High‐Risk HPV Early Oncoprotein (E6 and E7) Serological Markers in the Detection of Cervical Cancer: A Systematic Review and Meta‐Analysis. Journal of Medical Virology, 95, e27900. https://doi.org/10.1002/jmv.27900 |
[44] | Downham, L., Jaafar, I., Rol, M.L., Nyawira Nyaga, V., Valls, J., Baena, A., et al. (2023) Accuracy of HPV E6/E7 Oncoprotein Tests to Detect High-Grade Cervical Lesions: A Systematic Literature Review and Meta-Analysis. British Journal of Cancer, 130, 517-525. https://doi.org/10.1038/s41416-023-02490-w |
[45] | Li, Y., Wang, H., Zhang, Y., Jing, X., Wu, N., Hou, Y., et al. (2020) Correlation between Multi‐Type Human Papillomavirus Infections and Viral Loads and the Cervical Pathological Grade. International Journal of Gynecology & Obstetrics, 152, 96-102. https://doi.org/10.1002/ijgo.13406 |
[46] | Kim, J., Kim, B.K., Jeon, D., Lee, C.H., Roh, J., Kim, J., et al. (2020) Type-Specific Viral Load and Physical State of HPV Type 16, 18, and 58 as Diagnostic Biomarkers for High-Grade Squamous Intraepithelial Lesions or Cervical Cancer. Cancer Research and Treatment, 52, 396-405. https://doi.org/10.4143/crt.2019.152 |
[47] | Malagón, T., Louvanto, K., Ramanakumar, A.V., Koushik, A., Coutlée, F. and Franco, E.L. (2019) Viral Load of Human Papillomavirus Types 16/18/31/33/45 as a Predictor of Cervical Intraepithelial Neoplasia and Cancer by Age. Gynecologic Oncology, 155, 245-253. https://doi.org/10.1016/j.ygyno.2019.09.010 |
[48] | Nishimura, H., Yeh, P.T., Oguntade, H., Kennedy, C.E. and Narasimhan, M. (2021) HPV Self-Sampling for Cervical Cancer Screening: A Systematic Review of Values and Preferences. BMJ Global Health, 6, e003743. https://doi.org/10.1136/bmjgh-2020-003743 |
[49] | Nelson, E.J., Maynard, B.R., Loux, T., Fatla, J., Gordon, R. and Arnold, L.D. (2016) The Acceptability of Self-Sampled Screening for HPV DNA: A Systematic Review and Meta-analysis. Sexually Transmitted Infections, 93, 56-61. https://doi.org/10.1136/sextrans-2016-052609 |
[50] | Arbyn, M., Smith, S.B., Temin, S., Sultana, F. and Castle, P. (2018) Detecting Cervical Precancer and Reaching Underscreened Women by Using HPV Testing on Self Samples: Updated Meta-Analyses. BMJ, 363, k4823. https://doi.org/10.1136/bmj.k4823 |
[51] | Aarnio, R., Isacson, I., Sanner, K., Gustavsson, I., Gyllensten, U. and Olovsson, M. (2021) Comparison of Vaginal Self‐sampling and Cervical Sampling by Medical Professionals for the Detection of HPV and CIN2+: A Randomized Study. International Journal of Cancer, 148, 3051-3059. https://doi.org/10.1002/ijc.33482 |
[52] | Polman, N.J., Ebisch, R.M.F., Heideman, D.A.M., Melchers, W.J.G., Bekkers, R.L.M., Molijn, A.C., et al. (2019) Performance of Human Papillomavirus Testing on Self-Collected versus Clinician-Collected Samples for the Detection of Cervical Intraepithelial Neoplasia of Grade 2 or Worse: A Randomised, Paired Screen-Positive, Non-Inferiority Trial. The Lancet Oncology, 20, 229-238. https://doi.org/10.1016/s1470-2045(18)30763-0 |
[53] | Cho, H., Shim, S.R., Lee, J.K. and Hong, J.H. (2022) Accuracy of Human Papillomavirus Tests on Self-Collected Urine versus Clinician-Collected Samples for the Detection of Cervical Precancer: A Systematic Review and Meta-Analysis. Journal of Gynecologic Oncology, 33, e4. https://doi.org/10.3802/jgo.2022.33.e4 |
[54] | Zhang, J., Tian, X., Chen, Y., Huang, S., Cui, Z., Tian, R., et al. (2021) Feasibility and Accuracy of Menstrual Blood Testing for High-Risk Human Papillomavirus Detection with Capture Sequencing. JAMA Network Open, 4, e2140644. https://doi.org/10.1001/jamanetworkopen.2021.40644 |
[55] | 何昕珈, 李之薇, 徐静, 等. 尿液检测在宫颈癌筛查与HPV疫苗监测中的研究进展[J]. 现代妇产科进展, 2024, 33(7): 556-558, 560. |
[56] | Naseri, S., Young, S., Cruz, G. and Blumenthal, P.D. (2022) Screening for High-Risk Human Papillomavirus Using Passive, Self-Collected Menstrual Blood. Obstetrics & Gynecology, 140, 470-476. https://doi.org/10.1097/aog.0000000000004904 |
[57] | Stuebs, F.A., Schulmeyer, C.E., Mehlhorn, G., Gass, P., Kehl, S., Renner, S.K., et al. (2018) Accuracy of Colposcopy-Directed Biopsy in Detecting Early Cervical Neoplasia: A Retrospective Study. Archives of Gynecology and Obstetrics, 299, 525-532. https://doi.org/10.1007/s00404-018-4953-8 |
[58] | Wei, B., Zhang, B., Xue, P., Seery, S., Wang, J., Li, Q., et al. (2022) Improving Colposcopic Accuracy for Cervical Precancer Detection: A Retrospective Multicenter Study in China. BMC Cancer, 22, Article No. 388. https://doi.org/10.1186/s12885-022-09498-0 |
[59] | Yu, W., Long, C., Zhu, T., Zhu, H., Han, Z. and Li, F. (2020) High Resolution Multispectral Endoscopy Significantly Improves the Diagnostic Accuracy of Cervical Intraepithelial Lesions. Journal of Obstetrics and Gynaecology Research, 46, 939-944. https://doi.org/10.1111/jog.14241 |
[60] | Miyagi, Y., Takehara, K., Nagayasu, Y. and Miyake, T. (2019) Application of Deep Learning to the Classification of Uterine Cervical Squamous Epithelial Lesion from Colposcopy Images Combined with HPV Types. Oncology Letters, 19, 1602-1610. https://doi.org/10.3892/ol.2019.11214 |
[61] | Hu, L.M., et al. (2019) An Observational Study of Deep Learning and Automated Evaluation of Cervical Images for Cancer Screening. Journal of the National Cancer Institute, 111, 923-932. |