Skip to main content

Progress in the Study of Lymph Node Metastasis in Early-stage Cervical Cancer

Summary

Spread into regional lymph node is the major route of metastasis in cervical cancer. Although lymph node status is not involved in the International Federation of Gynecology and Obstetrics staging system of uterine cervical cancer, the presence or absence of lymph node metastasis provides important information for prognosis and treatment. In this review, we have attempted to focus on the incidence and patterns of lymph node metastasis, and the issues surrounding surgical assessment of lymph nodes. In addition, the preoperative prediction of lymph node status, as well as the intraoperative assessment by sentinel nodes will be reviewed. Finally, lymph node micrometastasis also will be discussed.

This is a preview of subscription content, access via your institution.

References

  1. Allemani C, Weir HK, Carreira H, et al. Global surveillance of cancer survival 1995–2009: analysis of individual data for 25, 676, 887 patients from 279 population-based registries in 67 countries (CONCORD-2). Lancet, 2015, 3B5(9972):977–1010

    Article  Google Scholar 

  2. Chen W, Zheng R, Baade PD, et al. Cancer statistics in China, 2015. CA Cancer J Clin, 2016, 66(2):115–132

    Article  PubMed  Google Scholar 

  3. Ferrandina G, Pedone Anchora L, Gallotta V, et al. Can We Define the Risk of Lymph Node Metastasis in Early-Stage Cervical Cancer Patients? A Large-Scale, Retrospective Study. Ann Surg Oncol, 2017, 24(8):2311–2318

    Article  PubMed  Google Scholar 

  4. Salvo G, Ramirez PT, Levenback CF, et al. Sensitivity and negative predictive value for sentinel lymph node biopsy in women with early-stage cervical cancer. Gynecol Oncol, 2017, 145(1):96–101

    Article  PubMed  PubMed Central  Google Scholar 

  5. Lee KBM, Lee JM, Park CY, et al. Lymph node metastasis and lymph vascular space invasion in microinvasive squamous cell carcinoma of the uterine cervix. Int J Gynecol Cancer, 2006, 16(3):1184–1187

    Article  PubMed  CAS  Google Scholar 

  6. Van Meurs H, Visser O, Buist MR, et al. Frequency of pelvic lymph node metastases and parametrial involvement in stage IA2 cervical cancer: a population-based study and literature review. Int J Gynecol Cancer, 2009, 19(1):21–26

    Article  PubMed  Google Scholar 

  7. Zhou J, Ran J, He ZY, et al. Tailoring Pelvic Lymphadenectomy for Patients with Stage IA2, I Bl, and II Al Uterine Cervical Cancer. J Cancer, 2015, 6(4):377–381

    Article  PubMed  PubMed Central  Google Scholar 

  8. Sakuragi N. Up-to-date management of lymph node metastasis and the role of tailored lymphadenectomy in cervical cancer. Int J Clin Oncol, 2007, 12(3):165–175

    Article  PubMed  Google Scholar 

  9. Gien LT, Covens A. Lymph node assessment in cervical cancer: prognostic and therapeutic implications. J Surg Oncol, 2009, 99(4):242–247

    Article  PubMed  CAS  Google Scholar 

  10. Benedetti-Panici P, Maneschi F, Scambia G, et al. Lymphatic spread of cervical cancer: an anatomical and pathological study based on 225 radical hysterectomies with systematic pelvic and aortic lymphadenectomy. Gynecol Oncol, 1996, 62:19–24

    Article  PubMed  CAS  Google Scholar 

  11. Benedetti-Panici P, Maneschi F, D’Andrea G, et al. Early cervical carcinoma: the natural history of lymph node involvement redefined on the basis of thorough parametrectomy and giant section study. Cancer, 2000, 88(10):2267–2274

    Article  PubMed  CAS  Google Scholar 

  12. Lee JM, Lee KB, Lee SK, et al. Pattern of lymph node metastasis and the optimal extent of pelvic lymphadenectomy in FIGO stage I B cervical cancer. J Obstet Gynaecol Re, 2007, 33(3):288–293

    Article  Google Scholar 

  13. Li D, Cai J, Kuang Y, et al. Surgical-pathologic risk factors of pelvic lymph node metastasis in stage I b1–II b cervical cancer. Acta Obstet Gynecol Scand, 2012, 91(7):802–809

    Article  PubMed  Google Scholar 

  14. Zhang HY, Sheng XG, Zhong Y, et al. The rule of metastatic pelvic lymph node distribution in patients with early stage cervical carcinoma. Chin J Oncol, 2008, 30(6):452–455

    Google Scholar 

  15. Delgado G, Bundy BN, Fowler WC, et al A prospective surgical pathological study of stage I squamous carcinoma of the cervix: a Gynecologic Oncology Group Study. Gynecol Oncol, 1989, 35(3):314–320

    Article  PubMed  CAS  Google Scholar 

  16. Khunamornpong S, Settakorn J, Sukpan K, et al. Cyclooxygenase-2 expression in squamous cell carcinoma of the uterine cervix is associated with lymph node metastasis. Gynecol Oncol, 2009, 112(1):241–247

    Article  PubMed  CAS  Google Scholar 

  17. Zaganelli FL, Carvalho FM, Almeida BG, et al. Intratumoral lymphatic vessel density and clinicopathologic features of patients with earlystage cervical cancer after radical hysterectomy. Int J Gynecol Cancer, 2010, 20(7):1225–1231

    Article  PubMed  Google Scholar 

  18. Sun JR, Zhang YN, Sun XM et al. Prediction model of pelvic lymph node metastasis in early stage cervical cancer and its clinical value. Minerva Chir, 2011, 66(6):537–545

    PubMed  CAS  Google Scholar 

  19. Liu T, Yang M, Yang S, et al. Metastasis-associated protein 1 is a novel marker predicting survival and lymph nodes metastasis in cervical cancer. Hum Pathol, 2013, 44(10):2275–2281

    Article  PubMed  CAS  Google Scholar 

  20. Wang W, Jia HL, Huang JM, et al. Identification of biomarkers for lymph node metastasis in early-stage cervical cancer by tissue-based proteomics. Br J Cancer, 2014, 10(7):1748–1758

    Article  CAS  Google Scholar 

  21. Kim DY, Shim SH, Kim SO, et al Preoperative nomogram for the identification of lymph node metastasis in early cervical cancer. Br J Cancer, 2014, 110(1):34–41

    Article  PubMed  Google Scholar 

  22. Togami S, Kamio M, Yanazume S, et al. Can pelvic lymphadenectomy be omitted in stage I A2 to II B uterine cervical cancer? Int J Gynecol Cancer, 2014, 24(6):1072–1076

    Article  PubMed  Google Scholar 

  23. Yanaranop M, Sathapornteera N, Nakrangsee S. Risk factors of pelvic lymph node metastasis in cervical adenocarcinoma following radical hysterectomy and pelvic lymphadenectomy. J Med Assoc Thai, 2014, 97(Suppl 11):S87–S95

    PubMed  Google Scholar 

  24. Liu Y, Zhao LJ, Li MZ, et al. The Number of Positive Pelvic Lymph Nodes and Multiple Groups of Pelvic Lymph Node Metastasis Influence Prognosis in Stage I A–II B Cervical Squamous Cell Carcinoma. Chin Med J, 2015, 128(15):2084–2089

    Article  PubMed  PubMed Central  Google Scholar 

  25. Yang S, Liu Y, Xia B, et al. DLL4 as a predictor of pelvic lymph node metastasis and a novel prognostic biomarker in patients with early-stage cervical cancer. Tumour Biol, 2016, 37(4):5063–5074

    Article  PubMed  CAS  Google Scholar 

  26. Wang Y, Yao T, Yu J, et al. Can pelvic lymphadenectomy be omitted in patients with stage IA2, I Bl, and IIA1 squamous cell cervical cancer? Springer Plus, 2016, 5(1):1262

    Article  PubMed  CAS  Google Scholar 

  27. Cao S, Sun J, Lin S, et al. HPIP: a predictor of lymph node metastasis and poor survival in cervical cancer. Onco Targets Ther, 2017, 10:4205–4211

    Article  PubMed  PubMed Central  Google Scholar 

  28. Xu D, Wang D, Wang S, et al. Correlation Between Squamous Cell Carcinoma Antigen Level and the Clinicopathological Features of Early-Stage Cervical Squamous Cell Carcinoma and the Predictive Value of Squamous Cell Carcinoma Antigen Combined With Computed Tomography Scan for Lymph Node Metastasis. Int J Gynecol Cancer, 2017, 27(9):1935–1942

    Article  PubMed  Google Scholar 

  29. Sartori E, Tisi G, Chiudinelli F, et al. Early stage cervical cancer: Adjuvant treatment in negative lymph node cases. Gynecol Oncol, 2007, 107(1):S170–S174

    Article  PubMed  Google Scholar 

  30. Pieterse QD, Kenter GG, Gaarenstroom KN, et al. The number of pelvic lymph nodes in the quality control and prognosis of radical hysterectomy for the treatment of cervical cancer. Eur J Surg Oncol, 2007, 33(2):216–221

    Article  PubMed  CAS  Google Scholar 

  31. Shah M, Lewin SN, Deutsch I, et al. Therapeutic Role of Lymphadenectomy for Cervical Cancer. Cancer, 2011, 117(2):310–317

    Article  PubMed  Google Scholar 

  32. Folien M, Levenback CF, Iyer RB, et al. Imaging in cervical cancer. Cancer, 2003, 98(9):2028–2038

    Article  Google Scholar 

  33. Chung HH, Kang SB, Cho JY, et al. Can preoperative MRI accurately evaluate nodal and parametrial invasion in early stage cervical cancer? Jpn J Clin Oncol, 2007, 37(5):370–375

    Article  PubMed  Google Scholar 

  34. Kinkel К. Pitfalls in staging uterine neoplasm with imaging: a review. Abdom Imaging, 2006, 31(2):164–173

    Article  PubMed  CAS  Google Scholar 

  35. Selman TJ, Mann C, Zamora J, et al. Diagnostic accuracy of tests for lymph node status in primary cervical cancer: a systematic review and metaanalysis. Can Med Assoc J, 2008, 178(7):855–862

    Article  Google Scholar 

  36. Suprasert P, Srisomboon J, Kasamatsu T. Radical hysterectomy for stage II B cervical cancer: a review, bit J Gynecol Cancer, 2005, 15(6):995–1001

    Article  CAS  Google Scholar 

  37. Niebling MG, Pleijhuis RG, Bastiaannet E, et al. A systematic review and meta-analyses of sentinel lymph node identification in breast cancer and melanoma, a plea for tracer mapping. Eur J Surg Oncol, 2016, 42(4):466–473

    Article  PubMed  CAS  Google Scholar 

  38. Slomovitz BM, Coleman RL, Oonk MH, et al. Update on sentinel lymph node biopsy for early-stage vulvar cancer. Gynecol Oncol, 2015, 138(2):472–477

    Article  PubMed  Google Scholar 

  39. Bats AS, Mathevet P, Buenerd A, et al. The sentinel node technique detects unexpected drainage pathways and allows nodal ultrastaging in early cervical cancer: insights from the multicenter prospective SENTICOL study. Ann Surg Oncol, 2013, 20(2):413–422

    Article  PubMed  Google Scholar 

  40. Altgassen C, Hertel H, Brandstadt A, et al. Multicenter validation study of the sentinel lymph node concept in cervical cancer: AGO study group. J Clin Oncol, 2008, 26(18):2943–2951

    Article  PubMed  Google Scholar 

  41. Lecuru F, Mathevet P, Querleu D, et al. Bilateral negative sentinel nodes accurately predict absence of lymph node metastasis in early cervical cancer: results of the SENTICOL study. J Clin Oncol, 2011, 29(13):1686–1691

    Article  PubMed  Google Scholar 

  42. Cormier B, Diaz JP, Shih K, et al. Establishing a sentinel lymph node mapping algorithm for the treatment of early cervical cancer. Gynecol Oncol, 2011, 122(2):275–280

    Article  PubMed  PubMed Central  Google Scholar 

  43. Slama J, Dundr P, Dusek L, et al. High false negative rate of frozen section examination of sentinel lymph nodes in patients with cervical cancer. Gynecol Oncol, 2013, 29(2):384–388

    Article  Google Scholar 

  44. Sonoda K, Yahata H, Okugawa K, et al. Value of Intraoperative Cytological and Pathological Sentinel Lymph Node Diagnosis in Fertility-Sparing Trachelectomy for Early-Stage Cervical Cancer. Oncology, 2018, 94(2):92–98

    Article  PubMed  Google Scholar 

  45. Cserni G. Intraoperative analysis of sentinel lymph nodes in breast cancer by one-step nucleic acid amplification. J Clin Pathol, 2012, 65(3):193–199

    Article  PubMed  CAS  Google Scholar 

  46. Tamaki Y. One-step nucleic acid amplification (OSNA): where do we go with it? Int J Clin Oncol, 2017, 22(1):3–10

    Article  PubMed  CAS  Google Scholar 

  47. Okamoto S, Niikura H, Nakabayashi K, et al. Detection of sentinel lymph node metastases in cervical cancer: assessment of KRT19 mRNA in the one-step nucleic acid amplification (OSNA) method. Gynecol Oncol, 2013, 130(3):530–536

    Article  PubMed  CAS  Google Scholar 

  48. Horn LC, Hentschel B, Fischer U, et al. Detection of micrometastases in pelvic lymph nodes in patients with carcinoma of the cervix uteri using step sectioning: frequency, topographic distribution and prognostic impact. Gynecol Oncol, 2008, 111(2):276–281

    Article  PubMed  Google Scholar 

  49. Lentz SE, Muderspach LI, Felix JC et al. Identification of micrometastases in histologically negative lymph nodes of early-stage cervical cancer patients. Obstet Gynecol, 2004, 103(6):1204–1210

    Article  PubMed  Google Scholar 

  50. Marchiole P, Buenerd A, Benchaib M, et al. Clinical significance of lympho vascular space involvement and lymph node micrometastases in early-stage cervical cancer: a retrospective case-control surgicopathological study. Gynecol Oncol, 2005, 97(3):727–732

    Article  PubMed  Google Scholar 

Download references

Author information

Affiliations

Authors

Corresponding author

Correspondence to Fang Fang.

Additional information

This work is supported by the Natural Science Foundation of Hubei Province (No. 2015CKB739).

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Huang, Bx., Fang, F. Progress in the Study of Lymph Node Metastasis in Early-stage Cervical Cancer. CURR MED SCI 38, 567–574 (2018). https://doi.org/10.1007/s11596-018-1915-0

Download citation

  • Received:

  • Revised:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11596-018-1915-0

Key words

  • lymph node metastasis
  • cervical cancer
  • sentinel lymph node
  • micrometastasis