Journal of Cancer Research and Clinical Oncology

, Volume 145, Issue 2, pp 457–462 | Cite as

Prognostic relevance of low-grade versus high-grade FIGO IB1 squamous cell uterine cervical carcinomas

  • Lars-Christian HornEmail author
  • Anne Katrin Höhn
  • Bettina Hentschel
  • Uta Fischer
  • Karl Bilek
  • Christine E. Brambs
Original Article – Clinical Oncology



Tumor grade is one of the more controversial factors with limited prognostic information in squamous cell carcinomas (SCC) of the uterine cervix.


Histologic slides of 233 surgically treated cervical SCC (FIGO IB1) were re-examined regarding the prognostic impact of the WHO-based grading system, using the different degree of keratinization, categorizing the tumors in G1, G2 and G3 (conventional tumor grade).


45.1% presented with well-differentiated tumors (G1), 29.2% with moderate (G2) and 25.8% with poor differentiation (G3). Tumor grade significantly correlated with decreased recurrence-free and overall survival. However, detailed analyses between G1- and G2-tumors failed to show any correlation with either recurrence-free or overall survival. G1- and G2-tumors were therefore merged into low-grade tumors and were compared to the high-grade group (G3-tumors). This binary conventional grading system showed an improved 5-years recurrence-free (low-grade: 90.2% vs. high-grade: 71.6%; p = 0.001) and overall survival rates (low-grade: 89.9% vs. high-grade: 71.1%; p = 0.001) for low-grade tumors. On multivariate analysis adjusted for lymph node metastasis, high-grade tumors represented a hazard ratio of 2.4 (95% CI 1.3–4.7) for reduced recurrence-free and 2.4 (95% CI 1.2–4.6) for overall survival. High-grade tumors showed a significantly higher risk for pelvic lymph node involvement [OR 2.7 (95% CI 1.4–5.5); p = 0.003]. The traditional three-tiered grading system failed to predict pelvic lymph node metastases.


A binary grading model for the conventional tumor grade (based on the degree of keratinization) in SCC of the uterine cervix may allow a better prognostic discrimination than the traditionally used three-tiered system.


Cervix Cancer Prognosis Grading Histopathology Treatment Squamous cell Survival 



The authors declare that there was no funding of the study.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.


  1. Brierley JD, Gospodarowicz MK, Wittekind C (2017) Cervix uteri. TNM classification of malignant tumors. Wiley-Blackwell, Chichester, pp 166–170Google Scholar
  2. Broders AC (1926) Carcinoma grading and practical application. Arch Pathol 2:376–381Google Scholar
  3. Bryne M, Koppang HS, Lilleng R, Kjaerheim A (1992) Malignancy grading of the deep invasive margins of oral squamous cell carcinomas has high prognostic value. J Pathol 166(4):375–381CrossRefGoogle Scholar
  4. Delgado G, Bundy B, Zaino R, Sevin BU, Creasman WT, Major F (1990) Prospective surgical-pathological study of disease-free interval in patients with stage IB squamous cell carcinoma of the cervix: a Gynecologic Oncology Group study. Gynecol Oncol 38(3):352–357CrossRefGoogle Scholar
  5. Höckel M, Horn LC, Hentschel B, Höckel S, Naumann G (2003 Nov-Dec) Total mesometrial resection: high resolution nerve-sparing radical hysterectomy based on developmentally defined surgical anatomy. Int J Gynecol Cancer 13(6):791–803CrossRefGoogle Scholar
  6. Horn LC, Fischer U, Raptis G, Bilek K, Hentschel B, Richter CE, Braumann UD, Einenkel J (2006) Pattern of invasion is of prognostic value in surgically treated cervical cancer patients. Gynecol Oncol 103(3):906–911CrossRefGoogle Scholar
  7. Horn LC, Hommel N, Roschlau U, Bilek K, Hentschel B, Einenkel J (2012) Peritumoral stromal remodeling, pattern of invasion and expression of c-met/HGF in advanced squamous cell carcinoma of the cervix uteri, FIGO stages III and IV. Eur J Obstet Gynecol Reprod Biol 163(1):76–80CrossRefGoogle Scholar
  8. Kadota K, Miyai Y, Katsuki N, Kushida Y, Matsunaga T, Okuda M, Yokomise H, Kanaji N, Bandoh S, Haba RA (2017) Grading system combining tumor budding and nuclear diameter predicts prognosis in resected lung squamous cell carcinoma. Am J Surg Pathol 41(6):750–760CrossRefGoogle Scholar
  9. Kalluri R, Weinberg RA (2009) The basics of epithelial-mesenchymal transition. J Clin Invest 119(6):1420–1428CrossRefGoogle Scholar
  10. Karamitopoulou E, Zlobec I, Kölzer V, Kondi-Pafiti A, Patsouris ES, Gennatas K, Lugli A (2013) Proposal for a 10-high-power-fields scoring method for the assessment of tumor budding in colorectal cancer. Mod Pathol 26(2):295–301CrossRefGoogle Scholar
  11. Koleli IK, Ozdogan E, Sariibrahim B, Ozturk LB, Karateke A (2014) Prognostic factors affecting lymph node involvement in cervical cancer. Eur J Gynaecol Oncol 35(4):425–428Google Scholar
  12. Kong TW, Kim J, Son JH, Kang SW, Paek J, Chun M, Chang SJ, Ryu HS (2016) Preoperative nomogram for prediction of microscopic parametrial infiltration in patients with FIGO stage IB cervical cancer treated with radical hysterectomy. Gynecol Oncol 142(1):109–114CrossRefGoogle Scholar
  13. Kristensen GB, Abeler VM, Risberg B, Trop C, Bryne M (1999) Tumor size, depth of invasion, and grading of the invasive tumor front are the main prognostic factors in early squamous cell cervical carcinoma. Gynecol Oncol 74(2):245–251CrossRefGoogle Scholar
  14. Kurman RJ, Amin MB (1999) Protocol for the examination of specimens from patients with carcinomas of the cervix: a basis for checklists. Cancer Committee, College of American Pathologists. Arch Pathol Lab Med 123(1):55–61Google Scholar
  15. Macdonald OK, Chen J, Dodson M, Lee CM, Gaffney DK (2009) Prognostic significance of histology and positive lymph node involvement following radical hysterectomy in carcinoma of the cervix. Am J Clin Oncol 32(4):411–416CrossRefGoogle Scholar
  16. Metindir J, Bilir G (2007) Prognostic factors affecting disease-free survival in early-stage cervical cancer patients undergoing radical hysterectomy and pelvic-paraaortic lymphadenectomy. Eur J Gynaecol Oncol 28(1):28–32Google Scholar
  17. Piura B, Rabinovich A, Friger M (2006) Surgical pathologic factors in patients with early-stage cervical carcinoma treated with radical hysterectomy and pelvic lymph node dissection: association with administration of adjuvant radiotherapy and effect on survival. Eur J Gynaecol Oncol 27(6):573–578Google Scholar
  18. Piver MS, Rutledge F, Smith JP (1974) Five classes of extended hysterectomy for women with cervical cancer. Obstet Gynecol 44(2):265–272Google Scholar
  19. Prall F (2007) Tumour budding in colorectal carcinoma. Histopathology 50(1):151–162CrossRefGoogle Scholar
  20. Sartori E, Tisi G, Chiudinelli F, La Face B, Franzini R, Pecorelli S (2007) Early stage cervical cancer: adjuvant treatment in negative lymph node cases. Gynecol Oncol 107(1 Suppl 1):S170–S174CrossRefGoogle Scholar
  21. Silva-Filho AL, Reis FM, Traiman P, Pedrosa MS, Miranda D, Triginelli SA (2005) Clinicopathological features influencing pelvic lymph node metastasis and vaginal and parametrial involvement in patients with carcinoma of the cervix. Gynecol Obstet Invest 59(2):92–96CrossRefGoogle Scholar
  22. Singh N, Arif S (2004) Histopathologic parameters of prognosis in cervical cancer–a review. Int J Gynecol Cancer 14(5):741–750CrossRefGoogle Scholar
  23. Stock RJ, Zaino R, Bundy BN, Askin FB, Woodward J, Fetter B, Paulson JA, DiSaia PJ, Stehman FB (1994) Evaluation and comparison of histopathologic grading systems of epithelial carcinoma of the uterine cervix: Gynecologic Oncology Group studies. Int J Gynecol Pathol 13(2):99–108CrossRefGoogle Scholar
  24. Stoler M, Bergeron C, Colgan TJ, Ferency AS, Herrington CS, Kim KR, Loening T, Schneider A, Sherman ME, Wilbur DC, Wright T (2014) Squamous cell tumors of the uterine cervix and its precursors. In: Kurman RJ, Carcangiou ML, Herrington S, Young RH (eds) WHO classification of tumours of female reproductive organs. IARC Press, Lyon, pp 172–182Google Scholar
  25. Taira T, Ishii G, Nagai K, Yoh K, Takahashi Y, Matsumura Y, Kojima M, Ohmatsu H, Goto K, Niho S, Takashima H, Inoue H, Ohe Y, Ochiai A (2012) Characterization of the immunophenotype of the tumor budding and its prognostic implications in squamous cell carcinoma of the lung. Lung Cancer 76(3):423–430CrossRefGoogle Scholar
  26. Takeda N, Sakuragi N, Takeda M, Okamoto K, Kuwabara M, Negishi H, Oikawa M, Yamamoto R, Yamada H, Fujimoto S (2002) Multivariate analysis of histopathologic prognostic factors for invasive cervical cancer treated with radical hysterectomy and systematic retroperitoneal lymphadenectomy. Acta Obstet Gynecol Scand 81(12):1144–1151CrossRefGoogle Scholar
  27. Travis W, Brambilla E, Muller-Hermelink H et al (2004) World Health Organization classification of tumours pathology and genetics tumours of the lung, pleura, thymus, and heart. IARC Press, LyonGoogle Scholar
  28. Vinh-Hung V, Bourgain C, Vlastos G, Cserni G, De Ridder M, Storme G, Vlastos AT (2007) Prognostic value of histopathology and trends in cervical cancer: a SEER population study. BMC Cancer 7:164CrossRefGoogle Scholar
  29. Wagner AE, Pappas L, Ghia AJ, Gaffney DK (2013) Impact of tumor size on survival in cancer of the cervix and validation of stage IIA1 and IIA2 subdivisions. Gynecol Oncol 129(3):517–521CrossRefGoogle Scholar
  30. Wells M, Östör AG, Crum CP, Franceschi S, Tommasino M, Nesland JM, Goodman AK, Sankaranarayanan R, Hanselaar AG, Albores-Saavedra J (2003) Epithelial Tumors of the uterine cervix. In: Tavassoli FA, Devilee P (eds) Tumors of the breast and female genital organs. IARC Press, Lyon, pp 261–272Google Scholar
  31. Wentz WB, Reagan JW (1959) Survival in cervical cancer with respect to cell type. Cancer 12:384–388CrossRefGoogle Scholar
  32. Xie X, Song K, Cui B, Jiang J, Zhang Y, Wang B, Yang X, Kong B (2016) Significance of the factors associated with parametrial involvement in stage IB to IIA cervical cancer. Int J Gynecol Cancer 26(5):939–943CrossRefGoogle Scholar
  33. Zaino RJ, Ward S, Delgado G, Bundy B, Gore H, Fetter G, Ganjei P (1992) Frauenhoffer E Histopathologic predictors of the behavior of surgically treated stage IB squamous cell carcinoma of the cervix. A Gynecologic Oncology Group study. Cancer 69(7):1750–1758CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Division of Gynecologic, Breast and Perinatal Pathology, Institute of PathologyUniversity Hospital LeipzigLeipzigGermany
  2. 2.Institute for Medical Informatics, Statistics and EpidemiologyUniversity LeipzigLeipzigGermany
  3. 3.Division of Gynecologic Oncologic Surgery, Department of Obstetrics and Gynecology (Institute of Trier)University Hospital LeipzigLeipzigGermany
  4. 4.Department of Obstetrics and GynecologyTechnical University MunichMunichGermany

Personalised recommendations