Skip to main content

Advertisement

Log in

Adenocarcinoma of the Uterine Cervix: Why Is it Different?

  • Gynecologic Cancers (NS Reed, Section Editor)
  • Published:
Current Oncology Reports Aims and scope Submit manuscript

Abstract

Adenocarcinoma (AC) of the uterine cervix is the second most frequent tumor type following squamous cell carcinoma (SCC). According to the National Comprehensive Cancer Network (NCCN) guidelines, there is no difference in the treatment strategy between SCC and AC. However, there are a number of studies that suggest a worse prognosis for AC compared to SCC. In this comprehensive review, we will try to find the reason why AC is different from SCC, and then discuss what we need to do to improve the prognosis of AC. Uterine cervical AC is clearly different from SCC based on its molecular pathogenesis, histological appearance, and clinical behavior. Therefore, it will be necessary to make a different treatment strategy, particularly for patients with locally advanced and metastatic or recurrent disease. It is most important to intensify our research into the molecular profile of AC, so that we can develop more appropriate targeted therapies. Because of its rarity, international collaboration among clinical trials with translational components will be key to increasing cure rates and improving survivorship.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1

Similar content being viewed by others

References

Papers of particular interest, published recently, have been highlighted as: • Of importance

  1. Kurman RJ, Carcangiu ML, Herrington S, Young R. WHO classification of tumours of female reproductive organs: IARC Press; 2014. This is an important book that describe the updated pathological classification of tumours of female reproductive organs. This is also valuable as a source of basic clinical information of these tumours.

  2. Guideline NCC. NCCN Clinical Practice Guidelines in oncology, cervical cancer. 2014.

    Google Scholar 

  3. Gien LT, Beauchemin MC, Thomas G. Adenocarcinoma: a unique cervical cancer. Gynecol Oncol. 2010;116:140–6.

    Article  CAS  PubMed  Google Scholar 

  4. Ramirez PT, Jhingran A, Macapinlac HA, et al. Laparoscopic extraperitoneal para-aortic lymphadenectomy in locally advanced cervical cancer: a prospective correlation of surgical findings with positron emission tomography/computed tomography findings. Cancer. 2011;117:1928–34.

    Article  PubMed  Google Scholar 

  5. Ramirez PT, Milam MR. Laparoscopic extraperitoneal paraaortic lymphadenectomy in patients with locally advanced cervical cancer. Gynecol Oncol. 2007;104:9–12.

    Article  PubMed  Google Scholar 

  6. Toita T, Kitagawa R, Hamano T, et al. Phase II study of concurrent chemoradiotherapy with high-dose-rate intracavitary brachytherapy in patients with locally advanced uterine cervical cancer: efficacy and toxicity of a low cumulative radiation dose schedule. Gynecol Oncol. 2012;126:211–6.

    Article  CAS  PubMed  Google Scholar 

  7. Huang YT, Wang CC, Tsai CS, et al. Long-term outcome and prognostic factors for adenocarcinoma/adenosquamous carcinoma of cervix after definitive radiotherapy. Int J Radiat Oncol Biol Phys. 2011;80:429–36.

    Article  PubMed  Google Scholar 

  8. Monk BJ, Sill MW, McMeekin DS, et al. Phase III trial of four cisplatin-containing doublet combinations in stage IVB, recurrent, or persistent cervical carcinoma: a Gynecologic Oncology Group study. J Clin Oncol: Off J Am Soc Clin Oncol. 2009;27:4649–55.

    Article  CAS  Google Scholar 

  9. Moore DH, Blessing JA, McQuellon RP, et al. Phase III study of cisplatin with or without paclitaxel in stage IVB, recurrent, or persistent squamous cell carcinoma of the cervix: a gynecologic oncology group study. J Clin Oncol: Off J Am Soc Clin Oncol. 2004;22:3113–9.

    Article  CAS  Google Scholar 

  10. Curtin JP, Blessing JA, Webster KD, et al. Paclitaxel, an active agent in nonsquamous carcinomas of the uterine cervix: a Gynecologic Oncology Group Study. J Clin Oncol: Off J Am Soc Clin Oncol. 2001;19:1275–8.

    CAS  Google Scholar 

  11. Kastritis E, Bamias A, Efstathiou E, et al. The outcome of advanced or recurrent non-squamous carcinoma of the uterine cervix after platinum-based combination chemotherapy. Gynecol Oncol. 2005;99:376–82.

    Article  CAS  PubMed  Google Scholar 

  12. Nagao S, Fujiwara K, Oda T, et al. Combination chemotherapy of docetaxel and carboplatin in advanced or recurrent cervix cancer—a pilot study. Gynecol Oncol. 2005;96:805–9.

    Article  CAS  PubMed  Google Scholar 

  13. Tewari KS, Sill MW, Long 3rd HJ, et al. Improved survival with bevacizumab in advanced cervical cancer. N Engl J Med. 2014;370:734–43.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  14. Aoki D. Annual report of Gynecologic Oncology Committee, Japan Society of Obstetrics and Gynecology, 2013. J Obstet Gynaecol Res. 2014;40:338–48.

    Article  PubMed  Google Scholar 

  15. Davy ML, Dodd TJ, Luke CG, Roder DM. Cervical cancer: effect of glandular cell type on prognosis, treatment, and survival. Obstet Gynecol. 2003;101:38–45.

    Article  PubMed  Google Scholar 

  16. Eifel PJ, Burke TW, Morris M, Smith TL. Adenocarcinoma as an independent risk factor for disease recurrence in patients with stage IB cervical carcinoma. Gynecol Oncol. 1995;59:38–44.

    Article  CAS  PubMed  Google Scholar 

  17. Hopkins MP, Morley GW. A comparison of adenocarcinoma and squamous cell carcinoma of the cervix. Obstet Gynecol. 1991;77:912–7.

    CAS  PubMed  Google Scholar 

  18. Kasamatsu T, Okada S, Tsuda H, et al. Early invasive adenocarcinoma of the uterine cervix: criteria for nonradical surgical treatment. Gynecol Oncol. 2002;85:327–32.

    Article  PubMed  Google Scholar 

  19. Baalbergen A, Ewing-Graham PC, Hop WC, Struijk P, Helmerhorst TJ. Prognostic factors in adenocarcinoma of the uterine cervix. Gynecol Oncol. 2004;92:262–7.

    Article  CAS  PubMed  Google Scholar 

  20. Monk BJ, Tian C, Rose PG, Lanciano R. Which clinical/pathologic factors matter in the era of chemoradiation as treatment for locally advanced cervical carcinoma? Analysis of two Gynecologic Oncology Group (GOG) trials. Gynecol Oncol. 2007;105:427–33.

    Article  PubMed Central  PubMed  Google Scholar 

  21. Castellsague X, Diaz M, de Sanjose S, et al. Worldwide human papillomavirus etiology of cervical adenocarcinoma and its cofactors: implications for screening and prevention. J Natl Cancer Inst. 2006;98:303–15.

    Article  PubMed  Google Scholar 

  22. Sherman ME, Wang SS, Carreon J, Devesa SS. Mortality trends for cervical squamous and adenocarcinoma in the United States Relation to incidence and survival. Cancer. 2005;103:1258–64.

    Article  PubMed  Google Scholar 

  23. Appleby P, Beral V, Berrington de Gonzalez A, et al. Carcinoma of the cervix and tobacco smoking: collaborative reanalysis of individual data on 13,541 women with carcinoma of the cervix and 23,017 women without carcinoma of the cervix from 23 epidemiological studies. Int J Cancer. 2006;118:1481–95.

    Article  CAS  PubMed  Google Scholar 

  24. Wang SS, Sherman ME, Hildesheim A, Lacey Jr JV, Devesa S. Cervical adenocarcinoma and squamous cell carcinoma incidence trends among white women and black women in the United States for 1976–2000. Cancer. 2004;100:1035–44.

    Article  PubMed  Google Scholar 

  25. Shimada M, Kigawa J, Nishimura R, et al. Ovarian metastasis in carcinoma of the uterine cervix. Gynecol Oncol. 2006;101:234–7.

    Article  PubMed  Google Scholar 

  26. Eifel PJ, Morris M, Oswald MJ, Wharton JT, Delclos L. Adenocarcinoma of the uterine cervix. Prognosis and patterns of failure in 367 cases. Cancer. 1990;65:2507–14.

    Article  CAS  PubMed  Google Scholar 

  27. Kuji S, Hirashima Y, Komeda S, et al. The relationship between positive peritoneal cytology and the prognosis of patients with FIGO stage I/II uterine cervical cancer. J Gynecol Oncol. 2014;25:90–6.

    Article  PubMed Central  PubMed  Google Scholar 

  28. Irie T, Kigawa J, Minagawa Y, et al. Prognosis and clinicopathological characteristics of Ib-IIb adenocarcinoma of the uterine cervix in patients who have had radical hysterectomy. European J Surg Oncolo: J European Soc Surg Oncol British Assoc Surg Oncol. 2000;26:464–7.

    Article  CAS  Google Scholar 

  29. Landoni F, Maneo A, Colombo A, et al. Randomised study of radical surgery versus radiotherapy for stage Ib-IIa cervical cancer. Lancet. 1997;350:535–40.

    Article  CAS  PubMed  Google Scholar 

  30. Rotman M, Sedlis A, Piedmonte MR, et al. A phase III randomized trial of postoperative pelvic irradiation in stage IB cervical carcinoma with poor prognostic features: follow-up of a Gynecologic Oncology Group study. Int J Radiat Oncol Biol Phys. 2006;65:169–76.

    Article  PubMed  Google Scholar 

  31. Park KJ, Kiyokawa T, Soslow RA, et al. Unusual endocervical adenocarcinomas: an immunohistochemical analysis with molecular detection of human papillomavirus. Am J Surg Pathol. 2011;35:633–46.

    Article  PubMed  Google Scholar 

  32. Kojima A, Mikami Y, Sudo T, et al. Gastric morphology and immunophenotype predict poor outcome in mucinous adenocarcinoma of the uterine cervix. Am J Surg Pathol. 2007;31:664–72.

    Article  PubMed  Google Scholar 

  33. Mikami Y, Kiyokawa T, Hata S, et al. Gastrointestinal immunophenotype in adenocarcinomas of the uterine cervix and related glandular lesions: a possible link between lobular endocervical glandular hyperplasia/pyloric gland metaplasia and ‘adenoma malignum’. Mod Pathol: Off J United States and Canadian Acad Pathol, Inc. 2004;17:962–72.

    Article  Google Scholar 

  34. Gilks CB, Young RH, Aguirre P, DeLellis RA, Scully RE. Adenoma malignum (minimal deviation adenocarcinoma) of the uterine cervix. A clinicopathological and immunohistochemical analysis of 26 cases. Am J Surg Pathol. 1989;13:717–29.

    Article  CAS  PubMed  Google Scholar 

  35. Avizienyte E, Loukola A, Roth S, et al. LKB1 somatic mutations in sporadic tumors. Am J Pathol. 1999;154:677–81.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  36. Jones MW, Silverberg SG, Kurman RJ. Well-differentiated villoglandular adenocarcinoma of the uterine cervix: a clinicopathological study of 24 cases. Int J gynecol Pathol: Off J Int Soc Gynecol Pathol. 1993;12:1–7.

    Article  CAS  Google Scholar 

  37. Zhou C, Gilks CB, Hayes M, Clement PB. Papillary serous carcinoma of the uterine cervix: a clinicopathologic study of 17 cases. Am J Surg Pathol. 1998;22:113–20.

    Article  CAS  PubMed  Google Scholar 

  38. Silver SA, Devouassoux-Shisheboran M, Mezzetti TP, Tavassoli FA. Mesonephric adenocarcinomas of the uterine cervix: a study of 11 cases with immunohistochemical findings. Am J Surg Pathol. 2001;25:379–87.

    Article  CAS  PubMed  Google Scholar 

  39. Chao A, Wang TH, Lee YS, et al. Molecular characterization of adenocarcinoma and squamous carcinoma of the uterine cervix using microarray analysis of gene expression. Int J Cancer. 2006;119:91–8.

    Article  CAS  PubMed  Google Scholar 

  40. Wright AA, Howitt BE, Myers AP, et al. Oncogenic mutations in cervical cancer: genomic differences between adenocarcinomas and squamous cell carcinomas of the cervix. Cancer. 2013;119:3776–83.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  41. Galic V, Herzog TJ, Lewin SN, et al. Prognostic significance of adenocarcinoma histology in women with cervical cancer. Gynecol Oncol. 2012;125:287–91.

    Article  PubMed  Google Scholar 

  42. Katsumata N, Yoshikawa H, Kobayashi H, et al. Phase III randomised controlled trial of neoadjuvant chemotherapy plus radical surgery vs radical surgery alone for stages IB2, IIA2, and IIB cervical cancer: a Japan Clinical Oncology Group trial (JCOG 0102). Br J Cancer. 2013;108:1957–63.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  43. Kim HS, Sardi JE, Katsumata N, et al. Efficacy of neoadjuvant chemotherapy in patients with FIGO stage IB1 to IIA cervical cancer: an international collaborative meta-analysis. European J Surg Oncol: J European Soc Surg Oncol British Assoc Surg Oncol. 2013;39:115–24.

    Article  CAS  Google Scholar 

  44. Takekida S, Fujiwara K, Nagao S, et al. Phase II study of combination chemotherapy with docetaxel and carboplatin for locally advanced or recurrent cervical cancer. Int J Gynecol Cancer: Off J Int Gynecol Cancer Soc. 2010;20:1563–8.

    Google Scholar 

  45. Nagai Y, Toita T, Wakayama A, et al. Concurrent chemoradiotherapy with paclitaxel and cisplatin for adenocarcinoma of the cervix. Anticancer Res. 2012;32:1475–9.

    CAS  PubMed  Google Scholar 

  46. Tang J, Tang Y, Yang J, Huang S. Chemoradiation and adjuvant chemotherapy in advanced cervical adenocarcinoma. Gynecol Oncol. 2012;125:297–302.

    Article  PubMed  Google Scholar 

  47. McCusker ME, Cote TR, Clegg LX, Tavassoli FJ. Endocrine tumors of the uterine cervix: incidence, demographics, and survival with comparison to squamous cell carcinoma. Gynecol Oncol. 2003;88:333–9.

    Article  PubMed  Google Scholar 

  48. Wistuba II, Syed S, Behrens C, et al. Comparison of molecular changes in cervical intraepithelial neoplasia in HIV-positive and HIV-indeterminate subjects. Gynecol Oncol. 1999;74:519–26.

    Article  CAS  PubMed  Google Scholar 

  49. Hirai Y, Utsugi K, Takeshima N, et al. Putative gene loci associated with carcinogenesis and metastasis of endocervical adenocarcinomas of uterus determined by conventional and array-based CGH. Am J Obstet Gynecol. 2004;191:1173–82.

    Article  CAS  PubMed  Google Scholar 

  50. Scotto L, Narayan G, Nandula SV, et al. Identification of copy number gain and overexpressed genes on chromosome arm 20q by an integrative genomic approach in cervical cancer: potential role in progression. Genes, Chromosomes and Cancer. 2008;47:755–65.

    Article  CAS  PubMed  Google Scholar 

  51. McCluggage WG, Shah R, Connolly LE, McBride HA. Intestinal-type cervical adenocarcinoma in situ and adenocarcinoma exhibit a partial enteric immunophenotype with consistent expression of CDX2. Int J Gynecolo Pathol: Off J Int Soc Gynecol Pathol. 2008;27:92–100.

    Article  CAS  Google Scholar 

  52. Tornesello ML, Buonaguro L, Buonaguro FM. Mutations of the TP53 gene in adenocarcinoma and squamous cell carcinoma of the cervix: a systematic review. Gynecol Oncol. 2013;128:442–8.

    Article  CAS  PubMed  Google Scholar 

  53. Mikami Y, McCluggage WG. Endocervical glandular lesions exhibiting gastric differentiation: an emerging spectrum of benign, premalignant, and malignant lesions. Adv Anat Pathol. 2013;20:227–37.

    Article  CAS  PubMed  Google Scholar 

Download references

Compliance with Ethics Guidelines

Conflict of Interest

Dr. Keiichi Fujiwara and Dr. Mojgan Devouassoux-Shisheboran have no conflict of interest.

Dr. Bradley Monk has received grants from Roche/Genentech.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Keiichi Fujiwara.

Additional information

This article is part of the Topical Collection on Gynecologic Cancers

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Fujiwara, K., Monk, B. & Devouassoux-Shisheboran, M. Adenocarcinoma of the Uterine Cervix: Why Is it Different?. Curr Oncol Rep 16, 416 (2014). https://doi.org/10.1007/s11912-014-0416-y

Download citation

  • Published:

  • DOI: https://doi.org/10.1007/s11912-014-0416-y

Keywords

Navigation