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FIGO 2018 stage IB endocervical adenocarcinomas: an international study of outcomes informed by prognostic biomarkers
  1. Simona Stolnicu1,
  2. Monica Boros2,
  3. Lien Hoang3,
  4. Noorah Almadani3,
  5. Louise de Brot4,
  6. Glauco Baiocchi5,
  7. Graziele Bonvolim5,
  8. Carlos Parra-Herran6,
  9. Sofia Lerias7,
  10. Ana Felix8,
  11. Andres Roma9,
  12. Anna Pesci10,
  13. Esther Oliva11,
  14. Kay Park12,
  15. Robert A Soslow12 and
  16. Nadeem R Abu-Rustum13
  1. 1Department of Pathology, University of Medicine, Pharmacy, Sciences and Technology, Targu Mures, Romania
  2. 2Department of Pathology, University of Oradea, Oradea, Romania
  3. 3Department of Pathology, Vancouver General Hospital, Vancouver, British Columbia, Canada
  4. 4Medical Oncology, A.C. Camargo Cancer Center, São Paulo, Brazil
  5. 5Department of Pathology, A C Camargo Cancer Center, São Paulo, Brazil
  6. 6Department of Pathology, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada
  7. 7Department of Pathology, Instituto Portugues de Oncologia, Lisbon, Portugal
  8. 8Department of Pathology, Universidade de Lisboa, Lisbon, Portugal
  9. 9Department of Pathology, University of California San Diego, La Jolla, California, USA
  10. 10Department of Pathology, IRCSS Ospedale Sacro Cuore Don Calabria, Negrar, Italy
  11. 11Department of Pathology, Massachusetts General Hospital, Boston, Massachusetts, USA
  12. 12Pathology, Memorial Sloan Kettering Cancer Center, New York, New York, USA
  13. 13Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York, USA
  1. Correspondence to Dr Simona Stolnicu, University of Medicine, Pharmacy, Sciences and Technology, Targu Mures 540142, Romania; simonastolnicu{at}


Objective Prognostic factors for endocervical adernocarcinomas are well known, but little is known about prognostic biomarkers influencing outcome for the newly defined International Federation of Gynecology and Obstetrics (FIGO) 2018 IB sub-stages. The aim of this study was to identify prognostic biomarkers influencing recurrence-free and overall survival for FIGO 2018 stage IB cervical adenocarcinoma sub-types. We sought to identify these factors using a large international multi-institutional series of cases.

Methods Stage IB endocervical adenocarcinomas were retrospectively collected from nine international institutions; full slide sets (n=464) were used to assign prognostic biomarkers. Inclusion criteria were the following: FIGO stage IB endocervical adenocarcinomas with follow-up in which all paraffin blocks/glass slides were available for review and/or additional studies and the patient was surgically treated from 1985 to 2019. The types of specimens included in the study were conizations, trachelectomies, and simple/radical hysterectomies with or without lymph node samples. We excluded in situ carcinomas, squamous cell carcinomas, adenosquamous carcinomas, tumors with a neuroendocrine component, carcinosarcomas, and any tumor showing clinical, macroscopic, or microscopic features suggesting a lower uterine segment, uterine corpus, or an adnexal primary origin. Tumors treated with neoadjuvant chemotherapy and/or radiation therapy were also excluded, as well as biopsies and loop electrosurgical excision procedures.

Results Of 464 cases, 225 (48%) were stage IB1, 177 (38%) were stage IB2, and 62 (13%) were stage IB3. Five-year and 10-year recurrence-free survivals were statistically different among stage IB sub-types (p=0.005). Silva pattern of invasion was significant for recurrence-free survival at 5 and 10 years (p=0.04); overall survival and recurrence-free survival were higher in human papillomavirus (HPV)-associated cases (p=0.007 and p=0.001, respectively) and in cases without lymphovascular invasion (p=0.004 and p=0.00001, respectively). Factors that significantly influenced recurrence-free survival were HPV-independent status (p=0.05; HR 2.31; 95% CI 1.02 to 5.46), presence of lymphovascular invasion (p=0.011; HR 3.50; 95% CI 1.33 to 9.19), and presence of lymph node metastasis (p=0.016; HR 2.66; 95% CI 1.20 to 5.90).

Conclusion HPV status and the presence of lymphovascular invasion are prognosticators in stage IB endocervical adenocarcinoma sub-types. These parameters should be included in future sub-staging modifications of FIGO stage IB endocervical adenocarcinomas and in treatment strategies.

  • adenocarcinoma
  • pathology

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  • Contributors Conceptualization: SS, RAS, NRA-R. Data curation: all authors. Formal analysis: MB. Funding acquisition: RAS, KP, NRA-R. Investigation: SS, RAS, MB, NRA-R. Methodology: SS, RAS, NRA-R. Project administration: NRA-R. Resources; RAS, KP, NRA-R. Software: MB. Supervision: NRA-R. Validation: RAS, NRA-R. Visualization: SS. Roles/writing original draft: SS, RAS, NRA-R. Writing - review and editing: all authors.

  • Funding This research was funded in part through the National Institutes of Health/National Cancer Institute Cancer Center Support Grant P30 CA008748.

  • Competing interests Outside the submitted work, NRA-R reports grants from Stryker/Novadaq, Olympus, and GRAIL.

  • Patient consent for publication Not required.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement Data are available upon reasonable request. Please contact the corresponding author for data requests.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.