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  • Molecular subclassification of vulvar squamous cell carcinoma: reproducibility and prognostic significance of a novel surgical technique

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Original research
Molecular subclassification of vulvar squamous cell carcinoma: reproducibility and prognostic significance of a novel surgical technique
  1. Emily F Thompson1,
  2. Lynn Hoang2,
  3. Anne Kathrin Höhn3,
  4. Andrea Palicelli4,
  5. Karen L Talia5,
  6. Nairi Tchrakian1,6,
  7. Janine Senz7,
  8. Rosebud Rusike8,
  9. Suzanne Jordan8,
  10. Amy Jamieson9,
  11. Jutta Huvila10,
  12. Jessica N McAlpine11,
  13. C Blake Gilks2,
  14. Michael Höckel12,
  15. Naveena Singh13 and
  16. Lars-Christian Horn3
  1. 1 Department of Molecular Oncology, BC Cancer Research Center, Vancouver, British Columbia, Canada
  2. 2 Department of Pathology and Laboratory Medicine, Vancouver General Hospital, Vancouver, British Columbia, Canada
  3. 3 Division of Gynecologic Pathology, University of Leipzig, Leipzig, Germany
  4. 4 Pathology Unit, Azienda Unità Sanitaria Locale - IRCCS di Reggio Emilia, Reggio Emilia, Italy
  5. 5 Royal Women’s Hospital and VCS Foundation, Melbourne, Victoria, Australia
  6. 6 Barts Health NHS Trust, London, UK
  7. 7 Department of Molecular Oncology, British Columbia Cancer Research Center, Vancouver, British Columbia, Canada
  8. 8 Barts Health NHS Trust, London, London, UK
  9. 9 Department of Gynecology and Obstetrics, Division of Gynecologic Oncology, The University of British Columbia, Vancouver, British Columbia, Canada
  10. 10 Department of Pathology, University of Turku, Turku, Finland
  11. 11 Gynecology and Obstetrics, Division Gynecologic Oncology, University of British Columbia, Vancouver, British Columbia, Canada
  12. 12 Leipzig School of Radical Pelvis Surgery, Division of Gynecologic Oncology, University Hospital Leipzig, Leipzig, Germany
  13. 13 Cellular Pathology, Barts Health and NHS Trust and Queen Mary University, London, UK
  1. Correspondence to Dr C Blake Gilks, Vancouver General Hospital, Vancouver, BC V5Z 1M9, Canada; blake.gilks{at}vch.ca

Abstract

Objectives Vulvar squamous cell carcinoma is subclassified into three prognostically relevant groups: (i) human papillomavirus (HPV) associated, (ii) HPV independent p53 abnormal (mutant pattern), and (iii) HPV independent p53 wild type. Immunohistochemistry for p16 and p53 serve as surrogates for HPV viral integration and TP53 mutational status. We assessed the reproducibility of the subclassification based on p16 and p53 immunohistochemistry and evaluated the prognostic significance of vulvar squamous cell carcinoma molecular subgroups in a patient cohort treated by vulvar field resection surgery.

Methods In this retrospective cohort study, 68 cases treated by vulvar field resection were identified from the Leipzig School of Radical Pelvic Surgery. Immunohistochemistry for p16 and p53 was performed at three different institutions and evaluated independently by seven pathologists and two trainees. Tumors were classified into one of four groups: HPV associated, HPV independent p53 wild type, HPV independent p53 abnormal, and indeterminate. Selected cases were further interrogated by (HPV RNA in situ hybridization, TP53 sequencing).

Results Final subclassification yielded 22 (32.4%) HPV associated, 41 (60.3%) HPV independent p53 abnormal, and 5 (7.3%) HPV independent p53 wild type tumors. Interobserver agreement (overall Fleiss’ kappa statistic) for the four category classification was 0.74. No statistically significant differences in clinical outcomes between HPV associated and HPV independent vulvar squamous cell carcinoma were observed.

Conclusion Interobserver reproducibility of vulvar squamous cell carcinoma subclassification based on p16 and p53 immunohistochemistry may support routine use in clinical practice. Vulvar field resection surgery showed no significant difference in clinical outcomes when stratified based on HPV status.

  • Vulvar Neoplasms
  • Gynecologic Surgical Procedures

Data availability statement

Data are available upon reasonable request.

https://doi.org/10.1136/ijgc-2021-003251

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    Data availability statement

    Data are available upon reasonable request.

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    Footnotes

    • Contributors ET: investigation, data curation, visualization, writing-original draft, and funding acquisition. LH: writing-review and editing. AKH: investigation and data curation. AP: investigation. KT: investigation, and writing-review and editing. NT: investigation. JS: investigation. RR: investigation. SJ: investigation. AJ: writing-review and editing. JH: investigation, data curation, formal analysis, visualization, and writing-review and editing. JNM: writing-review and editing. CBG: conceptualization, methodology, investigation and guarantor, writing-review and editing, and supervision. MH: writing-review and editing. NS: conceptualization, methodology, investigation, data curation, writing-review and editing, and supervision. L-CH: conceptualization, methodology, investigation, data curation, writing-review and editing, and supervision.

    • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial, or not-for-profit sectors.

    • Competing interests None declared.

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

    • 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.