Association between human papillomavirus status and the accuracy of [18F]-FDG PET/CT for detecting inguinal metastasis in penile cancer

Authors

  • Ida Marie Nordanger Department of Urology, Haukeland University Hospital, Bergen, Norway; Department. of Clinical Medicine, University of Bergen, Bergen, Norway https://orcid.org/0009-0009-0437-0600
  • Torjan Magne Haslerud Department of Radiology, NM/PET-Centre, Haukeland University Hospital, Bergen, Norway; Department of Radiology, NM/PET-Centre, Stavanger University Hospital, Stavanger, Norway
  • Alfred Honoré Department of Urology, Haukeland University Hospital, Bergen, Norway; Department. of Clinical Medicine, University of Bergen, Bergen, Norway https://orcid.org/0000-0003-0420-2585
  • Tor Kristian Thorkelsen Department of Urology, Haukeland University Hospital, Bergen, Norway https://orcid.org/0000-0002-3032-6883
  • Patrick Juliebø-Jones Department of Urology, Haukeland University Hospital, Bergen, Norway; Department. of Clinical Medicine, University of Bergen, Bergen, Norway https://orcid.org/0000-0003-4253-1283
  • Daniela Elena Costea Department. of Clinical Medicine, University of Bergen, Bergen, Norway; Department of Pathology, Haukeland University Hospital, Bergen, Norway https://orcid.org/0000-0001-7673-0358
  • Ellen Berget Department of Pathology, Haukeland University Hospital, Bergen, Norway https://orcid.org/0000-0003-3613-8186
  • Christian Beisland Department of Urology, Haukeland University Hospital, Bergen, Norway; Department. of Clinical Medicine, University of Bergen, Bergen, Norway https://orcid.org/0000-0002-3216-4937
  • Christian Arvei Moen Department of Urology, Haukeland University Hospital, Bergen, Norway; Department. of Clinical Medicine, University of Bergen, Bergen, Norway https://orcid.org/0000-0002-8356-0526

DOI:

https://doi.org/10.2340/sju.v60.45027

Keywords:

diagnostic accuracy, 18F-FDG PET/CT, human papillomavirus, lymph node metastasis, penile cancer, staging

Abstract

Objectives: [18F]-FDG positron emission tomography combined with computed tomography (PET/CT) allows the non-invasive assessment of inguinal lymph node (ILN) status in penile squamous cell carcinoma (PSCC). The aim of this study was to assess if the diagnostic accuracy of PET/CT was influenced by the human papillomavirus (HPV) status of the tumor.

Methods: This retrospective study included 81 treatment-naïve patients with PSCC who underwent surgery between 2010 and 2024 and had a PET/CT before ILN surgery. Inguinal results were compared with histopathology (n = 72) or follow-up findings (n = 9), stratified by HPV status.

Results: HPV DNA was detected in tumor tissue from 41 (51%) patients. The sensitivity and specificity of PET/CT to detect an ILN metastasis were 83% (69%–93%) and 68% (58%–76%), with no significant differences when stratified by HPV status (both P > 0.8). In multivariable logistic regression, after adjustment for the clinical nodal stage, the timing of PET/CT (before or after penile surgery), number of FDG-positive ILNs, the maximum standardized uptake value (SUVmax) of the ILNs and HPV status, SUVmax remained associated with ILN metastasis (OR 1.18, 95% CI: (1.05–1.38), P = 0.023). There was, however, no significant interaction between HPV status and SUVmax (P = 0.57).

Conclusions: The diagnostic accuracy of [18F]-FDG PET/CT regarding preoperative detection of ILN metastasis was not associated with the HPV status in penile cancer. These findings indicate that HPV status does not need to be considered when interpreting the inguinal findings of preoperative PET/CT scans.

Downloads

Download data is not yet available.

References

Thomas A, Necchi A, Muneer A, et al. Penile cancer. Nat Rev Dis Primers. 2021;7:11. https://doi.org/10.1038/s41572-021-00246-5 DOI: https://doi.org/10.1038/s41572-021-00246-5

Cubilla AL, Velazquez EF, Amin MB, et al. The World Health Organisation 2016 classification of penile carcinomas: a review and update from the International Society of Urological Pathology expert-driven recommendations. Histopathology. 2018;72:893–904. https://doi.org/10.1111/his.13429 DOI: https://doi.org/10.1111/his.13429

Sachdeva A, McGuinness L, Zapala L, et al. Management of lymph node-positive penile cancer: a systematic review. Eur Urol. 2024;85:257–73. https://doi.org/10.1016/j.eururo.2023.04.018 DOI: https://doi.org/10.1016/j.eururo.2023.04.018

Brouwer OR, Albersen M, Parnham A, et al. European Association of Urology–American Society of Clinical Oncology Collaborative Guideline on Penile Cancer: 2023 Update. Eur Urol. 2023;83:548–60. https://doi.org/10.1016/j.eururo.2023.02.027 DOI: https://doi.org/10.1016/j.eururo.2023.02.027

Gopman JM, Djajadiningrat RS, Baumgarten AS, et al. Predicting postoperative complications of inguinal lymph node dissection for penile cancer in an international multicentre cohort. BJU Int. 2015;116:196–201. https://doi.org/10.1111/bju.13009 DOI: https://doi.org/10.1111/bju.13009

Wever L, de Vries HM, Dell’Oglio P, et al. Incidence and risk factor analysis of complications after sentinel node biopsy for penile cancer. BJU Int. 2022;130:486–95. https://doi.org/10.1111/bju.15725 DOI: https://doi.org/10.1111/bju.15725

Ottenhof SR, Vegt E. The role of PET/CT imaging in penile cancer. Transl Androl Urol. 2017;6:833–8. https://doi.org/10.21037/tau.2017.04.36 DOI: https://doi.org/10.21037/tau.2017.04.36

Sadeghi R, Gholami H, Zakavi SR, et al. Accuracy of 18F-FDG PET/CT for diagnosing inguinal lymph node involvement in penile squamous cell carcinoma: systematic review and meta-analysis of the literature. Clin Nucl Med. 2012;37:436–41. https://doi.org/10.1097/RLU.0b013e318238f6ea DOI: https://doi.org/10.1097/RLU.0b013e318238f6ea

Jakobsen JK, Frahm Nielsen T, Ipsen P, et al. DaPeCa-7: comparative assessment of fluorodeoxyglucose positron emission tomography/computed tomography (CT) and conventional diagnostic CT in diagnosis of lymph node metastases, distant metastases and incidental findings in patients with invasive penile cancer. BJU Int. 2021;127:254–62. https://doi.org/10.1111/bju.15206 DOI: https://doi.org/10.1111/bju.15206

Lee SW, Kim SJ. Diagnostic performance of 18F-FDG PET/CT for lymph node staging in penile cancer. Clin Nucl Med. 2022;47:402–8. https://doi.org/10.1097/RLU.0000000000004081 DOI: https://doi.org/10.1097/RLU.0000000000004081

Vandermaesen K, Elst L, Defraigne C, et al. The prognostic role of HPV status in penile squamous cell carcinoma: a systematic review and meta-analysis. Int J Impot Res. 2025;37:782–93. https://doi.org/10.1038/s41443-025-01145-z DOI: https://doi.org/10.1038/s41443-025-01145-z

Moen CA, Falkenthal TE, Thorkelsen TK, et al. Penile cancers attributed to human papillomavirus are associated with improved survival for node-positive patients. Findings from a Norwegian Cohort Study Spanning 50 years. Eur Urol Oncol. 2024;7:778–85. https://doi.org/10.1016/j.euo.2023.10.013 DOI: https://doi.org/10.1016/j.euo.2023.10.013

Nordanger IM, Beisland C, Thorkelsen TK, et al. The prognostic value of human papillomavirus status in penile cancer: outcomes from a Norwegian cohort study. Clin Genitourin Cancer. 2024;22:102127. https://doi.org/10.1016/j.clgc.2024.102127 DOI: https://doi.org/10.1016/j.clgc.2024.102127

Brierley J, Gospodarowicz MK, Wittekind C. TNM classification of malignant tumours. Chichester, UK: Wiley; 2017. DOI: https://doi.org/10.1002/9780471420194.tnmc26.pub3

Amy Berrington de G, Cox DR. Interpretation of interaction: a review. Ann Appl Stat. 2007;1:371–85. https://doi.org/10.1214/07-AOAS124 DOI: https://doi.org/10.1214/07-AOAS124

R Core Team_. R: A language and environment for statistical ting [Internet]. Austria: R Foundation for Statistical Computing V; 2024. Available from: https://www.R-project.org/ [Cited date October 17, 2025]

Leijte JA, Graafland NM, Valdes Olmos RA, et al. Prospective evaluation of hybrid 18F-fluorodeoxyglucose positron emission tomography/computed tomography in staging clinically node-negative patients with penile carcinoma. BJU Int. 2009;104:640–4. https://doi.org/10.1111/j.1464-410X.2009.08450.x DOI: https://doi.org/10.1111/j.1464-410X.2009.08450.x

Souillac I, Rigaud J, Ansquer C, et al. Prospective evaluation of (18)F- fluorodeoxyglucose positron emission tomography-computerized tomography to assess inguinal lymph node status in invasive squamous cell carcinoma of the penis. J Urol. 2012;187:493–7. https://doi.org/10.1016/j.juro.2011.10.033 DOI: https://doi.org/10.1016/j.juro.2011.10.033

Schlenker B, Scher B, Tiling R, et al. Detection of inguinal lymph node involvement in penile squamous cell carcinoma by 18F-fluorodeoxyglucose PET/CT: a prospective single- center study. Urol Oncol. 2012;30:55–9. https://doi.org/10.1016/j.juro.2011.10.033 DOI: https://doi.org/10.1016/j.urolonc.2009.10.012

Hughes B, Leijte J, Shabbir M, et al. Non-invasive and minimally invasive staging of regional lymph nodes in penile cancer. World J Urol. 2009;27:197–203. https://doi.org/10.1007/s00345-008-0288-6 DOI: https://doi.org/10.1007/s00345-008-0288-6

Mirvald C, Garaz R, Sinescu I, et al. Current role of PET CT in staging and management of penile cancers. J. Clin. Med. 2024, 13(16), 4879. https://doi.org/10.20944/preprints202407.0356.v1 DOI: https://doi.org/10.3390/jcm13164879

Salazar A, Junior EP, Salles PGO, et al. (18)F-FDG PET/CT as a prognostic factor in penile cancer. Eur J Nucl Med Mol Imaging. 2019;46:855–63. https://doi.org/10.1007/s00259-018-4128-7 DOI: https://doi.org/10.1007/s00259-018-4128-7

Ottenhof SR, Djajadiningrat RS, Versleijen MWJ, et al. F-18 fluorodeoxyglucose positron emission tomography with computed tomography has high diagnostic value for pelvic and distant staging in patients with high-risk penile carcinoma. Eur Urol Focus. 2022;8:98–104. https://doi.org/10.1016/j.euf.2021.02.012 DOI: https://doi.org/10.1016/j.euf.2021.02.012

Bandini M, Ross JS, Zhu Y, et al. Association between human papillomavirus infection and outcome of perioperative nodal radiotherapy for penile carcinoma. Eur Urol Oncol. 2021;4:802–10. https://doi.org/10.1016/j.euo.2020.10.011 DOI: https://doi.org/10.1016/j.euo.2020.10.011

Bezerra SM, Chaux A, Ball MW, et al. Human papillomavirus infection and immunohistochemical p16(INK4a) expression as predictors of outcome in penile squamous cell carcinomas. Hum Pathol. 2015;46:532–40. https://doi.org/10.1016/j.humpath.2014.12.004 DOI: https://doi.org/10.1016/j.humpath.2014.12.004

Djajadiningrat RS, Jordanova ES, Kroon BK, et al. Human papillomavirus prevalence in invasive penile cancer and association with clinical outcome. J Urol. 2015;193:526–31. https://doi.org/10.1016/j.juro.2014.08.087 DOI: https://doi.org/10.1016/j.juro.2014.08.087

Hu J, Cui Y, Liu P, et al. Predictors of inguinal lymph node metastasis in penile cancer patients: a meta-analysis of retrospective studies. Cancer Manag Res. 2019;11:6425–41. https://doi.org/10.2147/CMAR.S206579 DOI: https://doi.org/10.2147/CMAR.S206579

Downloads

Additional Files

Published

2025-12-16

How to Cite

Nordanger, I. M., Haslerud, T. M., Honoré, A., Thorkelsen, T. K., Juliebø-Jones, P., Costea, D. E., … Moen, C. A. (2025). Association between human papillomavirus status and the accuracy of [18F]-FDG PET/CT for detecting inguinal metastasis in penile cancer. Scandinavian Journal of Urology, 60, 229–234. https://doi.org/10.2340/sju.v60.45027

Issue

Vol. 60 (2025)

Section

Publications

License

Copyright (c) 2025 Ida Marie Nordanger, Torjan Magne Haslerud, Alfred Honoré, Tor Kristian Thorkelsen, Patrick Juliebø-Jones, Daniela Elena Costea, Ellen Berget, Christian Beisland, Christian Arvei Moen

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 International License.

As from Volume 59 (2024) all published articles, unless otherwise specified, are published under CC-BY license, allowing third parties to copy and redistribute the material in any medium or format and to remix, transform, and build upon the material, with the condition of proper attribution to the original work. 

Crossref
Scopus
Google Scholar
Europe PMC