Risk factors for metastatic cutaneous squamous cell carcinoma: Refinement and replication based on 2 nationwide nested case-control studies

Selin Tokez, Zoe C. Venables, Loes M. Hollestein, Hongchao Qi, Edo M. Bramer, Barbara Rentroia-Pacheco, Renate R. van den Bos, Brian Rous, Irene M. Leigh, Tamar Nijsten, Antien L. Mooyaart, Marlies Wakkee*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

9 Citations (Scopus)
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Background: Risk factors for cutaneous squamous cell carcinoma (cSCC) metastasis have been investigated only in relatively small data sets. Objective: To analyze and replicate risk factors for metastatic cSCC. Methods: From English and Dutch nationwide cancer registry cohorts, metastatic cases were selected and 1:1 matched to controls. The variables were extracted from pathology reports from the National Disease Registration Service in England. In the Netherlands, histopathologic slides from the Dutch Pathology Registry were revised by a dermatopathologist. Model building was performed in the English data set using backward conditional logistic regression, whereas replication was performed using the Dutch data set. Results: In addition to diameter and thickness, the following variables were significant risk factors for metastatic cSCC in the English data set (n = 1774): poor differentiation (odds ratio [OR], 4.56; 95% CI, 2.99-6.94), invasion in (OR, 1.69; 95% CI, 1.05-2.71)/beyond (OR, 4.43; 95% CI, 1.98-9.90) subcutaneous fat, male sex (OR, 2.59; 95% CI, 1.70-3.96), perineural/lymphovascular invasion (OR, 2.12; 95% CI, 1.21-3.71), and facial localization (OR, 1.57; 95% CI, 1.02-2.41). Diameter and thickness showed significant nonlinear relationships with metastasis. Similar ORs were observed in the Dutch data set (n = 434 cSCCs). Limitations: Retrospective use of pathology reports in the English data set. Conclusion: cSCC staging systems can be improved by including differentiation, clinical characteristics such as sex and tumor location, and nonlinear relationships for diameter and thickness.

Original languageEnglish
Pages (from-to)64-71
Number of pages8
JournalJournal of the American Academy of Dermatology
Issue number1
Early online date5 Mar 2022
Publication statusPublished - 1 Jul 2022

Bibliographical note

Funding Information:
Funding sources: Supported by Alphatron. IRB approval status: Ethical approval and informed consent for the English data were not required because data were collected and reported by cancer registries using the statutory power provided by section 251 of the National Health Service act 2006. For the analyses using data from the Netherlands Cancer Registry and nationwide network and registry of histopathology and cytopathology (PALGA), approval was obtained from the scientific committees of the Netherlands Cancer Registry, PALGA, Dutch Transplant Foundation, and the Erasmus Medical Center (MEC-2020-0147), and a waiver of informed consent was granted following the code of conduct of the Foundation Federation of Dutch Medical Scientific Societies.

Publisher Copyright:
© 2022 American Academy of Dermatology, Inc.


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