Enhanced metastasis risk prediction in cutaneous squamous cell carcinoma using deep learning and computational histopathology
Enhanced metastasis risk prediction in cutaneous squamous cell carcinoma using deep learning and computational histopathology
Cutaneous squamous cell carcinoma (cSCC) is the most common skin cancer with metastatic potential and development of metastases carries a poor prognosis. To address the need for reliable risk stratification, we developed cSCCNet, a deep learning model using digital pathology of primary cSCC to predict metastatic risk. A retrospective cohort of 227 primary cSCC from four centres is used for model development. cSCCNet automatically selects the tumour area in standard histopathological slides and then stratifies primary cSCC into high- vs. low-risk categories, with heatmaps indicating most predictive tiles contributing to explainability. On a 20% hold-out testing cohort, cSCCNet achieves an area under the curve (AUC) of 0.95 and 95% accuracy in predicting risk of metastasis, outperforming gene expression-based tools and clinicopathologic classifications. Multivariate analysis including common clinicopathologic classifications confirm cSCCNet as an independent predictor for metastasis, implying it identifies predictive factors beyond known clinicopathologic risk factors. Histopathological analysis including multiplex immunohistochemistry suggests that tumour differentiation, acantholysis, desmoplasia, and the spatial localisation of lymphocytes relative to tumour tissue may be important in predicting risk of developing metastasis. Although further validation including prospective evaluation is required, cSCCNet has potential as a reliable and accurate tool for metastatic risk prediction that could be easily integrated into existing histopathology workflows.
Peleva, Emelia
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Chen, Yue
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Finke, Bernhard
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Rizvi, Hasan
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Healy, Eugene
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Lai, Chester
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Craig, Paul
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Rickaby, William
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Schoenherr, Christina
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Nourse, Craig
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Proby, Charlotte
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Inman, Gareth J.
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Leigh, Irene M.
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Harwood, Catherine A.
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Wang, Jun
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2 September 2025
Peleva, Emelia
39409659-4cab-4680-8c27-d55ac94cef2f
Chen, Yue
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Finke, Bernhard
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Rizvi, Hasan
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Healy, Eugene
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Lai, Chester
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Craig, Paul
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Rickaby, William
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Schoenherr, Christina
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Nourse, Craig
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Proby, Charlotte
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Inman, Gareth J.
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Leigh, Irene M.
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Harwood, Catherine A.
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Wang, Jun
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Peleva, Emelia, Chen, Yue, Finke, Bernhard, Rizvi, Hasan, Healy, Eugene, Lai, Chester, Craig, Paul, Rickaby, William, Schoenherr, Christina, Nourse, Craig, Proby, Charlotte, Inman, Gareth J., Leigh, Irene M., Harwood, Catherine A. and Wang, Jun
(2025)
Enhanced metastasis risk prediction in cutaneous squamous cell carcinoma using deep learning and computational histopathology.
npj Precision Oncology, 9 (1), [308].
(doi:10.1038/s41698-025-01065-7).
Abstract
Cutaneous squamous cell carcinoma (cSCC) is the most common skin cancer with metastatic potential and development of metastases carries a poor prognosis. To address the need for reliable risk stratification, we developed cSCCNet, a deep learning model using digital pathology of primary cSCC to predict metastatic risk. A retrospective cohort of 227 primary cSCC from four centres is used for model development. cSCCNet automatically selects the tumour area in standard histopathological slides and then stratifies primary cSCC into high- vs. low-risk categories, with heatmaps indicating most predictive tiles contributing to explainability. On a 20% hold-out testing cohort, cSCCNet achieves an area under the curve (AUC) of 0.95 and 95% accuracy in predicting risk of metastasis, outperforming gene expression-based tools and clinicopathologic classifications. Multivariate analysis including common clinicopathologic classifications confirm cSCCNet as an independent predictor for metastasis, implying it identifies predictive factors beyond known clinicopathologic risk factors. Histopathological analysis including multiplex immunohistochemistry suggests that tumour differentiation, acantholysis, desmoplasia, and the spatial localisation of lymphocytes relative to tumour tissue may be important in predicting risk of developing metastasis. Although further validation including prospective evaluation is required, cSCCNet has potential as a reliable and accurate tool for metastatic risk prediction that could be easily integrated into existing histopathology workflows.
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Enhanced metastasis risk prediction in cutaneous squamous cell carcinoma using deep learning and computational histopathology
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- Accepted Manuscript
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s41698-025-01065-7
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Accepted/In Press date: 21 July 2025
Published date: 2 September 2025
Identifiers
Local EPrints ID: 504606
URI: http://eprints.soton.ac.uk/id/eprint/504606
ISSN: 2397-768X
PURE UUID: 5fbdb368-01da-4e0a-9915-c1c71d1d269d
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Date deposited: 16 Sep 2025 16:50
Last modified: 23 Sep 2025 17:12
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Contributors
Author:
Emelia Peleva
Author:
Yue Chen
Author:
Bernhard Finke
Author:
Hasan Rizvi
Author:
Chester Lai
Author:
Paul Craig
Author:
William Rickaby
Author:
Christina Schoenherr
Author:
Craig Nourse
Author:
Charlotte Proby
Author:
Gareth J. Inman
Author:
Irene M. Leigh
Author:
Catherine A. Harwood
Author:
Jun Wang
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