The University of Southampton
University of Southampton Institutional Repository

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
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.
2397-768X
Peleva, Emelia
39409659-4cab-4680-8c27-d55ac94cef2f
Chen, Yue
894fe326-9381-4d8b-851f-d75668e61ec3
Finke, Bernhard
eddcff4e-2aac-4cf0-869f-64919bff9a07
Rizvi, Hasan
34b030f7-8987-43f6-94a0-8cc7e82fcde1
Healy, Eugene
400fc04d-f81a-474a-ae25-7ff894be0ebd
Lai, Chester
31e6848a-758b-45ba-8478-caa0acaa0398
Craig, Paul
cdf2b406-b13c-484a-a46f-9373b855ccee
Rickaby, William
349779b0-b396-4f52-9fc4-8abddec8fc6f
Schoenherr, Christina
6dab05ef-8828-4d60-b9cc-1852b66aec46
Nourse, Craig
44d9b62f-e0ec-4759-b9c3-557cc1b12591
Proby, Charlotte
d4ea66c4-feed-4664-812a-cc476f7dd92a
Inman, Gareth J.
7aa8491e-2759-4e7b-a0e9-abc3d0bdda19
Leigh, Irene M.
2d991daf-a467-42f5-bfa7-0a7b749bc136
Harwood, Catherine A.
527f74fc-26e7-4b84-b375-0983ed06b8a5
Wang, Jun
e57046ca-9c7b-41f8-a911-3ab32e8da12f
Peleva, Emelia
39409659-4cab-4680-8c27-d55ac94cef2f
Chen, Yue
894fe326-9381-4d8b-851f-d75668e61ec3
Finke, Bernhard
eddcff4e-2aac-4cf0-869f-64919bff9a07
Rizvi, Hasan
34b030f7-8987-43f6-94a0-8cc7e82fcde1
Healy, Eugene
400fc04d-f81a-474a-ae25-7ff894be0ebd
Lai, Chester
31e6848a-758b-45ba-8478-caa0acaa0398
Craig, Paul
cdf2b406-b13c-484a-a46f-9373b855ccee
Rickaby, William
349779b0-b396-4f52-9fc4-8abddec8fc6f
Schoenherr, Christina
6dab05ef-8828-4d60-b9cc-1852b66aec46
Nourse, Craig
44d9b62f-e0ec-4759-b9c3-557cc1b12591
Proby, Charlotte
d4ea66c4-feed-4664-812a-cc476f7dd92a
Inman, Gareth J.
7aa8491e-2759-4e7b-a0e9-abc3d0bdda19
Leigh, Irene M.
2d991daf-a467-42f5-bfa7-0a7b749bc136
Harwood, Catherine A.
527f74fc-26e7-4b84-b375-0983ed06b8a5
Wang, Jun
e57046ca-9c7b-41f8-a911-3ab32e8da12f

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).

Record type: Article

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.

Text
Enhanced metastasis risk prediction in cutaneous squamous cell carcinoma using deep learning and computational histopathology - Accepted Manuscript
Available under License Creative Commons Attribution.
Download (17MB)
Text
Supplementary material - Accepted Manuscript
Available under License Creative Commons Attribution.
Download (4MB)
Text
s41698-025-01065-7 - Version of Record
Available under License Creative Commons Attribution.
Download (2MB)
Text
Proof of acceptance
Restricted to Repository staff only
Request a copy

More information

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

Catalogue record

Date deposited: 16 Sep 2025 16:50
Last modified: 23 Sep 2025 17:12

Export record

Altmetrics

Contributors

Author: Emelia Peleva
Author: Yue Chen
Author: Bernhard Finke
Author: Hasan Rizvi
Author: Eugene Healy
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

Download statistics

Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.

View more statistics

Atom RSS 1.0 RSS 2.0

Contact ePrints Soton: eprints@soton.ac.uk

ePrints Soton supports OAI 2.0 with a base URL of http://eprints.soton.ac.uk/cgi/oai2

This repository has been built using EPrints software, developed at the University of Southampton, but available to everyone to use.

We use cookies to ensure that we give you the best experience on our website. If you continue without changing your settings, we will assume that you are happy to receive cookies on the University of Southampton website.

×