# Cutaneous squamous cell carcinoma

Source: https://onco.cc/cancers/cutaneous-scc/  
OnCo record `cutaneous-scc` (Cancer). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Cutaneous squamous cell carcinoma is a sun-related skin cancer with over a million US cases a year, almost all cured by removing them. The 2 to 5% that grow deep or spread respond to PD-1 immunotherapy (cemiplimab, pembrolizumab), which is now also given after surgery in high-risk cases; transplant recipients cannot safely receive it.

## Summary

Cutaneous squamous cell carcinoma (cSCC) arises from UV-damaged keratinocytes and has one of the highest mutational burdens of any cancer (TP53, NOTCH1/2, CDKN2A). Immunosuppression (transplant recipients have 65-100-fold higher risk) and chronic wounds are other causes. Most tumours are cured by excision or Mohs surgery; risk of recurrence and metastasis is stratified by BWH/AJCC-8 staging (depth, perineural invasion, differentiation, immunosuppression), with radiotherapy for high-risk or inoperable disease.

Cemiplimab (EMPOWER-CSCC-1, 2018) was the first systemic therapy approved for advanced cSCC, with ~45-50% response and durable disease control; pembrolizumab (KEYNOTE-629, 2020) and cosibelimab (anti-PD-L1, December 2024) followed. Neoadjuvant cemiplimab produced pathological complete response in 51% of stage II-IV disease (Gross, NEJM 2022), and the C-POST trial (2025) showed adjuvant cemiplimab after surgery and radiotherapy cut recurrence in high-risk patients, leading to an adjuvant approval. EGFR antibodies (cetuximab) and chemotherapy are reserved for immunotherapy-ineligible patients such as organ-transplant recipients.

Open: managing transplant recipients (checkpoint inhibitors cause graft rejection), chemoprevention (nicotinamide, acitretin), and the burden of field cancerisation.

## Fields

- Kind: Cancer
- Last checked: 2026-09-08
- Also known as: cSCC; Squamous Cell Carcinoma of the Skin
- Tags: gap-fill; skin
- Group: skin
- Burden: Second most common skin cancer; over one million cases per year in the US, almost all cured by removal; about 2-5% metastasise, which still amounts to several thousand deaths a year and is where PD-1 immunotherapy now helps.
- Subtypes: Low-risk cSCC (small, well-differentiated, no perineural invasion); High-risk cSCC (BWH T2b-T3; deep invasion, perineural invasion, poorly differentiated); Locally advanced unresectable cSCC; Metastatic cSCC; cSCC in organ-transplant recipients / immunosuppressed; Keratoacanthoma and in situ (Bowen) disease
- Biomarkers: BWH and AJCC-8 T stage; Perineural invasion, depth beyond fat, differentiation; Immunosuppression status; Gene-expression prognostic test (40-GEP, DecisionDx-SCC); PD-L1 (not required); TMB (very high)

## Sections of this record

The page is a hub with ten sections in reading order; large sections have their own page. The same plan as JSON: https://onco.cc/api/v1/cancers/cutaneous-scc/sections.json

- Overview (on the hub): The TL;DR, the family this cancer belongs to, the organ, who gets it and what the state of the art is. https://onco.cc/cancers/cutaneous-scc/#overview [1 subtype, 4 state-of-the-art points]
- What it is (on the hub): Anatomy, the subtypes and how they differ, how it is staged, and where advanced disease spreads. https://onco.cc/cancers/cutaneous-scc/#what-it-is [7 subtypes]
- Finding it (on the hub): How it shows itself, how it is confirmed, what screening exists, and the biomarkers clinicians test for. https://onco.cc/cancers/cutaneous-scc/#finding-it [6 biomarkers]
- Treating it (on the hub): The standard of care by setting, the medicines, surgery and radiotherapy named in it, and the regimens behind them. https://onco.cc/cancers/cutaneous-scc/#treating-it [4 settings, 1 regimen, 3 decisions with options]
- Evidence (on the hub): Trials recruiting now, the landmark trials, the key papers and what they mean, the latest literature, and the milestones year by year. https://onco.cc/cancers/cutaneous-scc/#evidence [11 trials, 2 key papers, 8 milestones]
- The science (on the hub): The molecular landscape: the targets and how often each appears, the pathways, the mechanics stages and the preclinical models. https://onco.cc/cancers/cutaneous-scc/#science [12 targets, 2 pathways]
- Where you are (own page): Cases by country, the UK and NHS pathway and other country lenses, and the expert centres with trials on record. https://onco.cc/cancers/cutaneous-scc/where-you-are/ [1 centre]
- Living with it (on the hub): The decisions you may face, the aids that walk through them, the warnings on record, the first sixty days and the questions to ask. https://onco.cc/cancers/cutaneous-scc/#living-with-it [16 questions, 6 red cards]
- What is coming (own page): Everything in development, the open problems and what is being done about them, the roadmaps, and what changed on this record. https://onco.cc/cancers/cutaneous-scc/coming/ [11 medicines, 11 trials, 4 open problems]
- Data (own page): Every connected record, the notes, the JSON, Markdown and RDF twins, and where the record came from and when it was checked. https://onco.cc/cancers/cutaneous-scc/data/ [74 connected records]

## Standard of care

- Localised low- and high-risk: Excision with margin control or Mohs micrographic surgery; adjuvant radiotherapy for high-risk features (perineural invasion, positive margins); nodal evaluation for very high risk. ([IMRT / IGRT (modern external beam)](https://onco.cc/technologies/imrt-igrt/), [Sentinel lymph node biopsy](https://onco.cc/technologies/sentinel-node/))
- High-risk after surgery and radiotherapy: Adjuvant cemiplimab (C-POST, 2025: reduced locoregional and distant recurrence). ([Cemiplimab](https://onco.cc/drugs/cemiplimab/))
- Locally advanced or metastatic: Cemiplimab, pembrolizumab or cosibelimab; neoadjuvant cemiplimab for resectable stage II-IV to shrink surgery (51% pCR). ([Cemiplimab](https://onco.cc/drugs/cemiplimab/), [Pembrolizumab](https://onco.cc/drugs/pembrolizumab/), [Cosibelimab](https://onco.cc/drugs/cosibelimab/))
- Immunotherapy-ineligible or refractory: Cetuximab ± radiotherapy, platinum-based chemotherapy, capecitabine; trials of intratumoural agents (RP1) and EGFR ADCs. ([Cetuximab](https://onco.cc/drugs/cetuximab/), [Carboplatin](https://onco.cc/drugs/carboplatin/), [Vusolimogene oderparepvec](https://onco.cc/drugs/vusolimogene-oderparepvec/))

## State of the art

- PD-1 blockade produces durable responses in about half of advanced cSCC, one of the best response rates of any solid tumour, explained by extreme UV mutational burden.
- Neoadjuvant cemiplimab (51% pCR) is redefining surgery for large tumours; adjuvant cemiplimab (C-POST) is the first to reduce recurrence after surgery and radiation.
- Cosibelimab adds an anti-PD-L1 option with a different toxicity profile.
- Transplant recipients remain the hardest group: immunotherapy risks graft loss; mTOR-inhibitor switching and acitretin are the preventive levers.

## Open problems

- Organ-transplant recipients: high incidence, no safe immunotherapy.
- Who needs adjuvant therapy: gene-expression tests vs clinicopathologic staging.
- Field cancerisation and multiple primaries in the elderly.
- Access to Mohs surgery and dermatology capacity.

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/Squamous-cell_carcinoma_of_the_skin
- NCCN Guidelines: Squamous Cell Skin Cancer: https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1465
- C-POST (NEJM 2025): https://doi.org/10.1056/NEJMoa2502449
- NCI PDQ: skin cancer: https://www.cancer.gov/types/skin/patient/skin-treatment-pdq

## Connected records

- cancers: [Advanced cutaneous squamous cell carcinoma](https://onco.cc/cancers/advanced-cutaneous-scc/), [Basal cell carcinoma](https://onco.cc/cancers/basal-cell-carcinoma/), [HPV-independent vulvar squamous cell carcinoma (p53-mutant)](https://onco.cc/cancers/hpv-independent-vulvar-cancer/), [Melanoma](https://onco.cc/cancers/melanoma/), [Merkel cell carcinoma](https://onco.cc/cancers/merkel-cell-carcinoma/), [Penile cancer](https://onco.cc/cancers/penile/), [Skin cancer (all types)](https://onco.cc/cancers/skin-cancer/)
- technologies: [Black salve and other escharotic pastes](https://onco.cc/technologies/black-salve-escharotics/), [Chemoprevention & risk-reducing surgery](https://onco.cc/technologies/chemoprevention/), [Dermoscopy, total-body photography & AI skin analysis](https://onco.cc/technologies/dermoscopy-ai/), [Electrochemotherapy](https://onco.cc/technologies/electrochemotherapy/), [Immune checkpoint inhibitors](https://onco.cc/technologies/checkpoint-inhibitor/), [IMRT / IGRT (modern external beam)](https://onco.cc/technologies/imrt-igrt/), [Monoclonal antibodies](https://onco.cc/technologies/monoclonal-antibody/), [Oncolytic viruses](https://onco.cc/technologies/oncolytic-virus/), [Sentinel lymph node biopsy](https://onco.cc/technologies/sentinel-node/), [Skin cancer screening (visual skin examination)](https://onco.cc/technologies/skin-cancer-screening/), [Superficial and orthovoltage radiotherapy for skin cancer](https://onco.cc/technologies/superficial-radiotherapy/)
- targets: [ACVR2A](https://onco.cc/targets/acvr2a/), [ARHGEF10](https://onco.cc/targets/arhgef10/), [CNTRL](https://onco.cc/targets/cntrl/), [EGFR](https://onco.cc/targets/egfr/), [ELN](https://onco.cc/targets/eln/), [PD-1](https://onco.cc/targets/pd1/), [PD-L1](https://onco.cc/targets/pdl1/), [TP53](https://onco.cc/targets/tp53/)
- drugs: [Acitretin](https://onco.cc/drugs/acitretin/), [Aminolevulinic acid (topical, for photodynamic therapy)](https://onco.cc/drugs/aminolevulinic-acid/), [Carboplatin](https://onco.cc/drugs/carboplatin/), [Cemiplimab](https://onco.cc/drugs/cemiplimab/), [Cetuximab](https://onco.cc/drugs/cetuximab/), [Cosibelimab](https://onco.cc/drugs/cosibelimab/), [HMBD-001](https://onco.cc/drugs/hmbd-001/), [Imiquimod](https://onco.cc/drugs/imiquimod/), [Nicotinamide](https://onco.cc/drugs/nicotinamide/), [Pembrolizumab](https://onco.cc/drugs/pembrolizumab/), [Vusolimogene oderparepvec](https://onco.cc/drugs/vusolimogene-oderparepvec/)
- companies: [Almirall](https://onco.cc/companies/almirall/), [Checkpoint Therapeutics](https://onco.cc/companies/checkpoint-therapeutics/), [Galderma](https://onco.cc/companies/galderma/), [LEO Pharma](https://onco.cc/companies/leo-pharma/), [Merck & Co. (MSD)](https://onco.cc/companies/merck/), [Rakuten Medical](https://onco.cc/companies/rakuten-medical/), [Regeneron](https://onco.cc/companies/regeneron/), [Replimune](https://onco.cc/companies/replimune/), [Sanofi](https://onco.cc/companies/sanofi/), [Summit Therapeutics](https://onco.cc/companies/summit-therapeutics/)
- pathways: [p53 / RB / cell-cycle checkpoint](https://onco.cc/pathways/p53-cell-cycle/), [PD-1 / PD-L1 immune checkpoint & T-cell activation](https://onco.cc/pathways/pd1-checkpoint/)
- terms: [Immune-related adverse events (irAEs)](https://onco.cc/terms/irae/), [Pathologic complete response (pCR)](https://onco.cc/terms/pcr/), [Tumour mutational burden (TMB)](https://onco.cc/terms/tmb/)
- trials: [A Phase Ib/II Study of an Anti-HER3 Antibody, HMBD-001, With Cetuximab +/- Docetaxel in Advanced Squamous Cell Cancers](https://onco.cc/trials/nct05910827/), [A Study of IDP-001 in Advanced or Metastatic Solid Tumors](https://onco.cc/trials/nct07602842/), [An Open-label Study Using ASP-1929 Photoimmunotherapy in Combination With Anti-PD1 Therapy in EGFR Expressing Advanced Solid Tumors](https://onco.cc/trials/nct04305795/), [CK-301-101](https://onco.cc/trials/ck-301-101/), [EMPOWER-CSCC-1](https://onco.cc/trials/empower-cscc-1/), [Flash Radiotherapy for Skin Cancer](https://onco.cc/trials/nct07455331/), [KEYNOTE-629](https://onco.cc/trials/keynote-629/), [Study Evaluating Cemiplimab Alone and Combined With RP1 in Treating Advanced Squamous Skin Cancer](https://onco.cc/trials/nct04050436/), [Study of Intralesional Cemiplimab in Adult Patients With Early Stage Cutaneous Squamous Cell Carcinoma](https://onco.cc/trials/nct06585410/), [Study of the Monoclonal Antibody IMT-009 in Patients With Advanced Solid Tumors or Lymphomas](https://onco.cc/trials/nct05565417/), [Study to Investigate the Efficacy and Safety of RP1 in Adult Patients With Organ Transplants and Advanced Skin Malignancies](https://onco.cc/trials/nct04349436/)
- people: [Dirk Schadendorf](https://onco.cc/people/dirk-schadendorf/)
- key papers: [Efficacy and safety of cosibelimab, an anti-PD-L1 antibody, in metastatic cutaneous squamous cell carcinoma](https://onco.cc/key-papers/paper-ck-301-101-jitc-2023/), [Esteva 2017: a deep neural network classifies skin cancer at dermatologist level](https://onco.cc/key-papers/paper-esteva-skin-cancer-deep-learning-nature-2017/)
- institutions: [University of Arizona Cancer Center](https://onco.cc/institutions/arizona-cancer-center/)

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JSON: https://onco.cc/api/v1/entities/cutaneous-scc.json