# Squamous cell carcinoma of the lung

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

## TL;DR

Squamous cell carcinoma is the second most common type of lung cancer and the one most tightly linked to smoking; it starts in the flat cells lining the large central airways. Unlike adenocarcinoma it rarely carries a mutation a tablet can target, so treatment rests on chemotherapy with immunotherapy, and pemetrexed and bevacizumab are not used.

## Summary

Squamous cell carcinoma shows keratinisation, intercellular bridges or, when poorly differentiated, expression of p40 or p63 without TTF-1; the WHO classification divides it into keratinising, non-keratinising and basaloid forms (the last has its own page) and in 2021 moved lymphoepithelial carcinoma into the squamous group (Nicholson 2022). Tumours are typically central and cavitate. Genomically it is a disease of complex, smoking-related damage rather than single drivers: the 178 tumours of the Cancer Genome Atlas averaged 360 exonic mutations each, TP53 was mutated in nearly all, NFE2L2 or KEAP1 in 34 percent and the squamous differentiation genes in 44 percent, and loss-of-function mutations in HLA-A were a new finding (TCGA 2012). EGFR mutations and ALK fusions are rare enough that guidelines test only never-smokers or mixed tumours.

How it differs from its parent: the non-small-cell lung cancer page and its driver subpages are largely about adenocarcinoma. In squamous disease the driver pathway rarely applies, pemetrexed is inactive and bevacizumab is avoided because of bleeding from central tumours, so the chemotherapy backbone is platinum with paclitaxel, nab-paclitaxel or gemcitabine.

How common: about 25 percent of lung cancers (NCI PDQ); Cancer Research UK lists it as the second most common type.

Treatment: for metastatic disease carboplatin with paclitaxel or nab-paclitaxel plus pembrolizumab, the KEYNOTE-407 regimen linked here, or cemiplimab with chemotherapy (EMPOWER-Lung 3) or the PD-L1-high pathway on the parent page; the EGFR antibody necitumumab added a small survival gain to gemcitabine and cisplatin in SQUIRE and is licensed but little used; afatinib and docetaxel are second-line options; the Lung-MAP master protocol tests biomarker-matched drugs in previously treated squamous disease. Early-stage disease is treated as the parent's resectable and stage III pages describe.

## Fields

- Kind: Cancer
- Last checked: 2026-09-24
- Also known as: Squamous-cell carcinoma of the lung; Lung squamous cell carcinoma; Squamous NSCLC; Squamous; Squamous cell carcinoma (~25-30%); Epidermoid carcinoma of the lung; Keratinising and non-keratinising squamous cell carcinoma of the lung
- Tags: subtype-page; wave4; lung
- Group: lung
- Burden: About 25 percent of lung cancers (NCI PDQ), and about 400,000 deaths a year worldwide in the 2012 genome atlas estimate (TCGA 2012). GLOBOCAN counts it within lung cancer.
- Subtypes: Keratinising squamous cell carcinoma; Non-keratinising squamous cell carcinoma (p40-positive, TTF-1-negative); Basaloid squamous cell carcinoma (own page); Lymphoepithelial carcinoma (own page); Squamous cell carcinoma in a never-smoker (test for drivers as adenocarcinoma)
- Biomarkers: p40 and p63 on immunohistochemistry, TTF-1 negative; PD-L1 tumour proportion score; TP53, NFE2L2 and KEAP1 mutations (prognostic, not yet actionable); Driver testing in never-smokers or mixed histology only

## 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/lung-squamous-cell-carcinoma/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/lung-squamous-cell-carcinoma/#overview
- 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/lung-squamous-cell-carcinoma/#what-it-is [5 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/lung-squamous-cell-carcinoma/#finding-it [4 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/lung-squamous-cell-carcinoma/#treating-it [3 settings, 2 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/lung-squamous-cell-carcinoma/#evidence [5 trials]
- 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/lung-squamous-cell-carcinoma/#science [4 targets]
- 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/lung-squamous-cell-carcinoma/where-you-are/
- 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/lung-squamous-cell-carcinoma/#living-with-it [13 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/lung-squamous-cell-carcinoma/coming/ [12 medicines]
- 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/lung-squamous-cell-carcinoma/data/ [36 connected records]

## Standard of care

- Metastatic, first line: Carboplatin with paclitaxel or nab-paclitaxel plus pembrolizumab (KEYNOTE-407); cemiplimab with chemotherapy or the parent's PD-L1-high pathway as alternatives. ([KEYNOTE-407](https://onco.cc/trials/keynote-407/), [Pembrolizumab](https://onco.cc/drugs/pembrolizumab/), [Carboplatin](https://onco.cc/drugs/carboplatin/), [Paclitaxel / nab-paclitaxel](https://onco.cc/drugs/paclitaxel/), [Nab-paclitaxel](https://onco.cc/drugs/nab-paclitaxel/), [Cemiplimab](https://onco.cc/drugs/cemiplimab/), [PD-L1-high non-small-cell lung cancer without a driver mutation](https://onco.cc/cancers/pdl1-high-nsclc/))
- Metastatic, later lines: Docetaxel with or without ramucirumab; afatinib; biomarker-matched drugs through Lung-MAP. ([Docetaxel](https://onco.cc/drugs/docetaxel/), [Ramucirumab](https://onco.cc/drugs/ramucirumab/), [Afatinib](https://onco.cc/drugs/afatinib/), [Lung-MAP (SWOG S1400 and S1900)](https://onco.cc/trials/lung-map/), [Lung-MAP S1400I: nivolumab with or without ipilimumab](https://onco.cc/trials/lung-map-s1400i/))
- Early stage: Treated as the parent's resectable and stage III pages describe. ([Resectable stage I to III non-small-cell lung cancer](https://onco.cc/cancers/resectable-nsclc/), [Unresectable stage III non-small-cell lung cancer](https://onco.cc/cancers/stage-iii-unresectable-nsclc/))

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/Squamous-cell_carcinoma_of_the_lung
- NCI PDQ (health professional): non-small cell lung cancer treatment, histological shares: https://www.cancer.gov/types/lung/hp/non-small-cell-lung-treatment-pdq
- Cancer Research UK: types of lung cancer: https://www.cancerresearchuk.org/about-cancer/lung-cancer/stages-types/types
- Nicholson 2022, JTO: the 2021 WHO classification of lung tumours: https://doi.org/10.1016/j.jtho.2021.11.003
- TCGA 2012, Nature: comprehensive genomic characterisation of squamous cell lung cancers: https://doi.org/10.1038/nature11404
- SQUIRE (Thatcher 2015, Lancet Oncology): necitumumab with gemcitabine and cisplatin in squamous NSCLC: https://doi.org/10.1016/s1470-2045(15)00021-2

## Connected records

- cancers: [Adenocarcinoma of the lung](https://onco.cc/cancers/lung-adenocarcinoma/), [Adenosquamous carcinoma of the lung](https://onco.cc/cancers/lung-adenosquamous-carcinoma/), [Basaloid squamous cell carcinoma of the lung](https://onco.cc/cancers/basaloid-squamous-cell-carcinoma-lung/), [Large cell carcinoma of the lung](https://onco.cc/cancers/large-cell-lung-carcinoma/), [Lymphoepithelial carcinoma of the lung](https://onco.cc/cancers/lymphoepithelial-carcinoma-lung/), [Non-small-cell lung cancer](https://onco.cc/cancers/nsclc/), [PD-L1-high non-small-cell lung cancer without a driver mutation](https://onco.cc/cancers/pdl1-high-nsclc/), [Resectable stage I to III non-small-cell lung cancer](https://onco.cc/cancers/resectable-nsclc/), [Unresectable stage III non-small-cell lung cancer](https://onco.cc/cancers/stage-iii-unresectable-nsclc/)
- drugs: [Afatinib](https://onco.cc/drugs/afatinib/), [Carboplatin](https://onco.cc/drugs/carboplatin/), [Cemiplimab](https://onco.cc/drugs/cemiplimab/), [Cisplatin](https://onco.cc/drugs/cisplatin/), [Docetaxel](https://onco.cc/drugs/docetaxel/), [Gemcitabine](https://onco.cc/drugs/gemcitabine/), [Nab-paclitaxel](https://onco.cc/drugs/nab-paclitaxel/), [Necitumumab](https://onco.cc/drugs/necitumumab/), [Nedaplatin](https://onco.cc/drugs/nedaplatin/), [Paclitaxel / nab-paclitaxel](https://onco.cc/drugs/paclitaxel/), [Pembrolizumab](https://onco.cc/drugs/pembrolizumab/), [Ramucirumab](https://onco.cc/drugs/ramucirumab/)
- trials: [EMPOWER-Lung 1](https://onco.cc/trials/empower-lung-1/), [KEYNOTE-407](https://onco.cc/trials/keynote-407/), [Lung-MAP (SWOG S1400 and S1900)](https://onco.cc/trials/lung-map/), [Lung-MAP S1400I: nivolumab with or without ipilimumab](https://onco.cc/trials/lung-map-s1400i/), [RC148 Plus Platinum-Based Chemotherapy vs Tislelizumab Plus Platinum-Based Chemotherapy for First-Line Squamous Non-Small Cell Lung Cancer (sqNSCLC)](https://onco.cc/trials/sqnsclc/)

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JSON: https://onco.cc/api/v1/entities/lung-squamous-cell-carcinoma.json