{"entity":{"id":"lung-squamous-cell-carcinoma","kind":"cancer","name":"Squamous cell carcinoma of the lung","aka":["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"],"tldr":"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.\n\nHow 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.\n\nHow common: about 25 percent of lung cancers (NCI PDQ); Cancer Research UK lists it as the second most common type.\n\nTreatment: 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.","asOf":"2026-09-24","wikipedia":"https://en.wikipedia.org/wiki/Squamous-cell_carcinoma_of_the_lung","links":[{"label":"NCI PDQ (health professional): non-small cell lung cancer treatment, histological shares","url":"https://www.cancer.gov/types/lung/hp/non-small-cell-lung-treatment-pdq"},{"label":"Cancer Research UK: types of lung cancer","url":"https://www.cancerresearchuk.org/about-cancer/lung-cancer/stages-types/types"},{"label":"Nicholson 2022, JTO: the 2021 WHO classification of lung tumours","url":"https://doi.org/10.1016/j.jtho.2021.11.003"},{"label":"TCGA 2012, Nature: comprehensive genomic characterisation of squamous cell lung cancers","url":"https://doi.org/10.1038/nature11404"},{"label":"SQUIRE (Thatcher 2015, Lancet Oncology): necitumumab with gemcitabine and cisplatin in squamous NSCLC","url":"https://doi.org/10.1016/s1470-2045(15)00021-2"},{"label":"Lancet Respir Med 2025: estimated worldwide variation and trends in incidence of lung cancer by histological subtype in 2022 and over time (GLOBOCAN 2022 with Cancer Incidence in Five Continents)","url":"https://doi.org/10.1016/s2213-2600(24)00428-4"},{"label":"Nicholson, J Thorac Oncol 2022: the 2021 WHO classification of lung tumours, impact of advances since 2015","url":"https://doi.org/10.1016/j.jtho.2021.11.003"}],"tags":["subtype-page","wave4","lung"],"related":["nsclc","lung-adenocarcinoma","basaloid-squamous-cell-carcinoma-lung","lymphoepithelial-carcinoma-lung","large-cell-lung-carcinoma","pdl1-high-nsclc","lung-adenosquamous-carcinoma"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":["pembrolizumab","carboplatin","paclitaxel","nab-paclitaxel","gemcitabine","cisplatin","necitumumab","nedaplatin","afatinib","docetaxel","ramucirumab","cemiplimab"],"companies":[],"institutions":[],"pathways":[],"terms":["ttf1-p40","haemoptysis"],"trials":["keynote-407","lung-map","lung-map-s1400i","sqnsclc","empower-lung-1"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["How common it is, worldwide and by sex. Of 1,572,045 lung cancers in men in 2022, 461,171 (29.4 percent) were squamous cell carcinoma; of 908,630 in women, 155,598 (17.1 percent). The highest age-standardised rates are in eastern Europe for men (21.70 per 100,000) and north America for women (5.28) (Lancet Respiratory Medicine 2025). The sex difference is the clearest signature of the smoking epidemic in the histology data: squamous cell carcinoma tracks tobacco more closely than adenocarcinoma does.","Where the 2021 WHO classification moved things. Lymphoepithelial carcinoma of the lung was moved into the squamous cell carcinomas in the fifth edition, and basaloid squamous cell carcinoma remains a recognised pattern; both have their own pages in this corpus (Nicholson 2022)."],"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"],"standardOfCare":[{"setting":"Metastatic, first line","approach":"Carboplatin with paclitaxel or nab-paclitaxel plus pembrolizumab (KEYNOTE-407); cemiplimab with chemotherapy or the parent's PD-L1-high pathway as alternatives.","refs":["keynote-407","pembrolizumab","carboplatin","paclitaxel","nab-paclitaxel","cemiplimab","pdl1-high-nsclc"]},{"setting":"Metastatic, later lines","approach":"Docetaxel with or without ramucirumab; afatinib; biomarker-matched drugs through Lung-MAP.","refs":["docetaxel","ramucirumab","afatinib","lung-map","lung-map-s1400i"]},{"setting":"Early stage","approach":"Treated as the parent's resectable and stage III pages describe.","refs":["resectable-nsclc","stage-iii-unresectable-nsclc"]}],"stateOfArt":[],"history":[],"pipeline":[],"openProblems":[],"parent":"nsclc"},"route":"/cancers/lung-squamous-cell-carcinoma/","neighbours":{"cancer":[{"id":"lung-adenocarcinoma","kind":"cancer","name":"Adenocarcinoma of the lung","route":"/cancers/lung-adenocarcinoma/"},{"id":"lung-adenosquamous-carcinoma","kind":"cancer","name":"Adenosquamous carcinoma of the lung","route":"/cancers/lung-adenosquamous-carcinoma/"},{"id":"basaloid-squamous-cell-carcinoma-lung","kind":"cancer","name":"Basaloid squamous cell carcinoma of the lung","route":"/cancers/basaloid-squamous-cell-carcinoma-lung/"},{"id":"large-cell-lung-carcinoma","kind":"cancer","name":"Large cell carcinoma of the lung","route":"/cancers/large-cell-lung-carcinoma/"},{"id":"lung-cancer","kind":"cancer","name":"Lung cancer (all types)","route":"/cancers/lung-cancer/"},{"id":"lymphoepithelial-carcinoma-lung","kind":"cancer","name":"Lymphoepithelial carcinoma of the lung","route":"/cancers/lymphoepithelial-carcinoma-lung/"},{"id":"nsclc","kind":"cancer","name":"Non-small-cell lung cancer","route":"/cancers/nsclc/"},{"id":"pdl1-high-nsclc","kind":"cancer","name":"PD-L1-high non-small-cell lung cancer without a driver mutation","route":"/cancers/pdl1-high-nsclc/"},{"id":"resectable-nsclc","kind":"cancer","name":"Resectable stage I to III non-small-cell lung cancer","route":"/cancers/resectable-nsclc/"},{"id":"stage-iii-unresectable-nsclc","kind":"cancer","name":"Unresectable stage III non-small-cell lung cancer","route":"/cancers/stage-iii-unresectable-nsclc/"}],"drug":[{"id":"afatinib","kind":"drug","name":"Afatinib","route":"/drugs/afatinib/"},{"id":"carboplatin","kind":"drug","name":"Carboplatin","route":"/drugs/carboplatin/"},{"id":"cemiplimab","kind":"drug","name":"Cemiplimab","route":"/drugs/cemiplimab/"},{"id":"cisplatin","kind":"drug","name":"Cisplatin","route":"/drugs/cisplatin/"},{"id":"docetaxel","kind":"drug","name":"Docetaxel","route":"/drugs/docetaxel/"},{"id":"gemcitabine","kind":"drug","name":"Gemcitabine","route":"/drugs/gemcitabine/"},{"id":"nab-paclitaxel","kind":"drug","name":"Nab-paclitaxel","route":"/drugs/nab-paclitaxel/"},{"id":"necitumumab","kind":"drug","name":"Necitumumab","route":"/drugs/necitumumab/"},{"id":"nedaplatin","kind":"drug","name":"Nedaplatin","route":"/drugs/nedaplatin/"},{"id":"paclitaxel","kind":"drug","name":"Paclitaxel / nab-paclitaxel","route":"/drugs/paclitaxel/"},{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"},{"id":"ramucirumab","kind":"drug","name":"Ramucirumab","route":"/drugs/ramucirumab/"}],"term":[{"id":"haemoptysis","kind":"term","name":"Haemoptysis (coughing up blood)","route":"/terms/haemoptysis/"},{"id":"pancoast-tumour","kind":"term","name":"Pancoast (superior sulcus) tumour","route":"/terms/pancoast-tumour/"},{"id":"ttf1-p40","kind":"term","name":"TTF-1 and p40 (how lung histology is decided)","route":"/terms/ttf1-p40/"}],"trial":[{"id":"nct05943795","kind":"trial","name":"A Clinical Study of SI-B001 Combined With Docetaxel in the Treatment of Non-small Cell Lung Adenocarcinoma and Lung Squamous Cell Carcinoma","route":"/trials/nct05943795/"},{"id":"nct07739199","kind":"trial","name":"A Study Comparing BL-B01D1 in Combination With PD-1/VEGF Bispecific Antibody Versus Chemotherapy in Combination With PD-1/VEGF Bispecific Antibody in First-line","route":"/trials/nct07739199/"},{"id":"nct07831863","kind":"trial","name":"A Study of 7MW3711 Compared With Docetaxel in Advanced Squamous NSCLC After Prior Chemoimmunotherapy","route":"/trials/nct07831863/"},{"id":"chart-lung","kind":"trial","name":"CHART","route":"/trials/chart-lung/"},{"id":"checkmate-017","kind":"trial","name":"CheckMate 017","route":"/trials/checkmate-017/"},{"id":"checkmate-9la","kind":"trial","name":"CheckMate 9LA","route":"/trials/checkmate-9la/"},{"id":"nct06319313","kind":"trial","name":"Efficacy and Safety of JMT101 Combined Wth Docetaxel / HB1801 in Patients With Squamous Cell Non-Small Cell Lung Cancer","route":"/trials/nct06319313/"},{"id":"empower-lung-1","kind":"trial","name":"EMPOWER-Lung 1","route":"/trials/empower-lung-1/"},{"id":"keynote-407","kind":"trial","name":"KEYNOTE-407","route":"/trials/keynote-407/"},{"id":"lung-map","kind":"trial","name":"Lung-MAP (SWOG S1400 and S1900)","route":"/trials/lung-map/"},{"id":"lung-map-s1400i","kind":"trial","name":"Lung-MAP S1400I: nivolumab with or without ipilimumab","route":"/trials/lung-map-s1400i/"},{"id":"oak","kind":"trial","name":"OAK","route":"/trials/oak/"},{"id":"nct07742956","kind":"trial","name":"Phase II Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Antitumor Activity of ALK201 for Injection in Combination With Ivonescimab In","route":"/trials/nct07742956/"},{"id":"nct07360132","kind":"trial","name":"Phase III Clinical Study of HB0025 Combined With Chemotherapy Versus Pembrolizumab Combined With Chemotherapy for the First-Line Treatment of Advanced Squamous","route":"/trials/nct07360132/"},{"id":"sqnsclc","kind":"trial","name":"RC148 Plus Platinum-Based Chemotherapy vs Tislelizumab Plus Platinum-Based Chemotherapy for First-Line Squamous Non-Small Cell Lung Cancer (sqNSCLC)","route":"/trials/sqnsclc/"},{"id":"revel","kind":"trial","name":"REVEL","route":"/trials/revel/"},{"id":"squire","kind":"trial","name":"SQUIRE","route":"/trials/squire/"},{"id":"nct07662811","kind":"trial","name":"SYHX2011 in Combination With Carboplatin and Enlonstobart as First-Line Therapy for Squamous Non-Small Cell Lung Cancer","route":"/trials/nct07662811/"}],"paper":[{"id":"paper-scagliotti-cisplatin-pemetrexed-histology-jco-2008","kind":"paper","name":"Phase III study comparing cisplatin plus gemcitabine with cisplatin plus pemetrexed in chemotherapy-naive patients with advanced-stage non-small-cell lung cancer","route":"/key-papers/paper-scagliotti-cisplatin-pemetrexed-histology-jco-2008/"}]}}