View source for Medicine:Cutaneous squamous-cell carcinoma

{{Infobox medical condition (new)
| name            = Cutaneous squamous-cell carcinoma
| synonyms        = Squamous-cell carcinoma of the skin, squamous-cell skin cancer, epidermoid carcinoma, squamous-cell epithelioma of the skin
| image           = Squamous Cell Carcinoma.jpg
| caption         = Cutaneous squamous-cell carcinoma tends to arise from actinic keratoses (premalignant lesions); surface is usually scaly and often ulcerates (as shown here).
| field           = Dermatology, [[Engineering:Plastic surgery|plastic surgery]], otorhinolaryngology
| symptoms        = Hard lump with a scaly top or ulceration.<ref name=Lyn2011/>
| complications   =
| onset           =
| duration        =
| causes          =
| risks           = Ultraviolet radiation, actinic keratosis, [[Chemistry:Tobacco smoking|tobacco smoking]], lighter skin, [[Chemistry:Arsenic|arsenic]] exposure, [[Physics:Radiation therapy|radiotherapy]], poor immune system function, HPV infection<ref name=Ga2015/>
| diagnosis       = Tissue biopsy<ref name=Ga2015/><ref name=NCI2017Diag/>
| differential    = Keratoacanthoma, actinic keratosis, [[Medicine:Melanoma|melanoma]], warts, basal cell cancer<ref name=Fer2017/>
| prevention      = Decreased UV radiation exposure, [[Chemistry:Sunscreen|sunscreen]]<ref name=WCR2014/><ref name=Jou2012/>
| treatment       = Surgical removal, [[Physics:Radiation therapy|radiotherapy]], [[Medicine:Chemotherapy|chemotherapy]], [[Medicine:Immunotherapy|immunotherapy]]<ref name=Ga2015/><ref name=NCI2017Tx/>
| medication      =
| prognosis       = Usually good<ref name=WCR2014/>
| frequency       = 2.2 million (2015)<!-- Prevalence --><ref name=GBD2015Pre/>
| deaths          = 51,900 (2015)<ref name=GBD2015De/>
}}
<!-- Definition and symptoms -->
'''Cutaneous squamous-cell carcinoma''' ('''cSCC'''), or '''squamous-cell carcinoma of the skin''', also known as '''squamous-cell skin cancer''', is, with [[Medicine:Basal-cell carcinoma|basal-cell carcinoma]] and [[Medicine:Melanoma|melanoma]], one of the three principal types of [[Medicine:Skin cancer|skin cancer]].<ref name=NCI2013TxPro>{{cite web|title=Skin Cancer Treatment (PDQ®)|url=http://www.cancer.gov/cancertopics/pdq/treatment/skin/HealthProfessional/page1/AllPages|website=NCI|access-date=30 June 2014|date=2013-10-25|url-status=live|archive-url=https://web.archive.org/web/20140705234200/http://www.cancer.gov/cancertopics/pdq/treatment/skin/HealthProfessional/page1/AllPages|archive-date=5 July 2014}}</ref> cSCC typically presents as a hard lump with a scaly top layer, but it may instead form an [[Medicine:Ulcer|ulcer]].<ref name=Lyn2011>{{cite book| vauthors = Dunphy LM |title=Primary Care: The Art and Science of Advanced Practice Nursing|date=2011|publisher=F.A. Davis|isbn=9780803626478|page=242|url=https://books.google.com/books?id=RR1hAQAAQBAJ&pg=PA242|url-status=live|archive-url=https://web.archive.org/web/20160520044442/https://books.google.com/books?id=RR1hAQAAQBAJ&pg=PA242|archive-date=2016-05-20}}</ref> Onset often occurs over a period of months.<ref name=Fer2017/> Cutaneous [[Medicine:Squamous-cell carcinoma|squamous-cell carcinoma]] is more likely to [[Medicine:Metastasis|spread to distant areas]] than basal cell cancer.<ref name=Cak2012>{{cite journal | vauthors = Cakir BÖ, Adamson P, Cingi C | title = Epidemiology and economic burden of nonmelanoma skin cancer | journal = Facial Plastic Surgery Clinics of North America | volume = 20 | issue = 4 | pages = 419–422 | date = November 2012 | pmid = 23084294 | doi = 10.1016/j.fsc.2012.07.004 }}</ref> When confined to the [[Biology:Epidermis|outermost layer of the skin]], a pre-invasive, or ''[[Biology:In situ|in situ]]'', form of cSCC is known as '''Bowen's disease'''.<ref name=Yanofsky2011>{{cite journal | vauthors = Yanofsky VR, Mercer SE, Phelps RG | title = Histopathological variants of cutaneous squamous cell carcinoma: a review | journal = Journal of Skin Cancer | volume = 2011 | pages = 210813 | year = 2011 | pmid = 21234325 | pmc = 3018652 | doi = 10.1155/2011/210813 | doi-access = free }}{{CC-notice|cc=bysa3}}</ref><ref name=Bath-Hextall2013>{{cite journal | vauthors = Bath-Hextall FJ, Matin RN, Wilkinson D, Leonardi-Bee J | title = Interventions for cutaneous Bowen's disease | journal = The Cochrane Database of Systematic Reviews | volume = 2016 | issue = 6 | pages = CD007281 | date = June 2013 | pmid = 23794286 | pmc = 6464151 | doi = 10.1002/14651858.CD007281.pub2 }}</ref>

<!-- Cause, mechanism and diagnosis -->
The most significant risk factor for cSCC is high lifetime exposure to ultraviolet radiation from the sun.<ref name=Ga2015/> Other risks include prior scars, chronic wounds, actinic keratosis, paler skin that sunburns easily, Bowen's disease, [[Chemistry:Arsenic|arsenic]] exposure, [[Physics:Radiation therapy|radiation therapy]], [[Chemistry:Tobacco smoking|tobacco smoking]], poor immune system function, prior basal cell carcinoma, and HPV infection.<ref name=Ga2015/><ref name=ACSrisk>{{cite web| url=https://www.cancer.org/cancer/basal-and-squamous-cell-skin-cancer/causes-risks-prevention/risk-factors.html| title=Basal and Squamous Cell Skin Cancer Risk Factors| work= American Cancer Society}}</ref><ref>{{Cite book|jstor=j.ctt1g69xq0.9| title = Textbook of Plastic and Reconstructive Surgery| vauthors = Opel S, Ghali S |date=2016|publisher=UCL Press|isbn=978-1-910634-39-4 |edition=1|pages=61–76|chapter=Skin Cancer for the Plastic Surgeon|doi=10.2307/j.ctt1g69xq0.9}}</ref> Risk from UV radiation is related to total exposure, rather than exposure early in life.<ref name=UV2010>{{cite journal | vauthors = Gallagher RP, Lee TK, Bajdik CD, Borugian M | title = Ultraviolet radiation | journal = Chronic Diseases in Canada | volume = 29 | issue = Suppl 1 | pages = 51–68 | date = 2010 | pmid = 21199599 | doi = 10.24095/hpcdp.29.S1.04 }}</ref> Tanning beds have become another frequent source of ultraviolet radiation.<ref name="UV2010"/> Risk is also elevated in certain genetic skin disorders, such as [[Medicine:Xeroderma pigmentosum|xeroderma pigmentosum]]<ref>{{cite journal | vauthors = Lehmann AR, McGibbon D, Stefanini M | title = Xeroderma pigmentosum | journal = Orphanet Journal of Rare Diseases | volume = 6 | issue = 1 | pages = 70 | date = November 2011 | pmid = 22044607 | pmc = 3221642 | doi = 10.1186/1750-1172-6-70 | doi-access = free }}</ref> and certain forms of [[Medicine:Epidermolysis bullosa|epidermolysis bullosa]].<ref>{{cite journal | vauthors = Bardhan A, Bruckner-Tuderman L, Chapple IL, Fine JD, Harper N, Has C, Magin TM, Marinkovich MP, Marshall JF, McGrath JA, Mellerio JE, Polson R, Heagerty AH | display-authors = 6 | title = Epidermolysis bullosa | journal = Nature Reviews. Disease Primers | volume = 6 | issue = 1 | pages = 78 | date = September 2020 | pmid = 32973163 | doi = 10.1038/s41572-020-0210-0 | s2cid = 221861310 }}</ref> cSCC begins from squamous cells found in the upper layers of the [[Biology:Epidermis|skin]].<ref name=NCI2016Def>{{cite web|title=NCI Dictionary of Cancer Terms|url=https://www.cancer.gov/publications/dictionaries/cancer-terms?cdrid=46595|website=National Cancer Institute|access-date=9 November 2016|url-status=live|archive-url=https://web.archive.org/web/20161109230919/https://www.cancer.gov/publications/dictionaries/cancer-terms?cdrid=46595|archive-date=9 November 2016|date = 2011-02-02}}</ref> Diagnosis is often based on skin examination, and confirmed by tissue biopsy.<ref name=Ga2015/><ref name=NCI2017Diag>{{cite web|title=Skin Cancer Treatment|url=https://www.cancer.gov/types/skin/patient/skin-treatment-pdq|website=National Cancer Institute|access-date=2 July 2017|language=en|date=21 June 2017|url-status=live|archive-url=https://web.archive.org/web/20170704222639/https://www.cancer.gov/types/skin/patient/skin-treatment-pdq|archive-date=4 July 2017}}</ref>

''In vivo'' and ''in vitro'' studies have shown that the upregulation of FGFR2, a subset of the fibroblast growth factor receptor (FGFR) immunoglobin family, has a critical role to play in the progression of cSCC cells.<ref name="onlinelibrary.wiley.com">{{cite journal | vauthors = Khandelwal AR, Kent B, Hillary S, Alam MM, Ma X, Gu X, DiGiovanni J, Nathan CO | display-authors = 6 | title = Fibroblast growth factor receptor promotes progression of cutaneous squamous cell carcinoma | journal = Molecular Carcinogenesis | volume = 58 | issue = 10 | pages = 1715–1725 | date = October 2019 | pmid = 31254372 | pmc = 6721978 | doi = 10.1002/mc.23012 }}</ref> Mutations in the TPL2 gene cause over-expression of FGFR2, which activates the [[Biology:MTORC1|mTORC1]] and AKT pathways in both primary and metastatic cSCC cell lines. By using a chemical substance, called a "pan FGFR inhibitor", [[Biology:Cell migration|cell migration]] and [[Biology:Cell proliferation|cell proliferation]] in cSCC have been attenuated ''in vitro''.<ref name="onlinelibrary.wiley.com"/><!--May 2023: Has this 2019 ''in vitro'' "finding" made its way into textbooks? If not, it may be refspam-->

<!-- Prevention and treatment -->
Avoiding exposure to ultraviolet radiation and the use of [[Chemistry:Sunscreen|sunscreen]] appear to be effective methods of preventing cutaneous squamous-cell carcinoma.<ref name=WCR2014>{{cite book|title=World Cancer Report 2014.|date=2014|publisher=World Health Organization|isbn=978-9283204299|pages=Chapter 5.14}}</ref><ref name=Jou2012>{{cite journal | vauthors = Jou PC, Feldman RJ, Tomecki KJ | title = UV protection and sunscreens: what to tell patients | journal = Cleveland Clinic Journal of Medicine | volume = 79 | issue = 6 | pages = 427–436 | date = June 2012 | pmid = 22660875 | doi = 10.3949/ccjm.79a.11110 | doi-access = free }}</ref> Treatment is typically by surgical removal.<ref name=Ga2015/> This can be by simple excision if the cancer is small; otherwise, [[Medicine:Mohs surgery|Mohs surgery]] is generally recommended.<ref name=Ga2015/> Other options may include [[Biology:Cryosurgery|application of cold]] and [[Physics:Radiation therapy|radiation therapy]].<ref name=NCI2017Tx>{{cite web|title=Skin Cancer Treatment|url=https://www.cancer.gov/types/skin/patient/skin-treatment-pdq#link/_119_toc|website=National Cancer Institute|access-date=2 July 2017|language=en|date=21 June 2017|url-status=live|archive-url=https://web.archive.org/web/20170704222639/https://www.cancer.gov/types/skin/patient/skin-treatment-pdq#link/_119_toc|archive-date=4 July 2017}}</ref> In cases in which [[Medicine:Metastasis|distant spread]] has occurred, [[Medicine:Chemotherapy|chemotherapy]] or biologic therapy may be used.<ref name=NCI2017Tx/>

<!-- Epidemiology and prognosis -->
As of 2015, about 2.2 million people worldwide have cSCC at any given time.<ref name=GBD2015Pre>{{cite journal | title = Global, regional, and national incidence, prevalence, and years lived with disability for 310 diseases and injuries, 1990-2015: a systematic analysis for the Global Burden of Disease Study 2015 | journal = Lancet | volume = 388 | issue = 10053 | pages = 1545–1602 | date = October 2016 | pmid = 27733282 | pmc = 5055577 | doi = 10.1016/S0140-6736(16)31678-6 | last1 = Vos | first1 = Theo | last2 = Allen | first2 = Christine | last3 = Arora | first3 = Megha | last4 = Barber | first4 = Ryan M. | last5 = Bhutta | first5 = Zulfiqar A. | last6 = Brown | first6 = Alexandria | last7 = Carter | first7 = Austin | last8 = Casey | first8 = Daniel C. | last9 = Charlson | first9 = Fiona J. | last10 = Chen | first10 = Alan Z. | last11 = Coggeshall | first11 = Megan | last12 = Cornaby | first12 = Leslie | last13 = Dandona | first13 = Lalit | last14 = Dicker | first14 = Daniel J. | last15 = Dilegge | first15 = Tina | last16 = Erskine | first16 = Holly E. | last17 = Ferrari | first17 = Alize J. | last18 = Fitzmaurice | first18 = Christina | last19 = Fleming | first19 = Tom | last20 = Forouzanfar | first20 = Mohammad H. | last21 = Fullman | first21 = Nancy | last22 = Gething | first22 = Peter W. | last23 = Goldberg | first23 = Ellen M. | last24 = Graetz | first24 = Nicholas | last25 = Haagsma | first25 = Juanita A. | last26 = Hay | first26 = Simon I. | last27 = Johnson | first27 = Catherine O. | last28 = Kassebaum | first28 = Nicholas J. | last29 = Kawashima | first29 = Toana | last30 = Kemmer | first30 = Laura | display-authors = 1 }}</ref> About 20% of all skin cancer cases consist of cSCC.<ref>{{cite journal | vauthors = Stratigos A, Garbe C, Lebbe C, Malvehy J, del Marmol V, Pehamberger H, Peris K, Becker JC, Zalaudek I, Saiag P, Middleton MR, Bastholt L, Testori A, Grob JJ | display-authors = 6 | title = Diagnosis and treatment of invasive squamous cell carcinoma of the skin: European consensus-based interdisciplinary guideline | journal = European Journal of Cancer | volume = 51 | issue = 14 | pages = 1989–2007 | date = September 2015 | pmid = 26219687 | doi = 10.1016/j.ejca.2015.06.110 | doi-access = free }}</ref> About 12% of males and 7% of females in the United States develop cSCC at some point in time.<ref name=Ga2015>{{cite journal | vauthors = Gandhi SA, Kampp J | title = Skin Cancer Epidemiology, Detection, and Management | journal = The Medical Clinics of North America | volume = 99 | issue = 6 | pages = 1323–1335 | date = November 2015 | pmid = 26476255 | doi = 10.1016/j.mcna.2015.06.002 }}</ref> While prognosis is usually good, when distant spread occurs five-year survival is ~34%.<ref name=Fer2017/><ref name=WCR2014/> In 2015, cSCC resulted in approximately 52,000 deaths globally.<ref name=GBD2015De>{{cite journal | title = Global, regional, and national life expectancy, all-cause mortality, and cause-specific mortality for 249 causes of death, 1980-2015: a systematic analysis for the Global Burden of Disease Study 2015 | journal = Lancet | volume = 388 | issue = 10053 | pages = 1459–1544 | date = October 2016 | pmid = 27733281 | pmc = 5388903 | doi = 10.1016/s0140-6736(16)31012-1 | last1 = Wang | first1 = Haidong | last2 = Naghavi | first2 = Mohsen | last3 = Allen | first3 = Christine | last4 = Barber | first4 = Ryan M. | last5 = Bhutta | first5 = Zulfiqar A. | last6 = Carter | first6 = Austin | last7 = Casey | first7 = Daniel C. | last8 = Charlson | first8 = Fiona J. | last9 = Chen | first9 = Alan Zian | last10 = Coates | first10 = Matthew M. | last11 = Coggeshall | first11 = Megan | last12 = Dandona | first12 = Lalit | last13 = Dicker | first13 = Daniel J. | last14 = Erskine | first14 = Holly E. | last15 = Ferrari | first15 = Alize J. | last16 = Fitzmaurice | first16 = Christina | last17 = Foreman | first17 = Kyle | last18 = Forouzanfar | first18 = Mohammad H. | last19 = Fraser | first19 = Maya S. | last20 = Fullman | first20 = Nancy | last21 = Gething | first21 = Peter W. | last22 = Goldberg | first22 = Ellen M. | last23 = Graetz | first23 = Nicholas | last24 = Haagsma | first24 = Juanita A. | last25 = Hay | first25 = Simon I. | last26 = Huynh | first26 = Chantal | last27 = Johnson | first27 = Catherine O. | last28 = Kassebaum | first28 = Nicholas J. | last29 = Kinfu | first29 = Yohannes | last30 = Kulikoff | first30 = Xie Rachel | display-authors = 1 }}</ref> The mean age at diagnosis is around 66 years.<ref name=Fer2017>{{cite book| vauthors = Ferri FF |title=Ferri's Clinical Advisor 2017 E-Book: 5 Books in 1|date=2016|publisher=Elsevier Health Sciences|isbn=9780323448383|page=1199 |url= https://books.google.com/books?id=rRhCDAAAQBAJ&pg=PA1199 |access-date=2 July 2017 |language=en |url-status=live |archive-url=https://web.archive.org/web/20170829075945/https://books.google.ca/books?id=rRhCDAAAQBAJ&pg=PA1199 |archive-date=29 August 2017}}</ref> Following the successful treatment of one case of cSCC, a person is at significant risk of developing further cSCC [[Medicine:Lesion|lesion]]s.<ref name=Ga2015/>


==Signs and symptoms==
[[File:Squamous Cell Carcinoma.png|thumb|305px|Cutaneous squamous-cell carcinoma]]

SCC of the skin begins as a small nodule and as it enlarges the center becomes necrotic and sloughs and the nodule turns into an ulcer, and generally are developed from an actinic keratosis. Once keratinocytes begin to grow uncontrollably, they have the potential to become cancerous and produce cutaneous squamous-cell carcinoma.<ref>{{Cite web |last=H |first=Carlos |date=2022-09-10 |title=How serious is a squamous-cell carcinoma? |url=https://www.curadermbcc.eu/blog/squamous-cell-carcinoma/ |access-date=2022-09-10 |website=CuradermBCC |language=en-US |archive-date=2022-09-10 |archive-url=https://web.archive.org/web/20220910232035/https://www.curadermbcc.eu/blog/squamous-cell-carcinoma/ |url-status=dead }}</ref>
* The lesion caused by cSCC is often [[Medicine:Symptom#Types|asymptomatic]]
* Ulcer or reddish skin plaque that is slow growing
* Intermittent bleeding from the tumor, especially on the lip
* The clinical appearance is highly variable
* Usually the tumor presents as an ulcerated lesion with hard, raised edges
* The tumor may be in the form of a hard plaque or a papule, often with an opalescent quality, with tiny blood vessels
* The tumor can lie below the level of the surrounding skin, and eventually ulcerates and invades the underlying tissue
* The tumor commonly presents on sun-exposed areas (e.g. back of the hand, scalp, lip, and superior surface of pinna)
* On the lip, the tumor forms a small ulcer, which fails to heal and bleeds intermittently
* Evidence of chronic skin photodamage, as in multiple actinic keratoses (solar keratoses)
* The tumor grows relatively slowly

===Spread===
* Unlike [[Medicine:Basal-cell carcinoma|basal-cell carcinoma]] (BCC), squamous-cell carcinoma (SCC) has a higher risk of [[Medicine:Metastasis|metastasis]].
* Risk of metastasis is higher clinically in SCC arising in scars, on the lower lips, ears, or mucosa, and occurring in immunosuppressed and solid organ transplant patients. Risk of metastasis is also higher in SCC that are >&nbsp;2&nbsp;cm in diameter, growth into the fat layer and [[Medicine:Perineural invasion|along nerves]], presence of [[Medicine:Lymphovascular invasion|lymphovascular invasion]], poorly differentiated cell architecture on histology, or thickness greater than 6 mm.<ref>{{cite journal | vauthors = Thompson AK, Kelley BF, Prokop LJ, Murad MH, Baum CL | title = Risk Factors for Cutaneous Squamous Cell Carcinoma Recurrence, Metastasis, and Disease-Specific Death: A Systematic Review and Meta-analysis | journal = JAMA Dermatology | volume = 152 | issue = 4 | pages = 419–428 | date = April 2016 | pmid = 26762219 | pmc = 4833641 | doi = 10.1001/jamadermatol.2015.4994 }}</ref><ref>{{cite journal | vauthors = Schmults CD, Blitzblau R, Aasi SZ, Alam M, Andersen JS, Baumann BC, Bordeaux J, Chen PL, Chin R, Contreras CM, DiMaio D, Donigan JM, Farma JM, Ghosh K, Grekin RC, Harms K, Ho AL, Holder A, Lukens JN, Medina T, Nehal KS, Nghiem P, Park S, Patel T, Puzanov I, Scott J, Sekulic A, Shaha AR, Srivastava D, Stebbins W, Thomas V, Xu YG, McCullough B, Dwyer MA, Nguyen MQ | display-authors = 6 | title = NCCN Guidelines® Insights: Squamous Cell Skin Cancer, Version 1.2022 | journal = Journal of the National Comprehensive Cancer Network | volume = 19 | issue = 12 | pages = 1382–1394 | date = December 2021 | pmid = 34902824 | doi = 10.6004/jnccn.2021.0059 | s2cid = 245153567 | doi-access = free }}</ref><ref name="Wysong 2023" />

==Causes==
Cutaneous squamous-cell carcinoma is the second-most common [[Medicine:Skin cancer|cancer of the skin]] (after basal-cell carcinoma, but more common than [[Medicine:Melanoma|melanoma]]). It usually occurs in areas exposed to the sun. Sunlight exposure and [[Biology:Immunosuppression|immunosuppression]] are risk factors for SCC of the skin, with chronic sun exposure being the strongest environmental risk factor.<ref name="mdconsult"/> There is a risk of [[Medicine:Metastasis|metastasis]] starting more than 10 years{{citation needed|date=July 2012}} after diagnosable appearance of squamous-cell carcinoma, but the risk is low,{{specify|date=July 2012}} though much{{specify|date=July 2012}} higher than with basal-cell carcinoma. Squamous-cell cancers of the lip and ears have high rates of local recurrence and distant metastasis.<ref>{{cite web|title=Squamous Cell Carcinoma|url=http://www.aad.org/public/publications/pamphlets/sun_squamous.html|website=American Academy of Dermatology|access-date=15 March 2017|date=25 December 2010|url-status=dead|archive-url=https://web.archive.org/web/20101225041745/http://www.aad.org/public/publications/pamphlets/sun_squamous.html|archive-date=25 December 2010}}</ref> In a recent study, it has also been shown that the deletion or severe down-regulation of a gene titled Tpl2 (tumor progression locus 2) may be involved in the progression of normal keratinocytes into becoming squamous-cell carcinoma.<ref>{{cite journal | vauthors = Decicco-Skinner KL, Trovato EL, Simmons JK, Lepage PK, Wiest JS | title = Loss of tumor progression locus 2 (tpl2) enhances tumorigenesis and inflammation in two-stage skin carcinogenesis | journal = Oncogene | volume = 30 | issue = 4 | pages = 389–397 | date = January 2011 | pmid = 20935675 | pmc = 3460638 | doi = 10.1038/onc.2010.447 }}</ref>

cSCC represents about 20% of the non-melanoma skin cancers; 80-90% of cSCCs with metastatic potential are located on the head and neck.<ref>{{cite journal | vauthors = Dreyfuss I, Kamath P, Frech F, Hernandez L, Nouri K | title = Squamous cell carcinoma: 2021 updated review of treatment | journal = Dermatologic Therapy | pages = e15308 | date = January 2022 | volume = 35 | issue = 4 | pmid = 34997811 | doi = 10.1111/dth.15308 | s2cid = 245812900 }}</ref>

Tobacco smoking also increases the risk for cutaneous squamous-cell carcinoma.<ref name=ACSrisk /><ref>{{cite journal | vauthors = Wensveen CA, Bastiaens MT, Kielich CJ, Berkhout MJ, Westendorp RG, Vermeer BJ, Bouwes Bavinck JN | title = Relation between smoking and skin cancer | journal = Journal of Clinical Oncology | volume = 19 | issue = 1 | pages = 231–238 | date = January 2001 | pmid = 11134217 | doi = 10.1200/JCO.2001.19.1.231 }}</ref>

The vast majority of cSCC cases are located on exposed skin, and are often the result of [[Physics:Ultraviolet|ultraviolet]] exposure. cSCC usually occurs on portions of the body commonly exposed to the sun; the face, ears, neck, hands, or arms. The primary sign is a growing bump that may have a rough, scaly surface, and flat, reddish patches.
Unlike basal-cell carcinoma, cSCC carries a higher risk of [[Medicine:Metastasis|metastasis]] than does basal-cell carcinoma, and may spread to the regional [[Biology:Lymph node|lymph node]]s,<ref>{{cite web | vauthors = Wells JW, Goyal N, Najjar T, Monroe MM | veditors = Meyers AD |title=Cutaneous Squamous Cell Carcinoma: Practice Essentials, Background, Pathophysiology |url=http://emedicine.medscape.com/article/1965430-overview |access-date=15 March 2017|date=28 June 2016|url-status=live |archive-url=https://web.archive.org/web/20170406191826/http://emedicine.medscape.com/article/1965430-overview|archive-date=6 April 2017}}</ref>

''Erythroplasia of Queyrat'' (SCC in situ of the glans or [[Medicine:Foreskin|prepuce]] in males,<ref name="Lookingbill"/> M<ref name="Fitz2"/>{{rp|733}}<ref name="Andrews"/>{{rp|656}}<ref name="Bolognia"/> or the [[Medicine:Vulva|vulva]] in females.<ref name=Zenilman2012/>) may be induced by human papilloma virus.<ref name="Wieland_2000">{{cite journal | vauthors = Wieland U, Jurk S, Weissenborn S, Krieg T, Pfister H, Ritzkowsky A | title = Erythroplasia of queyrat: coinfection with cutaneous carcinogenic human papillomavirus type 8 and genital papillomaviruses in a carcinoma in situ | journal = The Journal of Investigative Dermatology | volume = 115 | issue = 3 | pages = 396–401 | date = September 2000 | pmid = 10951274 | doi = 10.1046/j.1523-1747.2000.00069.x | doi-access = free }}</ref> It is reported to occur in the [[Medicine:Corneal limbus|corneoscleral limbus]].<ref>{{cite journal | vauthors = Shah IA, Sangi SA, Abbasi SA | title = Bowen's Disease | journal = Pakistan Journal of Ophthalmology | date = 1998 | volume = 14 | issue = 1 | pages = 37–38 | url = https://www.researchgate.net/publication/265972111 }}</ref><!--no title??--> Erythroplasia of Queyrat may also occur on the anal mucosa or the oral mucosa.<ref name=Katsambas2003 />

Genetically, cSCC tumors harbor high frequencies of [[Biology:Notch signaling pathway|NOTCH]] and [[Biology:P53|p53]] mutations as well as less frequent alterations in histone acetyltransferase [[Biology:EP300|EP300]], subunit of the SWI/SNF chromatin remodeling complex PBRM1, DNA-repair deubiquitinase USP28, and [[Biology:NF-κB|NF-κB]] signaling regulator CHUK.<ref name="ReferenceA">{{Cite journal |last1=Chang |first1=Darwin |last2=Shain |first2=A. Hunter |date=2021-07-16 |title=The landscape of driver mutations in cutaneous squamous cell carcinoma |journal=npj Genomic Medicine |volume=6 |issue=1 |pages=61 |doi=10.1038/s41525-021-00226-4 |issn=2056-7944 |pmc=8285521 |pmid=34272401}}</ref>

===Immunosuppression ===
People who have received solid organ transplants are at a significantly increased risk of developing [[Medicine:Squamous-cell carcinoma|squamous-cell carcinoma]] due to the use of chronic immunosuppressive medication.<ref>{{Cite journal |last1=Chang |first1=Darwin |last2=Shain |first2=A. Hunter |date=2021-07-16 |title=The landscape of driver mutations in cutaneous squamous cell carcinoma |journal=npj Genomic Medicine |language=en |volume=6 |issue=1 |page=61 |doi=10.1038/s41525-021-00226-4 |pmid=34272401 |pmc=8285521 |issn=2056-7944}}</ref> While the risk of developing all skin cancers increases with these medications, this effect is particularly severe for cSCC, with hazard ratios as high as 250 being reported, versus 40 for basal cell carcinoma.<ref>{{cite journal | vauthors = Tessari G, Girolomoni G | title = Nonmelanoma skin cancer in solid organ transplant recipients: update on epidemiology, risk factors, and management | journal = Dermatologic Surgery | volume = 38 | issue = 10 | pages = 1622–1630 | date = October 2012 | pmid = 22805312 | doi = 10.1111/j.1524-4725.2012.02520.x | s2cid = 40490951 }}</ref> The incidence of cSCC development increases with time posttransplant.<ref name=":0">{{cite journal | vauthors = O'Reilly Zwald F, Brown M | title = Skin cancer in solid organ transplant recipients: advances in therapy and management: part I. Epidemiology of skin cancer in solid organ transplant recipients | journal = Journal of the American Academy of Dermatology | volume = 65 | issue = 2 | pages = 253–261 | date = August 2011 | pmid = 21763561 | doi = 10.1016/j.jaad.2010.11.062 }}</ref> Heart and lung transplant recipients are at the highest risk of developing cSCC due to more intensive immunosuppressive medications used.<ref>{{Cite journal |last1=Chockalingam |first1=Ramya |last2=Downing |first2=Christopher |last3=Tyring |first3=Stephen K. |date=June 2015 |title=Cutaneous Squamous Cell Carcinomas in Organ Transplant Recipients |journal=Journal of Clinical Medicine |language=en |volume=4 |issue=6 |pages=1229–1239 |doi=10.3390/jcm4061229 |issn=2077-0383 |pmc=4484997 |pmid=26239556 |doi-access=free }}</ref>

Cutaneous squamous-cell carcinoma in individuals on immunotherapy or who have lymphoproliferative disorders (e.g. [[Medicine:Leukemia|leukemia]]) tend to be much more aggressive, regardless of their location.<ref>{{cite web|url=http://www.skincarephysicians.com/skincancernet/squamous_cell_carcinoma.html|title=Squamous Cell Carcinoma: What it Looks Like | work = SkinCancerNet | publisher = American Academy of Dermatology | date = 2008 |url-status=dead|archive-url=https://web.archive.org/web/20081221203504/http://www.skincarephysicians.com/skincancernet/squamous_cell_carcinoma.html|archive-date=2008-12-21}}</ref> The risk of cSCC, and non-melanoma skin cancers generally, varies with the immunosuppressive drug regimen chosen. The risk is greatest with calcineurin inhibitors like cyclosporine and tacrolimus, and least with mTOR inhibitors, such as sirolimus and everolimus. The antimetabolites azathioprine and mycophenolic acid have an intermediate risk profile.<ref>{{cite journal | vauthors = Kuschal C, Thoms KM, Schubert S, Schäfer A, Boeckmann L, Schön MP, Emmert S | title = Skin cancer in organ transplant recipients: effects of immunosuppressive medications on DNA repair | journal = Experimental Dermatology | volume = 21 | issue = 1 | pages = 2–6 | date = January 2012 | pmid = 22151386 | doi = 10.1111/j.1600-0625.2011.01413.x | s2cid = 25776283 | doi-access = free }}</ref>

==Diagnosis==
Diagnosis is confirmed via skin biopsy of the tissue or tissues suspected to be affected by SCC.
The pathological appearance of a squamous-cell cancer varies with the depth of the biopsy. For that reason, a biopsy including the subcutaneous tissue and basilar epithelium, to the surface is necessary for correct diagnosis. The performance of a shave biopsy (see skin biopsy) might not acquire enough information for a diagnosis. An inadequate biopsy might be read as actinic keratosis with follicular involvement. A deeper biopsy down to the dermis or subcutaneous tissue might reveal the true cancer. An excision biopsy is ideal, but not practical in most cases. An incisional or punch biopsy is preferred. A shave biopsy is least ideal, especially if only the superficial portion is acquired.{{citation needed|date=July 2017}}

=== Histological characteristics===
Histopathologically, the epidermis in cSCC ''in situ'' (Bowen's disease) will show hyperkeratosis and parakeratosis. There will also be marked acanthosis with elongation and thickening of the rete ridges. These changes will overly keratinocytic cells which are often highly atypical and may in fact have a more unusual appearance than invasive cSCC. The atypia spans the full thickness of the epidermis, with the keratinocytes demonstrating intense mitotic activity, pleomorphism, and greatly enlarged nuclei. They will also show a loss of maturity and polarity, giving the epidermis a disordered or "windblown" appearance.{{citation needed|date=November 2020}}

Two types of multinucleated cells may be seen: the first will present as a multinucleated giant cell, and the second will appear as a dyskeratotic cell engulfed in the cytoplasm of a keratinocyte. Occasionally, cells of the upper epidermis will undergo vacuolization, demonstrating an abundant and strongly eosinophilic cytoplasm. There may be a mild to moderate lymphohistiocytic infiltrate detected in the upper dermis.<ref name=Yanofsky2011/>

<gallery mode="packed" heights="190">
File:Histopathology of squamous cell carcinoma in situ.jpg|Histopathology of squamous-cell carcinoma ''in situ'' (black arrow), compared to normal skin, showing marked atypia.
File:Micrograph of squamous cell carcinoma in situ - 100x.jpg|Squamous-cell carcinoma ''in situ'', showing prominent dyskeratosis and aberrant mitoses at all levels of the epidermis, along with marked parakeratosis.<ref name=Yanofsky2011/>
</gallery>

===In situ disease===
{{Anchor|Erythroplasia of Queyrat}}

Bowen's disease is essentially equivalent to and used interchangeably with cSCC ''in situ'', when not having invaded through the [[Biology:Basement membrane|basement membrane]].<ref name=Yanofsky2011/> Depending on source, it is classified as precancerous<ref name=Bath-Hextall2013/> or cSCC ''in situ'' (technically cancerous but non-invasive).<ref>{{cite journal|url=https://emedicine.medscape.com/article/1960631-overview|website=[[Medicine:Medscape|Medscape]]| vauthors = Khalyl-Mawad J |title=Pathology of Cutaneous Squamous Cell Carcinoma and Bowen Disease|date=3 April 2021}} Updated: Jun 11, 2019</ref><ref>{{cite web|url=https://www.nhs.uk/conditions/bowens-disease/|title=Bowen's disease|website=National Health Service|date=17 October 2017}} Page last reviewed: 21 May 2019</ref> In cSCC ''in situ'' (Bowen's disease), atypical squamous cells proliferate through the whole thickness of the epidermis.<ref name=Yanofsky2011/> The entire tumor is confined to the epidermis and does not invade into the dermis.<ref name=Yanofsky2011/> The cells are often highly atypical under the microscope, and may in fact look more unusual than the cells of some invasive squamous-cell carcinomas.<ref name=Yanofsky2011/>

<gallery mode="packed" heights="150">
File:Micrograph of squamous cell carcinoma in situ - 400x.jpg|cSCC ''in situ'', high magnification, demonstrating an intact basement membrane.<ref name=Yanofsky2011/>
Image:Bowen disease (1).jpg|cSCC ''in situ''
Image:Bowen disease (2).jpg|cSCC ''in situ''
Image:Bowen disease (3).jpg|cSCC ''in situ''
Image:Bowen disease (4).jpg|cSCC ''in situ''
</gallery>

'''Erythroplasia of Queyrat''' is a particular type of Bowen's disease that can arise on the glans or [[Medicine:Foreskin|prepuce]] in males,<ref name="Lookingbill">{{cite book | vauthors = Marks Jr JG |title=Lookingbill and Marks' principles of dermatology |date=2006 |publisher=Saunders Elsevier |location=Philadelphia, PA |isbn=978-1-4160-3185-7 |edition=4th | page = 63}}</ref><ref name="Fitz2">{{cite book | vauthors = Freedberg IM, Fitzpatrick TB |title=Fitzpatrick's Dermatology in General Medicine. |date=2003 |publisher=McGraw-Hill, Medical Pub. Division |location=New York |isbn=978-0-07-138076-8 |edition=6th}}</ref>{{rp|733}}<ref name="Andrews">{{cite book | vauthors = James WD, Berger TG, Elston DM |title=Andrews' Diseases of the Skin: clinical Dermatology |publisher=Saunders Elsevier |year=2006 |isbn=0-7216-2921-0 }}</ref>{{rp|656}}<ref name="Bolognia">{{cite book | vauthors = Rapini RP, Bolognia JL, Jorizzo JL |title=Dermatology: 2-Volume Set |publisher=Mosby |location=St. Louis |year=2007 |pages=1050 |isbn=978-1-4160-2999-1 }}</ref> and the [[Medicine:Vulva|vulva]] in females.<ref name=Zenilman2012>{{cite book|veditors=Zenilman JM, Shahmanesh M|title=Sexually transmitted infections diagnosis, management, and treatment|date=2012|publisher=Jones & Bartlett Learning|location=Sudbury, Mass.|isbn=9781449619848|page=109|url=https://books.google.com/books?id=prC2AgAAQBAJ&pg=PA109}}</ref> It mainly occurs in uncircumcised males,<ref name=Zenilman2012 /><ref>{{cite book | vauthors = Berkow R | title = The Merck manual of medical information | publisher = Merck Research Laboratories | location = Whitehouse Station, N.J | year = 1997 | page = [https://archive.org/details/merckmanualofmed00berk/page/1057 1057] | isbn = 0911910875 | url-access = registration | url = https://archive.org/details/merckmanualofmed00berk/page/1057 }}</ref> over the age of 40.<ref name=Katsambas2003>{{cite book |veditors= Katsambas AD, Lotti TM|title=European handbook of dermatological treatments|date=2003 |publisher=Springer |location=Berlin [u.a.] |isbn=978-3-540-00878-1 |page=169 |edition=2nd |url=https://books.google.com/books?id=BXmpcf70a3oC&pg=PA169}}</ref>

===Invasive disease===
In invasive cSCC, tumor cells infiltrate through the basement membrane. The infiltrate can be somewhat difficult to detect in the early stages of invasion: however, additional indicators such as full thickness epidermal atypia and the involvement of hair follicles can be used to facilitate the diagnosis. Later stages of invasion are characterized by the formation of nests of atypical tumor cells in the dermis, often with a corresponding inflammatory infiltrate.<ref name=Yanofsky2011/>

<gallery mode="packed" heights="150">
File:Gross pathology of squamous cell carcinoma.jpg|Gross slice of squamous-cell carcinoma of the skin
File:Micrograph of invasive squamous cell carcinoma - 150x.jpg|Superficially invasive cutaneous squamous-cell carcinoma. These lesions often do not show the marked pleomorphism and atypical nuclei of cSCC ''in situ'', but manifest early keratinocyte invasion of the dermis.<ref name=Yanofsky2011/>
File:Micrograph of invasive squamous cell carcinoma - 200x.jpg|High magnification demonstrates the pleomorphism of the invading keratinocytes<ref name=Yanofsky2011/>
File:Ulcer border of a squamous cell skin cancer.jpg|Invasive nests with characteristic large celled centers. Ulceration (at left) is common in invasive cSCC.
</gallery>

===Degree of differentiation===
<gallery mode="packed" heights="150">
File:Micrograph of well-differentiated and invasive squamous-cell carcinoma.jpg|Well-differentiated (yet invasive) cSCC, showing prominent keratinization. It may form pearl-like structures where dermal nests of keratinocytes attempt to mature in a layered fashion. Well-differentiated cSCC has slightly enlarged hyperchromatic nuclei with abundant amounts of cytoplasm. Intercellular bridges will frequently be visible.<ref name=Yanofsky2011/>
File:Micrograph of moderately differentiated and invasive squamous-cell carcinoma.jpg|Moderately differentiated lesions of invasive cSCC show much less organization and maturation with significantly less keratin formation.<ref name=Yanofsky2011/>
File:Micrograph of clear-cell squamous-cell carcinoma.jpg|Poorly differentiated, where attempts at keratinization are often no longer evident. This is a clear-cell squamous-cell carcinoma. The dysplastic cells infiltrated cords through the dermis. Poorly differentiated cSCC has greatly enlarged pleomorphic nuclei showing a&nbsp;high degree of atypia and frequent mitoses.<ref name=Yanofsky2011/>
File:Micrograph of clear-cell squamous-cell carcinoma with focus of obvious squamous-cell features, annotated.jpg|Poorly differentiated [[Biology:Clear cell|clear-cell]] squamous-cell carcinoma. For this type of cSCC, immunostains will likely be required to classify it unless other areas of the tumor show obvious squamous-cell features such as seen here (arrow).
</gallery>

==Prevention==
Appropriate sun-protective clothing, use of broad-spectrum (UVA/UVB) [[Chemistry:Sunscreen|sunscreen]] with at least SPF 50, and avoidance of intense sun exposure may prevent [[Medicine:Skin cancer|skin cancer]].<ref>{{cite journal | vauthors = Gallagher RP, Lee TK, Bajdik CD, Borugian M | title = Ultraviolet radiation | journal = Chronic Diseases in Canada | volume = 29 | issue = Suppl 1 | pages = 51–68 | year = 2010 | pmid = 21199599 | doi = 10.24095/hpcdp.29.S1.04 }}</ref> A 2016 review of sunscreen for preventing cutaneous squamous-cell carcinoma found insufficient evidence to demonstrate whether it was effective.<ref>{{cite journal | vauthors = Sánchez G, Nova J, Rodriguez-Hernandez AE, Medina RD, Solorzano-Restrepo C, Gonzalez J, Olmos M, Godfrey K, Arevalo-Rodriguez I | display-authors = 6 | title = Sun protection for preventing basal cell and squamous cell skin cancers | journal = The Cochrane Database of Systematic Reviews | volume = 7 | issue = 9 | pages = CD011161 | date = July 2016 | pmid = 27455163 | pmc = 6457780 | doi = 10.1002/14651858.CD011161.pub2 }}</ref>

==Management==
Most cutaneous squamous-cell carcinomas are removed with surgery. A few selected cases are treated with topical medication. Surgical excision with a free margin of healthy tissue is a frequent treatment modality. Radiotherapy, given as [[Medicine:External beam radiotherapy|external beam radiotherapy]] or as [[Medicine:Brachytherapy|brachytherapy]] (internal radiotherapy), can also be used to treat cSCC. There is little evidence comparing the effectiveness of different treatments for non-metastatic cSCC.<ref>{{cite journal | vauthors = Lansbury L, Leonardi-Bee J, Perkins W, Goodacre T, Tweed JA, Bath-Hextall FJ | title = Interventions for non-metastatic squamous cell carcinoma of the skin | journal = The Cochrane Database of Systematic Reviews | issue = 4 | pages = CD007869 | date = April 2010 | pmid = 20393962 | doi = 10.1002/14651858.CD007869.pub2 }}</ref>

[[Medicine:Mohs surgery|Mohs surgery]] is frequently utilized; considered the treatment of choice for squamous-cell carcinoma of the skin, physicians have also utilized the method for the treatment of squamous-cell carcinoma of the mouth, throat, and neck.<ref>{{cite book | veditors = Gross KG, Steinman HK, Rapini RP |title=Mohs Surgery, Fundamentals and Techniques |publisher=Mosby |year=1999 }}</ref>  An equivalent method of the CCPDMA standards can be utilized by a pathologist in the absence of a Mohs-trained physician. [[Physics:Radiation|Radiation]] therapy is often used afterward in high risk cancer or patient types.<ref>{{cite journal | vauthors = Krausz AE, Ji-Xu A, Smile T, Koyfman S, Schmults CD, Ruiz ES | title = A Systematic Review of Primary, Adjuvant, and Salvage Radiation Therapy for Cutaneous Squamous Cell Carcinoma | language = en-US | journal = Dermatologic Surgery | volume = 47 | issue = 5 | pages = 587–592 | date = May 2021 | pmid = 33577212 | doi = 10.1097/DSS.0000000000002965 | s2cid = 231899301 }}</ref>  Radiation or [[Physics:Radiation therapy|radiotherapy]] can also be a standalone option in treating cSCC. As a [[Medicine:Non-invasive procedure|non-invasive]] option [[Medicine:Brachytherapy|brachytherapy]] serves a painless possibility to treat in particular but not only difficult to operate areas like the earlobes or genitals. An example of this kind of therapy is the high-dose brachytherapy Rhenium-SCT which makes use of the beta rays emitting property of [[Physics:Rhenium-188|rhenium-188]]. The radiation source is enclosed in a compound which is applied to a thin protection foile directly over the lesion. This way the radiation source can be applied to complex locations and minimize radiation to healthy tissue.<ref>{{cite journal | vauthors = Castellucci P, Savoia F, Farina A, Lima GM, Patrizi A, Baraldi C, Zagni F, Vichi S, Pettinato C, Morganti AG, Strigari L, Fanti S | display-authors = 6 | title = High dose brachytherapy with non sealed <sup>188</sup>Re (rhenium) resin in patients with non-melanoma skin cancers (NMSCs): single center preliminary results | journal = European Journal of Nuclear Medicine and Molecular Imaging | volume = 48 | issue = 5 | pages = 1511–1521 | date = May 2021 | pmid = 33140131 | pmc = 8113182 | doi = 10.1007/s00259-020-05088-z | s2cid = 226231693 | doi-access = free }}</ref>

After removal of the cancer, closure of the skin for patients with a decreased amount of skin laxity involves a split-thickness skin graft. A donor site is chosen and enough skin is removed so that the donor site can heal on its own. Only the epidermis and a partial amount of dermis is taken from the donor site which allows the donor site to heal. Skin can be harvested using either a mechanical dermatome or Humby knife.<ref>[https://jomi.com/article/290.16/Squamous-Cell-Carcinoma-Excision-from-Right-Forearm-with-Split-Thickness-Skin-Graft-from-the-Thigh], Hallock G. Squamous Cell Carcinoma Excision from Right Forearm with Split-Thickness Skin Graft from the Thigh. J Med Ins. 2020;2020(290.16) doi:https://jomi.com/article/290.16</ref>

Electrodessication and curettage (EDC) can be done on selected squamous-cell carcinoma of the skin. In areas where cSCC is known to be non-aggressive, and where the patient is not immunosuppressed, EDC{{clarify|date=September 2016}} can be performed with good to adequate cure rate.<ref>{{cite journal | vauthors = Firnhaber JM | title = Basal Cell and Cutaneous Squamous Cell Carcinomas: Diagnosis and Treatment | journal = American Family Physician | volume = 102 | issue = 6 | pages = 339–346 | date = September 2020 | pmid = 32931212 | url = https://pubmed.ncbi.nlm.nih.gov/32931212 }}</ref>

Treatment options for cSCC ''in situ'' (Bowen's disease) include [[Physics:Photodynamic therapy|photodynamic therapy]] with 5-aminolevulinic acid, [[Biology:Cryosurgery|cryotherapy]], topical 5-fluorouracil or imiquimod, and excision. A meta-analysis showed evidence that PDT is more effective than cryotherapy and has better cosmetic outcomes. There is generally a lack of evidence comparing the effectiveness of all treatment options.<ref name="Bath-Hextall2013"/>

High-risk squamous-cell carcinoma, as defined by that occurring around the eye, ear, or nose, is of large size, is poorly differentiated, and grows rapidly, requires more aggressive, multidisciplinary management.

Nodal spread:

# Surgical block dissection if palpable nodes or in cases of Marjolin's ulcers but the benefit of prophylactic block lymph node dissection with Marjolin's ulcers is not proven.
# Radiotherapy
# [[Chemistry:Adjuvant therapy|Adjuvant therapy]] may be considered in those with high-risk cSCC even in the absence of evidence for local metastasis. [[Chemistry:Imiquimod|Imiquimod]] (Aldara) has been used with success for squamous-cell carcinoma ''in situ'' of the skin and the penis, but the morbidity and discomfort of the treatment is severe. An advantage is the cosmetic result: after treatment, the skin resembles normal skin without the usual scarring and morbidity associated with standard excision. Imiquimod is not FDA-approved for any squamous-cell carcinoma.

In general, squamous-cell carcinomas have a high risk of local recurrence, and up to 50% do recur.<ref>{{cite journal | vauthors = Gross MD, Cardash HS | title = Transferring anterior occlusal guidance to the articulator | journal = The Journal of Prosthetic Dentistry | volume = 61 | issue = 3 | pages = 282–285 | date = March 1989 | pmid = 2921745 | doi = 10.1016/0022-3913(89)90128-5 }}</ref> Frequent skin exams with a dermatologist is recommended after treatment.

==Prognosis==
The long-term outcome of squamous-cell carcinoma is dependent upon several factors: the sub-type of the carcinoma, available treatments, location and severity, and various patient health-related variables (accompanying diseases, age, etc.). Generally, the long-term outcome is positive, with a metastasis rate of 1.9-5.2% and a mortality rate of 1.5-3.4%.<ref name="Wysong 2023" /><ref>{{cite journal | vauthors = Chollet A, Hohl D, Perrier P | title = [Risk of cutaneous squamous cell carcinomas: the role of clinical and pathological reports] | journal = Revue Médicale Suisse | volume = 8 | issue = 335 | pages = 743–746 | date = April 2012 | pmid = 22545495 }}</ref><ref>{{cite journal | vauthors = Brantsch KD, Meisner C, Schönfisch B, Trilling B, Wehner-Caroli J, Röcken M, Breuninger H | title = Analysis of risk factors determining prognosis of cutaneous squamous-cell carcinoma: a prospective study | journal = The Lancet. Oncology | volume = 9 | issue = 8 | pages = 713–720 | date = August 2008 | pmid = 18617440 | doi = 10.1016/S1470-2045(08)70178-5 }}</ref> 

When it does metastasize, the most commonly involved organs are the lungs, brain, bone and other skin locations.<ref name="MajorAnderson2017">{{cite journal | vauthors = Major A, Anderson M | title = Not Just Skin Deep: Distant Metastases from Cutaneous Squamous Cell Carcinoma | journal = The American Journal of Medicine | volume = 130 | issue = 8 | pages = e327–e328 | date = August 2017 | pmid = 28344135 | doi = 10.1016/j.amjmed.2017.02.031 | doi-access = free }}</ref> Squamous-cell carcinoma occurring in immunosuppressed people (such as those with organ transplant, human immunodeficiency virus infection, or chronic lymphocytic leukemia) the risk of developing cSCC and having metastasis is much higher than the general population.<ref>{{cite journal | vauthors = Chapman JR, Webster AC, Wong G | title = Cancer in the transplant recipient | journal = Cold Spring Harbor Perspectives in Medicine | volume = 3 | issue = 7 | pages = a015677 | date = July 2013 | pmid = 23818517 | pmc = 3685882 | doi = 10.1101/cshperspect.a015677 }}</ref>

One study found squamous-cell carcinoma of the penis had a much greater rate of mortality than some other forms of squamous-cell carcinoma, that is, about 23%,<ref>{{cite journal | vauthors = Bethune G, Campbell J, Rocker A, Bell D, Rendon R, Merrimen J | title = Clinical and pathologic factors of prognostic significance in penile squamous cell carcinoma in a North American population | journal = Urology | volume = 79 | issue = 5 | pages = 1092–1097 | date = May 2012 | pmid = 22386252 | doi = 10.1016/j.urology.2011.12.048 }}</ref> although this relatively high mortality rate may be associated with possibly latent diagnosis of the disease due to patients avoiding genital exams until the symptoms are debilitating, or refusal to submit to a possibly scarring operation upon the genitalia.

==Epidemiology==
[[File:Melanoma and other skin cancers world map - Death - WHO2004.svg|thumb|upright=1.15|[[Age adjustment|Age-standardized]] death from melanoma and other skin cancers per 100,000&nbsp;inhabitants in 2004.<ref>{{cite web |url=https://www.who.int/healthinfo/global_burden_disease/estimates_country/en/index.html |title=WHO Disease and injury country estimates |year=2009 |work=World Health Organization |access-date=Nov 11, 2009 |url-status=live |archive-url=https://web.archive.org/web/20091111101009/http://www.who.int/healthinfo/global_burden_disease/estimates_country/en/index.html |archive-date=2009-11-11 }}</ref>{{Div col|small=yes|colwidth=10em}}
{{legend|#b3b3b3|no data}}
{{legend|#ffff65|less than 0.7}}
{{legend|#fff200|0.7–1.4}}
{{legend|#ffdc00|1.4–2.1}}
{{legend|#ffc600|2.1–2.8}}
{{legend|#ffb000|2.8–3.5}}
{{legend|#ff9a00|3.5–4.2}}
{{legend|#ff8400|4.2–4.9}}
{{legend|#ff6e00|4.9–5.6}}
{{legend|#ff5800|5.6–6.3}}
{{legend|#ff4200|6.3–7}}
{{legend|#ff2c00|7–7.7}}
{{legend|#cb0000|more than 7.7}}
{{div col end}}]]
The incidence of cutaneous squamous-cell carcinoma continues to rise around the world. This is theorized to be due to several factors; including an aging population, a greater incidence of those who are immunocompromised and the increasing use of tanning beds.<ref name="Wysong 2023">{{cite journal |last1=Wysong |first1=Ashley |title=Squamous-Cell Carcinoma of the Skin |journal=New England Journal of Medicine |date=15 June 2023 |volume=388 |issue=24 |pages=2262–2273 |doi=10.1056/NEJMra2206348|pmid=37314707 |s2cid=259154802 }}</ref> 

A recent study estimated that there are between 180,000 and 400,000 cases of cSCC in the United States in 2013.<ref>{{cite journal | vauthors = Karia PS, Han J, Schmults CD | title = Cutaneous squamous cell carcinoma: estimated incidence of disease, nodal metastasis, and deaths from disease in the United States, 2012 | journal = Journal of the American Academy of Dermatology | volume = 68 | issue = 6 | pages = 957–966 | date = June 2013 | pmid = 23375456 | doi = 10.1016/j.jaad.2012.11.037 }}</ref> Risk factors for cSCC varies with age, gender, race, geography, and genetics. The incidence of cSCC increases with age and with those 75 years or older eing at a 5-10 times increased risk of developing cSCC as compared with those who are younger than 55 years old.<ref name="Wysong 2023" /> Males are affected with cSCC at a ratio of 3:1 in comparison to females.<ref name="Wysong 2023" /> Those who have light skin, red or blonde hair and light colored eyes are also at increased risk.<ref name="Wysong 2023" />

Squamous-cell carcinoma of the skin can be found on all areas of the body but is most common on frequently sun-exposed areas, such as the face, legs and arms.<ref>{{cite web |url=https://www.skincancer.org/skin-cancer-information/squamous-cell-carcinoma |title=Squamous Cell Carcinoma |year=2018 |work=T he Skin Cancer Foundation |access-date=Dec 12, 2018 }}</ref> Solid organ transplant recipients (heart, lung, liver, pancreas, among others) are also at a heightened risk of developing aggressive, high-risk cSCC. There are also a few rare congenital diseases predisposed to cutaneous malignancy. In certain geographic locations, exposure to arsenic in well water<ref name="pmid26231242">{{cite journal | vauthors = Karagas MR, Gossai A, Pierce B, Ahsan H | title = Drinking Water Arsenic Contamination, Skin Lesions, and Malignancies: A Systematic Review of the Global Evidence | journal = Current Environmental Health Reports | volume = 2 | issue = 1 | pages = 52–68 | date = March 2015 | pmid = 26231242 | pmc = 4522704 | doi = 10.1007/s40572-014-0040-x }}</ref> or from industrial sources may significantly increase the risk of cSCC.<ref name="mdconsult">{{cite web|url=http://www.mdconsult.com/das/pdxmd/body/107722350-3/761088681?type=med&eid=9-u1.0-_1_mt_1014682|title=MD Consult - Important Notice|access-date=15 March 2017|url-status=live|archive-url=https://web.archive.org/web/20160303173158/http://www.mdconsult.com/das/pdxmd/body/107722350-3/761088681?type=med&eid=9-u1.0-_1_mt_1014682|archive-date=3 March 2016}}</ref>

{{Clear}}

==Additional images==
<gallery>
File:Biopsy proven Squamous Cell Carcinoma- 2014-05-27 05-13.jpg|Biopsy-proven cutaneous squamous-cell carcinoma
File:Squamous-carcinoma-of-dorsum-of-hand.jpg|Squamous-cell carcinoma of the dorsum of the hand
File:Bowen11.jpg|cSCC ''in situ'' (''Bowen's disease'')
File:Squamous Cell Carcinoma, Right Upper Cheek.png|cSCC of the right upper cheek; lesion outlined in blue with a dashed line prior to biopsy
File:Giant squamous cell carcinoma of the cheek.jpg|Giant squamous cell carcinoma of the cheek
</gallery>

== See also ==
* List of cutaneous conditions associated with increased risk of nonmelanoma skin cancer

== References ==
{{Reflist}}

== External links ==
{{Medical resources
|  ICD10          = {{ICD10|C|44||c|43}}
|  ICD9           = {{ICD9|199}}
|  ICDO           = {{ICDO|8070|3}}
|  eMedicineSubj  = derm
|  eMedicineTopic = 401
|  MedlinePlus    = 000829
|  MeshID         = D002294
}}
* [http://www.dermnetnz.org/lesions/squamous-cell-carcinoma.html DermNet NZ: Squamous cell carcinoma]


<!-- retained ancestor category (for other types) -->

[[Category:Anatomical pathology]]
[[Category:Wikipedia medicine articles ready to translate]]

{{Sourceattribution|Cutaneous squamous-cell carcinoma}}