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This review analyzes epidemiologic and clinical patterns of scalp tumors to clarify pathogenesis and guide potential prevention and treatment. The central hypothesis proposes that hair limits carcinogenesis mainly through continuous IL-17–biased immunosurveillance rather than physical shielding. Hair loss disrupts immunosurveillance and enables neoplastic expansion, while hair follicles and stromal metabolic alterations support tumor promotion.",{"@graph":69,"@context":122},[70,84,105],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":40,"@type":76,"position":81},"https://docshare.wps.com/document/research-report/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/the-carcinogenesis-of-the-human-scalp-an-immunometabolic-centered-view/329489/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/the-carcinogenesis-of-the-human-scalp-an-immunometabolic-centered-view/329489.png","ImageObject",300,407,{"name":92,"@type":93},"Seraphina","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-24","2026-09-21",true,{"@type":102,"interactionType":103,"userInteractionCount":19},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What is the review’s main focus on scalp carcinogenesis?","Question",{"text":112,"@type":113},"It examines epidemiologic and clinical features of scalp cancer to explain mechanisms of pathogenesis and opportunities for prevention and treatment, emphasizing an immunometabolic-centered perspective.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How does the review explain the protective role of hair against skin cancer?",{"text":117,"@type":113},"Hair is proposed to protect not only as a physical barrier but by providing continuous IL-17–biased immunosurveillance that limits expansion of neoplastic cells.",{"name":119,"@type":110,"acceptedAnswer":120},"What changes in hair and stromal aging are described as contributing to tumor promotion?",{"text":121,"@type":113},"Loss of hair is linked to reduced immunosurveillance, while aging-associated stromal alterations and metabolic changes in stroma (including Sirt3-related pathways) are suggested to favor permissiveness for tumor promotion.","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},329489,1790553085,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":39,"category_name":40,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":19,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":44,"language":139,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":140,"faqs":141,"seo_title":142,"seo_description":67,"update_tm":143,"read_time":144,"preview_page_count":4},962075114101,"https://ap-avatar.wpscdn.com/avatar/e000253a75eb197efd?x-image-process=image/resize,m_fixed,w_180,h_180&k=1780044092746381165","Review  \nThe Carcinogenesis of the Human Scalp: An Immunometabolic-Centered View  \nBaruch Kaplan 1, Rebecca von Dannecker 2 and Jack L. Arbiser 3, *  \nCitation: Kaplan, B.; von Dannecker, R.; Arbiser, J.L. The Carcinogenesis of the Human Scalp: An Immunometabolic-Centered View. Int.  \nJ. Mol. Sci. 2024, 25, 12064. [https://](https://)[ ](https://)[doi.org/10.3390/ijms252212064](doi.org/10.3390/ijms252212064)  \nAcademic Editor: Hanna Mysliwiec  \nReceived: 30 September 2024  \nRevised: 30 October 2024  \nAccepted: 6 November 2024  \nPublished: 10 November 2024  \nCopyright: © 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ([https://](https://)[ ](https://)[creativecommons.org/licenses/by/](creativecommons.org/licenses/by/)[ ](creativecommons.org/licenses/by/)[4.0/](4.0/)) .  \n1 Adelson School of Medicine, Ariel University, Ariel 40700, Israel; [drbakaplan@gmail.com](drbakaplan@gmail.com)  \n2 Marilia Medical School, Marilia 17519-030, SP, Brazil; [rebeccavondannecker@gmail.com](rebeccavondannecker@gmail.com)  \n[3](3 Metroderm/United Dermatology Partners)[ Metroderm/United Dermatology Partners](3 Metroderm/United Dermatology Partners), [875 Johnson Ferry RD](875 Johnson Ferry RD), [Atlanta](Atlanta), [GA 30342](GA 30342), [USA](USA)  \n* Correspondence: [arbiser@hotmail.com](arbiser@hotmail.com)  \nAbstract: The human scalp is a common site of skin cancer in humans, with nonmelanoma skin cancer being exceedingly common. In this review, two dermatologists with extensive experience in cutaneous oncology will discuss unique features of the epidemiology of cancer of the scalp. Clinical observations on these common skin cancers lead to insight into the pathogenesis and potential prevention and treatment of cutaneous scalp neoplasia. Our hypothesis is that the presence of hair protects against the development of skin cancer but not by serving as a physical shield but rather by providing continuous IL-17-biased immunosurveillance. The loss of hair allows for a release from immunosurveillance, resulting in the expansion of neoplastic cells towards skin cancer. Both hair follicles and metabolic changes in stroma allow for permissiveness for tumor promotion.  \nKeywords: aging; stroma; Sirt3; ultraviolet light; IRF4  \n1. Introduction  \nThe scalp is an exceedingly common site for basal cell and squamous cell carcinoma and occasional melanomas. Benign lesions, including seborrheic keratoses and blue nevi, are also commonly found on the scalp. A major difference between the scalp and other common sun-exposed areas in terms of skin cancer risk is that the scalp is covered with hair during periods of peak sun exposure during youth. Carcinomas on the scalp are more common in men than women, but they may become evident in women with sparse hair. Androgenetic alopecia is also common in men, beginning in the 20–30-year-old age group and becoming more evident with age. Women too lose hair but not usually to the same extent as men. The incidence of scalp carcinomas is also higher in men than in women [1,2] . Androgenetic alopecia is thought to be mediated by dihydrotestosterone, and this has led to the use of dihydrotestosterone blockers as a common treatment for alopecia [3] .  \nTwo major differences exist in the scalp of elderly men vs. elderly women. The first is the presence of hair. While elderly women experience hair thinning, frank alopecia is uncommon. The second change is that of the stroma. Stromal changes may be responsible for the miniaturization of hair follicles, and stromal changes associated with miniaturization may also favor the development of actinic keratosis (AK) and nonmelanoma skin cancer (NMSC) [3,4] .  \nScalp stroma is subject to aging as is every other tissue. A candidate for aging in scalp stroma is Sirt3, a mitochondrial deacetylase which stimulates mitochondrial biogenesis [5,6] . TGF-beta","cbCaiaCH2you9Yky","https://ap.wps.com/l/cbCaiaCH2you9Yky","pdf",926652,"English","# Abstract\n# Introduction\n## Scalp cancer risk and sex differences\n## Hair loss, stroma aging, and Sirt3\n# Hair Cycle and Aging\n## Phases: anagen, catagen, telogen","[{\"question\":\"What is the review’s main focus on scalp carcinogenesis?\",\"answer\":\"It examines epidemiologic and clinical features of scalp cancer to explain mechanisms of pathogenesis and opportunities for prevention and treatment, emphasizing an immunometabolic-centered perspective.\"},{\"question\":\"How does the review explain the protective role of hair against skin cancer?\",\"answer\":\"Hair is proposed to protect not only as a physical barrier but by providing continuous IL-17–biased immunosurveillance that limits expansion of neoplastic cells.\"},{\"question\":\"What changes in hair and stromal aging are described as contributing to tumor promotion?\",\"answer\":\"Loss of hair is linked to reduced immunosurveillance, while aging-associated stromal alterations and metabolic changes in stroma (including Sirt3-related pathways) are suggested to favor permissiveness for tumor promotion.\"}]","The Carcinogenesis of the Human Scalp - An Immunometabolic-Centered View | PDF",1789984319,23]