[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-373878-105":59,"doc-detail-373878-en":131},{"code":4,"msg":5,"data":6},0,"success",[7,13,18,23,28,33,38,43,48,51,55],{"id":8,"doc_module":4,"doc_module_name":9,"category_name":10,"show_sort_weight":11,"slug":12},1,"Document","Story & Novel",90,"story-novel",{"id":14,"doc_module":4,"doc_module_name":9,"category_name":15,"show_sort_weight":16,"slug":17},2,"Literature",80,"literature",{"id":19,"doc_module":4,"doc_module_name":9,"category_name":20,"show_sort_weight":21,"slug":22},4,"Exam",70,"exam",{"id":24,"doc_module":4,"doc_module_name":9,"category_name":25,"show_sort_weight":26,"slug":27},5,"Comic",60,"comic",{"id":29,"doc_module":4,"doc_module_name":9,"category_name":30,"show_sort_weight":31,"slug":32},6,"Technology",50,"technology",{"id":34,"doc_module":4,"doc_module_name":9,"category_name":35,"show_sort_weight":36,"slug":37},7,"Healthcare",40,"healthcare",{"id":39,"doc_module":4,"doc_module_name":9,"category_name":40,"show_sort_weight":41,"slug":42},8,"Research & Report",30,"research-report",{"id":44,"doc_module":4,"doc_module_name":9,"category_name":45,"show_sort_weight":46,"slug":47},9,"Religion & Spirituality",20,"religion-spirituality",{"id":46,"doc_module":4,"doc_module_name":9,"category_name":49,"show_sort_weight":46,"slug":50},"World Cup","world-cup",{"id":52,"doc_module":4,"doc_module_name":9,"category_name":53,"show_sort_weight":52,"slug":54},10,"Lifestyle","lifestyle",{"id":56,"doc_module":4,"doc_module_name":9,"category_name":57,"show_sort_weight":24,"slug":58},19,"General","general",{"code":4,"msg":60,"data":61},"ok",{"site_id":62,"language":63,"slug":64,"title":65,"keywords":66,"description":67,"schema_data":68,"social_meta":124,"head_meta":126,"extra_data":128,"updated_unix":130},105,"en","special-issue-pathogenesis-and-treatments-of-head-and-neck-cancer","Special Issue - Pathogenesis and Treatments of Head and Neck Cancer","","Special Issue on head and neck cancers examines how disease mechanisms, risk patterns, and treatment strategies are evolving. The editorial reviews rising global incidence and qualitative epidemiologic shifts, including HPV-positive oropharyngeal cancers and oral cavity cancer trends with emerging younger-onset features. It links immune dysregulation, chronic inflammation, oral dysbiosis, and microbiome imbalance to a carcinogenesis-favorable microenvironment, highlighting FOXP3-mediated immune tolerance. It also outlines progress toward precision, minimally invasive, and immunotherapy-guided care.",{"@graph":69,"@context":123},[70,84,106],{"@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":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/special-issue-pathogenesis-and-treatments-of-head-and-neck-cancer/373878/",{"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/special-issue-pathogenesis-and-treatments-of-head-and-neck-cancer/373878.png","ImageObject",300,407,{"name":92,"@type":93},"dhado","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-29","2026-09-23",true,{"@type":102,"interactionType":103,"userInteractionCount":105},"InteractionCounter",{"@type":104},"ViewAction",11,{"@type":107,"mainEntity":108},"FAQPage",[109,115,119],{"name":110,"@type":111,"acceptedAnswer":112},"What major epidemiologic changes are highlighted for head and neck cancers?","Question",{"text":113,"@type":114},"The editorial emphasizes that while incidence and mortality rates have changed only modestly, absolute case numbers continue to rise. It also points to qualitative shifts such as increased HPV-positive oropharyngeal cancers and rapidly increasing oral cavity cancer incidence in parts of Europe, especially the UK.","Answer",{"name":116,"@type":111,"acceptedAnswer":117},"How does the document connect immune dysregulation to cancer development?",{"text":118,"@type":114},"It states that immune dysregulation, microbiota imbalance, and chronic inflammation create a microenvironment favorable for carcinogenesis. It specifically links oral dysbiosis and periodontitis to oxidative stress, epigenetic remodeling, and tumor immune tolerance.",{"name":120,"@type":111,"acceptedAnswer":121},"What treatment directions are described as emerging in the field?",{"text":122,"@type":114},"The editorial notes a shift toward precision-based, minimally invasive, and biologically guided care. It highlights the expanding role of immunotherapy, including PD-1/PD-L1 inhibitors, from recurrent/metastatic settings into earlier disease stages.","https://schema.org",{"og:url":83,"og:type":125,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":127,"canonical":83},"index,follow",{"doc_id":129,"site_id":62},373878,1790240496,{"code":4,"msg":5,"data":132},{"doc_id":129,"user_id":133,"nickname":92,"user_avatar":134,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":135,"file_id":136,"file_url":137,"file_type":138,"file_size":139,"view_count":105,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":24,"language":140,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":67,"update_tm":144,"read_time":145},5909893218464,"https://ap-avatar.wpscdn.com/davatar_085a072bc5b1113ac321206ff7593b45","Editorial  \nSpecial Issue “Pathogenesis and Treatments of Head and Neck Cancer”  \nMarko Tarle 1,2  \nReceived: 3 December 2025  \nRevised: 14 December 2025  \nAccepted: 15 December 2025  \nPublished: 16 December 2025  \nCitation: Tarle, M. Special Issue“Pathogenesis and Treatments of Head and Neck Cancer”. Int. J. Mol. Sci. 2025, 26, 12107. [https://doi.org/](https://doi.org/)[ ](https://doi.org/)[10.3390/ijms262412107](10.3390/ijms262412107)  \nCopyright: © 2025 by the author. 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://creativecommons.org/](https://creativecommons.org/)[ ](https://creativecommons.org/)[licenses/by/4.0/](licenses/by/4.0/)) .  \n1 Department of Maxillofacial Surgery, Dubrava University Hospital, 10000 Zagreb, Croatia; [tarlemarko1@gmail.com](tarlemarko1@gmail.com)  \n2 School of Dental Medicine, University of Zagreb, Gunduli´ceva 5, 10000 Zagreb, Croatia  \nHead and neck cancers (HNCs) are among the most common malignancies worldwide and represent a substantial global health burden. Recent GLOBOCAN estimates report nearly 950,000 new cases and approximately 480,000 deaths each year [1,2] . Although agestandardized incidence and mortality rates have changed only modestly in recent decades, the absolute number of cases continues to rise due to population growth and aging [3,4] . Beyond these global trends, the epidemiology of HNC is undergoing important qualitative shifts that challenge traditional risk-based and anatomical classifications. HPV-positive oropharyngeal squamous cell carcinomas (OPSCC) have now surpassed cervical cancer asthe most common HPV-associated malignancy in the United States, a shift driven largely by a sharp rise in HPV-positive OPSCC among men [5,6] . Most of these tumors originate in the crypt epithelium of the palatine tonsils and the base of the tongue, where the reticulated mucosa favors persistent HPV infection [7] . Men are disproportionately affected, exhibiting higher oral HPV prevalence, longer infection persistence, and substantially lower vaccination coverage than women [8] . The causes of this disparity, such as potential differences in mucosal immunity, patterns of oral HPV exposure, or unidentified biological factors, remain insufficiently explained and require focused investigation [9] . These observations emphasize that viral oncogenesis in the oropharynx cannot be fully understood without integrating host immune regulation and microenvironmental context.  \nIn Europe, particularly in the United Kingdom, there has been a steep rise in oral cavity cancer incidence, with an increase of more than 130% over the past two decades [10] . Earlier analyses showed a particularly sharp rise among patients younger than 45 years, while more recent data highlight a continued increase in tongue cancers among young nonsmoking women, suggesting the possible role of yet unidentified etiological factors beyond the classical ones of tobacco, alcohol, and HPV [11,12] . Together, these epidemiological patterns point toward a biologically heterogeneous disease spectrum that cannot be adequately captured by exposure history alone. In this context, the upcoming ninth edition of the TNM classification will further refine staging, especially in HPV-positive oropharyngeal carcinomas. The revision will more precisely define depth of invasion in oral cavity cancers and extranodal extension in neck metastases, while moving toward the integration of biological parameters that increasingly determine prognosis and treatment outcomes [13] . This evolution of staging frameworks mirrors a broader conceptual shift: HNC is increasingly viewed not as a uniform entity but as a constellation of biologically distinct diseases. The clinical and biological heterogeneity of HNC, traditionally described as two “faces” of the disease, one associated with cumulative tobacco and alcohol exposure an","cbCaii2LKg9Knrcg","https://ap.wps.com/l/cbCaii2LKg9Knrcg","pdf",176539,"English","# Editorial\n## Epidemiology and classification shifts\n## Immune dysregulation, microbiome, and chronic inflammation\n## Implications for treatment and precision approaches","[{\"question\":\"What major epidemiologic changes are highlighted for head and neck cancers?\",\"answer\":\"The editorial emphasizes that while incidence and mortality rates have changed only modestly, absolute case numbers continue to rise. It also points to qualitative shifts such as increased HPV-positive oropharyngeal cancers and rapidly increasing oral cavity cancer incidence in parts of Europe, especially the UK.\"},{\"question\":\"How does the document connect immune dysregulation to cancer development?\",\"answer\":\"It states that immune dysregulation, microbiota imbalance, and chronic inflammation create a microenvironment favorable for carcinogenesis. It specifically links oral dysbiosis and periodontitis to oxidative stress, epigenetic remodeling, and tumor immune tolerance.\"},{\"question\":\"What treatment directions are described as emerging in the field?\",\"answer\":\"The editorial notes a shift toward precision-based, minimally invasive, and biologically guided care. It highlights the expanding role of immunotherapy, including PD-1/PD-L1 inhibitors, from recurrent/metastatic settings into earlier disease stages.\"}]","Special Issue - Pathogenesis and Treatments of Head and Neck Cancer | PDF",1790200721,13]