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This mini review synthesizes modern insights on how virulence factors from red-complex organisms can shape the tumour microenvironment and influence carcinogenesis, with emphasis on immunological pathways.",{"@graph":14,"@context":73},[15,34,56],{"@type":16,"itemListElement":17},"BreadcrumbList",[18,23,27,31],{"item":19,"name":20,"@type":21,"position":22},"https://docshare.wps.com","Home","ListItem",1,{"item":24,"name":25,"@type":21,"position":26},"https://docshare.wps.com/document/","Document",2,{"item":28,"name":29,"@type":21,"position":30},"https://docshare.wps.com/document/healthcare/","Healthcare",3,{"item":32,"name":10,"@type":21,"position":33},"https://docshare.wps.com/document/red-complex-bacteria-immunological-background-leading-to-the-development-of-head-and-neck-cancers/354024/",4,{"url":32,"name":10,"@type":35,"image":36,"author":41,"headline":10,"publisher":44,"fileFormat":47,"inLanguage":8,"description":12,"dateModified":48,"datePublished":49,"encodingFormat":47,"isAccessibleForFree":50,"interactionStatistic":51},"DigitalDocument",{"url":37,"@type":38,"width":39,"height":40},"https://docshare.wps.com/thumbnails/red-complex-bacteria-immunological-background-leading-to-the-development-of-head-and-neck-cancers/354024.png","ImageObject",300,407,{"name":42,"@type":43},"Jordan Avery","Person",{"url":19,"name":45,"@type":46},"DocShare","Organization","application/pdf","2026-10-30","2026-09-22",true,{"@type":52,"interactionType":53,"userInteractionCount":55},"InteractionCounter",{"@type":54},"ViewAction",13,{"@type":57,"mainEntity":58},"FAQPage",[59,65,69],{"name":60,"@type":61,"acceptedAnswer":62},"What are red-complex bacteria in relation to head and neck cancers?","Question",{"text":63,"@type":64},"Red-complex bacteria consist of Porphyromonas gingivalis, Tannerella forsythia, and Treponema denticola. The review focuses on how these pathogens may contribute to HNC development through immunological mechanisms.","Answer",{"name":66,"@type":61,"acceptedAnswer":67},"Why is the link between periopathogens and head and neck cancers considered limited?",{"text":68,"@type":64},"Oral pathogens’ roles in periodontitis are well described, but data connecting specific periopathogens—especially T. forsythia and T. denticola—to HNC are still limited. This motivates the need for clearer molecular and immunological understanding.",{"name":70,"@type":61,"acceptedAnswer":71},"How can neutrophilic cells influence cancer-related processes in head and neck cancer?",{"text":72,"@type":64},"Neutrophilic cells can promote tumour growth, inhibit cancer cell senescence via IL-1Ra, and stimulate angiogenesis through factors such as VEGF, BV8, and MMP-9. The neutrophil-to-lymphocyte ratio (NLR) is also discussed as a biomarker of systemic inflammation with prognostic relevance.","https://schema.org",{"og:url":32,"og:type":75,"og:title":10,"og:site_name":45,"og:description":12},"article",{"robots":77,"canonical":32},"index,follow",{"doc_id":79,"site_id":7},354024,1790516601,{"code":4,"msg":82,"data":83},"success",[84,88,92,96,101,106,110,115,120,123,127],{"id":22,"doc_module":4,"doc_module_name":25,"category_name":85,"show_sort_weight":86,"slug":87},"Story & Novel",90,"story-novel",{"id":26,"doc_module":4,"doc_module_name":25,"category_name":89,"show_sort_weight":90,"slug":91},"Literature",80,"literature",{"id":33,"doc_module":4,"doc_module_name":25,"category_name":93,"show_sort_weight":94,"slug":95},"Exam",70,"exam",{"id":97,"doc_module":4,"doc_module_name":25,"category_name":98,"show_sort_weight":99,"slug":100},5,"Comic",60,"comic",{"id":102,"doc_module":4,"doc_module_name":25,"category_name":103,"show_sort_weight":104,"slug":105},6,"Technology",50,"technology",{"id":107,"doc_module":4,"doc_module_name":25,"category_name":29,"show_sort_weight":108,"slug":109},7,40,"healthcare",{"id":111,"doc_module":4,"doc_module_name":25,"category_name":112,"show_sort_weight":113,"slug":114},8,"Research & Report",30,"research-report",{"id":116,"doc_module":4,"doc_module_name":25,"category_name":117,"show_sort_weight":118,"slug":119},9,"Religion & Spirituality",20,"religion-spirituality",{"id":118,"doc_module":4,"doc_module_name":25,"category_name":121,"show_sort_weight":118,"slug":122},"World Cup","world-cup",{"id":124,"doc_module":4,"doc_module_name":25,"category_name":125,"show_sort_weight":124,"slug":126},10,"Lifestyle","lifestyle",{"id":128,"doc_module":4,"doc_module_name":25,"category_name":129,"show_sort_weight":97,"slug":130},19,"General","general",{"code":4,"msg":82,"data":132},{"doc_id":79,"user_id":133,"nickname":42,"user_avatar":134,"doc_module":4,"category_id":107,"category_name":29,"doc_title":10,"doc_description":12,"doc_content":135,"file_id":136,"file_url":137,"file_type":138,"file_size":139,"view_count":55,"is_deleted":4,"is_public":22,"is_downloadable":22,"audit_status":22,"page_count":102,"language":140,"language_code":8,"site_id":7,"html_lang":8,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":12,"update_tm":144,"read_time":145},1099523882367,"https://ap-avatar.wpscdn.com/davatar_9964176cb1d06d4a9deccf72a44ae3dc","TYPE Mini Review  \nPUBLISHED 01 April 2026  \nDOI 10.3389/fimmu.2026.1804268  \nOPEN ACCESS  \nEDITED BY  \nKeiji Nagano,  \nHealth Sciences University of Hokkaido, Japan  \nREVIEWED BY  \nLuiz Evaristo Ricci Volpato, University of Cuiab´a, Brazil  \n*CORRESPONDENCE  \nKarolina Kaz´mierczak-Siedlecka  \n [leokadia@gumed.edu.pl](leokadia@gumed.edu.pl)[ ](leokadia@gumed.edu.pl)Leszek Kalinowski  \n [leszek.kalinowski@gumed.edu.pl](leszek.kalinowski@gumed.edu.pl)  \nRECEIVED 04 February 2026  \nREVISED 11 March 2026  \nACCEPTED 17 March 2026  \nPUBLISHED 01 April 2026  \nCITATION  \nKaz´mierczak-Siedlecka K, Kucharski R, Kosin´ski A, Marano L, Makarewicz W and  \nKalinowski L (2026) Red-complex bacteria: immunological background leading to the development of head and neck cancers.  \nFront. Immunol. 17:1804268 .  \ndoi: 10.3389/fimmu.2026.1804268  \nCOPYRIGHT  \n© 2026 Kaz´mierczak-Siedlecka, Kucharski, Kosin´ ski, Marano, Makarewicz and Kalinowski. This is an open-access article distributed under the terms of the  \nCreative Commons Attribution License (CC BY) . The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.  \nRed-complex bacteria: immunological background leading to the development of head and neck cancers  \nKarolina Ka´zmierczak-Siedlecka 1,2*, Robert Kucharski 1,2, Adam Kosi ´nski 3,4, Luigi Marano 4, Wojciech Makarewicz 5 and Leszek Kalinowski 1,6*  \n1Department of Medical Laboratory Diagnostics – Fahrenheit Biobank [BBMRI.pl](BBMRI.pl), Medical University of Gdansk, Gdansk, Poland, 2 Neodentica Dentistry Center, Gdansk, Poland, 3 Department of Clinical Anatomy, Medical University of Gdansk, Gdansk, Poland, 4Academy of Applied Medical and Social Sciences, Elblag, Poland, 52nd Division of Radiology, Medical University of Gdansk, Gdansk, Poland, 6 BioTechMed Center, Department of Mechanics of Materials and Structures, Gdansk University of Technology, Gdansk, Poland  \nOral microbiome imbalance is involved in the development of head and neck cancers (HNCs) . There is a group of oral pathogens, such as Porphyromonas gingivalis, Tannerella forsythia, and Treponema denticola, that creates redcomplex. Currently, the oral pathogens ’ role in the pathogenesis of periodontitis is well-described; nevertheless, data regarding the link between HNCs and periopathogens are still limited, especially considering T. forsythia and T. denticola. These microbes utilise various virulence factors to promote the carcinogenesis process, affecting the immunological background. This paper presents modern insights into the role of red-complex bacteria in the development of HNCs, concentrating on the immunological aspects.  \nKEYWORDS  \nhead and neck cancers, immunology, Porphyromonas gingivalis, Tannerella forsythia, Treponema denticola, virulence factors  \n1 Introduction  \nMalignancies arising from the nasal/oral cavity, pharynx, larynx, paranasal sinuses, and salivary glands are classified as head and neck cancers (HNCs) (1) . They are ranked as the sixth most common malignant tumour globally. The GLOBOCAN 2020 database indicated that there are approximately 930,000 new cases and 467,000 deaths per year (2) . Approximately 90% of cases are diagnosed as head and neck squamous cell carcinoma (HNSCC), whereas approximately 70%–80% of cases are found at stage III/IV (2) . In addition to commonly known risk factors, oral microbiome imbalance also contributes to the development of HNCs. There is no consistent signature of oral dysbiosis in HNC patients; however, the abundance of some microbes, such as Fusobacterium, Leptotrichia, Treponema, Porphyromonas gingivalis, Enterobacterales, Pseudomonas, Prevotella, Bacteroidetes, Haemophilus, and Veillonella, was noted (3) . Red-complex pathogens are a g","cbCair3Oi5q8r9HU","https://ap.wps.com/l/cbCair3Oi5q8r9HU","pdf",1080215,"English","# Introduction\n## Head and neck cancer epidemiology and staging\n## Oral microbiome imbalance and red-complex pathogens\n## Neutrophilic cells and immunological pathways in the tumour microenvironment","[{\"question\":\"What are red-complex bacteria in relation to head and neck cancers?\",\"answer\":\"Red-complex bacteria consist of Porphyromonas gingivalis, Tannerella forsythia, and Treponema denticola. The review focuses on how these pathogens may contribute to HNC development through immunological mechanisms.\"},{\"question\":\"Why is the link between periopathogens and head and neck cancers considered limited?\",\"answer\":\"Oral pathogens’ roles in periodontitis are well described, but data connecting specific periopathogens—especially T. forsythia and T. denticola—to HNC are still limited. This motivates the need for clearer molecular and immunological understanding.\"},{\"question\":\"How can neutrophilic cells influence cancer-related processes in head and neck cancer?\",\"answer\":\"Neutrophilic cells can promote tumour growth, inhibit cancer cell senescence via IL-1Ra, and stimulate angiogenesis through factors such as VEGF, BV8, and MMP-9. The neutrophil-to-lymphocyte ratio (NLR) is also discussed as a biomarker of systemic inflammation with prognostic relevance.\"}]","Red-complex bacteria - immunological background leading to the development of head and neck cancers | PDF",1790108496,15]