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Dysregulated immune responses and chronic inflammation in both cell- and humoral-mediated disorders are linked to increased HNC development, especially in head and neck tissues. Interactions between these conditions can amplify risk by promoting tumor-favorable microenvironments and weakening immune surveillance and anti-tumor responses. The work highlights molecular mechanisms needed to support targeted prevention and therapeutic strategies, noting immunotherapy opportunities while emphasizing the need for further studies on efficacy and safety in this specific 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Cancers—A Narrative Review of Potential Physiopathological and Biological Mechanisms  \nNuno Vale 1,2,3, *, Mariana Pereira 1,2 and Rui Amaral Mendes 2,3,4, *  \nCitation: Vale, N.; Pereira, M.; Mendes, R.A. Systemic Inflammatory Disorders, Immunosuppressive Treatment and Increase Risk of Head and Neck Cancers—A Narrative Review of Potential Physiopathological and Biological Mechanisms. Cells 2023, 12, 2192 . [https://doi.org/10.3390/](https://doi.org/10.3390/)[ ](https://doi.org/10.3390/)cells12172192  \nAcademic Editor: Jozsef Dudas  \nReceived: 22 July 2023  \nRevised: 28 August 2023  \nAccepted: 30 August 2023  \nPublished: 1 September 2023  \nCopyright: © 2023 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 OncoPharma Research Group, Center for Health Technology and Services Research (CINTESIS), Rua Doutor Pl¡cido da Costa, 4200-450 Porto, Portugal; [mariana.m.pereira2097@gmail.com](mariana.m.pereira2097@gmail.com)  \n[2](2 CINTESIS@RISE)[ CINTESIS@RISE](2 CINTESIS@RISE), [Faculty of Medicine](Faculty of Medicine), [University of Porto](University of Porto), [Alameda Professor Hern](Alameda Professor Hern)¥[ni Monteiro](ni Monteiro), 4200-319 Porto, Portugal  \n3 Department of Community Medicine, Information and Health Decision Sciences (MEDCIDS), Faculty of Medicine, University of Porto, Rua Doutor Pl¡cido da Costa, 4200-450 Porto, Portugal  \n4 Department of Oral and Maxillofacial Medicine and Diagnostic Sciences, Case Western Reserve University, 10900 Euclid Ave, Cleveland, OH 44106-7401, USA  \n* [Correspondence: nunovale@med.up.pt](Correspondence: nunovale@med.up.pt) (N.V.); [rmendes@med.up.pt](rmendes@med.up.pt) (R.A.M.); Tel.: +351-220426537 (N.V.)  \nAbstract: Head and neck cancers (HNCs) are known to present multiple factors likely to influence their development. This review aims to provide a comprehensive overview of the current scientific literature on the interplay between systemic inflammatory disorders, immunosuppressive treatmentsand their synergistic effect on HNC risk. Both cell-mediated and humoral-mediated systemic inflammatory disorders involve dysregulated immune responses and chronic inflammation and these inflammatory conditions have been associated with an increased risk of HNC development, primarily in the head and neck region. Likewise, the interaction between systemic inflammatory disordersand immunosuppressive treatments appears to amplify the risk of HNC development, as chronic inflammation fosters a tumor-promoting microenvironment, while immunosuppressive therapies further compromise immune surveillance and anti-tumor immune responses. Understanding the molecular and cellular mechanisms underlying this interaction is crucial for developing targeted prevention strategies and therapeutic interventions. Additionally, the emerging field of immunotherapy provides potential avenues for managing HNCs associated with systemic inflammatory disorders, but further research is needed to determine its efficacy and safety in this specific context. Future studies are warranted to elucidate the underlying mechanisms and optimize preventive strategies and therapeutic interventions.  \nKeywords: head and neck cancers; immunosuppression; systemic inflammatory diseases  \n1. Introduction  \nHead and neck cancers (HNC) account for 3% of all cancers in the United States, with a fourth of the patients succumbing to the disease every year [1] . There are several classical risk factors associated with HNCs, such as alcohol use, smoking, human papillomavirus (HPV) and Epstein–Barr virus (EBV) infections—and more general risk factors include chron","cbCaidtY1cQYdasY","https://ap.wps.com/l/cbCaidtY1cQYdasY","pdf",1446852,25,"English","# Abstract\n# Introduction\n## Risk factors and chronic inflammation\n## Immune deficiency and transplant-related risk\n## Immunosuppression and impaired anti-tumor immunity","[{\"question\":\"What is the main purpose of this narrative review?\",\"answer\":\"To provide an overview of scientific evidence on how systemic inflammatory disorders and immunosuppressive treatments interact and jointly affect head and neck cancer risk.\"},{\"question\":\"How do systemic inflammatory disorders contribute to head and neck cancer development?\",\"answer\":\"They involve dysregulated immune responses and chronic inflammation that are associated with increased HNC development, particularly in head and neck regions.\"},{\"question\":\"Why does immunosuppressive treatment increase HNC risk?\",\"answer\":\"Chronic inflammation can create a tumor-promoting microenvironment, while immunosuppressive therapies further compromise immune surveillance and reduce anti-tumor immune responses.\"}]","Systemic Inflammatory Disorders, Immunosuppressive Treatment and Increase Risk of Head and Neck Cancers—A Narrative Review of Potential Physiopathological and Biological Mechanisms | PDF",1790228899,63]