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This narrative review examines p16ink4a, a cell-cycle arrest oncosuppressor protein, widely used in the head and neck as a surrogate for HPV infection. The literature and recent meta-analyses reduce HPV’s proposed biological role in LSCC and challenge p16ink4a’s reliability as a surrogate marker, while still suggesting its value as an independent predictor of survival.",{"@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/p16-expression-in-laryngeal-squamous-cell-carcinoma-a-surrogate-or-independent-prognostic-marker/331875/",{"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/p16-expression-in-laryngeal-squamous-cell-carcinoma-a-surrogate-or-independent-prognostic-marker/331875.png","ImageObject",300,407,{"name":92,"@type":93},"Patrick","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-30","2026-09-21",true,{"@type":102,"interactionType":103,"userInteractionCount":34},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"Why is p16ink4a used in the head and neck region?","Question",{"text":112,"@type":113},"p16ink4a is used as a surrogate marker of HPV infection, with prognostic associations reported in other cancers.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"What do recent studies suggest about HPV and p16ink4a in LSCC?",{"text":117,"@type":113},"Published papers and meta-analyses tend to minimize HPV’s biological role in LSCC and question p16ink4a’s reliability as a surrogate prognostic marker in this setting.",{"name":119,"@type":110,"acceptedAnswer":120},"What does the review propose for future research?",{"text":121,"@type":113},"Future work should evaluate p16ink4a specifically, considering possible inactivation and overexpression, staining patterns, and immunohistochemistry cutoffs, and emphasizing its independent role in predicting survival.","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},331875,1790148110,{"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":34,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":139,"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":41,"preview_page_count":4},549758146520,"https://ap-avatar.wpscdn.com/avatar/80002397d8c0411e94?_k=1775819394049821470","pathogens   \nReview  \np16 Expression in Laryngeal Squamous Cell Carcinoma: A Surrogate or Independent Prognostic Marker?  \nRoberto Gallus 1, Davide Rizzo 2,3, Giorgia Rossi 4, Luca Mureddu 2, *, Jacopo Galli 4,5, Alberto Artuso 1 and Francesco Bussu 2,3  \nCitation: Gallus, R.; Rizzo, D.; Rossi, G.; Mureddu, L.; Galli, J.; Artuso, A.; Bussu, F. p16 Expression in Laryngeal Squamous Cell Carcinoma: A Surrogate or Independent Prognostic Marker? Pathogens 2024, 13, 100 . [https://doi.org/10.3390/](https://doi.org/10.3390/)[ ](https://doi.org/10.3390/)pathogens13020100  \nAcademic Editors: Lawrence S. Young and Ramona Gabriela Ursu  \nReceived: 7 January 2024  \nRevised: 21 January 2024  \nAccepted: 22 January 2024  \nPublished: 24 January 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 Otolaryngology, Mater Olbia Hospital, 07026 Olbia, Italy; [roberto.gallus@materolbia.com](roberto.gallus@materolbia.com) (R.G.);  \n[alberto.artuso@materolbia.com](alberto.artuso@materolbia.com) (A.A.)  \n2 U.O.C. Otorinolaringoiatria, Azienda Ospedaliero Universitaria di Sassari, Viale San Pietro, 43,  \n07100 Sassari, Italy; [drizzo@uniss.it](drizzo@uniss.it) (D.R.); [fbussu@uniss.it](fbussu@uniss.it) (F.B.)  \n3 Otolaryngology Division, Department of Medicine, Surgery and Pharmacology, University of Sassari, Viale San Pietro, 43, 07100 Sassari, Italy  \n4 Unit of Otorhinolaryngology and Head-Neck Surgery,“A. Gemelli” Hospital Foundation IRCCS,  \n00168 Rome, Italy; [giorgia.ros@tiscali.it](giorgia.ros@tiscali.it) (G.R.); [jacopo.galli@unicatt.it](jacopo.galli@unicatt.it) (J.G.)  \n5 Department of Head-Neck and Sensory Organs, Catholic University of Sacred Heart, 00168 Rome, Italy  \n* [Correspondence: muredduluca@gmail.com](Correspondence: muredduluca@gmail.com); Tel.: +39-3284087578  \nAbstract: Laryngeal squamous cell carcinoma (LSCC) is a common malignancy that, despite scientific advancements, has not seen an improvement in its prognosis in the last decades. Few promising predictive markers have been found and none are relevant in clinical practice. p16ink4a, an oncosuppressor protein involved in cell cycle arrest, with a prognostic impact on other cancers, has been widely used in the head and neck region as a surrogate marker of HPV infection. Published papersand recent meta-analyses seem to minimize the biological role of HPV in the context of LSCC’s cancerogenesis, and to disprove the reliability of p16ink4a as a surrogate prognostic marker in this context, while still highlighting its potential role as an independent predictor of survival. Unfortunately, the available literature, in particular during the last two decades, is often not focused on its potential role as an independent biomarker and few relevant data are found in papers mainly focused on HPV. The available data suggest that future research should focus specifically on p16ink4a, taking into account both its potential inactivation and overexpression, different patterns of staining, and immunohistochemistry cutoffs, and should focus not on its potential role as a surrogate marker buton its independent role as a predictor of survival.  \nKeywords: p16ink4a overexpression; p16ink4a inactivation; LSCC; HPV; prognostic marker  \n1. Introduction  \nThe discovery and study of the role of high-risk Human Papillomaviruses (HPVs) in oropharyngeal squamous cell carcinomas (OPSCCs) during the last 20 years have completely changed our understanding of a subset of these tumors and have supported the identification of HPV-positive OPSCC as a distinct clinical entity [1–6] . The knowledge accumulated during this timeframe has led to the recent change in the American Joint Committee on Cancer (AJC","cbCaid0Pd5051FjM","https://ap.wps.com/l/cbCaid0Pd5051FjM","pdf",301925,12,"English","# Introduction\n## HPV-positive oropharyngeal cancers and AJCC TNM update\n## p16INK4a as a surrogate marker: clinical adoption and limitations\n# Prognostic evidence in head and neck cancers\n## Beyond HPV: evidence in laryngeal squamous cell carcinoma\n# Aim of the narrative review\n## Focus on p16INK4a as an independent biomarker","[{\"question\":\"Why is p16ink4a used in the head and neck region?\",\"answer\":\"p16ink4a is used as a surrogate marker of HPV infection, with prognostic associations reported in other cancers.\"},{\"question\":\"What do recent studies suggest about HPV and p16ink4a in LSCC?\",\"answer\":\"Published papers and meta-analyses tend to minimize HPV’s biological role in LSCC and question p16ink4a’s reliability as a surrogate prognostic marker in this setting.\"},{\"question\":\"What does the review propose for future research?\",\"answer\":\"Future work should evaluate p16ink4a specifically, considering possible inactivation and overexpression, staining patterns, and immunohistochemistry cutoffs, and emphasizing its independent role in predicting survival.\"}]","p16 Expression in Laryngeal Squamous Cell Carcinoma - A Surrogate or Independent Prognostic Marker? | PDF",1789995578]