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The Next Chapter in Cancer Diagnostics: Advances in HPV-Positive Head and Neck Cancer. Biomolecules 2024, 14, 925. [https://](https://)[ ](https://)[doi.org/10.3390/biom14080925](doi.org/10.3390/biom14080925)  \nAcademic Editor: Javier Martínez Useros  \nReceived: 18 June 2024  \nRevised: 24 July 2024  \nAccepted: 29 July 2024  \nPublished: 30 July 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 Faculty of Medicine, University of Rijeka, 51000 Rijeka, Croatia; [tea.krsek@gmail.com](tea.krsek@gmail.com)  \n2 Department of Medical Chemistry, Biochemistry and Clinical Chemistry, Faculty of Medicine, University of Rijeka, 51000 Rijeka, Croatia  \n3 Department of Otorhinolaryngology and Head and Neck Surgery, Clinical Hospital Centre Rijeka,  \n51000 Rijeka, Croatia; [tamara.braut@uniri.hr](tamara.braut@uniri.hr)  \n4 Department of Anesthesiology, Reanimatology, Emergency and Intensive Care Medicine, Faculty of Medicine, University of Rijeka, 51000 Rijeka, Croatia; [vlatkast@uniri.hr](vlatkast@uniri.hr)  \n5 Department of Clinical Medical Sciences I, Faculty of Health Studies, University of Rijeka,  \n51000 Rijeka, Croatia  \n* Correspondence: [lara.baticic@uniri.hr](lara.baticic@uniri.hr); Tel.: +385-(0)51-651271 † These authors contributed equally to this work.  \nAbstract: Human papillomavirus (HPV)-associated head and neck squamous cell carcinoma (HNSCC), particularly oropharyngeal squamous cell carcinoma (OPSCC), is an increasingly prevalent pathology worldwide, especially in developed countries. For diagnosing HPV in HNSCC, the combination of p16 immunohistochemistry (IHC) and polymerase chain reaction (PCR) offers high sensitivity and specificity, with p16 IHC being a reliable initial screen and PCR confirming HPV presence. Advanced techniques like next-generation sequencing (NGS) and RNA-based assays provide detailed insights but are primarily used in research settings. Regardless of HPV status, standard oncological treatments currently include surgery, radiation, and/or chemotherapy. This conventional approach does not account for the typically better prognosis of HPV-positive HNSCC patients, leading to increased chemo/radiation-induced secondary morbidities and reduced quality of life. Therefore, it is crucial to identify and detect HPV positivity and other molecular characteristics of HNSCC to personalize treatment strategies. This comprehensive review aims to summarize current knowledge on various HPV detection techniques and evaluate their advantages and disadvantages, with a focus on developing methodologies to identify new biomarkers in HPV-positive HNSCC. The review discusses direct and indirect HPV examination in tumor tissue, DNA-and RNA-based detection techniques, protein-based markers, liquid biopsy potentials, immune-related markers, epigenetic markers, novel biomarkers, and emerging technologies, providing an overall insight into the current state of knowledge.  \nKeywords: biomarkers; head and neck squamous cell carcinoma; HPV-16; human papillomavirus; oropharyngeal squamous cell carcinoma; p16  \n1. Introduction  \nHigh-risk human papillomavirus (HR-HPV) infection can cause malignant tumors to grow in a variety of squamous tissues across the body, including the areas of head and neck, especially the oropharynx (comprised of several tissues and structures, including the soft tissue, the base of the tongue, palatine tonsils, the posterior pharyngeal wall, and the back ","cbCaiv5fCEXYR8le","https://ap.wps.com/l/cbCaiv5fCEXYR8le","pdf",985411,21,"English","# Abstract\n# Keywords\n# Introduction","[{\"question\":\"Why is HPV-associated HNSCC increasingly important in cancer diagnostics?\",\"answer\":\"HPV-associated head and neck squamous cell carcinoma, particularly OPSCC, is becoming more prevalent globally. This changing epidemiology makes reliable diagnostic approaches more important for appropriate patient management.\"},{\"question\":\"How do p16 immunohistochemistry (IHC) and PCR work together for HPV diagnosis?\",\"answer\":\"p16 IHC provides a reliable initial screening step for HPV-associated disease. PCR then confirms the presence of HPV, improving diagnostic sensitivity and specificity.\"},{\"question\":\"What limitations exist in standard treatment approaches for HPV-positive patients?\",\"answer\":\"Current standard oncological treatments (surgery, radiation, and/or chemotherapy) do not fully reflect the typically better prognosis of HPV-positive HNSCC. This mismatch can contribute to higher secondary morbidities and reduced quality of life.\"}]","The Next Chapter in Cancer Diagnostics: Advances in HPV-Positive Head and Neck Cancer - review | PDF",1789992247,53]