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Existing knowledge largely comes from cervical-cancer epidemiology where lineages B, C, and D relate to high-grade lesions and cancer, while lineage A is predominant in head and neck squamous cell carcinoma, though site-specific data remain limited. Next-generation sequencing has clarified variant prevalence, distribution, and links between particular sublineages and cancer risk, motivating large-scale studies across HPV-related tumor sites and outcomes.",{"@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/research-report/","Research & 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proportion of cervical and oropharyngeal cancers is attributed to HPV16?","Question",{"text":63,"@type":64},"HPV16 accounts for approximately 60% of global cervical cancers and about 90% of global HPV-driven oropharyngeal cancers.","Answer",{"name":66,"@type":61,"acceptedAnswer":67},"How are HPV16 phylogenetic lineages and sublineages determined?",{"text":68,"@type":64},"They are identified by HPV genome sequencing and phylogenetic analysis of the entire viral genome, with variants grouped into lineages (A–D) and further into sublineages based on genetic variability ranges.",{"name":70,"@type":61,"acceptedAnswer":71},"Why are large-scale studies needed beyond cervical cancer?",{"text":72,"@type":64},"Epidemiological and in vitro evidence for HPV16 variants is still limited for head and neck cancers, so broader studies are required to evaluate associations with disease development and outcomes across multiple tumor 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State of the Art and Perspectives  \nLuisa Galati 1, *,†, Paola Di Bonito 2, Mariarosaria Marinaro 2, Maria Vincenza Chiantore 2 and Tarik Gheit 1, *  \nCitation: Galati, L.; Di Bonito, P.; Marinaro, M.; Chiantore, M.V.; Gheit, T. HPV16 Phylogenetic Variants in Anogenital and Head and Neck Cancers: State of the Art and Perspectives. Viruses 2024, 16, 904 . [https://doi.org/10.3390/](https://doi.org/10.3390/)[ ](https://doi.org/10.3390/)v16060904  \nAcademic Editor: Daniel DiMaio  \nReceived: 19 April 2024  \nRevised: 27 May 2024  \nAccepted: 29 May 2024  \nPublished: 3 June 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 International Agency for Research on Cancer, 69007 Lyon, France  \n2 Department of Infectious Diseases, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy;  \npaola.dibonito@iss.it (P.D.B.); [mariarosaria.marinaro@iss.it](mariarosaria.marinaro@iss.it) (M.M.); [mariavincenza.chiantore@iss.it](mariavincenza.chiantore@iss.it) (M.V.C.)  \n* Correspondence: [luisa.galati@ieo.it](luisa.galati@ieo.it) (L.G.); [gheitt@iarc.who.int](gheitt@iarc.who.int) (T.G.)  \n† Current address: Department of Experimental Oncology, European Institute of Oncology IRCCS, 20139 Milan, Italy.  \nAbstract: HPV16 is responsible for approximately 60% and 90% of global HPV–induced cervical and oropharyngeal cancers, respectively. HPV16 intratype variants have been identified by HPV genome sequencing and classified into four phylogenetic lineages (A–D) . Our understanding of HPV16 variants mostly derives from epidemiological studies on cervical cancer (CC) in which HPV16 B, C, and D lineages (previously named “non-European” variants) were mainly associated with high-grade cervical lesions and cancer. Although a predominance of HPV16 lineage A (previously named “European variants”) has been observed in head and neck squamous cell carcinoma (HNSCC), epidemiological and in vitro biological studies are still limited for this tumor site. Next Generation Sequencing (NGS) of the entire HPV genome has deepened our knowledge of the prevalence and distribution of HPV variants in CC and HNSCC. Research on cervical cancer has shown that certain HPV16 sublineages, such as D2, D3, A3, and A4, are associated with an increased risk of cervical cancer, and sublineages A4, D2, and D3 are linked to a higher risk of developing adenocarcinomas. Additionally, lineage C and sublineages D2 or D3 of HPV16 show an elevated risk of developing premalignant cervical lesions. However, it is still crucial to conduct large-scale studies on HPV16 variants in different HPV–related tumor sites to deeply evaluate their association with disease development and outcomes. This review discusses the current knowledge and updates on HPV16 phylogenetic variants distribution in HPV–driven anogenital and head and neck cancers.  \nKeywords: HNSCC; OPC; cervical cancer; HPV16; HPV variants; phylogeny; NGS  \n1. Introduction  \nHuman papillomaviruses (HPVs) are non-enveloped DNA viruses that infect both cutaneous and mucosal epithelia. To date, over 400 papillomaviruses (PVs) have been identified and over 200 are HPV genotypes classified into alpha, beta, gamma, mu, and nu genera [1] ([www.hpvcenter.se](www.hpvcenter.se)) (accessed on 13 March 2024). A clear association with human cancers has been established for the following mucosal alphapapillomavirus HPV types, namely HPV51, grouped in the alpha-5 species; HPV 56, in the alpha-6; HPV18, 39, 45, and 59, in the alpha-7; and HPV16, 31, 35, 33, 52, and 58, grouped as alpha-9 species. Therefore, they have been classified by the Int","cbCaigcpyFJDTpTJ","https://ap.wps.com/l/cbCaigcpyFJDTpTJ","pdf",2055564,15,"English","# Introduction\n## HPV classification and genomic regions\n## HPV16 lineages and sublineages\n# Abstract overview","[{\"question\":\"What proportion of cervical and oropharyngeal cancers is attributed to HPV16?\",\"answer\":\"HPV16 accounts for approximately 60% of global cervical cancers and about 90% of global HPV-driven oropharyngeal cancers.\"},{\"question\":\"How are HPV16 phylogenetic lineages and sublineages determined?\",\"answer\":\"They are identified by HPV genome sequencing and phylogenetic analysis of the entire viral genome, with variants grouped into lineages (A–D) and further into sublineages based on genetic variability ranges.\"},{\"question\":\"Why are large-scale studies needed beyond cervical cancer?\",\"answer\":\"Epidemiological and in vitro evidence for HPV16 variants is still limited for head and neck cancers, so broader studies are required to evaluate associations with disease development and outcomes across multiple tumor sites.\"}]","HPV16 Phylogenetic Variants in Anogenital and Head and Neck Cancers - State of the Art and Perspectives | PDF",1789990641,38]