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Studying the composition of the tumor microenvironment (TME) of HPV-related cancers may help develop therapeutic strategies or identify prognostic biomarkers with potential clinical significance. Among all the components of TME, mast cells (MCs) appear to be particularly relevant in HPV-related tumors. MCs are myeloid-derived immune cells that release a wide range of inflammatory mediators. It is now recognized that these immune cells are important players within the TME, where they can exert both anti- and pro-tumor activities depending on the type of MC-derived inflammatory mediators released. MCs may play an important role in the processes associated with cell transformation, development, and the progression of HPV-associated tumors; however, their specific functions in these neoplasms are not yet fully understood. This review addresses the current state of knowledge on MCs and their contribution to the molecular biology of HPV-related cancers. In addition, it highlights MCs\u2019 roles in the pro- or anti-tumor paradigm and discusses their emerging potential as therapeutic targets or prognostic biomarkers.<\/jats:p>","DOI":"10.3390\/ijms262412110","type":"journal-article","created":{"date-parts":[[2025,12,16]],"date-time":"2025-12-16T17:22:58Z","timestamp":1765905778000},"page":"12110","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Deciphering the Role of Mast Cells in HPV-Related Cancers"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0168-7284","authenticated-orcid":false,"given":"Zyanya P.","family":"Espinosa-Riquer","sequence":"first","affiliation":[{"name":"Unidad de Investigaci\u00f3n Biom\u00e9dica en C\u00e1ncer, Instituto Nacional de Cancerolog\u00eda, Mexico City 14080, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6809-0212","authenticated-orcid":false,"given":"J. 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