{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T12:24:15Z","timestamp":1784291055323,"version":"3.55.0"},"reference-count":133,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2025,2,3]],"date-time":"2025-02-03T00:00:00Z","timestamp":1738540800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>The number of new cancer cases is soaring, and currently, there are 440.5 per 100,000 new cases reported every year. A quarter of these are related to human papillomavirus (HPV) infections, particularly types 16 and 18. These include oropharyngeal, anal, vaginal, and penile cancers. A critical aspect of their oncogenic potential lies in their ability to manipulate host immune responses, facilitating immune evasion and carcinogenesis. High-risk HPVs target key immune components like granzymes A and B and MHC-I, which are crucial for the elimination of virus-infected and transformed cells, thereby weakening immune surveillance. Evidence suggests that high-risk HPVs downregulate the expression of tumor suppressors, such as p53 and pRB, and the activity of these immune components, weakening CTL and NK cell responses, thus enabling persistent infection and carcinogenesis. We discuss the implications of granzyme and MHC-I dysregulation for immune evasion, tumor progression, and potential therapeutic strategies. This review further explores the regulation of granzyme A, B, and MHC-I by high-risk HPVs, focusing on how viral oncoproteins, E6 and E7, interfere with granzyme-mediated cytotoxicity and antigen presentation. The complex interplay between high-risk HPVs, granzyme A, granzyme B, and MHC-I may provide insights into novel approaches for targeting HPV-associated cancers.<\/jats:p>","DOI":"10.3390\/v17020221","type":"journal-article","created":{"date-parts":[[2025,2,3]],"date-time":"2025-02-03T08:47:57Z","timestamp":1738572477000},"page":"221","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Regulation of Granzymes A and B by High-Risk HPV: Impact on Immune Evasion and Carcinogenesis"],"prefix":"10.3390","volume":"17","author":[{"given":"Mashego Nathan","family":"Maleka","sequence":"first","affiliation":[{"name":"Department of Biochemistry, Microbiology and Biotechnology, School of Molecular and Life Sciences, Private Bag X 1106, Sovenga, Polokwane 0727, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3179-8169","authenticated-orcid":false,"given":"Zukile","family":"Mbita","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Microbiology and Biotechnology, School of Molecular and Life Sciences, Private Bag X 1106, Sovenga, Polokwane 0727, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vivian","family":"Morafo","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Microbiology and Biotechnology, School of Molecular and Life Sciences, Private Bag X 1106, Sovenga, Polokwane 0727, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,2,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Nehme, Z., Pasquereau, S., and Herbein, G. 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