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The current study aimed to develop a robust HPV\u201016 detection method for formalin\u2010fixed cancer specimens.<\/jats:p><\/jats:sec><jats:sec><jats:title>Materials and Methods<\/jats:title><jats:p>To prevent false negatives resulting from DNA fragmentation, a DNA quality check step was added. Additionally, this study used multiplex polymerase chain reaction (PCR) covering the entire HPV\u201016 genome to mitigate effects caused by viral sequence variation. To prove this concept, we analyzed genomic DNA extracted from oropharyngeal cancer tissues known as HPV\u201016\u2010positive. Subsequently, the protocol was tested on oral squamous cell carcinoma (OSCC) samples in our cohort. Given the wide variation in HPV\u201016 positivity in previous studies, it remains elusive how frequently HPV\u201016 is positive in OSCC.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The results showed faint bands or smears in the multiplex PCR of 7 out of 112 cases. Droplet digital PCR confirmed variable positivity levels of HPV\u201016, suggesting two scenarios of HPV\u201016 positivity in cancer tissue: cancer cells derived from infected cells or only a portion being HPV\u201016\u2010positive. Finally, we comprehensively analyzed the case and identified the integration of a deleted HPV\u201016 genome into the intronic region of the host gene\u2009<jats:italic>TMEM94<\/jats:italic>\u2009on chromosome 17. To the best of our knowledge, this is the first evidence showing the integration of HPV\u201016 in OSCC cells and providing its complete viral sequence.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The established protocol should be applicable to various cancer tissues for analyzing the association with HPV\u201016 infection.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cam4.70544","type":"journal-article","created":{"date-parts":[[2025,2,21]],"date-time":"2025-02-21T05:40:50Z","timestamp":1740116450000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Robust <scp>HPV<\/scp>\u201016 Detection Workflow for Formalin\u2010Fixed Cancer Tissue and Its Application for Oral Squamous Cell Carcinoma"],"prefix":"10.1002","volume":"14","author":[{"given":"Shizuka","family":"Morodomi","sequence":"first","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery, Faculty of Life Sciences 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