{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,10]],"date-time":"2026-01-10T01:41:35Z","timestamp":1768009295224,"version":"3.49.0"},"reference-count":26,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2025,2,4]],"date-time":"2025-02-04T00:00:00Z","timestamp":1738627200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Histopathology"],"published-print":{"date-parts":[[2025,6]]},"abstract":"<jats:sec><jats:title>Aims<\/jats:title><jats:p>This study investigated the utility of combined p16 and p53 immunohistochemistry (IHC) for diagnosing high\u2010risk human papillomavirus (HR HPV)\u2010associated oral epithelial dysplasia (OED) and its associated clinical behaviour, including disease recurrence and transformation to malignancy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods and Results<\/jats:title><jats:p>The expression of p53 was evaluated in 105 cases of HR HPV\u2010positive oral cavity OED, of which 104 were scored as positive for p16. HPV status was confirmed by reverse transcriptase quantitative polymerase chain reaction (RT\u2010qPCR) for E6 mRNA or RNA <jats:italic>in situ<\/jats:italic> hybridization (ISH). Seven cases of p16\u2010positive oral cavity OED with abnormal p53 expression and\/or <jats:italic>TP53<\/jats:italic> mutation and negative HPV RNA ISH were excluded. Most cases (93%) demonstrated classic HPV\u2010associated basaloid morphology, and 7% were keratinizing. The most affected sites were the floor of the mouth\/ventral tongue (61%), followed by the lateral tongue (18%) and gingiva (13%). p53 IHC showed that 76% of cases demonstrated a null\u2010like \/ basal\u2010sparing pattern, while 24% demonstrated a mid\u2010epithelial\/basal sparing pattern. Ten cases exhibited an invasive or suspicious for microinvasive component on biopsy. Dysplasia recurred in 14 cases, and a single case transformed to squamous cell carcinoma.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The combination of p16 positivity and a basal\u2010sparing pattern of p53 is predictive of HR HPV in OED, eliminating the need for further HPV\u2010specific testing. Although HPV OED may co\u2010occur with invasive squamous cell carcinoma on biopsy, the transformation to malignancy is low.<\/jats:p><\/jats:sec>","DOI":"10.1111\/his.15413","type":"journal-article","created":{"date-parts":[[2025,2,5]],"date-time":"2025-02-05T02:18:36Z","timestamp":1738721916000},"page":"1082-1090","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Utility of p53 and p16 immunohistochemistry in the diagnosis of human papillomavirus\u2010associated oral epithelial dysplasia: a retrospective study of 105 patients"],"prefix":"10.1111","volume":"86","author":[{"given":"Damir","family":"Rosic","sequence":"first","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Schulich School of Medicine and Dentistry Western University  London ON Canada"},{"name":"Department of Pathology and Laboratory Medicine London Health Sciences Centre  London ON Canada"},{"name":"Interface Oral and Maxillofacial Surgery  London ON Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zia A","family":"Khan","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Schulich School of Medicine and Dentistry Western University  London ON Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Linda","family":"Jackson\u2010Boeters","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Schulich School of Medicine and Dentistry Western University  London ON Canada"},{"name":"Department of Pathology and Laboratory Medicine London Health Sciences Centre  London ON Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5404-2201","authenticated-orcid":false,"given":"Mark R","family":"Darling","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Schulich School of Medicine and Dentistry Western University  London ON Canada"},{"name":"Department of Pathology and Laboratory Medicine London Health Sciences Centre  London ON Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-9104-5892","authenticated-orcid":false,"given":"Erin","family":"Chapman","sequence":"additional","affiliation":[{"name":"Alberta Precision Laboratories  Calgary AB Canada"},{"name":"Department of Laboratory Medicine and Pathology University of Alberta  Edmonton AB Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lawrence","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine Vancouver General Hospital  Vancouver BC Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4067-6913","authenticated-orcid":false,"given":"Kelly Yi Ping","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Oral Biological and Medical Sciences, Faculty of Dentistry University of British Columbia  Vancouver BC Canada"},{"name":"School of Biomedical Engineering University of British Columbia  Vancouver BC Canada"},{"name":"Department of Integrative Oncology British Columbia Cancer Research Centre  Vancouver BC Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3064-8222","authenticated-orcid":false,"given":"Tony L","family":"Ng","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine Vancouver General Hospital  Vancouver BC Canada"},{"name":"Department of Integrative Oncology British Columbia Cancer Research Centre  Vancouver BC Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6081-5971","authenticated-orcid":false,"given":"Yen Chen Kevin","family":"Ko","sequence":"additional","affiliation":[{"name":"Department of Oral Biological and Medical Sciences, Faculty of Dentistry University of British Columbia  Vancouver BC Canada"},{"name":"Department of Pathology and Laboratory Medicine University of British Columbia  Vancouver BC Canada"},{"name":"Department of Pathology BC Cancer  Vancouver BC Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4541-2282","authenticated-orcid":false,"given":"Christina","family":"McCord","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Schulich School of Medicine and Dentistry Western University  London ON Canada"},{"name":"Department of Pathology and Laboratory Medicine London Health Sciences Centre  London ON Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,2,4]]},"reference":[{"key":"e_1_2_11_2_1","volume-title":"WHO classification of Tumours editorial board. Head and neck tumours [Internet]","author":"Woo SB","year":"2023"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.oooo.2013.01.020"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/modpathol.2017.71"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.oooo.2017.01.008"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.oraloncology.2012.07.002"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41379-020-0527-y"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.modpat.2023.100145"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.modpat.2023.100348"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/odi.13993"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.oooo.2017.12.011"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/his.14019"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.oooo.2019.09.019"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.27739"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1261\/rna.1755810"},{"key":"e_1_2_11_16_1","volume-title":"WHO classification of tumours editorial board. Head and neck tumours [Internet]","author":"Westra WH","year":"2023"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.oooo.2023.06.006"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/hed.26006"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0714.2011.01054.x"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/hed.21131"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.28727"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.modpat.2023.100153"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1097\/LGT.0000000000000572"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12105-022-01467-0"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1001\/archderm.142.11.1438"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1111\/odi.15069"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2133.2007.08374.x"}],"container-title":["Histopathology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/his.15413","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,5,2]],"date-time":"2025-05-02T01:22:26Z","timestamp":1746148946000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/his.15413"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,2,4]]},"references-count":26,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2025,6]]}},"alternative-id":["10.1111\/his.15413"],"URL":"https:\/\/doi.org\/10.1111\/his.15413","archive":["Portico"],"relation":{},"ISSN":["0309-0167","1365-2559"],"issn-type":[{"value":"0309-0167","type":"print"},{"value":"1365-2559","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,2,4]]},"assertion":[{"value":"2024-10-09","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-01-06","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-02-04","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}