{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T13:44:10Z","timestamp":1787319850071,"version":"build-2736575974"},"reference-count":28,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T00:00:00Z","timestamp":1759968000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T00:00:00Z","timestamp":1759968000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Histopathology"],"published-print":{"date-parts":[[2026,2]]},"abstract":"<jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Immunohistochemistry (IHC) for p16 is widely used as a surrogate marker for HPV involvement in oropharyngeal squamous cell carcinoma (OPSCC), among other tumours. Confirming HPV status in OPSCC is critical, as HPV\u2010positive tumours have better overall survival and may require de\u2010escalated therapy compared to HPV\u2010independent OPSCC in the future. However, discordance exists between p16 and HPV, and direct HPV testing is occasionally required to ensure an accurate diagnosis. The aim of this study is to highlight the genomic basis behind the limitation of relying on p16 IHC as a surrogate marker for HPV involvement.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and Results<\/jats:title>\n                    <jats:p>\n                      Through a multi\u2010institutional collaboration, this case series compiled four patients with a \u2018false\u2019 negative p16 staining pattern in HPV\u2010positive non\u2010keratinizing head and neck squamous cell carcinoma. All cases demonstrated minimal to no p16 IHC staining and were positive for HPV by direct RNA\n                      <jats:italic>in situ<\/jats:italic>\n                      hybridization. Through\n                      <jats:italic>CDKN2A<\/jats:italic>\n                      fluorescence\n                      <jats:italic>in situ<\/jats:italic>\n                      hybridization testing, three patients demonstrated a homozygous deletion of\n                      <jats:italic>CDKN2A<\/jats:italic>\n                      and one demonstrated a heterozygous deletion.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This series highlights the genomic basis for the \u2018false\u2019 negative p16 results, raising awareness of a significant diagnostic pitfall while emphasizing the importance of careful consideration of clinicopathologic parameters in the clinical workup of these cases.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/his.70021","type":"journal-article","created":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T09:14:09Z","timestamp":1760001249000},"page":"664-672","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["<scp>\n                      <i>CDKN2A<\/i>\n                    <\/scp>\n                    deletion in p16\u2010negative\/\n                    <scp>HPV<\/scp>\n                    \u2010positive head and neck squamous cell carcinoma: Highlighting the molecular basis behind the limitation of relying on p16 immunohistochemistry as a surrogate marker for\n                    <scp>HPV<\/scp>\n                    involvement"],"prefix":"10.1111","volume":"88","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2355-8341","authenticated-orcid":false,"given":"Trevor","family":"Teich","sequence":"first","affiliation":[{"name":"Department of Laboratory Medicine and Pathobiology University of 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