{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,11]],"date-time":"2026-05-11T11:45:44Z","timestamp":1778499944325,"version":"3.51.4"},"reference-count":24,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,1,3]],"date-time":"2026-01-03T00:00:00Z","timestamp":1767398400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,1,3]],"date-time":"2026-01-03T00:00:00Z","timestamp":1767398400000},"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":["The Laryngoscope"],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To determine the relationship between perineural invasion and 6\u2010month progression\u2010free survival (PFS)\/2\u2010year overall survival (OS) among patients with recurrent or metastatic (R\/M) head and neck squamous cell carcinoma (HNSCC) on pembrolizumab.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This study was a retrospective, observational study performed at a tertiary care academic center. Participants included patients with oral cavity, oropharynx, hypopharynx, and laryngeal head and neck squamous cell carcinoma who began pembrolizumab treatment at UCSF between May 2016 and May 2022. The primary outcome was 6\u2010month progression\u2010free survival and 6\u2010month time\u2010to\u2010progression (TTP). The secondary outcome was 2\u2010year overall survival. Disease progression was determined using radiographic criteria, adopted from the Response Evaluation Criteria in Solid Tumors.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      One hundred and thirty\u2010three patients with HNSCC were included. Immune checkpoint inhibitor (ICI) indication was recurrence\/metastasis for all patients. Forty (30%) patients had perineural invasion. On univariate analysis, patients with perineural invasion were more likely to have worse 6\u2010month PFS (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.011). After controlling for number of metastatic organs, receipt of concurrent systemic therapy, age, and PDL\u20101 status, presence of perineural invasion was associated with worse 6\u2010month PFS [HR 3.33 (1.32, 8.41),\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.011] and 6\u2010month time to progression (TTP) [HR 2.14 (1.09, 7.38),\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.032], but was not significantly associated with 2\u2010year OS [HR 1.35 (0.57, 3.19),\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.498].\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Presence of perineural invasion is associated with poorer 6\u2010month progression\u2010free survival on ICI in patients with HNSCC. Future studies should further explore how perineural invasion may alter response to immunotherapy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Level of Evidence<\/jats:title>\n                    <jats:p>3<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/lary.70350","type":"journal-article","created":{"date-parts":[[2026,1,3]],"date-time":"2026-01-03T08:54:46Z","timestamp":1767430486000},"page":"2199-2205","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Perineural Invasion and Survival in Pembrolizumab\u2010Treated Head and Neck Squamous\u00a0Cell Carcinoma"],"prefix":"10.1002","volume":"136","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5658-6125","authenticated-orcid":false,"given":"Angeline A.","family":"Truong","sequence":"first","affiliation":[{"name":"Department of Otolaryngology\u2010Head and Neck Surgery University of California  San Francisco California USA"},{"name":"Department of Microbiology and Immunology University of California  San Francisco California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Savinnie","family":"Ho","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology\u2010Head and Neck Surgery University of California  San Francisco California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4111-9975","authenticated-orcid":false,"given":"Rex H.","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology\u2010Head and Neck Surgery University of California  San Francisco California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xin","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Radiology and Biomedical Imaging University of California  San Francisco California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hyunseok","family":"Kang","sequence":"additional","affiliation":[{"name":"Department of Medicine University of California  San Francisco California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8121-3726","authenticated-orcid":false,"given":"Ivan H.","family":"El\u2010Sayed","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology\u2010Head and Neck Surgery University of California  San Francisco California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jonathan R.","family":"George","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology\u2010Head and Neck Surgery University of California  San Francisco California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chase M.","family":"Heaton","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology\u2010Head and Neck Surgery University of California  San Francisco California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ilya","family":"Likhterov","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology\u2010Head and Neck Surgery University of California  San Francisco California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4996-6362","authenticated-orcid":false,"given":"Mary Jue","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology\u2010Head and Neck Surgery University of California  San Francisco California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0306-6147","authenticated-orcid":false,"given":"Patrick K.","family":"Ha","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology\u2010Head and Neck Surgery University of California  San Francisco California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alain P.","family":"Algazi","sequence":"additional","affiliation":[{"name":"Department of Medicine University of California  San Francisco California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8180-4542","authenticated-orcid":false,"given":"Katherine C.","family":"Wai","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology\u2010Head and Neck Surgery University of California  San Francisco California USA"},{"name":"Department of Microbiology and Immunology University of California  San Francisco California 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