{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T10:07:35Z","timestamp":1785319655693,"version":"3.55.0"},"reference-count":69,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2025,3,11]],"date-time":"2025-03-11T00:00:00Z","timestamp":1741651200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000072","name":"National Institute for Dental and Craniofacial Research","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100000072","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01DE027185"],"award-info":[{"award-number":["R01DE027185"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["UH2CA267502"],"award-info":[{"award-number":["UH2CA267502"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01DE034056"],"award-info":[{"award-number":["R01DE034056"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R00DE030194"],"award-info":[{"award-number":["R00DE030194"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R21CA267803"],"award-info":[{"award-number":["R21CA267803"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Breakthrough Challenge Foundation"},{"name":"Penn Synergy Program"},{"name":"Stephen and Susan Kelly Family Fund for Head and Neck Cancers"},{"name":"William and Greta Lydecker Fund"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,7,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Limited understanding of the biology predisposing certain human papillomavirus-related (HPV+) oropharyngeal squamous cell carcinomas (OPSCCs) to relapse impedes therapeutic personalization. We aimed to identify molecular traits that distinguish recurrence-prone tumors.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Fifty HPV+ OPSCCs that later recurred (cases) and 50 nonrecurrent controls matched for stage, therapy, and smoking history were RNA-sequenced. Groups were compared by gene set enrichment analysis, and select differences were validated by immunohistochemistry. Features discriminating groups were scored in each tumor using gene set variation analysis, and scores were evaluated for recurrence prediction ability.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Cases downregulated pathways linked to antitumor immunity (FDR-adjusted P &amp;lt; .05) and contained fewer tumor-infiltrating lymphocytes (P &amp;lt; .001), including cytotoxic T-cells (P = .005). Cases also upregulated pathways related to cell division and other aspects of tumor progression. Upregulated and downregulated pathways were respectively used to define a tumor progression score (TPS) and immune suppression score (ISS) for each tumor. Correlation between TPS and ISS (r = .603, P &amp;lt; .001) was potentially explained by observed upregulation of DNA repair pathways in cases, which might enhance their progression directly and by limiting cytosolic DNA-induced inflammation. Accordingly, cases contained fewer double-strand breaks based on staining for phospho-RPA32 (P = .006) and \u03b3-H2AX (P = .005) and downregulated the cytosolic DNA sensing pathway. A combined score derived from TPS and ISS optimized recurrence prediction and stratified survival in a manner generalizable to 3 external cohorts.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>We describe a potential link in HPV+ OPSCCs between reduced DNA damage and other tumor-intrinsic and immune-related contributors to recurrence risk, opening opportunities to detect and target this high-risk biology.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/jnci\/djaf053","type":"journal-article","created":{"date-parts":[[2025,3,12]],"date-time":"2025-03-12T04:38:27Z","timestamp":1741754307000},"page":"1366-1376","source":"Crossref","is-referenced-by-count":3,"title":["Tumor-intrinsic and immune-related features associated with treatment failure in human papillomavirus-related oropharyngeal cancer"],"prefix":"10.1093","volume":"117","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0377-5771","authenticated-orcid":false,"given":"Malay K","family":"Sannigrahi","sequence":"first","affiliation":[{"name":"Department of Otorhinolaryngology-Head and Neck Surgery, University of Pennsylvania , Philadelphia, PA,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2017-5695","authenticated-orcid":false,"given":"Lovely","family":"Raghav","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology-Head and Neck Surgery, University of Pennsylvania , Philadelphia, PA,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0540-3592","authenticated-orcid":false,"given":"Dominick J","family":"Rich","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology-Head and Neck Surgery, University of Pennsylvania , Philadelphia, PA,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8297-3329","authenticated-orcid":false,"given":"Travis P","family":"Schrank","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology-Head and Neck Surgery, University of North Carolina at Chapel Hill , Chapel Hill, NC,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph A","family":"Califano","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology-Head and Neck Surgery, University of California San Diego , San Diego, CA,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7104-413X","authenticated-orcid":false,"given":"John N","family":"Lukens","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, University of Pennsylvania , Philadelphia, PA,","place":["United 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