{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T14:24:16Z","timestamp":1792074256892,"version":"4.4.0"},"reference-count":58,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"19","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCO"],"published-print":{"date-parts":[[2008,7,1]]},"abstract":"<jats:sec><jats:title>Purpose<\/jats:title><jats:p> To prospectively identify markers of response to therapy and outcome in an organ-sparing trial for advanced oropharyngeal cancer. <\/jats:p><\/jats:sec><jats:sec><jats:title>Patients and Methods<\/jats:title><jats:p> Pretreatment biopsies were examined for expression of epidermal growth factor receptor (EGFR), p16, Bcl-xL, and p53 as well as for p53 mutation. These markers were assessed for association with high-risk human papillomavirus (HPV), response to therapy, and survival. Patient variables included smoking history, sex, age, primary site, tumor stage, and nodal status. <\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p> EGFR expression was inversely associated with response to induction chemotherapy (IC) (P = .01), chemotherapy\/radiotherapy (CRT; P = .055), overall survival (OS; P = .001), and disease-specific survival (DSS; P = .002) and was directly associated with current smoking (P = .04), female sex (P = .053), and lower HPV titer (P = .03). HPV titer was significantly associated with p16 expression (P &lt; .0001); p16 was significantly associated with response to IC (P = .008), CRT (P = .009), OS (P = .001), and DSS (P = .003). As combined markers, lower HPV titer and high EGFR expression were associated with worse OS (\u03c1<jats:sub>EGFR<\/jats:sub> = 0.008; \u03c1<jats:sub>HPV<\/jats:sub> = 0.03) and DSS (\u03c1<jats:sub>EGFR<\/jats:sub> = 0.01; \u03c1<jats:sub>HPV<\/jats:sub> = 0.016). In 36 of 42 biopsies, p53 was wild-type, and only one HPV-positive tumor had mutant p53. The combination of low p53 and high Bcl-xL expression was associated with poor OS (P = .005) and DSS (P = .002). <\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p> Low EGFR and high p16 (or higher HPV titer) expression are markers of good response to organ-sparing therapy and outcome, whereas high EGFR expression, combined low p53\/high Bcl-xL expression, female sex, and smoking are associated with a poor outcome. Smoking cessation and strategies to target EGFR and Bcl-xL are important adjuncts to the treatment of oropharyngeal cancer. <\/jats:p><\/jats:sec>","DOI":"10.1200\/jco.2007.12.7662","type":"journal-article","created":{"date-parts":[[2008,5,13]],"date-time":"2008-05-13T01:10:48Z","timestamp":1210641048000},"page":"3128-3137","source":"Crossref","is-referenced-by-count":515,"title":["EGFR, p16, HPV Titer, Bcl-xL and p53, Sex, and Smoking As Indicators of Response to Therapy and Survival in Oropharyngeal Cancer"],"prefix":"10.1200","volume":"26","author":[{"given":"Bhavna","family":"Kumar","sequence":"first","affiliation":[{"name":"From the Department of Otolaryngology\u2013Head and Neck Surgery, Department of Periodontics and Oral Medicine, Department of Pathology, Comprehensive Cancer Center, Department of Internal Medicine, Division of Hematology-Oncology, Department of Radiation Oncology, Department of Biostatistics, Department of Pediatrics, and Department of Pharmacology, University 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Department of Pediatrics, and Department of Pharmacology, University of Michigan, Ann Arbor, MI"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francis P.","family":"Worden","sequence":"additional","affiliation":[{"name":"From the Department of Otolaryngology\u2013Head and Neck Surgery, Department of Periodontics and Oral Medicine, Department of Pathology, Comprehensive Cancer Center, Department of Internal Medicine, Division of Hematology-Oncology, Department of Radiation Oncology, Department of Biostatistics, Department of Pediatrics, and Department of Pharmacology, University of Michigan, Ann Arbor, MI"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark E.","family":"Prince","sequence":"additional","affiliation":[{"name":"From the Department of Otolaryngology\u2013Head and Neck Surgery, Department of Periodontics and Oral Medicine, Department of Pathology, Comprehensive Cancer Center, Department of Internal Medicine, Division of 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