Background: This study aimed to identify prognostic clinicopathologic factors that could predict treatment failure and to analyze clinical data from p16+ oropharyngeal squamous cell carcinoma (OPSCC) patients who underwent surgery. Methods: Data from p16+ OPSCC patients who underwent surgery at Severance Hospital of Yonsei University were retrospectively reviewed. Results: The average smoking history was 14.6 pack-years (range 0–94 pack-years). Of the 188 patients, 73 (38.8%) underwent transoral robotic surgery (TORS) for surgical treatment of their primary lesions, and the remaining 115 patients (61.2%) underwent conventional surgery. Extracapsular nodal spread was detected in 87 patients (46.3%). At histologic examination, 67 patients (35.6%) showed positive surgical margins, and 121 patients (64.4%) had negative surgical margins. Postoperative adjuvant treatment was performed for 167 patients (88.8%). During the follow-up period, there were 18 recurrences including 2 local recurrences, 10 regional recurrences, and 6 distant metastases. During the study period, 17 deaths occurred. The univariate analysis showed that the American Joint Committee on Cancer (AJCC) 8th-edition staging system, lymphovascular invasion, more than four metastatic lymph nodes, and a smoking history of more than 10 pack-years were significantly associated with treatment failure. In the multivariate analysis, only the AJCC 8th-edition staging system was significantly associated with the patient’s survival. Conclusion: Surgical treatment methods including TORS for p16+ OPSCC patients showed excellent oncologic results, and many previously known clinicopathologic factors did not show a significant relationship with patient prognosis. Only the newly revised AJCC 8th-edition staging system showed a significant relationship with patient survival, and this should be considered in the setting of p16+ OPSCC treatment guidelines in the future.
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