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Objective: To determine the impact of prior open neck biopsy on the prognosis of patients with human papillomavirus (HPV)-related oropharyngeal squamous cell carcinoma (OPSCC) who are subsequently treated with a definitive surgical paradigm, including adjuvant therapy when indicated.Study Design: Retrospective cohort.Setting: Tertiary care university hospital.Subjects and Methods: Patients with open neck biopsies who were treated with definitive surgery, with or without adjuvant therapy, for HPV-related OPSCC between 1998 and 2012 were compared with a matched control group who did not undergo open neck biopsy. Outcomes were disease-free survival, overall survival, disease-specific survival, incidence of tumor deposit in dermal scar, patterns of recurrence, and neck dissection complications.Results: Forty-five patients who underwent open neck biopsy were compared with 90 matched controls. Tumor deposits in dermal scars from the prior open neck biopsy were found in 3 patients (7%) during completion neck dissection. Overall complications of the neck dissection were not significantly increased in the open biopsy group over matched controls (20% vs 12%, respectively; P > .05). Five-year Kaplan-Meier estimates for disease-free survival, overall survival, and disease-specific survival were not significantly different between the open biopsy and control groups (93% vs 91%, 98% vs 97%, 98% vs 99%, respectively; all P > .05). Recurrence rates were also not significantly different between groups.Conclusions: Patients with HPV-related OPSCC who have undergone a prior open neck biopsy can be successfully treated with a definitive surgical paradigm. Although needle biopsy is preferable to establish a diagnosis, previous open neck biopsy does not affect prognosis in these patients. [ABSTRACT FROM AUTHOR]