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OBJECTIVES: This study evaluates the oncologic outcome with regard to survival and locoregional tumor control in a cohort of patients with oropharyngeal squamous cell carcinoma (OPSCC) treated according to a uniform algorithm. STUDY DESIGN: Retrospective chart review. METHODS: A total of 427 consecutive patients with OPSCC were treated from 1990 to 2006. Treatment modalities were surgery alone (n = 102), surgery with adjuvant radio(chemo)therapy (n = 159), and primary radio(chemo)therapy (n = 166). Study endpoints were the five-year overall survival (OS) and disease-specific survival (DSS) stratified for primary tumor subsite, stage, T and N category, and age. RESULTS: The five-year OS and DSS for the entire cohort were 57.9% and 68.6%, respectively. OS and DSS for surgery alone were 70.3% and 76.5%, for surgery with radiation 66.6% and 78.9%, and for primary radiation 40.8% and 52.6%, respectively. Survival was significantly better for low stages (stage I/II vs. III/IV), small tumors (T1/2 vs. T3/4), limited nodal involvement (N0/1 vs. N2/3), and younger age at diagnosis. CONCLUSIONS: Together with our previous study on quality of life, we were able to show that our selection process gives excellent oncologic outcome in combination with high levels of function and quality of life. Surgery alone for early OPSCC and surgery followed by radiation for advanced OPSCC remain valuable treatment options. Primary radiochemotherapy is a strong alternative for patients who are not candidates for function-preserving surgery.