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Objectives. Although human papillomavirus (HPV) infection is considered as a favorable prognostic factor in oropharyngeal cancer, the prognosis of HPV-associated tonsil cancer has rarely been studied especially when surgery was the main treatment. In this study, the authors investigated the effect of p16 over-expression (HPV infection) on tonsil cancer prognosis according to the type of treatment, HPV presence by PCR, and expression of p53 and epidermal growth factor receptor (EGFR) by immunohistochemistry (IHC). Methods. Medical records of 33 tonsil cancer patients were reviewed. Using formalin-fixed and paraffin-embedded tumor specimens, PCR-based genotyping of HPV and IHC of p16, p53 and EGFR were performed. The effects of HPV presence and the expression of IHC markers were analyzed on the recurrence-free survival. Five-year disease-free survival (DFS) rates were evaluated according to p16 expression status. Results. An over-expression of p16 was observed in 27 (81.9%) out of 33 cases. Surgery-based treatment was provided for 21 (63.6%) patients. There was no association between p16 immunoreactivity and HPV presence, nor with p53 and EGFR expression. Regardless of main treatment modalities, five-year DFS did not differ by p16 expression status (P=0.051). However, over-expression of p16 was associated with a lower recurrence in multivariable analyses (P=0.046). Conclusion. Regardless of main treatment modalities, an over-expression of p16 (HPV infection) is associated with a lower recurrence in tonsil cancers. However it is not associated with simple HPV presence or p53 and EGFR over-expression.