Management of oropharyngeal cancer depends on several factors. Immediate surgery or radiotherapy may be considered. If the patient is operable, the choice depends on the extent of the disease, the contributing factors, and the expected functional results. For HPV-positive cancers, studies show comparable efficacy between surgery and radiotherapy. For early-stage cancers, unimodal treatment should be preferred. For HPV-negative cancers, the results of retrospective and observational studies are in favor of surgery. These studies have some limitations. In observational and/or retrospective studies, reclassification biases and the applicability of propensity scores weaken the validity of studies showing differences in management. Tumor and patient comparability are others majors interpretation biases. It is precipitate to conclude that surgery is superior for HPV-negative oropharyngeal cancers. Toxicity, therefore, becomes a criterion of choice for treatment. Unimodal management by surgery allows limited toxicity for the early stages. Surgery has less impact on salivation. Radiotherapy is rather less deleterious for swallowing in the early stages. For the advanced stages of HPV-induced tumors, the non-superiority of surgery should lead to the choice of radiochemotherapy. For oropharyngeal cancers, the possible benefit of surgery in HPV-negative oropharyngeal cancers must be confirmed in randomized studies. For the early stages of oropharyngeal cancer with unimodal treatment, management could be decided by shared decision making.
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