| Summary: | In the last decade, the recognition of the strongly positive prognostic impact of human papilloma virus (HPV) infection on the natural history of squamous cell carcinoma of the oropharynx has reshaped the historical monolithic view of a “one-size-fits-all approach” for head and neck cancer. Unlike their HPV negative counterparts, patients affected by HPV positive oropharyngeal cancer are usually in their prime with a low burden of comorbidities: most importantly, they are less likely to die for their disease, for second primary tumors or for intercurrent mortality. On these grounds, the scientific community was confronted with a pragmatic question: can the morbidity induced by standard concurrent chemo-radiotherapy be reduced without compromising efficacy? Worldwide, several prospective studies were launched, with the common aim to look for alternative treatment paradigms in the frame of de-intensification. This mini-review focuses on three new important trials published in 2019 and discusses their potential implications for clinical practice in the management of patients with HPV positive oropharyngeal cancer. Keywords: Head and neck cancer, Oropharynx, HPV, Radiotherapy, De-intensification
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