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HPV\u2010related tumours display clinical and molecular characteristics that are distinct from HPV\u2010unrelated tumours, which are generally induced by alcohol and tobacco abuse. Detection of biologically active HPV in HNSCC has prognostic relevance, which warrants the separate classification of HPV\u2010induced tumours and is a prerequisite for further optimisation of treatment protocols for this distinct group. Current guidelines for the treatment of oropharyngeal squamous cell carcinoma (OPSCC) have not incorporated specific treatment modalities for HPV\u2010related tumours. The development of such treatment options is still in a preclinical phase or in early clinical trials. Recent data on treatment response of OPSCC have been obtained by retrospectively analysing HPV\u2010status and indicate that patients with HPV\u2010related tumours show a favourable prognosis, independent of the type of treatment. These patients may benefit from de\u2010intensified treatment, which should be assessed in prospective clinical trials. The development and future use of new antiviral and immunomodulatory therapeutics may be instrumental in this approach to improve survival rates and decrease disease\u2010and\u2010treatment\u2010related morbidity. In this review we will focus on present therapeutic HPV\u2010targeting strategies and discuss future directions for de\u2010intensified treatment of HPV\u2010positive HNSCC. 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