Background and Objectives: to describe current scientific knowledge regarding the treatment options in advanced oropharyngeal cancer. The standard care for advanced oropharyngeal cancer (OPSCC) has been chemoradiotherapy, although surgical approaches followed by adjuvant treatment have been proposed. The best therapy for each patient should be decided by an interdisciplinary tumour-board. Different strategies should be considered for the specific patient’s treatment: surgery, chemotherapy and radiation therapy or combinations of them. The treatment choice is influenced by tumour variability and prognostic factors, but it also depends on cancer extension, extranodal extension, nervous invasion, human papilloma virus (HPV) presence, making the decisional algorithm not always clear. HPV-related OPSCC is strongly associated with a favourable overall survival (OS) and disease-free survival rate (DSS); by contrast, HPV-negative OPSCC often flags a worse prognosis. Consequently, the American Joint Committee on Cancer (AJCC) differentiates OPSCC treatment and prognosis based on HPV status. Methods: we carried out a review of current scientific literature to analyze the different indications and limitations of surgical treatment options in OPSCC stage III and IV. Conclusion: robotic surgery or open approaches with reconstructive flaps can be considered in advanced stages, resulting in the de-intensification of subsequent systemic therapy and fewer related side effects. Furthermore, in the event of the primary failure of systemic therapy or disease recurrence, the surgical approach constitutes an additional therapeutic option which lengthens patient survival functions.
