Current Evidence of a Deintensification Strategy for Patients with HPV-Related Oropharyngeal Cancer

SIMPLE SUMMARY: Human papillomavirus (HPV)-related oropharyngeal cancer represents a distinct disease entity, showing favorable treatment responses and survival outcomes. While the deintensification of treatment for HPV-related oropharyngeal cancer is widely considered necessary, details concerning patient selection and optimal strategies are undetermined. The heterogeneity of study populations and interventions in trials complicate the ability of physicians to apply the results in daily practice. The evolving landscape also requires physicians to consistently update the results of these trials. This article reviews the most recent evidence on the deintensification of HPV-related oropharyngeal cancer. We aim to provide physicians with some guidance regarding management options and assist researchers in appropriately designing trials in the future. ABSTRACT: Human papillomavirus (HPV)-related oropharyngeal cancer differs from HPV-negative oropharyngeal cancer in terms of etiology, epidemiology, and prognosis. Younger and lower comorbidity patient demographics and favorable prognosis allow HPV-related oropharyngeal cancer patients to anticipate longer life expectancy. Reducing long-term toxicities has become an increasingly important issue. Treatment deintensification to reduce toxicities has been investigated in terms of many aspects, and the reduction of radiotherapy (RT) dose in definitive treatment, replacement of platinum-based chemotherapy with cetuximab, response-tailored dose prescription after induction chemotherapy, and reduction of adjuvant RT dose after transoral surgery have been evaluated. We performed a literature review of prospective trials of deintensification for HPV-related oropharyngeal cancer. In phase II trials, reduction of RT dose in definitive treatment showed comparable survival outcomes to historical results. Two phase III randomized trials reported inferior survival outcomes for cetuximab-based chemoradiation compared with cisplatin-based chemoradiation. In a randomized phase III trial investigating adjuvant RT, deintensified RT showed noninferior survival outcomes in patients without extranodal extension but worse survival in patients with extranodal extension. Optimal RT dosage and patient selection require confirmation in future studies. Although many phase II trials have reported promising outcomes, the results of phase III trials are needed to change the standard treatment. Since high-level evidence has not been established, current deintensification should only be performed as part of a clinical study with caution. Implementation in clinical practice should not be undertaken until evidence from phase III randomized trials is available.