Virk JS, et al. - Via systematic searching MEDLINE and Embase for articles between 01/2008 and 12/2017, researchers determined survival outcomes for N3 nodal disease, especially for patients with human papilloma virus (HPV)-positive head and neck squamous cell carcinoma (HNSCC). In HNSCC patients treated with CRT or surgery + adjuvant RT/CRT, articles on N3 nodal disease were included if they reported on oropharyngeal or HPV+ subgroups. Nine studies had met the criteria for inclusion. Eight of these studies (N = 5,304) permitted further comparison: 4 were on CRT, 2 were on surgery + RT/CRT and 2 on both. Data reported that 3-year overall survival was better for HPV+ HNSCC (range, 55.2%-81%). The current literature fails to support de-escalation of HPV− N3 disease treatment. Observation of HPV+ patients attaining a post-CRT CR is reasonable, but additional prospective studies are needed given the heterogeneity and risk of bias in these current studies. For non-CR cohort, planned ND should remain the standard of care.