<p>The 8th edition of the American Joint Committee on Cancer (AJCC8) staging system for head and neck squamous cell carcinoma (HNSCC) introduced several modifications from the 7th edition (AJCC7), including change in staging of high-risk human papillomavirus (HPV)-associated oropharyngeal cancer. The purpose of this analysis was to compare epidemiology of HNSCC and prognostic utility of the 7th and 8th editions of AJCC staging system. Patients with newly diagnosed HNSCC were identified in the US Surveillance, Epidemiology, and End Results 17 registries research database (SEER 17). Age-adjusted incidence rates were calculated by sex, tumor subsite, race/ethnicity, and age. Disease stage was assessed using AJCC7 in patients diagnosed from 2014 to 2017 and AJCC8 in patients diagnosed from 2018 to 2021. Overall survival (OS) was calculated using the Kaplan-Meier method. Overall, 45,289 patients with HNSCC were identified from 2014 to 2017 and 47,310 from 2018 to 2021. The age-adjusted incidence rate for HNSCC was 11.4 per 100,000 persons from 2014 to 2017 and 11.2 per 100,000 persons from 2018 to 2021. In both groups, incidence was higher in males, older age groups, and white patients, and the most common disease site was the oropharynx. Fewer patients were classified with stage III-IV disease using AJCC8 criteria (36.9%) compared with AJCC7 (58.8%). By AJCC7 staging, the 36-month OS rate was 85.5%, 74.6%, 69.9%, and 60.7% for stage I, II, III, and IV, respectively. By AJCC8 staging, the 36-month OS rate was 87.8%, 77.2%, 66.8%, and 45.5%, respectively. In a specialized dataset of 38,503 cases from 2010 to 2017 assessed using AJCC7, the 60-month OS rate for HPV-positive and HPV-negative stage IV cases in the oropharynx was 75.3% and 46.3%, respectively. Based on epidemiologic data in HNSCC using AJCC7 compared with AJCC8, overall incidence of HNSCC has remained unchanged but AJCC8 is associated with better discrimination of OS outcomes, especially for stage III/IV disease.</p>