HPV Vaccination and Risk of Head and Neck Cancers: A Large Real-World Cohort Study.

IMPORTANCE: Human papillomavirus (HPV) is a primary cause of head and neck cancers (HNC), especially oropharyngeal squamous cell carcinoma (OPSCC). The real-world effectiveness of HPV vaccination in preventing HNC has not been well-defined. OBJECTIVE: This study aimed to determine whether HPV vaccination is associated with a reduced incidence of HNC overall and by subsite in a large U.S. observational cohort. DESIGN: We conducted a retrospective cohort study using de-identified electronic medical records from 66 U.S. healthcare organizations. We matched 716,630 HPV-vaccinated individuals (ages 9-45) 1:1 with 716,630 non-vaccinated controls based on age, sex, and comorbidities. RESULTS: Among 1.4 million matched individuals, 40 HNC cases occurred in the vaccinated group versus 130 in controls (HR, 0.315). The greatest reduction was seen for OPSCC (HR, 0.087). HNC risk was also reduced in those aged 9-26 years (HR, 0.323), and this risk reduction persisted for 5 to 13 years post-vaccination. CONCLUSIONS: HPV vaccination is associated with a substantially lower risk of HNC-most pronounced for OPSCC and among younger recipients. These findings suggest that broad HPV immunization coverage may provide potential public health benefits by reducing the risk of HNC.