This retrospective cohort study followed the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting guideline. We used the TriNetX platform, a large-scale global database, to evaluate the association of 9v-HPV vaccination for adolescent and young males aged 9 to 26 years with HPV-related cancers, including head and neck, penile, rectal, and anal cancers. TriNetX has stored electronic health records for approximately 190 million patients from 170 health care centers globally as of December 2025.17 Data collected in TriNetX included health care visits, diagnoses, procedures, medications, and laboratory results. In this study, the vaccinated cohort included males aged 9 to 26 years receiving at least one 9v-HPV vaccination with a health examination between January 2016 and December 2024. The unvaccinated cohort included males aged 9 to 26 years who underwent a health examination during the corresponding period but never received any HPV vaccination. Age categorization was based on the current recommendation for HPV vaccination.18 ‚19 Details of the data extraction code and cohort selection flowchart are provided in eTable 1 and eFigure 1 in Supplement 1.
The primary outcome in this study was a composite measure encompassing any diagnosis of the following cancers, as defined by the International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10): head and neck cancers, penile cancer, esophageal cancer (upper two-thirds only), and anal cancer (eTable 2 in Supplement 1).20 The secondary outcomes included the individual diagnoses of each of the 4 cancers. Data were extracted on February 14, 2026. Outcome follow-up started 180 days after the index date. The index date was defined as the date of the first dose with health examination in the vaccinated group and the date of the first health examination in the unvaccinated group.
The TriNetX platform complied with the Health Insurance Portability and Accountability Act and General Data Protection Regulation.21 Therefore, informed consent was not required because this study utilized only deidentified and aggregated patient data. Although deidentified TriNetX studies generally do not require institutional review board approval,22 this study was reviewed and approved for publication by the institutional review board of Nara Prefecture General Medical Center.