Early Life-Course Patterns Of Registry-Defined Subsequent Cancers After HPV-Related Malignancies In A U.S. Population-Based Cohort

BackgroundSubsequent primary malignancies following human papillomavirus (HPV)-related cancers represent an important survivorship concern. However, evidence remains limited regarding sociodemographic and clinical factors associated with registry-defined subsequent cancers among children, adolescents, and young adults in U.S. population-based cohorts. MethodsWe conducted a retrospective population-based analysis of 1,326 individuals diagnosed with HPV-related cancers using Surveillance, Epidemiology, and End Results (SEER) data. Registry-defined subsequent cancer was operationalized as the occurrence of additional primary HPV-related malignancies according to SEER multiple primary rules. Multivariable logistic regression models estimated associations with sex, age group, area-level socioeconomic status (Yost Index quintiles), persistent poverty census tract status, and primary cancer site. Sex-stratified analyses by cancer site were performed. ResultsRegistry-defined subsequent cancers were significantly associated with female sex and young adult age (20-29 years). Females had higher odds of subsequent cancer compared with males (OR = 1.06, 95% CI: 1.03-1.10), and individuals aged 20-29 years had higher odds than those aged 0-9 years (OR = 1.10, 95% CI: 1.05-1.16). Associations persisted after adjustment for socioeconomic indicators. No significant associations were observed with Yost Index quintiles or persistent poverty. Sex-stratified analyses showed higher odds of subsequent cancer for anal cancer among males and vulvar cancer among females relative to oropharyngeal cancer. ConclusionsSex and age are key determinants of registry-defined subsequent cancers following HPV-related malignancies, independent of area-level socioeconomic context. These findings support age- and sex-specific survivorship surveillance strategies across early life-course stages.