Human papillomavirus-associated subsequent malignant neoplasms among childhood cancer survivors.

ABSTRACT

OBJECTIVE: Emerging evidence suggests a higher risk of human papillomavirus-associated subsequent malignant neoplasms (HPV-SMNs) in childhood cancer survivors. However, comprehensive population-based risk estimates for HPV-SMNs are lacking. METHODS: We utilized longitudinal data obtained from the Surveillance, Epidemiology, and End Results program between 1975 and 2018 to establish a cohort comprising childhood cancer individuals who survived for at least 5 years. Standardized incidence ratio (SIR) with corresponding 95 % confidence interval (95 %CI) was used to evaluate the relative risk of HPV-SMNs. The competing risk regression model was performed to identify risk factors associated with HPV-SMNs. RESULTS: A total of 35,397 childhood cancer survivors were included. Among them, 42 individuals subsequently developed HPV-SMNs (median time from primary cancer, 25 years). HPV-SMN anatomic sites included cervix (N=16), oropharynx (N=15), anus (N=5), vulva\vagina (N=5), and penis (N=1). The 40-year cumulative incidence rate of HPV-SMNs was estimated to be 0.51 %. All survivors had a 10-fold increased risk of developing HPV-SMNs compared to individuals of similar age in the general population (SIR 10.1, 95 %CI 7.3-13.6). The competing risk regression model indicted that age at diagnosis and the type of primary malignancy could potentially influence the development of HPV-SMNs. Furthermore, multivariable Cox regression analysis confirmed that the presence of HPV-SMNs significantly increased the risk of mortality for survivors (hazard ratio 2.63, 95 %CI 1.68-4.14). CONCLUSIONS: Childhood cancer survivors have a significantly elevated risk of developing HPV-SMNs, accompanied by poor survival outcomes. Encouraging HPV vaccination and robust surveillance protocols may improve long-term health outcomes in childhood cancer survivors.