Human Papillomavirus-Associated Subsequent Malignancies among Long-Term Survivors of Pediatric and Young Adult Cancers

Long-term survivors of pediatric and young adult (PAYA) cancers have a high incidence of subsequent neoplasms, but few risk factors other than cancer treatment have been identified. We aimed to describe the burden of human papillomavirus (HPV)-associated malignancies among survivors of PAYA cancers to assess whether HPV infections might be a reasonable area of future etiologic research on subsequent malignancies in this population. We used longitudinal data from 9 population-based registries of the Surveillance, Epidemiology, and End Results program collected between 1973 and 2010 to assemble a cohort of individuals who were diagnosed with any cancer between the ages of 0 and 29 years and survived at least 5 years post-diagnosis. We estimated sex-specific standardized incidence ratios (SIRs) with corresponding 95% confidence limits (CL) of HPV-associated subsequent malignancies (cervical, vaginal, vulvar, penile, anal, tongue, tonsillar, and oropharyngeal). Our study population comprised 64,547 long-term survivors of PAYA cancers diagnosed between 1973 and 2010. Compared with females in the general US population, female PAYA cancer survivors had a 40% relative excess of HPV-associated malignancies overall (SIR = 1.4, 95% CL: 1.2, 1.8). Compared with males in the general US population, male PAYA cancer survivors had a 150% relative excess of HPV-associated malignancies overall (SIR = 2.5, 95% CL: 1.9, 3.4). Our findings suggest an excess of HPV-associated malignancies among PAYA cancer survivors compared with the general US population. We hypothesize that a portion of subsequent malignancies among PAYA cancer survivors may be directly attributable to HPV infection. This hypothesis warrants exploration in future studies.