Abstract 5763: Risk factors, trends, and disparities in HPV-associated subsequent malignant neoplasms among adolescent and young adult cancer survivors
Authors: Ou Judy Y. , Bennion Natalie , Parker Kellee , Fair Douglas , Hanson Heidi A. , Kepka Deanna , Warner Echo L. , Ramsay Joemy M. , Kaddas Heydon K. , Kirchhoff Anne C. 
Published: April 2023

Abstract
Background: Subsequent malignant neoplasms (SMN) are a leading cause of premature mortality among adolescent and young adult (AYA) cancer survivors, who have unique health needs. Human Papillomavirus-related second cancers (HPV-SMN) are generally preventable through screenings and vaccination. We identified disparities in HPV-SMN among AYA survivors by demographics and first cancer therapy, and examined temporal trends in incidence of HPV-SMN.
Methods: We identified diagnoses of any HPV-SMN, oropharyngeal-SMN, and cervical-SMN among AYA survivors in the SEER 9 1976-2015 registries starting two months after the first cancer. Standardized incidence ratios (SIR) compared risk between AYA survivors and general population. We used Fine and Gray competing risk models to estimate hazard ratios (HR) of therapy on risk for HPV-SMN while controlling for cancer site and demographic confounders. Age-period-cohort (APC) models identified temporal trends in HPV-SMN incidence.
Results: Of 374,408 survivors diagnosed with a first primary cancer ages 15-44, a total of 1,369 had an HPV-SMN occurring on average five years after the first cancer. Compared to the general population, AYA survivors had increased risks of 70% for any HPV-SMN (95%CI=1.61-1.79) and 117% for oropharyngeal-SMN (95%CI=2.00-2.35). Cervical-SMN risk was generally lower in survivors (SIR=0.85, 95%=CI 0.76-0.95). Hispanic AYA survivors had a significant increase in cervical-SMN relative to the general population (SIR=1.46, 95%CI=1.01-2.06). AYAs who were uninsured or on Medicaid at diagnosis had significant increases in HPV-SMN risk relative to the general populations (Uninsured SIR=5.23, 95%CI=2.26-10.31; Medicaid SIR=5.95, 95%CI=4.07-8.40). AYAs first diagnosed with Kaposi sarcoma, leukemia, Hodgkin, and Non-Hodgkin lymphoma had increased risk for HPV-SMN relative to the general population. Among survivors with HPV-related first primary cancers, radiation was associated with increased risk for HPV-SMN (HR=1.35, 95%CI-1.03-1.77). Among survivors whose first primary cancer was not HPV-related, chemotherapy was associated with increased risk for HPV-SMN (HR=1.20, 95%CI=1.00-1.44) but the general effect of treatment was not significant (p=0.16). In APC models, incidence of oropharyngeal-SMN significantly declined over time.
Conclusion and Impact: While the overall risk is low, AYA survivors are at higher risk for HPV-SMNs than the general population, largely driven by oropharyngeal-SMN. Hispanic survivors are the only group at higher risk for cervical-SMN than the general population suggesting a need to improve their cervical cancer screening. Uninsured/Medicaid AYA survivors also face higher HPV-SMN risks. Improving access to screening and HPV vaccination is needed to reduce the burden of HPV-SMN in AYA survivors.
Citation Format: Judy Y. Ou, Natalie Bennion, Kellee Parker, Douglas Fair, Heidi A. Hanson, Deanna Kepka, Echo L. Warner, Joemy M. Ramsay, Heydon K. Kaddas, Anne C. Kirchhoff. Risk factors, trends, and disparities in HPV-associated subsequent malignant neoplasms among adolescent and young adult cancer survivors. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5763.