HPV-unrelated oropharyngeal cancer has elevated risk of synchronous hepatobiliary second primary malignancies compared to HPV-related oropharyngeal cancer: a population-based study from SEER.

BACKGROUND

Our aim was to compare risk of synchronous and metachronous hepatobiliary second primary malignancies (SPMs) in survivors of human papillomavirus (HPV)-related [i.e., p16(+)] and HPV-unrelated [i.e., p16(-)] oropharyngeal cancer (OPC).

METHODS

A retrospective study was conducted for cases with OPC diagnosis during years 2018-2021 who had known p16 status using data of USA from Surveillance, Epidemiology, and End Results (SEER) Program [Incidence - SEER Research Limited-Field Data, 22 Registries (excl IL and MA), Nov 2023 Sub (2000-2021)]. In the statistical analyses, death was considered as a competing event for the development of a hepatobiliary SPM. Bias due to unbalanced baseline characteristics was eliminated by adjustments using propensity score and inverse probability of treatment weighting (IPTW). Risk of development of a hepatobiliary SPM was assessed using propensity-score-adjusted time-varying Cox proportional hazard regression [adjusted hazard ratio (aHR) with 95 % confidence interval (95 % CI)].

RESULTS

Overall, 25759 cases with tumor status of p16(-) (6353) and p16(+) (19406) with median (interquartile range) follow-up times of 14 (6, 26) and 20 (9, 32) months, respectively, were included. From these, 48 had a hepatobiliary SPM. Compared to HPV-related OPC, HPV-unrelated OPC had significantly elevated risk of synchronous all hepatobiliary SPMs [aHR= 2.39 (95 % CI, 1.11-5.15); P = 0.026] and synchronous hepatocellular carcinoma (HCC) SPM [aHR= 2.86 (95 % CI, 1.18-6.92); P = 0.020], but not metachronous ones. Curves of cumulative incidence of a hepatobiliary (or HCC) SPM and cumulative survival probability for those with a hepatobiliary SPM, both stratified by p16 status and adjusted by IPTW, were generated. The median survival time among patients with a hepatobiliary SPM was shorter for HPV-unrelated OPC (0.8 years) compared to HPV-related OPC (2.6 years).

CONCLUSION

The observed elevated risk was likely due to heavy alcohol and tobacco use and the protective role of HPV infection against HCC development in carriers of hepatitis C virus.