Exploring the Impact of Human Papillomavirus Status, Comorbidity, Polypharmacy, and Treatment Intensity on Outcome of Elderly Oropharyngeal Cancer Patients Treated With Radiation Therapy With or Without Chemotherapy

Abstract

Purpose: To explore the impact of tumor human papillomavirus (HPV) status, comorbidity, polypharmacy, and treatment intensity on overall survival (OS) of elderly oropharyngeal cancer (OPC) patients.

Methods and materials: All elderly (>70 years) OPC patients receiving definitive (chemo-) radiation therapy in 2000 to 2013 were reviewed. Charlson comorbidity index (CCI, comorbidity alone) and the comorbidity-polypharmacy score (CPS, comorbidity and medication) were calculated. Overall survival was compared between HPV-positive (HPV+) and HPV-negative (HPV-) cohorts. Multivariable analyses (MVA) incorporating either the CCI (MVA-CCI) or the CPS (MVA-CPS) identified survival predictors.

Results: Among 231 of 287 patients (80%) with p16 staining, 117 were HPV+ and 114 HPV-. Systemic treatments were administered in 48 patients (21%) (chemotherapy 17; epidermal growth factor receptor inhibitor 31). The distribution of CCI (P=.59), CPS (P=.23), and age (P=.50) were similar between HPV+ versus HPV- cohorts. Median follow-up was 4.3 years. The HPV+ patients had better 5-year OS (57% vs 32%, P<.001) versus HPV- patients. Multivariable analysis adjusted for T-/N-category confirmed that HPV+ status (MVA-CCI: hazard ratio [HR] 0.58, P=.01; MVA-CPS: HR 0.60, P=.02), Zubrod scale score (0-1) (MVA-CCI: HR 0.44, P<.001; MVA-CPS: HR 0.43, P<.001), and higher radiation therapy dose (MVA-CCI: HR 0.97, P=.001; MVA-CPS: HR 0.96, P<.001) were correlated with higher OS. A marginal inverse correlation between CPS and OS was observed in the entire cohort (HR 1.05, P=.05) and was stronger for the HPV+ cohort (HR 1.11, P=.02). Nonsignificant higher OS was also found with ≤20 pack-years of smoking (MVA-CCI: P=.10; MVA-CPS: P=.15) and with systemic treatments (MVA-CCI: P=.13; MVA-CPS: P=.19). No association with OS was found for CCI (P=.46).

Conclusion: Elderly HPV+ OPC patients have longer survival than their HPV- counterparts. Lower Zubrod scale score and higher radiation therapy dose are associated with longer OS, whereas fewer smoking pack-years and systemic agents have nonsignificant associations. Comorbidity-polypharmacy score, but not CCI, is correlated with OS, especially in HPV+ patients, suggesting the potential importance of assessing polypharmacy in addition to comorbidity burden in this population.