The Rise of HPV in the Elderly: A Changing Landscape of Oropharyngeal Carcinoma

Background: As the human papillomavirus (HPV) epidemic continues to grow, the number of elderly patients with oropharynx squamous cell carcinoma (OPSCC) is rapidly increasing. Despite this observation, this cohort remains understudied as they are often excluded from clinical trials. Objectives: We aimed to determine HPV prevalence in this cohort and its impact on survival and disease outcomes. Methods: We identified patients aged ≥ 70 with nonrecurrent, nonmetastatic OPSCC treated with curative intent at our institution from 2007-2018 and analyzed demographics, treatment characteristics, and outcomes. Survival analyses were used for outcome-specific endpoints. Results: In total, 88 patients were identified with a median age of 73 (interquartile range [IQR]:71-78). The majority was male (78%), white (66%), former smokers (61%), and non- or moderate drinkers (80%). The median Charlson Comorbidity Index (CCI) was 6 (IQR: 5-7) and 82% of patients were ECOG 0 or 1. Of note, 70% of the cohort was HPV positive (HPV+), and of these patients, 68% had PCR subtype confirmation, with 83% serotype 16. Fifty one percent of patients were AJCC 8th edition stage I/II and 49% were stage III/IV. Thirty-six percent of patients underwent surgery and 24% received adjuvant RT. Of those receiving definitive RT (n=57), 88% were treated with concurrent chemotherapy and of those, 50% underwent induction chemotherapy (n=25). Twenty-three percent of patients experienced a treatment interruption with no statistical difference between HPV+ and HPV- patients (P=0.24). Two patients (both HPV-) died on treatment due to an unrelated health condition. Median follow-up time was 2.5 years (IQR: 0.9-4.7). At 5 years, overall survival (OS) was 79.2% for HPV+ patients and 34.8% for HPV- patients (P=0.002); and disease specific survival (DSS) was 86% for HPV+ and 45.7% for HPV- patients (P=0.004). Estimated locoregional control (LRC) at 5 years was 83.0% for HPV+ and 58.0% for HPV- patients (P=0.013). By multivariable analyses, adjusting for age, race, gender, alcohol use, smoking history, CCI, and ECOG, HPV+ status was significantly associated with improved OS, DSS, LRC (OS: HR 0.27, [95% CI: 0.11, 0.64], P=0.003; DSS: HR 0.22, [95% CI: 0.072, 0.67], P=0.008; LRC: HR 0.26, [95% CI: 0.082, 0.82], P=0.021). Conclusions: In our cohort of elderly patients with OPSCC, the majority was HPV+. Consistent with prior studies in younger populations, positive HPV status was associated with improved survival and disease outcomes in elderly patients. There are many challenges when managing elderly patients with OPSCC, but as the population ages and the HPV epidemic evolves, clinical trials should include elderly patients with HPV+ OPSCC to explore the role of de-intensification treatment regimens in treating this growing, complex population.