HPV-Associated Oropharyngeal Cancer Among Elderly Patients: Dramatically Increased Prevalence and Clinical Implications

Abstract

Oropharyngeal squamous cell carcinoma (OPSCC) is increasing in incidence among elderly patients. However, the role of HPV, which historically has been associated with younger patients, in driving this trend is unclear. Moreover, the prognostic significance of HPV for elderly patients with OPSCC is uncertain given their competing comorbidities and difficulty withstanding standard multimodality therapy. The National Cancer Data Base was queried for patients with OPSCC diagnosed from 2010-2015 with known HPV status and receiving either definitive radiotherapy (RT) with or without concomitant chemotherapy or surgery with or without adjuvant RT and/or chemotherapy. Elderly patients were defined as those aged 70 years or older. Trends in the proportion of HPV-positive cases over time were assessed with linear regression. Multivariable Cox regression and propensity score matching were used to adjust survival analyses for clinical and demographic covariates. Statistical interactions between age and the effect of HPV on survival were assessed using tests of interaction and multivariable non-linear continuous interaction models. Overall, 19,358 patients met inclusion criteria, including 14,593 undergoing RT (2,343 elderly) and 4,765 undergoing surgery (597 elderly). The proportion of OPSCC associated with HPV increased from 45.1% in 2010 to 63.3% in 2015 among elderly patients (P<0.001). Similar trends in HPV-positivity were seen among subgroups aged 70-79 (47% to 66%, P<0.001) and 80 and older (37% to 53%, P<0.001) during this time period. HPV-positivity was independently associated with improved survival for elderly patients undergoing RT (HR=0.63, 95% CI 0.55-0.73, P<0.001) and surgery (HR= 0.37, 95% CI 0.25-0.53, P<0.001) in multivariable analysis. In propensity score-matched cohorts, 3-year overall survival (OS) was 66.4% versus 55.4% in elderly patients with HPV+ and HPV- OPSCC undergoing RT, respectively (P<0.001). Similarly, in propensity score-matched cohorts of elderly patients undergoing surgery, 3-year OS was 88.5% versus 69.1% for HPV+ and HPV- OPSCC. Although HPV-positivity was associated with significantly improved OS among all age groups receiving RT, the magnitude of the effect diminished with increasing age (interaction P<0.001). No interaction between age and the impact of HPV-status on OS was seen for surgical patients (interaction P = 0.85). The epidemiologic landscape of HPV-positive OPSCC is evolving, with a dramatic increase in the proportion of OPSCC associated with HPV among elderly patients over a short time span. HPV remains a powerful predictor of improved survival following either definitive RT or surgery in elderly patients, although the survival difference between HPV+ versus HPV- OPSCC receiving RT is less pronounced in the elderly than in younger patients.