T cell fraction impacts oncologic outcomes in human papillomavirus associated oropharyngeal squamous cell carcinoma.

Abstract

We investigated T cell clonality (TCC) and T cell fraction (TCF) in human papilloma virus associated oropharyngeal squamous cell carcinoma (HPV(+)OPSCC) progressors [cases] vs. non-progressors [controls]. This nested case-control study included patients undergoing intent-to-cure surgery±adjuvant therapy from 6/1/2007-10/3/2016. Patients experiencing local/regional/distant disease (progressors), and a consecutive sample of non-progressors were matched (2 controls: 1 case) on tumor subsite, T-stage and number of metastatic lymph nodes. We performed imunosequencing of the CDR3 regions of human TCRβ chains. 34 progressors and 65 non-progressors were included. There was no statistically significant difference in baseline TCF (range: 0.039-1.084) and TCC (range: 0.007-0.240) (p>0.05). Female sex was associated with higher TCF (p=0.03), while extranodal extension (ENE) was associated with lower TCF (p=0.01). There was a positive correlation between tumor size and clonality (R=0.34, p<0.01). The strongest predictor of progression-free survival (PFS) was TCF (HR 0.80, 95%CI 0.66-0.96, p=0.02). The strongest predictors of cancer specific survival (CSS) were TCF (HR0.69, 95%CI 0.47-1.00, p<0.05) and Adult Comorbidity Evaluation-27 (ACE-27) score (p<0.05). Similarly, the strongest predictors of overall survival (OS) were TCF (HR 0.62, 95%CI 0.43-0.91, p=0.01) and ACE-27 score (p=0.03). On multivariable modeling, TCF≥0.4 was independently associated with PFS (HR 0.34, 95%CI 0.14-0.85, p=0.02) while an ACE-27 score of≥2 independently predicted CSS (HR 3.85, 95%CI 1.07-13.85, p=0.04) and OS (HR 3.51, 95%CI 1.10-11.20, p=0.03). In patients with HPV(+)OPSCC, TCF was higher in female patients and those without ENE, suggesting differential immune responses. Lower TCF was significantly and independently associated with disease progression. Better ACE-27 scores appear to predict improved oncologic control.