Tumor PD-L1 expression is associated with improved survival and lower recurrence risk in young women with oral cavity squamous cell carcinoma.

Young patients with oral cavity squamous cell carcinoma (OCSCC) are often recognized as a distinct epidemiological cohort. In this study, genomic and immune-based metrics were correlated with long-term outcomes for a young patient population treated at a single institution. A fully clinically annotated, retrospective cohort of 81 patients aged ≤45 years with OCSCC is described, and the impact of clinicopathological features on long-term survival outcomes is reported. Genomic and immune parameters were integrated utilizing a whole-exome sequencing and immunohistochemical approach among females in the cohort. It was found that young OCSCC patients had favorable outcomes (10-year disease-free survival 79.1%, overall survival 80.0%) regardless of sex, particularly if they presented with oral tongue primaries and early stage disease. While mutational analysis appeared similar to that of older patients with OCSCC who lack a smoking history, a comparatively high degree of PD-L1 expression and PD-1/L1 concordance (P=0.001) was found among young female OCSCC patients. Subjects with greater membranous PD-L1 positivity and the presence of tumor-infiltrating lymphocytes had a decreased risk of recurrence (P=0.01 and P=0.01, respectively) and improved survival (P=0.04 and P=0.03, respectively). These findings warrant further validation and support the investigation of immunotherapeutic approaches targeting PD-1/L1 interactions in young OCSCC patients.

Survival and human papillomavirus in oropharynx cancer in TAX 324: a subset analysis from an international phase III trial.

BACKGROUND: The association between human papillomavirus (HPV) and overall survival (OS) in oropharynx cancer (OPC) was retrospectively examined in TAX 324, a phase III trial of sequential therapy for locally advanced head and neck cancer. METHODS: Accrual for TAX 324 was completed in 2003 and data updated through 2008. Pretherapy tumor biopsies were studied by PCR for human papillomavirus type 16 and linked to OS, progression-free survival (PFS) and demographics. RESULTS: Of 264 patients with OPC, 111 (42%) had evaluable biopsies; 56 (50%) were HPV+ and 55 (50%) were HPV-. HPV+ patients were significantly younger (54 versus 58 years, P = 0.02), had T1/T2 primary cancers (49% versus 20%, P = 0.001), and had a performance status of zero (77% versus 49%, P = 0.003). OS and PFS were better for HPV+ patients (OS, hazard ratio = 0.20, P < 0.0001). Local-regional failure was less in HPV+ patients (13% versus 42%, P = 0.0006); at 5 years, 82% of HPV+ patients were alive compared with 35% of HPV- patients (P < 0.0001). CONCLUSIONS: HPV+ OPC has a different biology compared with HPV- OPC; 5-year OS, PFS, and local-regional control are unprecedented. These results support the possibility of selectively reducing therapy and long-term morbidity in HPV+ OPC while preserving survival and approaching HPV- disease with more aggressive treatment.