Peritumoral cuffing by T-cell tumor-infiltrating lymphocytes distinguishes HPV-related oropharyngeal squamous cell carcinoma from oral cavity squamous cell carcinoma.

BACKGROUND

It is unclear why human papillomavirus (HPV)-related head and neck squamous cell carcinoma (HNSCC) has improved clinical behavior compared to HPV-negative HNSCC. We sought to better characterize the immune microenvironment of tongue cancers by examining the CD3 and CD8 TIL pattern in HPV-positive and HPV-negative tumors.

METHODS

Histologic sections from 40 oral tongue and oropharyngeal cases were analyzed (n=21 HPV DNA-positive, n=19 HPV DNA-negative). CD3 and CD8 T-cell immunostaining were performed on whole-slide sections to quantify tumor-infiltrating lymphocyte (TIL) density and assess its morphology.

RESULTS

A subset of cases (HPV-positive) displayed a unique TIL pattern consisting of circumferential peritumoral population T cells, which was absent in the HPV-negative cases. The presence of peritumoral cuffing was strongly predictive of improved recurrence-free survival compared to cases that lacked this morphologic pattern of immune infiltrate. Four HPV-positive cases lacked the pattern, including two cases with disease recurrence.

CONCLUSIONS

For the first time, we show an architectural pattern of immune infiltrate in HNSCC is seen exclusively in HPV-positive patients with improved recurrence-free survival and suggests an organized host immunological response contributes to disease control.