Tumour-infiltrating lymphocytes predict for outcome in HPV-positive oropharyngeal cancer

Abstract

Background:Human papillomavirus (HPV)-positive oropharyngeal cancer (OPSCC) is associated with improved survival compared with HPV-negative disease. However, a minority of HPV-positive patients have poor prognosis. Currently, there is no generally accepted strategy for identifying these patients.Methods:We retrospectively analysed 270 consecutively treated OPSCC patients from three centres for effects of clinical, pathological, immunological, and molecular features on disease mortality. We used Cox regression to examine associations between factors and OPSCC death, and developed a prognostic model for 3-year mortality using logistic regression analysis.Results:Patients with HPV-positive tumours showed improved survival (hazard ratio (HR), 0.33 (0.21–0.53)). High levels of tumour-infiltrating lymphocytes (TILs) stratified HPV-positive patients into high-risk and low-risk groups (3-year survival; HPV-positive/TILhigh=96%, HPV-positive/TILlow=59%). Survival of HPV-positive/TILlow patients did not differ from HPV-negative patients (HR, 1.01; P=0.98). We developed a prognostic model for HPV-positive tumours using a ‘training' cohort from one centre; the combination of TIL levels, heavy smoking, and T-stage were significant (AUROC=0·87). This model was validated on patients from the other centres (detection rate 67% false-positive rate 5.6% AUROC=0·82).Interpretation:Our data suggest that an immune response, reflected by TIL levels in the primary tumour, has an important role in the improved survival seen in most HPV-positive patients, and is relevant for the clinical evaluation of HPV-positive OPSCC.

Integrated Omic Analysis of Oropharyngeal Carcinomas Reveals Human Papillomavirus (HPV)–dependent Regulation of the Activator Protein 1 (AP-1) Pathway

“…Of particular interest was the apparent enrichment of nine proteins involved in lymphocyte activation in HPVϩ OPC (supplemental Table S6), many of which participate in antigen processing and presentation for immune recognition. A recent report described an association between higher levels of tumor infiltrating lymphocytes and HPV positivity and improved outcome (40). Our study does suggest the influence of the tumor microenvironment, particularly related to the tumor infiltrating lymphocytes in HPVϮ OPC, which secrete cytokines and can stimulate the expression of several identified proteins (e.g.…”

Periductal stromal collagen topology of pancreatic ductal adenocarcinoma differs from that of normal and chronic pancreatitis

“…26 The slide was digitalized using an Aperio CS2 scanner system and the Positive Pixel Count algorithm (v9) was used to quantify alpha-smooth muscle actin positivity in the individual cores.…”

Combination immunotherapy with TLR agonists and checkpoint inhibitors suppresses head and neck cancer

“…High numbers of CD8 + T cells in the TME positively correlate with overall survival in patients with colorectal cancer, in HPV-positive HNSCC, and in patients with other solid tumors (12)(13)(14)(15). Recent T cell receptor (TCR) sequencing analyses show that tumor infiltrating lymphocytes (TILs) recognize and target mutated neoantigens, which are then clonally expanded and enriched at the tumor site (16).…”