Tumor-infiltrating lymphocyte quantification stratifies early-stage human papillomavirus oropharynx cancer prognosis

Farhoud Faraji; Nicholas Fung; Munfarid Zaidi; Christine C Gourin; David W Eisele; Lisa M Rooper; Carole Fakhry

doi:10.1002/lary.28044

Tumor-infiltrating lymphocyte quantification stratifies early-stage human papillomavirus oropharynx cancer prognosis

Laryngoscope. 2020 Apr;130(4):930-938. doi: 10.1002/lary.28044. Epub 2019 May 9.

Authors

Farhoud Faraji¹, Nicholas Fung², Munfarid Zaidi², Christine C Gourin², David W Eisele², Lisa M Rooper³, Carole Fakhry^{2

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Affiliations

¹ Division of Otolaryngology-Head and Neck Surgery, Department of Surgery, University of California San Diego Health, San Diego, California.
² Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins School of Medicine, Baltimore, Maryland.
³ Department of Pathology, Johns Hopkins School of Medicine, Baltimore, Maryland.
⁴ Bloomberg-Kimmel Institute for Cancer Immunotherapy at Johns Hopkins, Baltimore, Maryland.
⁵ Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, U.S.A.

PMID: 31070246
DOI: 10.1002/lary.28044

Abstract

Objectives/hypothesis: To evaluate if a simple method for assessing tumor-infiltrating lymphocytes (TIL) in primary tumor specimens improves the prognostic value of the American Joint Committee on Cancer, 8th Edition (AJCC8) cancer staging system in human papillomavirus-positive oropharyngeal squamous cell carcinoma (HPV-OPC).

Study design: Retrospective study.

Methods: In this study, TIL density was quantified on hematoxylin and eosin (H&E)-stained specimens from patients presenting to Johns Hopkins Hospital between 2009 and 2017 who underwent primary surgical therapy and had primary tumor specimens available for analysis. The prognostic effect of TIL density was evaluated by Kaplan-Meier method and Cox proportional hazards models considering recurrence-free survival (RFS) as the primary outcome.

Results: This study included 132 patients. Ninety-five percent were classified by clinical criteria with AJCC8 early-stage disease (stage I: 82%, stage II: 13%). After 84 months of follow-up, 15 recurrences were observed. Among clinically early-stage disease, TIL_high status was associated with improved RFS compared to TIL_low (P = .002). Adjusted analysis showed TIL_high status was associated with 79% lower risk of recurrence than TIL_low (adjusted hazard ratio [aHR]: 0.210, 95% confidence interval [CI]: 0.061-0.723). In clinical stage I disease, TIL_high status was associated with improved RFS compared to TIL_low in both univariate and multivariate analyses (hazard ratio: 0.235, P = .021; aHR: 0.218; 95% CI: 0.058-0.822). TIL density similarly stratified risk in pathologically staged disease.

Conclusions: In patients with AJCC8 stage I disease, low TIL density was associated with diminished RFS. Our data suggest that assessing TIL density on H&E-stained primary tumor specimens may enhance the prognostic resolution of the AJCC8 staging criteria for HPV-OPC.

Level of evidence: 4 Laryngoscope, 130:930-938, 2020.

Keywords: Oropharynx; human papillomavirus; prognosis; squamous cell carcinoma; tumor infiltrating lymphocyte.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Carcinoma, Squamous Cell / pathology*
Carcinoma, Squamous Cell / virology
Female
Humans
Lymphocytes, Tumor-Infiltrating / pathology*
Male
Middle Aged
Neoplasm Staging
Oropharyngeal Neoplasms / pathology*
Oropharyngeal Neoplasms / virology
Papillomaviridae*
Papillomavirus Infections / pathology*
Papillomavirus Infections / virology
Prognosis
Retrospective Studies

Grants and funding

Oral Cancer Foundation/International