Impact of Tumor‐Infiltrating Lymphocytes on Disease Progression in Human Papillomavirus‐Related Oropharyngeal Carcinoma

Abstract

ObjectiveWe aim to explore the prognostic value of tumor‐infiltrating lymphocytes (TILs) in the primary tumor and metastatic lymph nodes of patients with HPV(+)OPSCC. We hypothesize that TILS density at both sites is associated with disease‐free survival in HPV(+)OPSCC.Study DesignMatched case‐control study among HPV(+)OPSCC patients who underwent intent‐to‐cure surgery. Cases developed locoregional or distant recurrence. Controls were matched based on age, sex, pathologic T, N, and overall stage, year of surgery, type of adjuvant treatment received, and the Adult Comorbidity Evaluation‐27 (ACE‐27) score.SettingSingle tertiary care center, May 2007 to December 2016.MethodsTumoral TILs (tTILs) density was defined as % TILs; stromal TILs (sTILs) density was defined as absent/sparse or moderate/dense crowding. Associations between TILs and time to disease progression were assessed using Cox regression models.ResultsForty‐four case‐control pairs (N = 88) were included: 42 (48%) AJCC pStage I, 39 (44%) pStage II, and 7 (8%) pStage III. tTILs density ≥10% (hazard ratio [HR] 0.41, 95% confidence interval [CI] 0.17‐0.99, p = .048) and a moderate/dense sTILs density (HR 0.21, 95% CI 0.06‐0.75, p = .016) in the primary tumor were significantly associated with decreased risk of progression. TILs density in the lymph node was associated with decreased risk of progression but did not reach statistical significance. The tTILs and sTILs density correlated strongly between the primary tumor and lymph node. Concordance between the pathologists' was moderate (60%‐70%).ConclusionsIn HPV(+)OPSCC, a higher density of tumoral and stromal TILs in the primary tumor and possibly the lymph node may predict a lower risk of disease progression.

Integrative Spatial Analysis of H&E and IHC Images Identifies Prognostic Immune Subtypes Correlated with Progression-Free Survival in Human Papillomavirus (HPV)-Related Oropharyngeal Squamous Cell Carcinoma

“…The methodology for the identification and selection of this matched case-control cohort has been previously published [13]. After obtaining institutional review board approval (IRB 20-012036), we queried a departmental REDCap oropharyngeal database to identify patients with HPV(+) OPSCC of the tonsil or base of the tongue who underwent intent-to-cure surgery +/- adjuvant therapy between 05/2007 and 12/2016.…”

“…We compared manual annotation and DL for TILs density assessment. In our previous study, manual annotation categorized the TIL density into three groups: <10%, 10-39%, and ≥40% [13]. We applied the same classification criteria for the DL approach to calculate the ratio of TILs to tumor tiles to measure TIL density.…”

“…While some studies have reported a significant association between TILs and survival in HPV(+) OPSCC, others suggest that TIL density may be prognostic only in lower-stage disease [12]. However, most of these TIL-based analyses rely on manual quantification performed by pathologists, which introduces inherent inter-observer variability even among experts [13] and is prohibitively time-consuming for clinical use.…”

Integrative Spatial Analysis of H&amp;E and IHC Images Identifies Prognostic Immune Subtypes Correlated with Progression-Free Survival in Human Papillomavirus (HPV)-Related Oropharyngeal Squamous Cell Carcinoma

“…The methodology for the identi cation and selection of this matched case-control cohort has been previously published [13]. After obtaining institutional review board approval (IRB 20-012036), we queried a departmental REDCap oropharyngeal database to identify patients with HPV(+) OPSCC of the tonsil or base of the tongue who underwent intent-to-cure surgery +/-adjuvant therapy between 05/2007 and 12/2016.…”

“…While some studies have reported a signi cant association between TILs and survival in HPV(+) OPSCC, others suggest that TIL density may be prognostic only in lower-stage disease [12]. However, most of these TIL-based analyses rely on manual quanti cation performed by pathologists, which introduces inherent inter-observer variability even among experts [13] and is prohibitively time-consuming for clinical use.…”