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.

No abstract

6049 Background: In the head and neck, human papillomavirus-related oropharyngeal squamous cell carcinoma (HPV(+)OPSCC) has a better prognosis and more tumor infiltrating lymphocytes (TILs) compared to its HPV(-) counterpart. Within HPV(+)OPSCC, the prognostic value of TILs in the primary tumor and in metastatic lymph nodes is not well understood. Methods: This is a matched case-control study at a tertiary care center of HPV(+)OPSCC patients who underwent primary surgery between 05/2007–12/2016. Cases developed locoregional recurrence or distant metastases during follow-up, while controls did not during a similar duration of follow-up. Pairs were matched on age, American Joint Committee on Cancer (AJCC) 8th edition pathologic stage, sex, year of surgery, degree of adjuvant treatment, comorbidities, and smoking status. One representative H&E slide of the primary tumor and lymph node (when nodal disease was present) from each patient was independently reviewed by two pathologists (JG, MR) blinded to outcome, for tumor TILs (tTILs) density (defined as % TILs), presence/absence of desmoplastic stroma, and when stroma was present, for stromal TILs (sTILs) density (defined as relative crowding of TILs). The Brandwein-Gensler pattern of invasion (POI) score was used to grade the primary tumor. Interrater agreement was assessed using Cohen’s kappa. Associations between TILs and time to disease progression were assessed using Cox proportional hazards regression models. Results: 41 case-control pairs (N=82) were included in the study: 38 (46%) were AJCC pStage I, 37 (45%) were pStage II, and 7 (9%) were pStage III; 22 (27%) underwent surgery alone, 15 (18%) underwent surgery with adjuvant radiotherapy, and 45 (55%) underwent surgery with adjuvant chemoradiation. Interrater agreement was fair for tTILs density in the primary tumor ( k=0.24) and lymph node ( k=0.23), moderate for desmoplastic stroma in the primary tumor ( k=0.58) and lymph node ( k=0.64), moderate for sTILs density in the primary tumor ( k=0.58) and lymph node ( k=0.48), and fair for the POI score ( k=0.17). tTILs density ≥10% (HR 0.35, 95% CI 0.14-0.90, p=0.028) and a moderate/dense sTILs density (HR 0.15, 95% CI 0.04-0.68, p=0.014) in the primary tumor were significantly associated with decreased risk of disease progression. An aggressive POI score of III or IV was significantly associated with increased risk of disease progression (HR 4.00, 95% CI 1.34-11.96, p=0.013). None of the study measures in the lymph node were significantly associated with disease progression. Conclusions: In HPV(+)OPSCC, a higher density of tumor and stromal TILs and nonaggressive POI in the primary tumor specimen may indicate a lower risk of disease progression. TILs may serve as a powerful prognostic marker for the adaptive immune response to this disease.

No abstract