Toll-like receptor 5 and 7 expression may impact prognosis of HPV-positive oropharyngeal squamous cell carcinoma patients

Abstract

A large subset of oropharyngeal squamous cell carcinomas (OPSCCs) is associated with HPV infection and has better outcome than non-viral-related tumors. Various malignancies also carry a role for TLRs, key activators of inflammation and innate immunity. We examined the expression of TLRs in OPSCC, and their association with HPV status and treatment outcome. TLR 5, 7, 9, and p16 were studied by immunohistochemistry and HPV status was detected with in situ hybridization in 202 tumors of consecutively treated OPSCC patients using tissue microarray method. The relations between TLR expression and HPV status, p16 expression, clinicopathological factors, and survival were analyzed. TLR 5, 7, and 9 expression patterns differed between HPV-positive and -negative tumors, and they were statistically significantly associated with history of smoking, heavy drinking, tumor site, grade, size (T), metastasis (N), and stage. Moreover, in HPV-positive tumors the expression of TLR 5 and 7 correlated with tumor recurrence. After adjustment, among HPV-positive OPSCC patients, high TLR 5 and low TLR 7 expression were associated with poor disease-specific survival. Our results indicate that TLR 5 and 7 may have a role in the prognostication of HPV-positive OPSCC, however, further studies are needed to clarify the comprehensive role of these TLRs in OPSCC.

TLR5 and TLR7 are differentially expressed in human papillomavirus-positive and negative base of tongue squamous cell carcinoma, and TLR7 may have an independent prognostic influence

“…TLR5, 7 and 9 expression differed between HPV þ and HPV À OPSCC, and in general HPV þ OPSCC exhibited lower TLR5 and higher TLR7 expression levels than HPV À OPSCC [15]. Furthermore, high expression of TLR5 and low expression of TLR7 correlated with worse disease-specific survival (DSS) in HPV þ OPSCC [15]. To validate the data in a new cohort in another Nordic population and in a specific OPSCC subsite, biopsies from 77 BOTSCC patients from Stockholm, Sweden, were analyzed for TLR5 and TLR7 expression and the data were correlated with clinical outcome.…”

“…HPV þ BOTSCC was defined as having an HPV DNA positive tumor with p16 INK4A overexpression (p16 þ ) [18]. In total, 49 HPV þ BOTSCCs and 28 HPV À BOTSCCs fulfilling these criteria according to our previous studies [5,7,14] were analyzed for TLR5 and TLR7 expression [15]. The study was performed in compliance with permission (2009/1278-31/4) granted by the Regional Ethical Review Board in Stockholm.…”

“…age, stage, high CD8 þ tumor-infiltrating lymphocyte (TIL) counts, HPV16 E2 mRNA expression, absent/weak CD44, or high LRIG1 or CD98 expression and use mathematical models [3,[9][10][11][12][13][14]. In addition, we recently explored the impact of Toll-like receptors (TLR) in OPSCC and their influence on survival [15]. In that study tumor biopsies of 202 OPSCC diagnosed in Helsinki, Finland, were analyzed for the presence of TLR5, 7 and 9, and the expression of some of these TLRs was correlated with clinical outcome.…”

“…In that study tumor biopsies of 202 OPSCC diagnosed in Helsinki, Finland, were analyzed for the presence of TLR5, 7 and 9, and the expression of some of these TLRs was correlated with clinical outcome. TLR5, 7 and 9 expression differed between HPV þ and HPV À OPSCC, and in general HPV þ OPSCC exhibited lower TLR5 and higher TLR7 expression levels than HPV À OPSCC [15]. Furthermore, high expression of TLR5 and low expression of TLR7 correlated with worse disease-specific survival (DSS) in HPV þ OPSCC [15].…”

“…To validate the data in a new cohort in another Nordic population and in a specific OPSCC subsite, biopsies from 77 BOTSCC patients from Stockholm, Sweden, were analyzed for TLR5 and TLR7 expression and the data were correlated with clinical outcome. Since TLRs initiate immune responses [15][16][17], we also examined if TLR5 and/or TLR7 expression was correlated with CD4 þ and/or CD8 þ TIL counts in the tumors, because the presence of high CD8 þ TIL counts is reported to be a good prognostic marker in HPV þ OPSCC [9,12,13].…”