Jouhi Lauri, Mohamed Hesham, Mäkitie Antti, Remes Satu Maria, Haglund Caj, Atula Timo, Hagström Jaana
Otorhinolaryngology - Head and Neck Surgery, University of Helsinki and Helsinki University Hospital, P.O Box 263, 00029 HUS, Helsinki, Finland.
Pathology, University of Helsinki, HUSLAB, and Helsinki University Hospital, P.O Box 21, 00014 University of Helsinki, Helsinki, Finland.
Cancer Immunol Immunother. 2017 Dec;66(12):1619-1629. doi: 10.1007/s00262-017-2054-3. Epub 2017 Aug 30.
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.
很大一部分口咽鳞状细胞癌（OPSCC）与HPV感染相关，并且比非病毒相关肿瘤具有更好的预后。各种恶性肿瘤中Toll样受体（TLR）也发挥作用，TLR是炎症和先天免疫的关键激活因子。我们检测了OPSCC中TLR的表达及其与HPV状态和治疗结果的关联。采用组织芯片方法，通过免疫组织化学研究了202例连续治疗的OPSCC患者肿瘤组织中TLR 5、7、9和p16的表达，并通过原位杂交检测HPV状态。分析了TLR表达与HPV状态、p16表达、临床病理因素及生存之间的关系。HPV阳性和阴性肿瘤之间TLR 5、7和9的表达模式不同，并且它们与吸烟史、重度饮酒、肿瘤部位、分级、大小（T）、转移（N）和分期在统计学上显著相关。此外，在HPV阳性肿瘤中，TLR 5和7的表达与肿瘤复发相关。校正后，在HPV阳性的OPSCC患者中，高TLR 5表达和低TLR 7表达与疾病特异性生存率低相关。我们的结果表明，TLR 5和7可能在HPV阳性OPSCC的预后判断中发挥作用，然而，需要进一步研究以阐明这些TLR在OPSCC中的综合作用。
