In HPV-negative oropharyngeal squamous cell carcinoma, elevated toll-like receptor 2 immunoexpression may increase the risk of disease-specific mortality

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Kylmä , A K , Jouhi , L , Mohamed , H , Randen-Brady , R , Mäkitie , A , Atula , T , Haglund , C , Sorsa , T & Hagström , J 2020 , ' In HPV-negative oropharyngeal squamous cell carcinoma, elevated toll-like receptor 2 immunoexpression may increase the risk of disease-specific mortality ' , Oral Oncology , vol. 107 , 104778 . https://doi.org/10.1016/j.oraloncology.2020.104778

Title: In HPV-negative oropharyngeal squamous cell carcinoma, elevated toll-like receptor 2 immunoexpression may increase the risk of disease-specific mortality
Author: Kylmä, Anna Kaisa; Jouhi, Lauri; Mohamed, Hesham; Randen-Brady, Reija; Mäkitie, Antti; Atula, Timo; Haglund, Caj; Sorsa, Timo; Hagström, Jaana
Contributor organization: HUSLAB
Department of Pathology
University of Helsinki
Helsinki University Hospital Area
HUS Head and Neck Center
Korva-, nenä- ja kurkkutautien klinikka
Clinicum
Department of Ophthalmology and Otorhinolaryngology
Research Program in Systems Oncology
Faculty of Medicine
HUS Abdominal Center
II kirurgian klinikka
Department of Surgery
CAN-PRO - Translational Cancer Medicine Program
Research Programs Unit
Department of Oral and Maxillofacial Diseases
Medicum
Date: 2020-08
Language: eng
Number of pages: 8
Belongs to series: Oral Oncology
ISSN: 1368-8375
DOI: https://doi.org/10.1016/j.oraloncology.2020.104778
URI: http://hdl.handle.net/10138/329757
Abstract: Objectives: In oropharyngeal squamous cell carcinoma (OPSCC), toll-like receptors (TLR) 5 and 7 associate with the tumor's human papilloma virus (HPV) status (Jouhi et al., 2017). TLR 2, on the other hand, has been linked to head and neck squamous cell carcinoma (HNSCC), and to oral carcinogenesis (Farnebo et al., 2015; Binder Gallimidi et al., 2015). Here we investigated the presence of TLR 2 and 4 in HPV-positive and HPV-negative OPSCC, and their relationship to opportunistic oral pathogen Treponema denticola chymotrypsin-like protease (Td-CTLP) immunoexpression, clinical parameters, and patient outcome. Materials and methods: Clinicopathological data of 198 unselected consecutive OPSCC patients came from hospital registries. Immunoexpression of TLRs 2 and 4 we evaluated by immunohistochemistry, and earlier in this patient series we studied immunoexpression of Td-CTLP and HPV DNA, HPV mRNA, and p16 status. Results: Immunoexpression of both TLRs 2 and 4 showed a significant association with HPV-status. Strong expression was associated with HPV-positivity and mild expression with HPV-negativity. Patients with strong TLR 2 immunoexpression in the HPV negative subgroup had significantly poorer 5-year DSS (58%) than did patients with mild TLR 2 expression (77%), and strong TLR 2 immunoexpression remained as an independent factor linked to increased disease mortality in the multivariable setting (P = 0.019). No association existed between TLR 2 or 4 and Td-CTLP expression. Conclusion: Our results support the role of TLR 2 receptor as a possible target for development of therapeutics as earlier proposed (Farnebo et al., 2015). The involvement of Td and other oral pathogens in carcinogenesis of OPSCC, remains open and calls for further study.
Subject: Oropharyngeal squamous cell carcinoma
Human papillomavirus
Toll-like receptor
Treponema denticola
Chymotrypsin-like protease
Dentilisin
HUMAN-PAPILLOMAVIRUS
TREPONEMA-DENTICOLA
PORPHYROMONAS-GINGIVALIS
CANCER
EXPRESSION
HEAD
CARCINOGENESIS
RECOGNITION
PROGRESSION
EPIDEMIC
3122 Cancers
313 Dentistry
3126 Surgery, anesthesiology, intensive care, radiology
Peer reviewed: Yes
Rights: cc_by_nc_nd
Usage restriction: openAccess
Self-archived version: acceptedVersion


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