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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dc.contributor.author Kylmä, Anna Kaisa
dc.contributor.author Jouhi, Lauri
dc.contributor.author Mohamed, Hesham
dc.contributor.author Randen-Brady, Reija
dc.contributor.author Mäkitie, Antti
dc.contributor.author Atula, Timo
dc.contributor.author Haglund, Caj
dc.contributor.author Sorsa, Timo
dc.contributor.author Hagström, Jaana
dc.date.accessioned 2021-05-10T21:48:32Z
dc.date.available 2021-12-18T03:45:58Z
dc.date.issued 2020-08
dc.identifier.citation 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
dc.identifier.other PURE: 144025398
dc.identifier.other PURE UUID: bee1c7f8-a472-466e-8224-9d4b006f9d59
dc.identifier.other WOS: 000552964400009
dc.identifier.other ORCID: /0000-0001-6079-7881/work/80218855
dc.identifier.other ORCID: /0000-0002-6560-1128/work/80223736
dc.identifier.uri http://hdl.handle.net/10138/329757
dc.description.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. en
dc.format.extent 8
dc.language.iso eng
dc.relation.ispartof Oral Oncology
dc.rights cc_by_nc_nd
dc.rights.uri info:eu-repo/semantics/openAccess
dc.subject Oropharyngeal squamous cell carcinoma
dc.subject Human papillomavirus
dc.subject Toll-like receptor
dc.subject Treponema denticola
dc.subject Chymotrypsin-like protease
dc.subject Dentilisin
dc.subject HUMAN-PAPILLOMAVIRUS
dc.subject TREPONEMA-DENTICOLA
dc.subject PORPHYROMONAS-GINGIVALIS
dc.subject CANCER
dc.subject EXPRESSION
dc.subject HEAD
dc.subject CARCINOGENESIS
dc.subject RECOGNITION
dc.subject PROGRESSION
dc.subject EPIDEMIC
dc.subject 3122 Cancers
dc.subject 313 Dentistry
dc.subject 3126 Surgery, anesthesiology, intensive care, radiology
dc.title In HPV-negative oropharyngeal squamous cell carcinoma, elevated toll-like receptor 2 immunoexpression may increase the risk of disease-specific mortality en
dc.type Article
dc.contributor.organization HUSLAB
dc.contributor.organization Department of Pathology
dc.contributor.organization University of Helsinki
dc.contributor.organization Helsinki University Hospital Area
dc.contributor.organization HUS Head and Neck Center
dc.contributor.organization Korva-, nenä- ja kurkkutautien klinikka
dc.contributor.organization Clinicum
dc.contributor.organization Department of Ophthalmology and Otorhinolaryngology
dc.contributor.organization Research Program in Systems Oncology
dc.contributor.organization Faculty of Medicine
dc.contributor.organization HUS Abdominal Center
dc.contributor.organization II kirurgian klinikka
dc.contributor.organization Department of Surgery
dc.contributor.organization CAN-PRO - Translational Cancer Medicine Program
dc.contributor.organization Research Programs Unit
dc.contributor.organization Department of Oral and Maxillofacial Diseases
dc.contributor.organization Medicum
dc.description.reviewstatus Peer reviewed
dc.relation.doi https://doi.org/10.1016/j.oraloncology.2020.104778
dc.relation.issn 1368-8375
dc.rights.accesslevel openAccess
dc.type.version acceptedVersion

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