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

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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.

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Abbreviations

CI:

Confidence interval

CRT:

Chemoradiotherapy

DSS:

Disease-specific survival

HR:

Hazard ratio

ISH:

In situ hybridization

OPSCC:

Oropharyngeal squamous cell carcinoma

RFS:

Recurrence-free survival

RT:

Radiotherapy

SCC:

Squamous cell carcinoma

Sx:

Surgery

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Acknowledgements

We thank Mrs. Elina Aspiala and Mrs. Päivi Peltokangas for technical assistance and Mr. Tero Vahlberg for statistical advice. This work was supported by the Orion Farmos Foundation, the Research Foundation of Finnish Otolaryngological Association, the Sigrid Jusélius Foundation, and the Finnish Dentist Association Apollonia.

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  1. Timo Atula and Jaana Hagström equal contribution.

Authors and Affiliations

  1. Otorhinolaryngology - Head and Neck Surgery, University of Helsinki and Helsinki University Hospital, P.O Box 263, 00029 HUS, Helsinki, Finland

    Lauri Jouhi, Antti Mäkitie & Timo Atula

  2. Pathology, University of Helsinki, HUSLAB, and Helsinki University Hospital, P.O Box 21, 00014 University of Helsinki, Helsinki, Finland

    Hesham Mohamed, Satu Maria Remes & Jaana Hagström

  3. Surgery, University of Helsinki and Helsinki University Hospital, P.O Box 22, 00014 University of Helsinki, Helsinki, Finland

    Caj Haglund

  4. Division of Ear, Nose and Throat Diseases, Department of Clinical Sciences, Intervention and Technology, Karolinska Institutet and Karolinska Hospital, Stockholm, Sweden

    Antti Mäkitie

  5. Research Programs Unit, Translational Cancer Biology, University of Helsinki, P.O Box 63, 00014 University of Helsinki, Helsinki, Finland

    Caj Haglund & Jaana Hagström

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  1. Lauri Jouhi
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  2. Hesham Mohamed
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Correspondence to Lauri Jouhi.

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Jouhi, L., Mohamed, H., Mäkitie, A. et al. Toll-like receptor 5 and 7 expression may impact prognosis of HPV-positive oropharyngeal squamous cell carcinoma patients. Cancer Immunol Immunother 66, 1619–1629 (2017). https://doi.org/10.1007/s00262-017-2054-3

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