HPV involvement in tonsillar cancer: Prognostic significance and clinically relevant markers

Authors

  • Eliška Rotnáglová,

    1. Department of Otorhinolaryngology and Head and Neck Surgery, 1st Faculty of Medicine, Charles University in Prague, Motol University Hospital, Prague, Czech Republic
    2. Department of Experimental Virology, Institute of Hematology and Blood Transfusion, Prague, Czech Republic
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  • Ruth Tachezy,

    1. Department of Experimental Virology, Institute of Hematology and Blood Transfusion, Prague, Czech Republic
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  • Martina Saláková,

    1. Department of Experimental Virology, Institute of Hematology and Blood Transfusion, Prague, Czech Republic
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  • Bohumír Procházka,

    1. Department of Scientific information and Biostatistics, National Institute of Public Health, Prague, Czech Republic
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  • Eva Košl'abová,

    1. Department of Otorhinolaryngology and Head and Neck Surgery, 1st Faculty of Medicine, Charles University in Prague, Motol University Hospital, Prague, Czech Republic
    2. Department of Experimental Virology, Institute of Hematology and Blood Transfusion, Prague, Czech Republic
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  • Eva Veselá,

    1. Department of Pathology and Molecular Medicine, 2nd Faculty of Medicine, Charles University in Prague, Prague, Czech Republic
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  • Viera Ludvíková,

    1. Department of Experimental Virology, Institute of Hematology and Blood Transfusion, Prague, Czech Republic
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  • Eva Hamšíková,

    1. Department of Experimental Virology, Institute of Hematology and Blood Transfusion, Prague, Czech Republic
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  • Jan Klozar

    Corresponding author
    1. Department of Otorhinolaryngology and Head and Neck Surgery, 1st Faculty of Medicine, Charles University in Prague, Motol University Hospital, Prague, Czech Republic
    • Department of Otolaryngology and Head and Neck Surgery, 1st Faculty of Medicine, Charles University in Prague, Motol University Hospital, Institute for Postgraduate Medical Education, V Úvalu 84, 150 06 Prague 5, Czech Republic
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    • Fax: +420/224434319


Abstract

The association of high-risk human papillomaviruses (HR HPVs) with tonsillar cancer (TC) has been documented. Because patients with HPV-associated tumors show better survival rates, modification of their treatment regimen is being considered. It is therefore crucial to find markers for the identification of patients whose tumors are linked to viral infection. A cohort of 109 patients with primary TC was screened for HPV DNA presence in the tumor tissues and HPV-specific antibodies in sera. Data regarding risk factors and clinical parameters were collected. Forty-five specimens were analyzed for the expression of viral E6 and E2-region mRNA, and the p16 and p53 protein expression status was assessed by immunohistochemistry. The overall prevalence of HPV DNA in TC tissues was 65.1%. Ninety-three percent of HR HPV DNA-positive samples expressed E6*I mRNA. E2-region mRNA expression was detected in 36% of positive samples, which implies that the virus is integrated in 64% of HPV DNA/RNA-positive tumors. p16 overexpression and the presence of antibodies specific to HPV16 E6/E7 oncoproteins correlated well with HPV DNA and RNA presence. The disease-specific survival rate of patients with HPV DNA-positive tumors was significantly higher than that of HPV DNA-negative patients. In addition to providing further evidence of the involvement of HPV infection in the etiopathogenesis of a proportion of TC cases, our study demonstrates that p16 immunostaining and anti-E6/E7 antibodies as surrogate markers of HPV involvement represent specific, sensitive and clinically accessible assays for the identification of TC patients who have a considerably better prognosis.

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