HPV involvement in tonsillar cancer: Prognostic significance and clinically relevant markers
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 identific...
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creator | Rotnáglová, Eliška Tachezy, Ruth Saláková, Martina Procházka, Bohumír Košl'abová, Eva Veselá, Eva Ludvíková, Viera Hamšíková, Eva Klozar, Jan |
description | 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. |
doi_str_mv | 10.1002/ijc.25889 |
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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.</description><identifier>ISSN: 0020-7136</identifier><identifier>ISSN: 1097-0215</identifier><identifier>EISSN: 1097-0215</identifier><identifier>DOI: 10.1002/ijc.25889</identifier><identifier>PMID: 21190188</identifier><identifier>CODEN: IJCNAW</identifier><language>eng</language><publisher>Hoboken: Wiley Subscription Services, Inc., A Wiley Company</publisher><subject>Adult ; Antibodies ; Antibodies, Viral - blood ; Biological and medical sciences ; Biomarkers, Tumor - metabolism ; Cancer ; Cohort Studies ; Data processing ; DNA ; DNA, Viral - metabolism ; Female ; Gene expression ; HPV ; Human papillomavirus 16 ; Humans ; Immunohistochemistry ; Infection ; Male ; Medical sciences ; Middle Aged ; Otorhinolaryngology. Stomatology ; p53 protein ; Papillomaviridae - genetics ; Papillomaviridae - immunology ; Papillomaviridae - pathogenicity ; Polymerase Chain Reaction ; Prognosis ; Proteins ; Risk factors ; Risk groups ; Survival ; Tonsil ; tonsillar cancer ; Tonsillar Neoplasms - metabolism ; Tonsillar Neoplasms - pathology ; Tonsillar Neoplasms - virology ; Tumor Virus Infections - metabolism ; Tumors ; Upper respiratory tract, upper alimentary tract, paranasal sinuses, salivary glands: diseases, semeiology</subject><ispartof>International journal of cancer, 2011-07, Vol.129 (1), p.101-110</ispartof><rights>Copyright © 2011 UICC</rights><rights>2015 INIST-CNRS</rights><rights>Copyright © 2011 UICC.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3879-eef86b08b142b62e79519c28ea4905ae2be4b3fdc101fd02384399322522bf5b3</citedby><cites>FETCH-LOGICAL-c3879-eef86b08b142b62e79519c28ea4905ae2be4b3fdc101fd02384399322522bf5b3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fijc.25889$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fijc.25889$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1417,27924,27925,45574,45575</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=24211747$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21190188$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Rotnáglová, Eliška</creatorcontrib><creatorcontrib>Tachezy, Ruth</creatorcontrib><creatorcontrib>Saláková, Martina</creatorcontrib><creatorcontrib>Procházka, Bohumír</creatorcontrib><creatorcontrib>Košl'abová, Eva</creatorcontrib><creatorcontrib>Veselá, Eva</creatorcontrib><creatorcontrib>Ludvíková, Viera</creatorcontrib><creatorcontrib>Hamšíková, Eva</creatorcontrib><creatorcontrib>Klozar, Jan</creatorcontrib><title>HPV involvement in tonsillar cancer: Prognostic significance and clinically relevant markers</title><title>International journal of cancer</title><addtitle>Int J Cancer</addtitle><description>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.</description><subject>Adult</subject><subject>Antibodies</subject><subject>Antibodies, Viral - blood</subject><subject>Biological and medical sciences</subject><subject>Biomarkers, Tumor - metabolism</subject><subject>Cancer</subject><subject>Cohort Studies</subject><subject>Data processing</subject><subject>DNA</subject><subject>DNA, Viral - metabolism</subject><subject>Female</subject><subject>Gene expression</subject><subject>HPV</subject><subject>Human papillomavirus 16</subject><subject>Humans</subject><subject>Immunohistochemistry</subject><subject>Infection</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Middle Aged</subject><subject>Otorhinolaryngology. Stomatology</subject><subject>p53 protein</subject><subject>Papillomaviridae - genetics</subject><subject>Papillomaviridae - immunology</subject><subject>Papillomaviridae - pathogenicity</subject><subject>Polymerase Chain Reaction</subject><subject>Prognosis</subject><subject>Proteins</subject><subject>Risk factors</subject><subject>Risk groups</subject><subject>Survival</subject><subject>Tonsil</subject><subject>tonsillar cancer</subject><subject>Tonsillar Neoplasms - metabolism</subject><subject>Tonsillar Neoplasms - pathology</subject><subject>Tonsillar Neoplasms - virology</subject><subject>Tumor Virus Infections - metabolism</subject><subject>Tumors</subject><subject>Upper respiratory tract, upper alimentary tract, paranasal sinuses, salivary glands: diseases, semeiology</subject><issn>0020-7136</issn><issn>1097-0215</issn><issn>1097-0215</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp90D1PwzAQBmALgaB8DPwBlAUBQ1rbcRKbDVV8FCHRAZiQIse9VAbXAbst6r_naAtMMJ2te3Snewk5ZLTLKOU9-2K6PJdSbZAOo6pMKWf5Julgj6Yly4odshvjC6WM5VRskx3OmKJMyg55vhk-JdbPWzeHCfgpvpNp66N1TofEaG8gnCfD0I59G6fWJNGOvW3sspNoP0qMsx6_zi2SAA7mGodMdHiFEPfJVqNdhIN13SOPV5cP_Zv07v560L-4S00mS5UCNLKoqayZ4HXBoVQ5U4ZL0ELRXAOvQdRZMzKMsmZEeSZFplTGec553eR1tkdOVnPfQvs-gzitJjYawBM8tLNYySIrCykKgfL0X4kbSlVwLEjPVtSENsYATfUWLB62QFR9xV5h7NUydrRH67GzegKjH_mdM4LjNdARs2oCxmfjrxMoS1Gi663ch3Ww-HtjNbjtr1Z_AhQfmNU</recordid><startdate>20110701</startdate><enddate>20110701</enddate><creator>Rotnáglová, Eliška</creator><creator>Tachezy, Ruth</creator><creator>Saláková, Martina</creator><creator>Procházka, Bohumír</creator><creator>Košl'abová, Eva</creator><creator>Veselá, Eva</creator><creator>Ludvíková, Viera</creator><creator>Hamšíková, Eva</creator><creator>Klozar, Jan</creator><general>Wiley Subscription Services, Inc., A Wiley Company</general><general>Wiley-Blackwell</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7T2</scope><scope>7U1</scope><scope>7U2</scope><scope>7U9</scope><scope>C1K</scope><scope>H94</scope><scope>7X8</scope></search><sort><creationdate>20110701</creationdate><title>HPV involvement in tonsillar cancer: Prognostic significance and clinically relevant markers</title><author>Rotnáglová, Eliška ; Tachezy, Ruth ; Saláková, Martina ; Procházka, Bohumír ; Košl'abová, Eva ; Veselá, Eva ; Ludvíková, Viera ; Hamšíková, Eva ; Klozar, Jan</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3879-eef86b08b142b62e79519c28ea4905ae2be4b3fdc101fd02384399322522bf5b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>Adult</topic><topic>Antibodies</topic><topic>Antibodies, Viral - blood</topic><topic>Biological and medical sciences</topic><topic>Biomarkers, Tumor - metabolism</topic><topic>Cancer</topic><topic>Cohort Studies</topic><topic>Data processing</topic><topic>DNA</topic><topic>DNA, Viral - metabolism</topic><topic>Female</topic><topic>Gene expression</topic><topic>HPV</topic><topic>Human papillomavirus 16</topic><topic>Humans</topic><topic>Immunohistochemistry</topic><topic>Infection</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Middle Aged</topic><topic>Otorhinolaryngology. Stomatology</topic><topic>p53 protein</topic><topic>Papillomaviridae - genetics</topic><topic>Papillomaviridae - immunology</topic><topic>Papillomaviridae - pathogenicity</topic><topic>Polymerase Chain Reaction</topic><topic>Prognosis</topic><topic>Proteins</topic><topic>Risk factors</topic><topic>Risk groups</topic><topic>Survival</topic><topic>Tonsil</topic><topic>tonsillar cancer</topic><topic>Tonsillar Neoplasms - metabolism</topic><topic>Tonsillar Neoplasms - pathology</topic><topic>Tonsillar Neoplasms - virology</topic><topic>Tumor Virus Infections - metabolism</topic><topic>Tumors</topic><topic>Upper respiratory tract, upper alimentary tract, paranasal sinuses, salivary glands: diseases, semeiology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Rotnáglová, Eliška</creatorcontrib><creatorcontrib>Tachezy, Ruth</creatorcontrib><creatorcontrib>Saláková, Martina</creatorcontrib><creatorcontrib>Procházka, Bohumír</creatorcontrib><creatorcontrib>Košl'abová, Eva</creatorcontrib><creatorcontrib>Veselá, Eva</creatorcontrib><creatorcontrib>Ludvíková, Viera</creatorcontrib><creatorcontrib>Hamšíková, Eva</creatorcontrib><creatorcontrib>Klozar, Jan</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Health and Safety Science Abstracts (Full archive)</collection><collection>Risk Abstracts</collection><collection>Safety Science and Risk</collection><collection>Virology and AIDS Abstracts</collection><collection>Environmental Sciences and Pollution Management</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>International journal of cancer</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Rotnáglová, Eliška</au><au>Tachezy, Ruth</au><au>Saláková, Martina</au><au>Procházka, Bohumír</au><au>Košl'abová, Eva</au><au>Veselá, Eva</au><au>Ludvíková, Viera</au><au>Hamšíková, Eva</au><au>Klozar, Jan</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>HPV involvement in tonsillar cancer: Prognostic significance and clinically relevant markers</atitle><jtitle>International journal of cancer</jtitle><addtitle>Int J Cancer</addtitle><date>2011-07-01</date><risdate>2011</risdate><volume>129</volume><issue>1</issue><spage>101</spage><epage>110</epage><pages>101-110</pages><issn>0020-7136</issn><issn>1097-0215</issn><eissn>1097-0215</eissn><coden>IJCNAW</coden><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.</abstract><cop>Hoboken</cop><pub>Wiley Subscription Services, Inc., A Wiley Company</pub><pmid>21190188</pmid><doi>10.1002/ijc.25889</doi><tpages>10</tpages></addata></record> |
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subjects | Adult Antibodies Antibodies, Viral - blood Biological and medical sciences Biomarkers, Tumor - metabolism Cancer Cohort Studies Data processing DNA DNA, Viral - metabolism Female Gene expression HPV Human papillomavirus 16 Humans Immunohistochemistry Infection Male Medical sciences Middle Aged Otorhinolaryngology. Stomatology p53 protein Papillomaviridae - genetics Papillomaviridae - immunology Papillomaviridae - pathogenicity Polymerase Chain Reaction Prognosis Proteins Risk factors Risk groups Survival Tonsil tonsillar cancer Tonsillar Neoplasms - metabolism Tonsillar Neoplasms - pathology Tonsillar Neoplasms - virology Tumor Virus Infections - metabolism Tumors Upper respiratory tract, upper alimentary tract, paranasal sinuses, salivary glands: diseases, semeiology |
title | HPV involvement in tonsillar cancer: Prognostic significance and clinically relevant markers |
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