Study of the concordance between p16 immunohistochemistry and HPV-PCR genotyping for the viral diagnosis of oropharyngeal squamous cell carcinoma
Abstract Objective The diagnosis of HPV-related oropharyngeal cancer in clinical practice is based on p16 immunohistochemistry and PCR detection of viral DNA (HPV-PCR). The primary objective of this study was to evaluate the concordance between these 2 diagnostic tests. The secondary objective was t...
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creator | Fonmarty, D Cherrière, S Fleury, H Eimer, S Majoufre-Lefebvre, C Castetbon, V de Monès, E |
description | Abstract Objective The diagnosis of HPV-related oropharyngeal cancer in clinical practice is based on p16 immunohistochemistry and PCR detection of viral DNA (HPV-PCR). The primary objective of this study was to evaluate the concordance between these 2 diagnostic tests. The secondary objective was to study the clinical characteristics of these patients. Materials and methods This single-centre prospective study was conducted between February 2010 and July 2012. Immunohistochemical analysis of p16 and HPV-PCR were performed on tumour biopsies. Concordance was evaluated according to Cohen's kappa coefficient and was interpreted according to the Landis and Koch scale. The patients’ clinical data were analysed as a function of the diagnostic test results. Results Seventy-one patients were included in this study. The prevalence of HPV was 43.7% according to p16 and 31% according to HPV-PCR. The concordance study revealed a kappa coefficient of 0.615. A tumour of the tonsil or base of the tongue was detected in 100% of p16+/HPV-PCR+ cases. Smoking and alcohol abuse were significantly less frequent among HPV+ patients regardless of the method of detection. These patients were older and presented tumours with a lower grade of histological differentiation. Conclusion p16 immunohistochemistry or HPV-PCR used alone appear to be insufficient. These results confirm the high prevalence of HPV-related oropharyngeal squamous cell carcinoma (OSCC) and the previously reported specific clinical and histological features, apart from age. It appears essential for future clinical trials to be stratified according to smoking and tumour HPV status, defined by means of reliable virological tests targeting E6/E7 mRNA and no longer a simple positive response to the p16 marker, as is frequently the case at the present time. New tests suitable for use in routine practice therefore need to be developed. |
doi_str_mv | 10.1016/j.anorl.2015.01.003 |
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The primary objective of this study was to evaluate the concordance between these 2 diagnostic tests. The secondary objective was to study the clinical characteristics of these patients. Materials and methods This single-centre prospective study was conducted between February 2010 and July 2012. Immunohistochemical analysis of p16 and HPV-PCR were performed on tumour biopsies. Concordance was evaluated according to Cohen's kappa coefficient and was interpreted according to the Landis and Koch scale. The patients’ clinical data were analysed as a function of the diagnostic test results. Results Seventy-one patients were included in this study. The prevalence of HPV was 43.7% according to p16 and 31% according to HPV-PCR. The concordance study revealed a kappa coefficient of 0.615. A tumour of the tonsil or base of the tongue was detected in 100% of p16+/HPV-PCR+ cases. Smoking and alcohol abuse were significantly less frequent among HPV+ patients regardless of the method of detection. These patients were older and presented tumours with a lower grade of histological differentiation. Conclusion p16 immunohistochemistry or HPV-PCR used alone appear to be insufficient. These results confirm the high prevalence of HPV-related oropharyngeal squamous cell carcinoma (OSCC) and the previously reported specific clinical and histological features, apart from age. It appears essential for future clinical trials to be stratified according to smoking and tumour HPV status, defined by means of reliable virological tests targeting E6/E7 mRNA and no longer a simple positive response to the p16 marker, as is frequently the case at the present time. New tests suitable for use in routine practice therefore need to be developed.</description><identifier>ISSN: 1879-7296</identifier><identifier>EISSN: 1879-730X</identifier><identifier>DOI: 10.1016/j.anorl.2015.01.003</identifier><identifier>PMID: 25687724</identifier><language>eng</language><publisher>France: Elsevier Masson SAS</publisher><subject>Biomarkers, Tumor - genetics ; Carcinoma, Squamous Cell - diagnosis ; Carcinoma, Squamous Cell - epidemiology ; Carcinoma, Squamous Cell - virology ; Cyclin-Dependent Kinase Inhibitor p16 ; DNA, Viral - analysis ; Female ; France - epidemiology ; Genotype ; HPV ; Human papillomavirus 16 - genetics ; Human papillomavirus 16 - pathogenicity ; Human Papillomavirus DNA Tests ; Humans ; Immunohistochemistry - methods ; Male ; Middle Aged ; Neoplasm Grading ; Neoplasm Proteins - genetics ; Neoplasm Staging ; Oropharyngeal cancer ; Oropharyngeal Neoplasms - diagnosis ; Oropharyngeal Neoplasms - epidemiology ; Oropharyngeal Neoplasms - virology ; Otolaryngology ; P16 ; Papillomavirus Infections - complications ; Papillomavirus Infections - diagnosis ; Papillomavirus Infections - epidemiology ; Papillomavirus Infections - virology ; PCR ; Polymerase Chain Reaction ; Predictive Value of Tests ; Prevalence ; Prognosis ; Prospective Studies ; Reproducibility of Results ; Risk Factors ; Sensitivity and Specificity</subject><ispartof>European annals of otorhinolaryngology, head and neck diseases, 2015-06, Vol.132 (3), p.135-139</ispartof><rights>Elsevier Masson SAS</rights><rights>2015 Elsevier Masson SAS</rights><rights>Copyright © 2015 Elsevier Masson SAS. All rights reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c529t-f03ee2fda2d69e4148b33c1486e81a4cef10e7aef32f173df774b47d95683fb83</citedby><cites>FETCH-LOGICAL-c529t-f03ee2fda2d69e4148b33c1486e81a4cef10e7aef32f173df774b47d95683fb83</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.anorl.2015.01.003$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25687724$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Fonmarty, D</creatorcontrib><creatorcontrib>Cherrière, S</creatorcontrib><creatorcontrib>Fleury, H</creatorcontrib><creatorcontrib>Eimer, S</creatorcontrib><creatorcontrib>Majoufre-Lefebvre, C</creatorcontrib><creatorcontrib>Castetbon, V</creatorcontrib><creatorcontrib>de Monès, E</creatorcontrib><title>Study of the concordance between p16 immunohistochemistry and HPV-PCR genotyping for the viral diagnosis of oropharyngeal squamous cell carcinoma</title><title>European annals of otorhinolaryngology, head and neck diseases</title><addtitle>Eur Ann Otorhinolaryngol Head Neck Dis</addtitle><description>Abstract Objective The diagnosis of HPV-related oropharyngeal cancer in clinical practice is based on p16 immunohistochemistry and PCR detection of viral DNA (HPV-PCR). The primary objective of this study was to evaluate the concordance between these 2 diagnostic tests. The secondary objective was to study the clinical characteristics of these patients. Materials and methods This single-centre prospective study was conducted between February 2010 and July 2012. Immunohistochemical analysis of p16 and HPV-PCR were performed on tumour biopsies. Concordance was evaluated according to Cohen's kappa coefficient and was interpreted according to the Landis and Koch scale. The patients’ clinical data were analysed as a function of the diagnostic test results. Results Seventy-one patients were included in this study. The prevalence of HPV was 43.7% according to p16 and 31% according to HPV-PCR. The concordance study revealed a kappa coefficient of 0.615. A tumour of the tonsil or base of the tongue was detected in 100% of p16+/HPV-PCR+ cases. Smoking and alcohol abuse were significantly less frequent among HPV+ patients regardless of the method of detection. These patients were older and presented tumours with a lower grade of histological differentiation. Conclusion p16 immunohistochemistry or HPV-PCR used alone appear to be insufficient. These results confirm the high prevalence of HPV-related oropharyngeal squamous cell carcinoma (OSCC) and the previously reported specific clinical and histological features, apart from age. It appears essential for future clinical trials to be stratified according to smoking and tumour HPV status, defined by means of reliable virological tests targeting E6/E7 mRNA and no longer a simple positive response to the p16 marker, as is frequently the case at the present time. New tests suitable for use in routine practice therefore need to be developed.</description><subject>Biomarkers, Tumor - genetics</subject><subject>Carcinoma, Squamous Cell - diagnosis</subject><subject>Carcinoma, Squamous Cell - epidemiology</subject><subject>Carcinoma, Squamous Cell - virology</subject><subject>Cyclin-Dependent Kinase Inhibitor p16</subject><subject>DNA, Viral - analysis</subject><subject>Female</subject><subject>France - epidemiology</subject><subject>Genotype</subject><subject>HPV</subject><subject>Human papillomavirus 16 - genetics</subject><subject>Human papillomavirus 16 - pathogenicity</subject><subject>Human Papillomavirus DNA Tests</subject><subject>Humans</subject><subject>Immunohistochemistry - methods</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Neoplasm Grading</subject><subject>Neoplasm Proteins - genetics</subject><subject>Neoplasm Staging</subject><subject>Oropharyngeal cancer</subject><subject>Oropharyngeal Neoplasms - diagnosis</subject><subject>Oropharyngeal Neoplasms - epidemiology</subject><subject>Oropharyngeal Neoplasms - virology</subject><subject>Otolaryngology</subject><subject>P16</subject><subject>Papillomavirus Infections - complications</subject><subject>Papillomavirus Infections - diagnosis</subject><subject>Papillomavirus Infections - epidemiology</subject><subject>Papillomavirus Infections - virology</subject><subject>PCR</subject><subject>Polymerase Chain Reaction</subject><subject>Predictive Value of Tests</subject><subject>Prevalence</subject><subject>Prognosis</subject><subject>Prospective Studies</subject><subject>Reproducibility of Results</subject><subject>Risk Factors</subject><subject>Sensitivity and Specificity</subject><issn>1879-7296</issn><issn>1879-730X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFUk1v1DAQjRCIVqW_AAn5yCXBH9k4PoCEVoUiVaKigLhZjj3e9ZLYqZ0U5Wfwj3G6LQcu-DKW5s28eW-mKF4SXBFMmjeHSvkQ-4pisqkwqTBmT4pT0nJRcoZ_PH38U9GcFOcpHXB-rG0FFs-LE7ppWs5pfVr8vplms6Bg0bQHpIPXIRrlNaAOpl8AHo2kQW4YZh_2Lk1B72HIMS5IeYMur7-X19svaAc-TMvo_A7ZEO973bmoemSc2vmQXFopQgzjXsXF7yCn0u2shjAnpKHvkVZROx8G9aJ4ZlWf4PwhnhXfPlx83V6WV58_ftq-vyr1hoqptJgBUGsUNY2AmtRtx5jOoYGWqFqDJRi4AsuoJZwZy3nd1dyILJ3ZrmVnxetj3zGG2xnSJLOudRTlIU8lSdOKhohsWYayI1THkFIEK8fohixEEizXdciDvF-HXNchMZHZ61z16oFg7gYwf2sezc-At0cAZJl3DqJM2kH23rgIepImuP8QvPunXvfOO636n7BAOoQ5-uygJDJRieXNehHrQZDNegx1w_4AOze0ow</recordid><startdate>20150601</startdate><enddate>20150601</enddate><creator>Fonmarty, D</creator><creator>Cherrière, S</creator><creator>Fleury, H</creator><creator>Eimer, S</creator><creator>Majoufre-Lefebvre, C</creator><creator>Castetbon, V</creator><creator>de Monès, E</creator><general>Elsevier Masson SAS</general><scope>6I.</scope><scope>AAFTH</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>7X8</scope></search><sort><creationdate>20150601</creationdate><title>Study of the concordance between p16 immunohistochemistry and HPV-PCR genotyping for the viral diagnosis of oropharyngeal squamous cell carcinoma</title><author>Fonmarty, D ; Cherrière, S ; Fleury, H ; Eimer, S ; Majoufre-Lefebvre, C ; Castetbon, V ; de Monès, E</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c529t-f03ee2fda2d69e4148b33c1486e81a4cef10e7aef32f173df774b47d95683fb83</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Biomarkers, Tumor - genetics</topic><topic>Carcinoma, Squamous Cell - diagnosis</topic><topic>Carcinoma, Squamous Cell - epidemiology</topic><topic>Carcinoma, Squamous Cell - virology</topic><topic>Cyclin-Dependent Kinase Inhibitor p16</topic><topic>DNA, Viral - analysis</topic><topic>Female</topic><topic>France - epidemiology</topic><topic>Genotype</topic><topic>HPV</topic><topic>Human papillomavirus 16 - genetics</topic><topic>Human papillomavirus 16 - pathogenicity</topic><topic>Human Papillomavirus DNA Tests</topic><topic>Humans</topic><topic>Immunohistochemistry - methods</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Neoplasm Grading</topic><topic>Neoplasm Proteins - genetics</topic><topic>Neoplasm Staging</topic><topic>Oropharyngeal cancer</topic><topic>Oropharyngeal Neoplasms - diagnosis</topic><topic>Oropharyngeal Neoplasms - epidemiology</topic><topic>Oropharyngeal Neoplasms - virology</topic><topic>Otolaryngology</topic><topic>P16</topic><topic>Papillomavirus Infections - complications</topic><topic>Papillomavirus Infections - diagnosis</topic><topic>Papillomavirus Infections - epidemiology</topic><topic>Papillomavirus Infections - virology</topic><topic>PCR</topic><topic>Polymerase Chain Reaction</topic><topic>Predictive Value of Tests</topic><topic>Prevalence</topic><topic>Prognosis</topic><topic>Prospective Studies</topic><topic>Reproducibility of Results</topic><topic>Risk Factors</topic><topic>Sensitivity and Specificity</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Fonmarty, D</creatorcontrib><creatorcontrib>Cherrière, S</creatorcontrib><creatorcontrib>Fleury, H</creatorcontrib><creatorcontrib>Eimer, S</creatorcontrib><creatorcontrib>Majoufre-Lefebvre, C</creatorcontrib><creatorcontrib>Castetbon, V</creatorcontrib><creatorcontrib>de Monès, E</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>European annals of otorhinolaryngology, head and neck diseases</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Fonmarty, D</au><au>Cherrière, S</au><au>Fleury, H</au><au>Eimer, S</au><au>Majoufre-Lefebvre, C</au><au>Castetbon, V</au><au>de Monès, E</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Study of the concordance between p16 immunohistochemistry and HPV-PCR genotyping for the viral diagnosis of oropharyngeal squamous cell carcinoma</atitle><jtitle>European annals of otorhinolaryngology, head and neck diseases</jtitle><addtitle>Eur Ann Otorhinolaryngol Head Neck Dis</addtitle><date>2015-06-01</date><risdate>2015</risdate><volume>132</volume><issue>3</issue><spage>135</spage><epage>139</epage><pages>135-139</pages><issn>1879-7296</issn><eissn>1879-730X</eissn><abstract>Abstract Objective The diagnosis of HPV-related oropharyngeal cancer in clinical practice is based on p16 immunohistochemistry and PCR detection of viral DNA (HPV-PCR). The primary objective of this study was to evaluate the concordance between these 2 diagnostic tests. The secondary objective was to study the clinical characteristics of these patients. Materials and methods This single-centre prospective study was conducted between February 2010 and July 2012. Immunohistochemical analysis of p16 and HPV-PCR were performed on tumour biopsies. Concordance was evaluated according to Cohen's kappa coefficient and was interpreted according to the Landis and Koch scale. The patients’ clinical data were analysed as a function of the diagnostic test results. Results Seventy-one patients were included in this study. The prevalence of HPV was 43.7% according to p16 and 31% according to HPV-PCR. The concordance study revealed a kappa coefficient of 0.615. A tumour of the tonsil or base of the tongue was detected in 100% of p16+/HPV-PCR+ cases. Smoking and alcohol abuse were significantly less frequent among HPV+ patients regardless of the method of detection. These patients were older and presented tumours with a lower grade of histological differentiation. Conclusion p16 immunohistochemistry or HPV-PCR used alone appear to be insufficient. These results confirm the high prevalence of HPV-related oropharyngeal squamous cell carcinoma (OSCC) and the previously reported specific clinical and histological features, apart from age. It appears essential for future clinical trials to be stratified according to smoking and tumour HPV status, defined by means of reliable virological tests targeting E6/E7 mRNA and no longer a simple positive response to the p16 marker, as is frequently the case at the present time. New tests suitable for use in routine practice therefore need to be developed.</abstract><cop>France</cop><pub>Elsevier Masson SAS</pub><pmid>25687724</pmid><doi>10.1016/j.anorl.2015.01.003</doi><tpages>5</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Biomarkers, Tumor - genetics Carcinoma, Squamous Cell - diagnosis Carcinoma, Squamous Cell - epidemiology Carcinoma, Squamous Cell - virology Cyclin-Dependent Kinase Inhibitor p16 DNA, Viral - analysis Female France - epidemiology Genotype HPV Human papillomavirus 16 - genetics Human papillomavirus 16 - pathogenicity Human Papillomavirus DNA Tests Humans Immunohistochemistry - methods Male Middle Aged Neoplasm Grading Neoplasm Proteins - genetics Neoplasm Staging Oropharyngeal cancer Oropharyngeal Neoplasms - diagnosis Oropharyngeal Neoplasms - epidemiology Oropharyngeal Neoplasms - virology Otolaryngology P16 Papillomavirus Infections - complications Papillomavirus Infections - diagnosis Papillomavirus Infections - epidemiology Papillomavirus Infections - virology PCR Polymerase Chain Reaction Predictive Value of Tests Prevalence Prognosis Prospective Studies Reproducibility of Results Risk Factors Sensitivity and Specificity |
title | Study of the concordance between p16 immunohistochemistry and HPV-PCR genotyping for the viral diagnosis of oropharyngeal squamous cell carcinoma |
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