HPV Involvement in Head and Neck Cancers: Comprehensive Assessment of Biomarkers in 3680 Patients
We conducted a large international study to estimate fractions of head and neck cancers (HNCs) attributable to human papillomavirus (HPV-AFs) using six HPV-related biomarkers of viral detection, transcription, and cellular transformation. Formalin-fixed, paraffin-embedded cancer tissues of the oral...
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| Published in | JNCI : Journal of the National Cancer Institute Vol. 108; no. 6; p. djv403 |
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| Main Authors | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
United States
Oxford University Press (OUP)
01.06.2016
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| Subjects | |
| Online Access | Get full text |
| ISSN | 0027-8874 1460-2105 |
| DOI | 10.1093/jnci/djv403 |
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| Abstract | We conducted a large international study to estimate fractions of head and neck cancers (HNCs) attributable to human papillomavirus (HPV-AFs) using six HPV-related biomarkers of viral detection, transcription, and cellular transformation.
Formalin-fixed, paraffin-embedded cancer tissues of the oral cavity (OC), pharynx, and larynx were collected from pathology archives in 29 countries. All samples were subject to histopathological evaluation, DNA quality control, and HPV-DNA detection. Samples containing HPV-DNA were further subject to HPV E6*I mRNA detection and to p16(INK4a), pRb, p53, and Cyclin D1 immunohistochemistry. Final estimates of HPV-AFs were based on HPV-DNA, HPV E6*I mRNA, and/or p16(INK4a) results.
A total of 3680 samples yielded valid results: 1374 pharyngeal, 1264 OC, and 1042 laryngeal cancers. HPV-AF estimates based on positivity for HPV-DNA, and for either HPV E6*I mRNA or p16(INK4a), were 22.4%, 4.4%, and 3.5% for cancers of the oropharynx, OC, and larynx, respectively, and 18.5%, 3.0%, and 1.5% when requiring simultaneous positivity for all three markers. HPV16 was largely the most common type. Estimates of HPV-AF in the oropharynx were highest in South America, Central and Eastern Europe, and Northern Europe, and lowest in Southern Europe. Women showed higher HPV-AFs than men for cancers of the oropharynx in Europe and for the larynx in Central-South America.
HPV contribution to HNCs is substantial but highly heterogeneous by cancer site, region, and sex. This study, the largest exploring HPV attribution in HNCs, confirms the important role of HPVs in oropharyngeal cancer and drastically downplays the previously reported involvement of HPVs in the other HNCs. |
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| AbstractList | BACKGROUNDWe conducted a large international study to estimate fractions of head and neck cancers (HNCs) attributable to human papillomavirus (HPV-AFs) using six HPV-related biomarkers of viral detection, transcription, and cellular transformation.METHODSFormalin-fixed, paraffin-embedded cancer tissues of the oral cavity (OC), pharynx, and larynx were collected from pathology archives in 29 countries. All samples were subject to histopathological evaluation, DNA quality control, and HPV-DNA detection. Samples containing HPV-DNA were further subject to HPV E6*I mRNA detection and to p16(INK4a), pRb, p53, and Cyclin D1 immunohistochemistry. Final estimates of HPV-AFs were based on HPV-DNA, HPV E6*I mRNA, and/or p16(INK4a) results.RESULTSA total of 3680 samples yielded valid results: 1374 pharyngeal, 1264 OC, and 1042 laryngeal cancers. HPV-AF estimates based on positivity for HPV-DNA, and for either HPV E6*I mRNA or p16(INK4a), were 22.4%, 4.4%, and 3.5% for cancers of the oropharynx, OC, and larynx, respectively, and 18.5%, 3.0%, and 1.5% when requiring simultaneous positivity for all three markers. HPV16 was largely the most common type. Estimates of HPV-AF in the oropharynx were highest in South America, Central and Eastern Europe, and Northern Europe, and lowest in Southern Europe. Women showed higher HPV-AFs than men for cancers of the oropharynx in Europe and for the larynx in Central-South America.CONCLUSIONSHPV contribution to HNCs is substantial but highly heterogeneous by cancer site, region, and sex. This study, the largest exploring HPV attribution in HNCs, confirms the important role of HPVs in oropharyngeal cancer and drastically downplays the previously reported involvement of HPVs in the other HNCs. We conducted a large international study to estimate fractions of head and neck cancers (HNCs) attributable to human papillomavirus (HPV-AFs) using six HPV-related biomarkers of viral detection, transcription, and cellular transformation. Formalin-fixed, paraffin-embedded cancer tissues of the oral cavity (OC), pharynx, and larynx were collected from pathology archives in 29 countries. All samples were subject to histopathological evaluation, DNA quality control, and HPV-DNA detection. Samples containing HPV-DNA were further subject to HPV E6*I mRNA detection and to p16(INK4a), pRb, p53, and Cyclin D1 immunohistochemistry. Final estimates of HPV-AFs were based on HPV-DNA, HPV E6*I mRNA, and/or p16(INK4a) results. A total of 3680 samples yielded valid results: 1374 pharyngeal, 1264 OC, and 1042 laryngeal cancers. HPV-AF estimates based on positivity for HPV-DNA, and for either HPV E6*I mRNA or p16(INK4a), were 22.4%, 4.4%, and 3.5% for cancers of the oropharynx, OC, and larynx, respectively, and 18.5%, 3.0%, and 1.5% when requiring simultaneous positivity for all three markers. HPV16 was largely the most common type. Estimates of HPV-AF in the oropharynx were highest in South America, Central and Eastern Europe, and Northern Europe, and lowest in Southern Europe. Women showed higher HPV-AFs than men for cancers of the oropharynx in Europe and for the larynx in Central-South America. HPV contribution to HNCs is substantial but highly heterogeneous by cancer site, region, and sex. This study, the largest exploring HPV attribution in HNCs, confirms the important role of HPVs in oropharyngeal cancer and drastically downplays the previously reported involvement of HPVs in the other HNCs. BACKGROUND:We conducted a large international study to estimate fractions of head and neck cancers (HNCs) attributable to human papillomavirus (HPV-AFs) using six HPV-related biomarkers of viral detection, transcription, and cellular transformation.METHODS:Formalin-fixed, paraffin-embedded cancer tissues of the oral cavity (OC), pharynx, and larynx were collected from pathology archives in 29 countries. All samples were subject to histopathological evaluation, DNA quality control, and HPV-DNA detection. Samples containing HPV-DNA were further subject to HPV E6*I mRNA detection and to p16(INK4a), pRb, p53, and Cyclin D1 immunohistochemistry. Final estimates of HPV-AFs were based on HPV-DNA, HPV E6*I mRNA, and/or p16(INK4a) results.RESULTS:A total of 3680 samples yielded valid results: 1374 pharyngeal, 1264 OC, and 1042 laryngeal cancers. HPV-AF estimates based on positivity for HPV-DNA, and for either HPV E6*I mRNA or p16(INK4a), were 22.4%, 4.4%, and 3.5% for cancers of the oropharynx, OC, and larynx, respectively, and 18.5%, 3.0%, and 1.5% when requiring simultaneous positivity for all three markers. HPV16 was largely the most common type. Estimates of HPV-AF in the oropharynx were highest in South America, Central and Eastern Europe, and Northern Europe, and lowest in Southern Europe. Women showed higher HPV-AFs than men for cancers of the oropharynx in Europe and for the larynx in Central-South America.CONCLUSIONS:HPV contribution to HNCs is substantial but highly heterogeneous by cancer site, region, and sex. This study, the largest exploring HPV attribution in HNCs, confirms the important role of HPVs in oropharyngeal cancer and drastically downplays the previously reported involvement of HPVs in the other HNCs. |
| Author | Pawlita, Michael Velasco, Julio Mehanna, Hisham Mehrotra, Ravi Pirog, Edyta C. Molina, Carla Halec, Gordana Lloveras, Belen Oh, Jin-Kyoung Clavero, Omar Jain, Asha López-Revilla, Rubén León, Xavier Ruiz-Cabezas, Juan C. Benevolo, Maria Ruacan, Arzu Szafarowski, Tomasz Lombardi, Luis Estuardo González, Manuel E. Tinoco, Leopoldo Kang, Chang-Suk Ajayi, Oluseyi F. Goodman, Marc T. Muñoz, Nubia Cadena, Enrique Malami, Sani Guimerà, Núria Alòs, Llúcia Holzinger, Dana Ndiaye, Cathy Ferrera, Annabelle Duarte, Flora Albanesi, Estela I. Xavier Bosch, F. Biegner, Thorsten Morales, Hesler Sanjosé, Silvia de Nessa, Ashrafun Quint, Wim Alemany, Laia Poljak, Mario Alvarado-Cabrero, Isabel Mena, Marisa Duran-Padilla, Marco A. Quirós, Beatriz Tous, Sara Dabed, Pablo Hall, Gillian Garcia-Rojo, Marcial Iljazovic, Ermina Costes, Valérie Germar, Maria Julieta V. Alejo, Maria Bravo, Ignacio G. Félix, Ana Mandys, Václav Quer, Miquel Viarheichyk, Halina Castellsagué, Xavier Laco, Jan Kasamatsu, Elena Claros, Edith |
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| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/26823521$$D View this record in MEDLINE/PubMed https://hal.science/hal-01881034$$DView record in HAL |
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| ContentType | Journal Article |
| Contributor | Leiva, Virginia Murillo, Raúl Shin, Hai-Rim Costes, Valerie Calix, Eda Sofía Mehrotra, Ravi Argueta, Victor Vega, Pedro A Spriano, Giuseppe Halec, Gordana Oh, Jin-Kyoung Camacho, Fernando López-Revilla, Rubén Benevolo, Maria Lombardi, Luis Estuardo Ceballos, María Esther Gutiérez Díaz Tinoco, Leopoldo Cabezas, Juan Carlos Ruíz Tommasino, Massimo Searhei, Achynovich Magaña-León, Claudia Olave, Elsa Márquez, Lily Marcela Cadena, Enrique Jaramillo, Leyda Holzinger, Dana Viveros, Patricia Alonso Singh, Mamta Marroquin, Sergio Ferrera, Annabelle Albanesi, Estela Irene Biegner, Thorsten Kim, Dong-chul Abdulkareem, F B Toledo, Luxely Nessa, Ashrafun Daramola, A O Suárez, Gustavo Adolfo Hernández Chang-Suk, Kang Alvarado-Cabrero, Isabel Oros, Cuauhtémoc Pinzón, Carlos Eduardo Guerra, Walter Bhalla, Maheep Iljazovic, Ermina Molinero, Marco Ramis, Claudia Prado, Rodrigo Ahmed, Faruk Salic, Obdulia Erzi, Sandra Laco, Jan Kasamatsu, Elena Padilla, Nelly Sarai Claros, Edith Quinto, Rina Pawlita, Michael Rodriguez, Ximena Muñoz, Flora Duarte Miciquevich, Su |
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| Copyright | The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com. Distributed under a Creative Commons Attribution 4.0 International License |
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| References | 2016012817074904000_108.6.djv403.2 2016012817074904000_108.6.djv403.1 2016012817074904000_108.6.djv403.9 2016012817074904000_108.6.djv403.8 2016012817074904000_108.6.djv403.7 2016012817074904000_108.6.djv403.27 2016012817074904000_108.6.djv403.6 2016012817074904000_108.6.djv403.5 2016012817074904000_108.6.djv403.4 2016012817074904000_108.6.djv403.3 2016012817074904000_108.6.djv403.22 2016012817074904000_108.6.djv403.21 2016012817074904000_108.6.djv403.20 2016012817074904000_108.6.djv403.26 2016012817074904000_108.6.djv403.25 2016012817074904000_108.6.djv403.24 2016012817074904000_108.6.djv403.23 2016012817074904000_108.6.djv403.19 2016012817074904000_108.6.djv403.18 2016012817074904000_108.6.djv403.17 2016012817074904000_108.6.djv403.16 2016012817074904000_108.6.djv403.11 2016012817074904000_108.6.djv403.10 2016012817074904000_108.6.djv403.15 2016012817074904000_108.6.djv403.14 2016012817074904000_108.6.djv403.13 Geraets (2016012817074904000_108.6.djv403.12) 2012; 228 |
| References_xml | – ident: 2016012817074904000_108.6.djv403.13 doi: 10.1002/ijc.28963 – ident: 2016012817074904000_108.6.djv403.19 doi: 10.1007/s12105-012-0370-7 – ident: 2016012817074904000_108.6.djv403.14 doi: 10.1002/ijc.27605 – ident: 2016012817074904000_108.6.djv403.21 doi: 10.1016/S1470-2045(12)70137-7 – ident: 2016012817074904000_108.6.djv403.10 doi: 10.1016/S1470-2045(10)70230-8 – ident: 2016012817074904000_108.6.djv403.6 doi: 10.1093/jnci/djg107 – ident: 2016012817074904000_108.6.djv403.5 doi: 10.1016/j.vaccine.2012.05.070 – ident: 2016012817074904000_108.6.djv403.15 doi: 10.1038/bjc.2013.296 – ident: 2016012817074904000_108.6.djv403.26 doi: 10.1002/ijc.24339 – volume: 228 start-page: 534 issue: (4) year: 2012 ident: 2016012817074904000_108.6.djv403.12 article-title: RIS HPV TT study group. Detection of rare and possibly carcinogenic human papillomavirus genotypes as single infections in invasive cervical cancer publication-title: J Pathol doi: 10.1002/path.4065 – ident: 2016012817074904000_108.6.djv403.7 doi: 10.1158/0008-5472.CAN-11-3934 – ident: 2016012817074904000_108.6.djv403.4 – ident: 2016012817074904000_108.6.djv403.18 – ident: 2016012817074904000_108.6.djv403.2 doi: 10.1002/(SICI)1096-9896(199909)189:1<12::AID-PATH431>3.0.CO;2-F – ident: 2016012817074904000_108.6.djv403.8 doi: 10.1016/S1470-2045(14)70471-1 – ident: 2016012817074904000_108.6.djv403.27 doi: 10.1016/S1470-2045(09)70096-8 – ident: 2016012817074904000_108.6.djv403.17 doi: 10.1002/ijc.22980 – ident: 2016012817074904000_108.6.djv403.22 doi: 10.1093/jnci/djv086 – ident: 2016012817074904000_108.6.djv403.25 doi: 10.1200/JCO.2011.36.4596 – ident: 2016012817074904000_108.6.djv403.9 doi: 10.1158/1055-9965.EPI-04-0551 – ident: 2016012817074904000_108.6.djv403.16 doi: 10.1002/ijc.28142 – ident: 2016012817074904000_108.6.djv403.23 doi: 10.1200/JCO.2013.50.3870 – ident: 2016012817074904000_108.6.djv403.11 – ident: 2016012817074904000_108.6.djv403.3 – ident: 2016012817074904000_108.6.djv403.1 – ident: 2016012817074904000_108.6.djv403.20 doi: 10.1002/path.4405 – ident: 2016012817074904000_108.6.djv403.24 doi: 10.1002/hed.22015 |
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| Snippet | We conducted a large international study to estimate fractions of head and neck cancers (HNCs) attributable to human papillomavirus (HPV-AFs) using six... BACKGROUNDWe conducted a large international study to estimate fractions of head and neck cancers (HNCs) attributable to human papillomavirus (HPV-AFs) using... BACKGROUND:We conducted a large international study to estimate fractions of head and neck cancers (HNCs) attributable to human papillomavirus (HPV-AFs) using... |
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| SubjectTerms | Adult Aged Biomarkers, Tumor - analysis Cancer Carcinoma, Squamous Cell - chemistry Carcinoma, Squamous Cell - virology Cross-Sectional Studies Cyclin D1 - analysis Cyclin-Dependent Kinase Inhibitor p16 - analysis DNA, Viral - isolation & purification Female Genotype Head and Neck Neoplasms - virology Human papillomavirus 16 - isolation & purification Humans Immunohistochemistry International Cooperation Life Sciences Male Middle Aged Oropharyngeal Neoplasms - chemistry Oropharyngeal Neoplasms - virology Papillomaviridae - genetics Papillomaviridae - isolation & purification Papillomavirus Infections - complications Papillomavirus Infections - virology Predictive Value of Tests Salivary Proline-Rich Proteins - analysis Tumor Suppressor Protein p53 - analysis |
| Title | HPV Involvement in Head and Neck Cancers: Comprehensive Assessment of Biomarkers in 3680 Patients |
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