Literature DB >> 26823521

HPV Involvement in Head and Neck Cancers: Comprehensive Assessment of Biomarkers in 3680 Patients.

Xavier Castellsagué1, Laia Alemany1, Miquel Quer1, Gordana Halec1, Beatriz Quirós1, Sara Tous1, Omar Clavero1, Llúcia Alòs1, Thorsten Biegner1, Tomasz Szafarowski1, Maria Alejo1, Dana Holzinger1, Enrique Cadena1, Edith Claros1, Gillian Hall1, Jan Laco1, Mario Poljak1, Maria Benevolo1, Elena Kasamatsu1, Hisham Mehanna1, Cathy Ndiaye1, Núria Guimerà1, Belen Lloveras1, Xavier León1, Juan C Ruiz-Cabezas1, Isabel Alvarado-Cabrero1, Chang-Suk Kang1, Jin-Kyoung Oh1, Marcial Garcia-Rojo1, Ermina Iljazovic1, Oluseyi F Ajayi1, Flora Duarte1, Ashrafun Nessa1, Leopoldo Tinoco1, Marco A Duran-Padilla1, Edyta C Pirog1, Halina Viarheichyk1, Hesler Morales1, Valérie Costes1, Ana Félix1, Maria Julieta V Germar1, Marisa Mena1, Arzu Ruacan1, Asha Jain1, Ravi Mehrotra1, Marc T Goodman1, Luis Estuardo Lombardi1, Annabelle Ferrera1, Sani Malami1, Estela I Albanesi1, Pablo Dabed1, Carla Molina1, Rubén López-Revilla1, Václav Mandys1, Manuel E González1, Julio Velasco1, Ignacio G Bravo1, Wim Quint1, Michael Pawlita1, Nubia Muñoz1, Silvia de Sanjosé1, F Xavier Bosch1.   

Abstract

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.
© The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

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Year:  2016        PMID: 26823521     DOI: 10.1093/jnci/djv403

Source DB:  PubMed          Journal:  J Natl Cancer Inst        ISSN: 0027-8874            Impact factor:   13.506


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