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

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.

• Authors: Xavier Castellsagué, Laia Alemany, Miquel Quer, Gordana Halec, Beatriz Quirós, Sara Tous, Omar Clavero, Llúcia Alòs, Thorsten Biegner, Tomasz Szafarowski, Maria Alejo, Dana Holzinger, Enrique Cadena, Edith Claros, Gillian Hall, Jan Laco, Mario Poljak, Maria Benevolo, Elena Kasamatsu, Hisham Mehanna, Cathy Ndiaye, Núria Guimerà, Belen Lloveras, Xavier León, Juan C Ruiz-Cabezas, Isabel Alvarado-Cabrero, Chang-Suk Kang, Jin-Kyoung Oh, Marcial Garcia-Rojo, Ermina Iljazovic, Oluseyi F Ajayi, Flora Duarte, Ashrafun Nessa, Leopoldo Tinoco, Marco A Duran-Padilla, Edyta C Pirog, Halina Viarheichyk, Hesler Morales, Valérie Costes, Ana Félix, Maria Julieta V Germar, Marisa Mena, Arzu Ruacan, Asha Jain, Ravi Mehrotra, Marc T Goodman, Luis Estuardo Lombardi, Annabelle Ferrera, Sani Malami, Estela I Albanesi, Pablo Dabed, Carla Molina, Rubén López-Revilla, Václav Mandys, Manuel E González, Julio Velasco, Ignacio G Bravo, Wim Quint, Michael Pawlita, Nubia Muñoz, Silvia de Sanjosé, F Xavier Bosch, ICO International HPV in Head and Neck Cancer Study Group
• Journal: Journal of the National Cancer Institute (J Natl Cancer Inst) Vol. 108 Issue 6 Pg. djv403 (Jun 2016) ISSN: 1460-2105 [Electronic] United States
• PMID: 26823521 (Publication Type: Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)
• Copyright: © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: [email protected].

Chemical References

• Biomarkers, Tumor
• CCND1 protein, human
• Cyclin-Dependent Kinase Inhibitor p16
• DNA, Viral
• Salivary Proline-Rich Proteins
• Tumor Suppressor Protein p53
• Cyclin D1

Topics

• Adult
• Aged
• Biomarkers, Tumor (analysis)
• Carcinoma, Squamous Cell (chemistry, 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
• Male
• Middle Aged
• Oropharyngeal Neoplasms (chemistry, virology)
• Papillomaviridae (genetics, isolation & purification)
• Papillomavirus Infections (complications, virology)
• Predictive Value of Tests
• Salivary Proline-Rich Proteins (analysis)
• Tumor Suppressor Protein p53 (analysis)