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

J Natl Cancer Inst

Cancer Epidemiology Research Program, Catalan Institute of Oncology (ICO), IDIBELL, L'Hospitalet de Llobregat, Catalonia, Spain (XC, LAle, BQ, ST, OC, MM, IGB, SdS, FXB); CIBER Epidemiología y Salud Pública (CIBERESP), Madrid, Spain (XC, LAle, SdS); Hospital Sant Pau, Barcelona, Spain (MQ, XL); German Cancer Research Center (DKFZ), Heidelberg, Germany (GHale, DH, MPa); Hospital Clínic, University of Barcelona, Spain (LAlò); Department of Pathology, University Hospital Tuebingen, Tuebingen, Germany (TB); Department of Otorhinolaryngology, Faculty of Medicine and Dentistry, Warsaw Medical University, Czerniakowski Hospital, Warsaw, Poland (TS); Hospital General de l'Hospitalet, L'Hospitalet de Llobregat, Barcelona, Spain (MA); Instituto Nacional de Cancerología, Bogotá, Colombia (ECa, NM); Universidad Nacional de Colombia, Bogotá, Colombia (ECa); Insituto Oncológico del Oriente Boliviano (IOOB), Laboratorio Privado de Patología Oncos, Santa Cruz, Bolivia (ECl); Manchester Royal Infirmary, Manchester, UK (GHall); The Fingerland Department of Pathology, Charles University Faculty of Medicine and University Hospital, Hradec Kralove, Czech Republic (JL); University of Ljubljana, Faculty of Medicine, Institute of Microbiology and Immunology, Ljubljana, Slovenia (MPo); Regina Elena National Cancer Institute, Rome, Italy (MB); Instituto de Investigaciones en Ciencias de la Salud, Universidad Nacional de Asunción, Asunción, Paraguay (EK); Institute of Head and Neck Studies and Education, University of Birmingham, Birmingham, UK (HMe); Department of Social and Preventive Medicine, Université de Montréal, Montreal, Canada (CN); DDL Diagnostic Laboratory, Rijswijk, the Netherlands (NG, WQ); Pathology Department, Hospital del Mar IMIM, Universitat Pompeu Fabra, Barcelona, Spain (BL); Laboratorio Clínico y Molecular, Hospital SOLCA, Guayaquil, Ecuador (JCRC); Hospital de Oncología Centro Médico Nacional Siglo XXI, IMSS Mexico, D.F., Mexico (IAC); Yeouido St. Mary's

Published: June 2016

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.

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http://dx.doi.org/10.1093/jnci/djv403DOI Listing

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