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.

• MeSH
• cyklin D1 analýza   MeSH
• DNA virů izolace a purifikace   MeSH
• dospělí MeSH
• genotyp MeSH
• imunohistochemie MeSH
• infekce papilomavirem komplikace   virologie   MeSH
• inhibitor p16 cyklin-dependentní kinasy analýza   MeSH
• lidé středního věku MeSH
• lidé MeSH
• lidský papilomavirus 16 izolace a purifikace   MeSH
• mezinárodní spolupráce MeSH
• nádorové biomarkery analýza   MeSH
• nádorový supresorový protein p53 analýza   MeSH
• nádory hlavy a krku virologie   MeSH
• nádory orofaryngu chemie   virologie   MeSH
• Papillomaviridae genetika   izolace a purifikace   MeSH
• prediktivní hodnota testů MeSH
• průřezové studie MeSH
• senioři MeSH
• slinné proteiny bohaté na prolin analýza   MeSH
• spinocelulární karcinom chemie   virologie   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH