Rising prevalence rates of high-risk human papillomaviruses (hrHPV) infection in oropharyngeal carcinoma (up to 80 %) have been reported in North America and Scandinavia. We have analysed 424 German and 163 Brazilian head and neck squamous cell carcinomas (HNSCC) from the oral cavity (OSCC), oropharynx (OPSCC) and hypopharynx (HPSCC) using p16 immunohistochemistry, HPV DNA PCR and sequencing, hrHPV DNA in situ hybridisation (ISH) and hrHPV E6/E7 RNA ISH. In the German series, 52/424 cases (12.3 %) were p16-positive/hrHPV-positive (OSCC 3.8 % [10/265], OPSCC 34.4 % [42/122], HPSCC 0 % [0/37]). In addition, there were 9 cases that were p16-positive/hrHPV-negative (5 OPSCC and 4 OSCC). In the Brazilian series, the overall hrHPV DNA prevalence by PCR was 11.0 % ([18/163]; OSCC 6 % [5/83], OPSCC 15.5 % [11/71], HPSCC 22.2 % [2/9]). Ten of these cases were hrHPV-positive/p16-positive. The remaining 8 hrHPV-positive/p16-negative cases were also negative in both ISH assays. Furthermore, 5 p16-positive/hrHPV-negative cases (2 OPSCC and 3 OSCC) were identified. In both series, HPV16 was by far the most common HPV type detected. We confirm that regardless of geographical origin, the highest hrHPV prevalence in HNSCC is observed in oropharyngeal carcinomas. The proportion of HPV-associated OPSCC was substantially higher in the German cohort than in the Brazilian series (34.4 vs. 15.5 %), and in both groups, the prevalence of hrHPV in OPSCC was much lower than in recent reports from North America and Scandinavia. We suggest, therefore, that it may be possible to define areas with high (e.g. USA, Canada, Scandinavia), intermediate (e.g. Germany) and low (e.g. Brazil) prevalences of HPV infection in OPSCC.
HPV Head and neck squamous cell carcinoma Oropharyngeal squamous cell carcinoma Oral squamous cell carcinoma p16
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The present work was performed in partial fulfilment of the requirements for the Doctor of Medicine degree from the Friedrich-Alexander-Universität Erlangen-Nürnberg, Germany (FH), and during the Ph.D. Program in Cell and Molecular Biology from Instituto Oswaldo Cruz, Rio de Janeiro, Brazil (MOS). It was supported by grants from the Berliner Krebsgesellschaft (NIFF 201004), the Wilhelm Sander Foundation (2012.029.1), the Manfred Stolte Foundation and the INCT para controle do câncer (grants CNPq 573806/2008-0 and FAPERJ E-26/110.432/2010) (Brazil). Mário Barros was supported by the Alexander von Humboldt Foundation. MOS was supported by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), Brazil, and the Deutscher Akademischer Austausch Dienst (DAAD), Germany.
Conflict of interest
The authors declare that they do not have any conflicts of interest.
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