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Abstract
Purpose of Review
This study assesses the current state of knowledge of head and neck squamous cell carcinomas (HNSCC), which are malignancies arising from the orifices and adjacent mucosae of the aerodigestive tracts. These contiguous anatomical areas are unique in that 2 important human oncoviruses, Epstein-Barr virus (EBV) and human papillomavirus (HPV), are causally associated with nasopharyngeal and oropharyngeal cancers, respectively. Mortality rates have remained high over the last 4 decades, and insufficient attention paid to the unique viral and clinical oncology of the different subgroups of HNSCC.
Recent Findings
We have compared and contrasted the 2 double-stranded DNA viruses and the relevant molecular oncogenesis of their respective cancers against other head and neck cancers. Tobacco and alcohol ingestion are also reviewed, as regard the genetic progression/mutation accumulation model of carcinogenesis. The importance of stringent stratification when searching for cancer mutations and biomarkers is discussed. Evidence is presented for a dysplastic/pre-invasive cancerous phase for HPV+ oropharyngeal cancers, and analogous with other HPV+ cancers. This raises the possibility of strategies for cancer screening as early diagnosis will undoubtedly save lives.
Summary
Staging and prognostication have changed to take into account the distinct biological and prognostic pathways for viral+ and viral− cancers. Diagnosis of pre-cancers and early stage cancers will reduce mortality rates. Multi-modal treatment options for HNSCC are reviewed, especially recent developments with immunotherapies and precision medicine strategies. Knowledge integration of the viral and molecular oncogenic pathways with sound planning, hypothesis generation, and clinical trials will continue to provide therapeutic options in the future.
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Details

1 University Hospital OWL, University of Bielefeld, University Hospital Department of Otolaryngology & Head and Neck Surgery, Campus Klinikum Bielefeld Mitte, Bielefeld, Germany (GRID:grid.7491.b) (ISNI:0000 0001 0944 9128)
2 University Hospital OWL, Centre for Pathology and Molecular Oncology, Campus Klinikum Bielefeld, Bielefeld, Germany (GRID:grid.461805.e) (ISNI:0000 0000 9323 0964)
3 University Hospital OWL, Department of Clinical Oncology, Campus Klinikum Bielefeld, Bielefeld, Germany (GRID:grid.461805.e) (ISNI:0000 0000 9323 0964)