Abstract
Epstein-Barr virus-positive nasopharyngeal carcinoma (EBV(+) NPC), and human papillomavirus-positive head and neck squamous cell carcinoma (HPV(+) HNSCC) are two distinct types of aggressive head and neck cancers with early age onsets. Their recently identified genomic landscapes by whole-exome sequencing (WES) clearly reveal critical roles of: (1) inflammation via NF-kB activation, (2) survival via PI3K aberrations, and perhaps (3) immune evasion via MHC loss in these cancers as summarized in this review. Immediate outcomes of these WES studies include the identification of potential prognostic biomarkers, and druggable events for these cancers. The impact of these genomic findings on the development of precision medicine and immunotherapies will be discussed. For both of these cancers, the main lethality comes from metastases and disease recurrences which may represent therapy resistance. Thus, potential curing of these cancers still relies on future identification of key genomic drivers and likely druggable events in recurrent and metastatic forms of these intrinsically aggressive cancers of the head and neck.
Highlights
The global incidence of head and neck cancer has recently climbed to ~0.74 million new cases per year based on 2015 cancer statistics [1]
With the upper respiratory tract being the first site of contact with environmental carcinogens including certain chemicals, air pollutants [2], as well as oncogenic viruses [3,4], the incidence of head and neck cancer will probably continue to rise in the decade
We showed that patients with Epstein-Barr virus (EBV)(+) Nasopharyngeal carcinoma (NPC) tumors harboring less somatic mutations were found to be associated with better overall survival and disease-free survival than those with higher mutational rates in their tumors [43]
Summary
The global incidence of head and neck cancer has recently climbed to ~0.74 million new cases per year based on 2015 cancer statistics [1]. These findings implicate a clear etiologic contribution by HPV via APOBEC-mediated mutagenesis, which is different from the defective DNA mismatch repair signature contributed by EBV in NPC These mutational signatures of EBV(+) NPC and HPV(+) HNSCC appear to reflect major differences in viral or environmental carcinogen-driven mutational forces for these cancers. As far as MHC Class I/II genes are concerned, both of these virally associated cancer types, as well as HPV(−) oropharyngeal cancer, all showed relatively higher rates of mutations of MHC Class I gene than that of MHC Class II genes (Figure 1) This suggests that MHC Class I gene defects can be more important and relevant for both viral and non-viral mediated tumorigenesis or disease progression. It is believed that the ultimate answers for curative treatments do lie partially on these important genomic information, as recurrent and metastatic forms of these tumors are mostly fatal
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