Abstract
In the last decades, the human papillomavirus (HPV) emerged as an etiological cause of head and neck squamous cell carcinoma (HNSCC), especially in the oropharynx. The role of two intracellular DNA sensors, which belong to the PYHIN family (interferon-inducible protein 16 (IFI16) and absent in melanoma 2 protein (AIM2)), has been analyzed in relation to HPV infection and head and neck carcinogenesis. In particular, IFI16 and AIM2 expression depends on HPV infection in HNSCC. They represent viral restriction factors and are key components of the intrinsic immunity activated against different viruses, including HPV. This review analyzed and summarized the recent findings about the role of PYHIN proteins in HPV+ and HPV− HNSCC.
Highlights
Head and neck squamous cell carcinoma (HNSCC) represents the sixth most prevalent type of cancer, including about 6% of all cases of tumors worldwide
- Upregulation of interferon-inducible protein 16 (IFI16), APOBEC3A, and APOBEC3B in human papillomavirus (HPV)+ HNSCCs; - absent in melanoma 2 protein (AIM2) gene expression levels are predominantly unchanged in HPV+ HNSCCs compared to their HPV− counterparts, in which AIM2 is predominantly upregulated; - Positive correlation between IFI16 and APOBEC3A expression in HPV+ HNSCCs; - Upregulation of IFI16 correlates with lower occurrence of nodal metastases in HPV−
From the literature reviewed above, it appears that the different molecular profiles and prognoses of HPV− vs. HPV+ HNSCCs may be partly ascribed to the emerging etiopathological role played by PYHIN proteins in these tumors
Summary
Head and neck squamous cell carcinoma (HNSCC) represents the sixth most prevalent type of cancer, including about 6% of all cases of tumors worldwide. The PYRIN and HIN domain(PYHIN) family consists of five interferon-inducible proteins that have recently emerged as intracellular DNA sensors. These include the interferon-inducible protein 16 (IFI16), absent in melanoma 2 protein (AIM2), myeloid cell nuclear differentiation antigen (MNDA), pyrin and HIN domain family 1 (PYHIN1 or IFIX), and PYRIN domain (PYD)-only protein 3 (POP3) [5,6]. We will describe our current understanding of the emerging role of PYHIN proteins in HNSCC pathogenesis, focusing in particular on IFI16 and AIM2, whose expression depends on HPV infection [8,9,10,11,12,13,14]
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