Human-papillomavirus- (HPV-) positive oropharyngeal squamous cell carcinomas (OPSCC) are reported to be more responsive to treatment and to be related to a favorable prognosis compared with non-HPV carcinomas. However, the molecular basis of the responsiveness is unclear. Interferon inducible IFI16, which is implicated in the control of cell growth, apoptosis, angiogenesis, and immunomodulation in various types of cancers, is reported to be frequently expressed in the HPV-positive head and neck SCC and to correlate with a better prognosis. In this study, we hypothesized that HPV related OPSCC expresses IFI16 resulting in favorable prognosis. To clarify the relationship between the prognosis of HPV related OPSCC patients and IFI16 status, we examined immunohistologically the pretreatment specimens of OPSCC for the expression of p16 as a surrogate marker of HPV infection and IFI16. We could not show that the expression of IFI16 is associated with that of p16. There was no significant difference in the survival rate between IFI16 positive and negative groups. Patients with p16 negative tumor exhibited worse survival rate regardless of IFI16 status. In this limited case series, we could not conclude that IFI16 expression is altered in p16 positive OPSCC and that it would be a new predictive marker or a useful therapeutic tool. 1. Introduction Mucosal human papillomavirus (HPV) infections are well known to associate with invasive carcinomas of cervix and anogenital region. Recently, HPV has been found to be etiologically involved in 20% to 25% of head and neck squamous cell carcinoma (SCC), mostly in the oropharynx [1]. HPV-positive oropharyngeal cancers are reported to be more responsive to treatment and to show a favorable prognosis compared with non-HPV carcinomas [2]. However, the molecular basis of the responsiveness is unclear. IFI16 is a member of the Interferon- (IFN-) inducible HIN200 gene family which can be induced by IFN stimulation followed by several intracellular signaling cascades. The family includes a group of human (IFI16, IFIX, MNDA, and AIM2) and mouse (Ifi202a, Ifi202b, Ifi203, Ifi204, and D3/Ifi205) genes and they mediate the necessary biological responses [3]. These proteins share a partially conserved repeat of 200 amino acid residues (the HIN-200 domain) towards the C-terminus, which allows these proteins to bind dsDNA. Most p200-family proteins also contain a homotypic protein-protein interaction PYRIN domain (PYD) in the N-terminus [4]. IFI16 is implicated in the control of cell growth, apoptosis, angiogenesis, and
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