Differential Impact of IL-10 Expression on Survival and Relapse between HPV16-Positive and -Negative Oral Squamous Cell Carcinomas

Abstract

Human papillomavirus (HPV) is a risk factor in a subset of oropharyngeal cancer; however, the contribution of HPV in the malignancy of oral squamous cell carcinomas (OSCC) is not fully understood in Taiwanese. Herein, 61 patients with no risk factors and 117 patients with one or more risk factors were enrolled in this study. HPV16/18 infection rate in non-smokers, non-drinkers and non-betel quid chewers was higher than their counterparts. The development of HPV-infected cancer has been shown to be associated with interleukin-10 (IL-10) expression. To this end, IL-10 mRNA expression in OSCC tumors was evaluated by real-time RT-PCR. Data showed that HPV-positive patients had higher IL-10 mRNA levels than in HPV-negative patients. Kaplan-Meier and Cox-regression analysis indicated that the prognostic significance of IL-10 mRNA on overall survival and relapse free survival was only observed in HPV-positive OSCC, but not in HPV-negative OSCC. Mechanistically, the elevation of IL-10 by E6 was responsible for increased colony formation and migration capability in OSCC cells. Therefore, we suggest that IL-10 induced by E6 promotes cell growth and migration capability and consequent poor survival and relapse in HPV-positive OSCC.

Salivary Immunosuppressive Cytokines IL-10 and IL-13 Are Significantly Elevated in Oral Squamous Cell Carcinoma Patients

“…These results are consistent with other studies regarding IL-10 status in OSCC, although these studies have analyzed the IL-10 protein and mRNA levels in OSCC tumor tissues (35,36). Moreover, Hamzavi et al studied and compared the tissue expression, serum, and salivary levels of IL-10 and found no correlation among them in either controls or OSCC subjects (30), which reflects different levels of regulation of this cytokine in different compartments of the body.…”

Clinical relevance of immune parameters in the tumor microenvironment of head and neck cancers

“…IL‐10, a cytokine with immunosuppressive qualities, has been linked with HPV status in oral cavity SCC, whereas IL‐10 mRNA expression correlated with HPV‐positive oral cavity SCC tumors. Higher expression in the HPV‐positive group was associated with worse OS and DFS, whereas there was no correlation in the HPV‐negative group . Macrophage migration‐inhibitory factor (MIF) is a proinflammatory mediator expressed by various cell types.…”

Role of tumour-associated macrophages in oral squamous cells carcinoma progression: an update on current knowledge

“…IL-10 is a cytokine that modulates immune responses, causing suppressive regulatory T cell differentiation that contributes to tumour cell proliferation [55]. Since persistent viral infection promotes IL-10 upregulation and impaired T-cell responses [56], it is believed that this cytokine plays a critical role in human papilloma virus (HPV)- and Epstein-Barr virus (EBV)-related OSCC progression [57, 58]. Moreover, IL-10 indicates poor outcomes in HPV-unrelated OSCC, especially when INF-γ secretion [59] and transforming growth factor beta 1 (TGF-β1) levels [60] are low.…”

“…However, this methodology is time and cost demanding and probably unfeasible in clinical situations, especially in less developed countries where the prevalence of OSCC is higher. However, from the available evidence, it is possible to suggest that screening for TAM markers in oral biopsies certainly may contribute to accurate assessment of OSCC behaviour, being a valuable tool for the estimation of prognosis in cases related and unrelated to viral infection [57–60, 68]. …”