Effects Of Metformin On Head And Neck Squamous Cell Carcinoma: A Systematic Review

Objective: By the method of systematic review,we summarized the available literature associated with potential effects of metformin on head and neck squamous cell carcinoma(HNSCC),especially the antitumor effect of metformin,in an attempt to provide evidence for the future use of metformin in the treatment of head and neck cancer.Methods:The search strategies were formulated based on the principle of PICO.The related studies were searched from Cochrane Library,Pubmed,Embase and the Chinese Biomedical Literature Database.Retrieval of all documented articles about metformin and head and neck cancer both in and abroad was carried out.The searching results were screened according to the inclusion criteria and exclusion criteria.Cochrane collaboration bias risk assessment tool was used to evaluate the quality of the literature and to extract the basic information(according to the prepared form),and the results were analyzed and discussed.Results:After literature filteration,29 studies met the inclusion criteria and were used for qualitative analysis,which included 8 clinical studies and 22 basic researches(One of them includes both basic research and clinical research).Due to the unanticipated heterogeneity,the included literature did not conform to the condition to merge for a Meta analysis.Therefore,we could only use the method of qualitative systematic review analysis,which was divided into two parts:1 A total of 8 articles were included in the clinical study,including 6retrospective cohort studies and 2 case-control studies.The results from the present analysis showed that application of metformin could reduce rates ofthe local recurrence and metastasis of HNSCC,and improve the overall survival rate and disease-free survival rate.Individuals using metformin had a lower incidence of HNSCC than those not using metformin.2 A total of 22 articles were included in the basic study,all of which were performed in vitro and/or in vivo animal experiments.These results from the present analysis suggested that metformin alone and metformin with other traditional chemotherapy drugs both exhibited potential anti-tumor effects,such as inhibiting tumor cell proliferation,promoting cell apoptosis and inducing cell cycle arrest and regulating related gene and protein involved in carcinogenesis signal pathways.Although the research on effects of metformin on HNSCC is limited,the evidence from the present analysis suggests that metformin has a potential impact on head and neck cancer.The antitumor effect of metformin in cells and transplanted tumor models is confirmed,and its biological mechanisms are also disclosed to a certain extent.Conclusions:In this review,we collected the relevant research by retrospective method,elaborated the anti-tumor effects of metformin from the clinical and basic aspects.It is suggested that metformin has a good prospect for clinical application for the treatment of HNSCC.Although there are only a few studies have been conducted,the available evidence has shown that the effect of metformin on HNSCC is confirmed.