HPV阳性头颈鳞癌对放疗敏感，其机制仍不明确，可能与病毒基因E6有关。预实验提示miRNA-27a在HPV阳性头颈鳞癌中的表达明显高于HPV阴性头颈鳞癌，且受E6的正向调控；靶基因预测发现SMG-1可能是miRNA-27a的靶基因；且SMG-1与HPV密切相关，并与头颈鳞癌的放疗敏感性相关。在上述基础上，提出科研假设：病毒基因E6通过DGCR8调控miRNA-27a的表达，miRNA-27a则通过靶基因SMG-1增强HPV阳性头颈鳞癌的放疗敏感性。本研究以头颈鳞癌组织、HPV阳性及阴性头颈鳞癌细胞株及其荷瘤动物作为研究对象，采用基因转染和（或）RNA干扰改变E6、DGCR8、miRNA-27a和SMG-1的表达水平，探讨上述分子之间的调控关系及其对放疗敏感性的影响。本课题不仅阐述HPV阳性头颈鳞癌对放疗敏感性的机制，并为miRNA-27a作为头颈鳞癌治疗靶点提供依据。

HPV-positive head and neck squamous cell carcinoma (HNSCC) is sensitive to radiotherapy, however, the mechanism is still unknown, which is possibly related to the regulation of virogene E6. Our preliminary studies found that miRNA-27a expression was significantly higher in HPV-positive HNSCC than that in HPV-negative HNSCC, which was also upregulated by E6. The miRNA targets-prediction analysis indicated that SMG-1 was a possible target-gene of miRNA-27a, and SMG-1 was closely related with the infection of HPV and the radiosensitivity in HNSCC. As mentioned above, we speculate that E6 could regulate miRNA-27a expression by affecting DGCR8, and miRNA-27a could enhance the radiosensitivity of HPV-positive HNSCC through targeting SMG-1. In this research, we take HNSCC tissues, HPV-positive and HPV-negative HNSCC cell lines, and xenografts as the study objects, we aim to explore the relationships between E6, DGCR8, miRNA-27a and SMG-1 as well as their effects on radiosensitivity, through changing the expression of these molecules by gene transfection and (or) RNA inference. In summary, this research is expected to demonstrate the mechanism of radiosensitivity in HPV-positive HNSCC, and to evaluate the possibility that miRNA-27a is used as a novel therapy target for HNSCC.