乳腺癌作为女性发病率最高的恶性肿瘤其病因尚未明确。HPV感染导致宫颈癌的发生已被公认，但其是否同样为乳腺癌的致病原因仍不明确。我们前期研究发现新鲜乳腺癌中组织存在HR-HPV的感染，40%的感染标本中可发现挖空细胞，组织芯片检测发现HPV感染可能通过影响P53及P21基因导致细胞恶性转化。本课题从临床入手，应用HC2、PCR及组织芯片免疫组化染色结合的技术在临床标本中筛选乳腺癌相关HR-HPV亚型。克隆并构建携带乳腺癌相关HR-HPV DNA序列的重组逆转录病毒载体，感染人正常乳腺上皮细胞MCF-10A，证实乳腺癌相关HR-HPV能使乳腺上皮细胞出现形态学改变，产生挖空细胞，发生恶性转化，并通过基因检测探讨其可能发生的机制。本研究不仅筛选出可能导致乳腺癌发生的乳腺癌相关的HR-HPV亚型，同时还能为阐明HPV感染可导致乳腺癌发生及其分子机制奠定基础，为乳腺癌的预防和治疗提供新思路。

Breast cancer is a kind of the women malignant tumor with high mortality and morbidity, but the mechanism behind still remains unclear. It has been recognized that HPV infection can cause cervical cancer. However, weather HPV infection can also cause breast cancer is not clear. Our previous study has found that HR-HPV infection also existed in fresh tissues of breast cancer specimens. We found koilocytes in about 40% of the infected mammalian tissue. Tissue microarray assay showed that HPV infection may lead to malignant transformation of cells by affecting P53 and P21 gene. This project aims to use molecular biology techniques such as HC2, PCR, and tissue microarray immunohistochemical staining to identify breast cancer related HR-HPV subtype in clinical mammalian specimens, including cloning and construction of recombinant retroviral vector carrying breast cancer related HR-HPV DNA sequence, MCF-10A infection of human normal mammary epithelial cells, confirming that the HR-HPV infection can cause morphological changes of mammary epithelial cells, produce koilocytes, promoting malignant transformation and clarifying its possible mechanism through genetic testing. The purpose of this study include: 1) Identification of HR-HPV subtype that can induce breast cancer. 2) Elucidating if HPV infection can lead to the occurrence of breast cancer and its molecular mechanism. 3) Provides new perspective for the prevention and treatment of breast cancer.