Association between DeltaNp73 expression and HPV infection in cervical cancer

Abstract

BACKGROUND: Cervical cancer is a common genital tract cancer in women. Persistent infection of high-risk Human papillomavirus (HPV) is recognized as a necessary cause of cervical cancer. The high-risk HPV encodes two oncoproteins E6 and E7, which disrupt the tumour suppressive functions of p53 and pRb. p73 is a member of p53 tumor suppressor family and shares both structural homology and functional similarities with p53. It exists as two major forms: transactivation active TAp73 isoform and dominant negative DeltaNp73 isoform, with opposing pro- and anti-apoptotic functions, respectively. Our previous study has demonstrated the differential expressions of p73 and its prognostic significance in cervical cancer. As HPV is the important pathogen for the development of cervical cancer, the relationship between p73 and HPV warrants further study. OBJECTIVE: To assess the association between the expression of DNp73 and HPV16/18 infections in cervical cancer. METHODS: Totally 118 cervical cancers and 113 normal cervical tissues were recruited and paraffin sections were prepared for immunohistochemical staining of DNp73. Genomic DNAs were extracted from cervical cancer tissues for detection of HPV infection. RESULTS: The expression of DNp73 was significantly higher in cervical cancer cells than that in normal cervical epithelial cells (p<0.001). HPV16 and HPV18 infections were detected in 48.3% and 21.2% of cancer patients, respectively. Cancers with HPV infection tended to have higher DNp73 expression. Most of HPV16 positive cancers showed significantly higher DNp73 expression than HPV16 negative cancers (p=0.035). Conclusions: Oncogenic DNp73 was over-expressed in cervical cancer, especially in HPV16 infected cells. The underlying mechanism is under investigation.