Relationships between the presence of HPV 16/18 DNA in peripheral blood lymphocytes and p16INK4a protein expression in human papillomavirus-associated neoplastic cervical lesions

• Main Authors: Ya-Wen Peng, 彭雅汶
• Other Authors: Huei Lee
• Format: Others
• Language: zh-TW
• Published: 2004
• Online Access: http://ndltd.ncl.edu.tw/handle/30087105479458993903

碩士 === 中山醫學大學 === 毒理學研究所 === 92 === 捌 英文摘要 Cervical cancer has been the major cause for cancer-related morbidity and mortality for females worldwide. The significant contribution of human papillomavirus to cervical carcinogenesis has also been intensively investigated, and many reports have shown that p16INK4a may serve as an early biomarker of cervical cancer since p16INK4a was up-regulated by E2F through Rb inactivation by HPV 16 E7. Our preliminary data showed that HPV DNA signals were detected in peripheral blood lymphocytes (PBL) of lung cancer and cervical cancer patients by in situ hybridization. In this study, we attempted to investigate the correlation between p16INK4a protein expression and human papillomavirus infection in PBL and tumor tissues from patients with high-grade squamous intraepithelial lesion (HSIL) or early invasive cervical cancer (EICC) to verify the presence of HPV DNA in PBL plays a crucial role in cervical carcinogenesis. Paired tissues and peripheral blood samples from 68 patients, including 36 HSIL patients and 32 EICC patients, were collected for studies. The presence of HPV type 16/18 DNA and E7 mRNA in tissue and PBL was examined by nested-PCR and PCR-RFLP, respectively. Results showed that the presence of HPV 16 and/or 18 DNA in tissues was significantly correlated with those in PBL from all cases (P = 0.005 for HPV 16, P = 0.022 for HPV 18 and P < 0.001 for HPV 16 or 18), especially those 26 patients with HPV DNA in both PBL and tissues. This result revealed that HPV infection in cervical tissues can be indirectly indicated by a direct detection of HPV DNA in blood circulation. Moreover, our data supported that HPV E7 mRNA expression was respectively correlated with Rb and p16 immunostainings in cervical tissues from patients with HSIL and EICC (P < 0.001). This result seemed to confirm the previous reports showing that p16 up-regulation may be mediated through Rb inactivation by HPV 16/18 E7. In addition, the positive p16 immunostaining was positively correlated with the presence of HPV 16 or 18 DNA in cervical tissues of HSIL (P < 0.001), but not in EICC. Interestingly, a positive correlation was also observed in PBL of HSIL (P = 0.044 for HPV 16, P = 0.009 for HPV 16 or 18), but still not in EICC. In conclusion, the present study clearly revealed the positive association between the presence of HPV 16 or 18 DNA in PBL and p16 overexpression in tissues of patients with cervical lesions.