Exploring the association of human papillomavirus with carcinogenesis or prognosis of nasopharyngeal carcinomas

• Main Authors: Hsuan-PeiWei, 魏瑄貝
• Other Authors: Wu-Chou Su
• Format: Others
• Language: en_US
• Published: 2011
• Online Access: http://ndltd.ncl.edu.tw/handle/24186505281214573913

碩士 === 國立成功大學 === 分子醫學研究所 === 99 === Nasopharyngeal carcinoma (NPC), a head and neck neoplasm derived from epithelium of nasopharynx, is endemic in the Arctic, the Middle East/North Africa, southern China, the Middle/ Southeast Asia, including Taiwan. Various risk factors are involved in carcinogenesis of NPC, such as genetic, environment, and viral (Epstein-Barr virus) factors. On the other hand, human papillomavirus (HPV), especially high-risk HPVs, play a crucial role in cervical cancer development. The HPV oncogenesis mainly due to the insertion of E6 and E7 genes into host genomes, leading to instability of host genomes, inhibition of cell cycle regulation, and consequently cell transformation. Previous investigations indicated that HPV genomes had been detected not only in cervical cancer but also in NPC specimens. However, while studies showed that HPV genome can be detected in NPC specimens, the correlations between HPV and NPC occurrence are still elusive. For instance, even if the PCR results suggested that the HPV genomes exist in a specimen, it can not distinguish whether the HPV genome is located in NPC cells or in the surrounding normal cells. Therefore, to clarify these issues, we first studied the prevalence of HPV genomes in 43 NPC and 40 control nasopharyngeal specimens using commercial HPV genechips. In addition, we performed high-risk HPV in situ hybridization to localize high-risk HPV genomes in another 46 archival NPC specimens. Correlation between tumor HPV status and clinical parameters of these patients was subsequently analyzed. We found that HPV cab be equally detected in both NPC (34.9%, 15/43) and control (42.5%, 17/40) specimens. Most (89.5%, 17/19) of the high risk HPV-positive NPC neoplasm showed an unique cytoplasm/perinuclear staining pattern, which is different from the dot/punctate nuclear staining pattern indicating HPV DNA integration as in cervical cancers. Besides, high-risk HPVs were not always clonally proliferated in NPC cells during the process of lymph node metastasis. Also, tumor high risk HPV status did not correlate with gender, WHO subtype or prognosis of these patients. Patients whose tumor had high-risk HPVs are elder than those without HPVs, which is also epidemiologically different from HPV-related oropharyngeal cancers. Taken together, our study did not support that high risk HPV as a crucial viral carcinogenic factor of NPC in Taiwan.