a.HPVと子宮頸部癌基盤的研究成果の臨床的展開へ(4.腫瘍)

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Cancer is a multistep process withthe clinical invasive tumor being the final stage in a long saga of cellular genetic events. Invasive cancer of the cervix is preceded by histologically distinct intraepithelial lesions (CINs). These precursor lesions are closely associated with HPV infection. Until now, more than 80 types of HPV were identified and sequenced. Among them, HPV types 16, 18, and other high-risk types such as HPV 31, 33, 39, 45, 51, 56, 58 and 59 are closely involved in the development of CINs and cervical cancer. Oncoproteins E6 and E7 of high-risk HPVs such as 16 and 18 bind directly to p53 and Rb proteins, respectively and block their anti-oncogenic function, allowing the uncontrolled growth of the HPV infected cells. The recent research has shown that telomerase activation by E6 and inactivation of Rb/p16 pathway by E7 are essential for immortalization of epithelial cells. HPV infections is the major risk factor for cervical neoplasia, although the full celltransformation requires the additional genetic changes on the target cells including activation of oncogenes, and/or inactivation of anti-oncogenes and mismatched DNA repair genes. Prevention of HPV infection is the first step protection from cervical cancer. HPV is sexually transmitted in ordinary life and is detected around 10% of normal females. Many epidemiologic studies have shown a strong association of high risk HPV types with high-grade CINs integrated in host DNA with highrisk HPVs genomes mostly likely progress toward upper stage in oncogenesis. Therefore, high-grade CIN or even low-grade CIN with high-risk HPV should be aggressively treated by a surgical technique. Pap smear test has been utilized in gynecologic field as a cancer screening test for many years with furitful results. Additional application of HPV test using a conventional typing method with high sensitivity/specificity in practical medicine may reduce the cancer-death more and also redure the cost. The development of successful HPV-specific vaccines may offer an attractive alternative to existing screening and treatment programs for cervical cancer in near future.
社団法人日本産科婦人科学会の論文
2000-08-01

a.HPVと子宮頸部癌基盤的研究成果の臨床的展開へ(4.腫瘍)

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