| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2006: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 2005: ¥2,000,000 (Direct Cost: ¥2,000,000)
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| Research Abstract |
As a result of multi-institutions collaborative investigation intended to elucidate the natural history by observating CIN1/2, it developed that there were two steps by the process during carcinogenesis of CIN1/2. The study subjects consisted of 570 women aged 54 or younger with cytologically and histologically confirmed CIN 1/2. CIN cases included 479 CIN 1 and 91 CIN 2. The median follow-up time was 38.1 months. The 570 subjects were divided into 361 (63.3%) patients with regression, 172 (28.6%) patients with persistence and 46 (8.1%) patients with progression. The median regression time was 6.5 months and the median progression time was 17.9 months, suggesting that regression is an early event and progression is a late event in the national history of CIN 1/2. Thus, the first step is a step to persist without regression of the CIN1/2 within two years usually disappearing. The second step is the step that persisted CIN1/2 which continued progresses to CIN3. We used hazard ratio after
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adjustment of Age, CIN grade and HPV category to evaluate various prognostic factors, because the three factors were closely associated with both regression and progression in the univariate analysis. Age, CIN grade, HPV risk category, smoking, marital status, and number of sexual partners were significantly associated with CIN persistence, whereas CIN grade, HPV risk category and HLA class II allele (HLA DRB1*1302) had significant association with CIN progression.
In such a background we paid attention to the type of HPV and the haplotype of the HLA Class I antigen in elements of the uterine cervix cancer.
It is obvious that high-risk HPV infection is a direct trigger in the carcinogenesis of uterine cervix cancer, but evasion from virus immunity and tumor immunity by the host is indispensable in carcinogenesis process. These immune mechanism due to cell-mediated immunity through the T lymphocyte, and co-existence of HLA class I molecules and the HPV specific peptide is important for this system. The complex of HLA class I molecules with peptide consisting of around 9-10 amino acids, is recognized as an antigen by a T lymphocytes. The binding affinity of the peptide is HLA type specific, so that the immune response depends on the difference of the HLA haplotypes.
13 kinds of cell lines, which were derived from cervical cancer, were analysed both HPV and HLA typings. HPV16 was detected by seven lines of those, and HPV18 was detected by three, and it was not detected from one. Three of seven HPV16 positive lines were positive for A*1101 and five of these positive for A*2401, but did not accumulate the HLA of seven HPV16 positive lines in a specific haplotype in B, C locus. The distribution in which locus did not have regional control and significant difference. About half in HLA A, B locus and about two-thirds in C locus were coverd by these seven HPV16 positive cell lines, A susceptibility of the cervical cancer by the difference of the HLA might be identified in future by comparing the HLA distribution of the uterine cervix cancer patient of the specific HPV (especially HPV16) positive with normal regional control. Less
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