| Summary: | 博士 === 國防醫學院 === 生命科學研究所 === 99 === Infection of certain high-risk type of human papillomavirus (HPV) is considered as carcinogen of many kinds of cancer, such as carcinoma of the cervix, oral cavity and anus. This thesis consists of three parts to investigate molecular epidemiology of HPV infection that include Part 1: Comparison of HPV detection by two methods in vaginal samples; Part 2: A cohort study of HPV infection in cervix and adenocarcinoma of rectum and recto-sigmoid junction and Part 3: Molecular epidemiology of human leukocyte antigen (HLA) class II with the natural history of high risk HPV infection and the cervical intraepithelial neoplasia. The participants living in seven Taiwan townships were enrolled during the period from 1991 to 1992 in Part 2 and 3, and from 2008 to 2009 in Part 1. Regarding Part 2 and 3, the cases of newly developed diseases were ascertained through computerized data-linkage with profiles of National Cancer Registry, National Death Certification Registry or the National Cervical Neoplasia Screening Registry in Taiwan as of December 31, 2006. Association between HLA and natural history of HPV only focused on major high-risk types (HPV types 16, 18, 52 and 58) in Part 3.
The purpose of Part 1 was to evaluate the performance of PCR-based HPV Blot in comparison with FDA-approved HCII test for detection of 13 high-risk HPV types. The kappa values of method reproducibility were 0.6233 and 0.7036 in HCII test and HPV Blot, respectively, and the positive rates were 13.4% by HCII test and 15.1% by HPV Blot. The concordance rate between two methods was 93.58% with a kappa value of 0.7374. Our long-term follow-up study in Part 2 found an increased risk of adenocarcinoma of the rectum and recto-sigmoid junction for women with cervical cells infected with HPV types other than 6 and 11 at study entry, showing hazard ratio (HR) (95% confidence interval [CI]) was 2.2 (1.0-4.6) after adjustment for age and body mass index.
In Part 3, there was a significant association between DRB1*0403 allele and high HPV18 viral load over 1,000 copies in 50 ng of total DNA prepared from cervical cells at study entry, showing odds ratio(OR) (95% CI) was 7.2 (2.0-25.2). After adjustment for age and viral load at study entry, haplotype HLA-DRB1*0405-DQA1*0301-DQB1*0302 was significantly associated with persistent HPV18 infection, showing OR (95% CI) was 13.3 (1.7-105.9). DRB1*0403 allele was also associated with a significantly increased risk of high-grade squamous intraepithelial lesion (SIL) or cancer, showing a multivariate-adjusted hazard ratio (95% CI) of 18.1 (2.6-128.5). Among participants with infection of HPV types 16, 52 or 58 at study entry, DRB1*0301 was significantly associated with persistent infection of those high-risk HPV types after multiple comparison correction, showing OR (95% CI) was 0.2 (0.1-0.6). After adjustment for persistent infection of HPV types 16, 52 or 58, DRB1*0407, DQA1*0102, DQB1*06 allele and HLA-DRB1*DR2-DQA1*0102-DQB1*0601 haplotype were significantly associated with the development of low-grade SIL or worse or cervical cancer during the follow-up, showing HR (95% CI) were 3.5 (1.0-11.9), 2.1 (1.1-4.1), 2.1(1.1-4.0) and 3.4 (1.4-8.2), respectively.
There are three major findings in present dissertation. Firstly, our study demonstrated equivalent performance of HPV Blot with HCII test for detection of 13 oncogenic HPV DNA in vaginal swab samples; secondly, women with cervical cells infected with HPV types other than 6 and 11 had an increased risk of consequent adenocarcinoma of the rectum and recto-sigmoid junction; and lastly, various HLA class II alleles/haplotypes may play different roles at various stages in the progression from viral load and persistence to oncogenesis of different HPVs in Taiwanese women.
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