人類乳突病毒與子宮頸癌之分子流行病學研究

Abstract

中文摘要 研究一 台灣婦女感染人類乳突病毒的型別盛行率及其決定因子 背景：人類乳突病毒感染是子宮頸癌的必要因子，但是台灣婦女感染人類乳突病毒的型別盛行率及其決定因子的相關研究卻相當缺少。 方法：本橫斷調查之研究對象係選自1991-1992年間在台灣七鄉鎮市所收案的5487名婦女，利用聚合酵素連鎖反應及基因晶片雜交法檢測子宮頸細胞中的人類乳突病毒DNA 並加以定型，再採用邏輯式迴歸分析 (logistic regression)計算危險對比值 (odds ratio, OR) 及其95%信賴區間 (confidence interval, CI)。 結果：(薏竹: 請加入盛行率資料) 婦女感染人類乳突病毒的決定因子，包括第一次性經驗年齡、終生性伴侶數目、子宮內避孕器的使用、保險套的使用以及身體質量指數 (BMI)。 結論：台灣婦女感染人類乳突病毒的盛行率相當高，而其相關因子多半和性行為有關，加強民眾安全性行為的衛生教育，將可預防人類乳突病毒之感染。

研究二 人類乳突病毒16型DNA與血清標記與子宮頸癌之相關研究 背景：第16型人類乳突病毒是最常被探討的高危險人類乳突病毒之一，其生物標記又分成DNA及血清標記兩種，過去的研究多半只探討單一標記與罹患子宮頸癌危險性的相關，本研究同時探討第16型人類乳突病毒DNA與血清標記與子宮頸癌之相關。 方法：本重疊病例對照研究，包括從收案兩年後到2002年間，新發病的43名子宮頸癌原位癌以及侵襲癌病例，以及以年齡、居住地區、採檢時間配對的200名對照組婦女。利用聚合酵素連鎖反應及基因晶片雜交法檢測子宮頸細胞中的第16型人類乳突病毒DNA，利用酵素免疫法測定血清抗體，並以條邏輯式迴歸分析，計算發生子宮頸癌的危險對比值(odds ratio, OR)以及95%信賴區間(confidence interval, CI)。 結果：第16型人類乳突病DNA和抗體陽性都是對子宮頸癌的危險因子，其危險對比值(95%信賴區間)分別為25.0 (6.9-91.5) 以及6.3 (1.3-31.6)。在控制高危險型人類乳突病毒DNA陽性狀況後，只有教育程度和使用口服避孕藥是發生子宮頸癌的共同因子。 結論：第16型人類乳突病DNA和抗體陽性都是對子宮頸癌的危險因子。

Abstract Part I: Type-specific prevalence and determinants of Human papillomavirus infection among women in Taiwan Background：Infection with Human papillomavirus (HPV) is a necessary cause of cervical cancer. However, there were few studies to investigate the prevalence and determinants of HPV infection among women in Taiwan. Methods：In this cross-sectional survey, we enrolled 5487 women aged 30-64 years old from seven townships in Taiwan. Cervical cells collected at enrollment were tested for HPV genotypes by polymerase chain reactions and genechip hybridization. Logistic regression models were used to estimate odds ratio (OR) with its 95% confidence interval (CI) for each determinant of HPV infection. Result：The overall age-adjusted prevalence of HPV infection was 12.9%. Prevalence of HPV infection was significantly associated with the age at first sexual intercourse, number of lifetime sexual partners, use of intrauterine device, use of condom and body mass index. Conclusions：The prevalence of HPV infection is relatively high among women in Taiwan. As most determinants of HPV infection are related to sexual behavior, comprehensive health education on safe sexual activities is highly recommended.

Part II: Associations between cervical cancer and biomarkers of HPV type 16 infection Background：HPV type 16 (HPV 16) was the most important high risk type of HPV. Biomarkers of HPV 16 infection include HPV DNA in cervical cells and antibodies against HPV 16 (anti-HPV 16) in serum, but there were few studies to investigate the combined effects of these two biomarkers on cervical cancer. Methods：This nested case control study included 43 cases of newly diagnosed cervical cancer (including carcinoma in situ and invasive carcinoma) and 200 unaffected controls matched with cases on age, residential township and date at enrollment. Cervical cells collected at enrollment were tested for HPV genotypes by polymerase chain reactions and genechip hybridization. Anti-HPV 16 was tested by enzyme-linked immunoassay. Conditional logistic regression models were used to estimate odds ratio (OR) with its 95% confidence interval (CI) for these two biomarkers separately and jointly. Results：A significantly increased risk of cervical cancer was associated with the positivity of HPV DNA and anti-HPV 16 showing OR (95% CI) of 25.0 (6.9-91.5) and 6.3 (1.3-31.6), respectively. Educational level and use of oral contraceptive were significantly associated with cervical cancer after adjustment for the infection of all high risk types of HPV. Conclusions：Positivity of both HPV 16 DNA in cervical cells and anti-HPV 16 in serum are important risk factors for cervical cancer.