本文關(guān)鍵詞： 宮頸癌 人乳頭瘤病毒 疫苗 有效性 META分析　出處：《吉林大學(xué)》2014年碩士論文　論文類型：學(xué)位論文

【摘要】：背景及目的：宮頸癌是女性惡性腫瘤中危害婦女健康生命安全的第二大殺手，全球范圍內(nèi)每年大概有270,000萬(wàn)人死于宮頸癌及相關(guān)并發(fā)癥。高危型人乳頭瘤病毒持續(xù)感染是宮頸病變發(fā)生發(fā)展的主要原因之一，世界范圍內(nèi)HPV16和HPV18感染占全部HPV相關(guān)性宮頸病變的70%。二價(jià)和四價(jià)宮頸癌疫苗的相繼問(wèn)世，及國(guó)外大規(guī)模臨床隨機(jī)雙盲對(duì)照試驗(yàn)對(duì)宮頸癌疫苗安全性有效性的探究，為宮頸癌的一級(jí)預(yù)防指明了方向。本文旨在通過(guò)循證醫(yī)學(xué)meta分析的方法對(duì)目前已經(jīng)進(jìn)入臨床研究的宮頸癌疫苗對(duì)HPV16及HPV18持續(xù)6個(gè)月感染的預(yù)防作用，及對(duì)HPV相關(guān)性宮頸病變預(yù)防作用有效性進(jìn)行分析。為宮頸癌疫苗臨床大規(guī)模使用提供詢證醫(yī)學(xué)證據(jù)。 方法: （1）實(shí)驗(yàn)研究設(shè)計(jì)：計(jì)算機(jī)檢索2000年1月至2013年11月以來(lái)發(fā)表的關(guān)于人乳頭瘤病毒（HPV）疫苗用于預(yù)防HPV持續(xù)感染以及宮頸病變的隨機(jī)對(duì)照試驗(yàn)研究。 （2）研究對(duì)象（participants）：健康未孕女性。年齡介于12歲至25歲之間。受試者國(guó)籍種族不限。 （3）干預(yù)措施（interventions）：實(shí)驗(yàn)組受試者接受HPV預(yù)防性疫苗。 （4）對(duì)照組（comparisons）：以受試者接受安慰劑或者是其他疫苗為對(duì)照。 （5）結(jié)局（outcomes）：①HPV感染持續(xù)存在（HPV感染持續(xù)6個(gè)月及以上）。②宮頸上皮內(nèi)瘤變I級(jí)（CINⅠ）及以上的發(fā)病率。③宮頸上皮內(nèi)瘤變Ⅱ級(jí)（CINⅡ）及以上發(fā)病率。 對(duì)入選文獻(xiàn)提取數(shù)據(jù)后應(yīng)用RevMan5.2軟件進(jìn)行meta分析。 結(jié)果: 1.人乳頭瘤病毒疫苗對(duì)宮頸HPV16持續(xù)6個(gè)月感染的meta分析：入選5項(xiàng)研究共納入17815人次。其中干預(yù)組8893人，對(duì)照組8883人。干預(yù)組與對(duì)照組HPV16持續(xù)6個(gè)月感染的相對(duì)危險(xiǎn)度如圖4.1（a）。納入的研究異質(zhì)性檢驗(yàn)結(jié)果提示P=0.97，I2=0%，說(shuō)明各研究之間同質(zhì)性好，應(yīng)用固定效應(yīng)模型，合并計(jì)算相對(duì)危險(xiǎn)度為0.05，即疫苗有效性為95%，可信區(qū)間為[0.03,0.09]。圖示4.1（a）森林圖顯示各研究的置信區(qū)間均不包括0，表明各研究的效應(yīng)量均有統(tǒng)計(jì)學(xué)意義，Z=10.61（P＜0.00001），表明人乳頭瘤病毒疫苗對(duì)HPV16持續(xù)6個(gè)月的感染有預(yù)防作用。圖示4.1（b）漏斗圖圖形對(duì)稱，說(shuō)明研究資料的無(wú)發(fā)表偏倚。 2.人乳頭瘤病毒疫苗對(duì)宮頸HPV18持續(xù)6個(gè)月感染的meta分析：共納入的3項(xiàng)研究試驗(yàn)人數(shù)共計(jì)13921人次。其中干預(yù)組6967人，對(duì)照組6954人。干預(yù)組與對(duì)照組HPV18持續(xù)6個(gè)月感染的相對(duì)危險(xiǎn)度如圖4.2（a）。納入的研究異質(zhì)性檢驗(yàn)結(jié)果提示P=0.51，I2=0%，說(shuō)明各研究之間同質(zhì)性好，應(yīng)用固定效應(yīng)模型，合并計(jì)算相對(duì)危險(xiǎn)度為0.22，即疫苗有效性為78%，可信區(qū)間為[0.13,0.39]。圖示4.2（a）森林圖顯示各菱形完全位于中線左側(cè)未與中線相交，Z=5.51（P＜0.00001），表明人乳頭瘤病毒疫苗對(duì)HPV18持續(xù)6個(gè)月的感染有預(yù)防作用。圖示4.2（b）漏斗圖圖形對(duì)稱，說(shuō)明研究資料的無(wú)發(fā)表偏倚。 3.人乳頭瘤病毒疫苗對(duì)宮頸上皮內(nèi)瘤變I級(jí)及以上發(fā)病率預(yù)防作用的meta分析：共納入文獻(xiàn)8篇。參加實(shí)驗(yàn)人數(shù)共計(jì)26601人次。其中干預(yù)組13290人，對(duì)照組13311人。干預(yù)組與對(duì)照組發(fā)生宮頸上皮內(nèi)瘤變的相對(duì)危險(xiǎn)度如圖4.3.1（a）。納入的研究異質(zhì)性檢驗(yàn)結(jié)果提示P=0.02，I2=58%，說(shuō)明各研究之間存在異質(zhì)性，應(yīng)用隨機(jī)效應(yīng)模型，合并計(jì)算相對(duì)危險(xiǎn)度為0.18，即疫苗有效性為82%，可信區(qū)間為[0.08,0.37]。圖示4.3（a）森林圖顯示各菱形完全位于中線左側(cè)未與中線相交，Z=4.64（P＜0.00001），表明人乳頭瘤病毒疫苗對(duì)CINI級(jí)及以上發(fā)病有預(yù)防作用。圖示4.3.1（b）漏斗圖圖形對(duì)稱尚可，說(shuō)明研究資料不存在發(fā)表偏倚。 4.二價(jià)人乳頭瘤病毒疫苗對(duì)宮頸上皮內(nèi)瘤變I級(jí)及以上的預(yù)防作用的meta分析：共納入4篇文獻(xiàn)，總?cè)藬?shù)為20222，其中干預(yù)組10114人，對(duì)照組10108人。納入的研究異質(zhì)性檢驗(yàn)結(jié)果提示P=0.12，I2=49%，說(shuō)明各研究之間異質(zhì)性較小，應(yīng)用固定效應(yīng)模型，合并計(jì)算相對(duì)危險(xiǎn)度為0.34，即疫苗有效性為66%，可信區(qū)間為[0.28,0.42]。圖示4.3.2.1（a）森林圖顯示各菱形完全位于中線左側(cè)未與中線相交，Z=10.54（P＜0.00001），表明二價(jià)人乳頭瘤病毒疫苗對(duì)宮頸上皮內(nèi)瘤變I級(jí)及以上有預(yù)防作用。圖示4.3.2.1（b）漏斗圖圖形對(duì)稱性良好，說(shuō)明研究資料的不存在發(fā)表偏倚。 5.四價(jià)人乳頭瘤病毒疫苗對(duì)宮頸上皮內(nèi)瘤變I級(jí)及以上的預(yù)防作用的meta分析：分析共納入4篇文獻(xiàn)，總?cè)藬?shù)為6379，其中干預(yù)組3176人，對(duì)照組3203人。納入的研究異質(zhì)性檢驗(yàn)結(jié)果提示P=0.46，I2=0%，說(shuō)明各研究之間無(wú)異質(zhì)性，應(yīng)用固定效應(yīng)模型，合并計(jì)算相對(duì)危險(xiǎn)度為0.09，即疫苗有效性為91%，可信區(qū)間為[0.04,0.21]。圖示4.3.2.2（a）森林圖顯示各菱形完全位于中線左側(cè)未與中線相交，Z=5.57（P＜0.00001），表明四價(jià)人乳頭瘤病毒疫苗對(duì)宮頸上皮內(nèi)瘤變I級(jí)及以上有預(yù)防作用。圖示4.3.2.2（b）漏斗圖圖形對(duì)稱良好，說(shuō)明研究資料不存在發(fā)表偏倚。 6．人乳頭瘤病毒疫苗對(duì)宮頸上皮內(nèi)瘤變Ⅱ級(jí)及以上預(yù)防作用的meta分析：共納入文獻(xiàn)11篇。參加實(shí)驗(yàn)人數(shù)共計(jì)75490人次。其中干預(yù)組37727人，對(duì)照組37763人。如4.4.1（a）納入的研究異質(zhì)性檢驗(yàn)結(jié)果提示P＜0.00001，I2=82%，說(shuō)明各研究之間存在明顯異質(zhì)性，應(yīng)用隨機(jī)效應(yīng)模型，合并計(jì)算相對(duì)危險(xiǎn)度為0.07，即疫苗有效性為93%，可信區(qū)間為[0.02,0.22]。圖示4.4.1（a）森林圖顯示各菱形完全位于中線左側(cè)未與中線相交，Z=4.73（P＜0.00001），表明人乳頭瘤病毒疫苗對(duì)CINⅡ級(jí)及以上發(fā)病率有預(yù)防作用。圖示4.4.1（b）漏斗圖圖形對(duì)稱較好，說(shuō)明研究資料不存在發(fā)表偏倚。 7.二價(jià)人乳頭瘤病毒疫苗對(duì)宮頸上皮內(nèi)瘤變CINⅡ級(jí)及以上的預(yù)防作用：共納入6篇文獻(xiàn)，總?cè)藬?shù)為53471，其中干預(yù)組26733人，對(duì)照組26738人。納入的研究異質(zhì)性檢驗(yàn)結(jié)果提示P＜0.00001，I2=87%，，說(shuō)明各研究之間存在明顯異質(zhì)性，應(yīng)用隨機(jī)效應(yīng)模型，合并計(jì)算相對(duì)危險(xiǎn)度為0.09，即疫苗有效性為91%，可信區(qū)間為[0.042,0.38]。圖示4.4.2.1（a）森林圖顯示各菱形完全位于中線左側(cè)未與中線相交，Z=3.32（P=0.0009），表明二價(jià)人乳頭瘤病毒疫苗對(duì)宮頸上皮內(nèi)瘤變Ⅱ級(jí)及以上有預(yù)防作用。圖示4.4.2.1（b）漏斗圖圖形對(duì)稱良好，說(shuō)明研究資料不存在發(fā)表偏倚。 8.四價(jià)人乳頭瘤病毒疫苗對(duì)宮頸CINⅡ+的預(yù)防作用分析：共納入5篇文獻(xiàn)，總?cè)藬?shù)為22019，，其中干預(yù)組10994人，對(duì)照組11025人。納入的研究異質(zhì)性檢驗(yàn)結(jié)果提示P=0.84，I2=0%，應(yīng)用固定效應(yīng)模型，合并計(jì)算相對(duì)危險(xiǎn)度為0.04，即疫苗有效性為96%，可信區(qū)間為[0.01,0.11]。圖示4.4.2.2（a）森林圖顯示各菱形完全位于中線左側(cè)，Z=5.96（P＜0.00001），表明四價(jià)人乳頭瘤病毒疫苗對(duì)宮頸上皮內(nèi)瘤變Ⅱ級(jí)及以上有預(yù)防作用。圖示4.4.2.2（b）漏斗圖圖形對(duì)稱良好，說(shuō)明研究資料不存在發(fā)表偏倚。 結(jié)論： 1.人乳頭瘤病毒預(yù)防性疫苗可以降低HPV16及HPV18持續(xù)感染的風(fēng)險(xiǎn)。 2.人乳頭瘤病毒預(yù)防性疫苗可以降低CINⅠ級(jí)及以上宮頸病變患病率的風(fēng)險(xiǎn)。 3.人乳頭瘤病毒預(yù)防性疫苗可以降低CINⅡ級(jí)及以上宮頸病變患病率的風(fēng)險(xiǎn)。
[Abstract]:Background and objective: cervical cancer is endangering the life safety of the second women's health killer of women malignant tumor, there are about 2 billion 700 million people died of cervical cancer and related complications worldwide. HPV infection is one of the main reasons for the occurrence and development of cervical lesions, one after another in the world accounted for the relationship between cervical HPV in 70%., two divalent and tetravalent vaccine against cervical cancer HPV16 and HPV18 infection, and foreign large-scale clinical randomized controlled trial on cervical cancer vaccine safety and effectiveness, and pointed out the direction for the primary prevention of cervical cancer. This paper aims to prevent evidence based analysis method of meta medicine has now entered the clinic study on the cervical cancer vaccine of HPV16 and HPV18 infection in 6 months, and for HPV associated cervical lesions were analyzed. The preventive effect is effective for cervical cancer The large-scale use of the vaccine provides evidence of medical evidence.
Method:
(1) experimental research design: computer search for a randomized controlled trial of human papillomavirus (HPV) vaccine used to prevent HPV persistent infection and cervical lesions since January 2000 to November 2013.
(2) study object (participants): healthy unpregnant women. Age between 12 and 25 years. The nationality of the subjects is not limited.
(3) intervention (interventions): the subjects in the experimental group received HPV prophylactic vaccine.
(4) the control group (comparisons): the subjects received placebo or other vaccines as control.
(5) outcome (outcomes): (1) HPV infection persisted (HPV infection lasted for 6 months or more). 2. The incidence of cervical intraepithelial neoplasia I grade (CIN I) and above. 3. The incidence of cervical intraepithelial neoplasia grade II (CIN II) or above.
After extracting the data from the selected literature, the RevMan5.2 software was used for meta analysis.
Result:
1. human papilloma virus vaccine for cervical HPV16 persistent infection: analysis of 6 months of meta: a total of 5 studies were included in the intervention group of 17815 people. 8893 people, 8883 people in the control group. The intervention group and the control group HPV16 infection 6 months relative risk as shown in Figure 4.1 (a). In the study of heterogeneity test results indicated that P=0.97, I2=0%, explains the study between homogeneity, using fixed effect model, and calculate the relative risk of 0.05, vaccine effectiveness was 95%, 4.1 confidence interval [0.03,0.09]. diagram (a) shows the confidence interval of the forest research doesn't include the 0, the study indicates that the effect of the amount of statistical significance, Z=10.61 (P < 0.00001), shows that human papillomavirus vaccines have a preventive effect on HPV16 for 6 months of infection. Figure 4.1 (b) funnel plot symmetry, no publication bias of the data.
2. human papilloma virus vaccine for cervical HPV18 persistent infection: analysis of 6 months of meta: 3 studies were included in the total number of 13921 people. In the intervention group of 6967 people, 6954 people in the control group. The intervention group and the control group HPV18 infection 6 months relative risk as shown in Figure 4.2 (a) into. The study of heterogeneity test showed that P=0.51, I2=0%, explains the study between homogeneity, using fixed effect model, and calculate the relative risk of 0.22, vaccine effectiveness was 78%, 4.2 confidence interval [0.13,0.39]. diagram (a) shows the diamond forest located in the midline and left without completely intersecting line, Z=5.51 (P < 0.00001), shows that human papillomavirus vaccines have a preventive effect on HPV18 for 6 months of infection. Figure 4.2 (b) funnel plot symmetry, no publication bias of the data.
Analysis of 3. human papilloma virus vaccine I level and above, the incidence of preventive effect on cervical intraepithelial neoplasia meta: a total of 8 articles were included in the experiment. A total of 26601 people. In the intervention group of 13290 people, 13311 people in the control group. The intervention group and the control group had cervical intraepithelial neoplasia relative risk figure 4.3.1 (a). The study included heterogeneity test showed that P=0.02, I2=58%, indicating the existence of heterogeneity between the studies and application of random effect model, and calculate the relative risk of 0.18, vaccine effectiveness was 82%, 4.3 confidence interval [0.08,0.37]. diagram (a) shows the forest located in the midline of each diamond completely on the left side and not intersecting line, Z=4.64 (P < 0.00001), shows that human papillomavirus vaccines have a preventive effect on CINI level and above 4.3.1 (b). The incidence of funnel plot symmetry can, explain the research data do not exist to express bias.
Analysis of 4. valence two HPV vaccine I level and preventive effect of above of cervical intraepithelial neoplasia meta: a total of 4 articles were included, the total number of 20222, including 10114 in the intervention group and the control group of 10108 people. The research into the heterogeneity test results suggest that P=0.12, I2=49%, the study of heterogeneity the application of small, fixed effect model, and calculate the relative risk of 0.34, vaccine effectiveness was 66%, CI [0.28,0.42]. icon 4.3.2.1 (a) showed that the forest map completely on the left side of the center line with diamond intersecting line, Z=10.54 (P < 0.00001), showed that the two price of HPV vaccine for cervical epithelium neoplasia of I and above have a preventive role. The 4.3.2.1 (b) funnel plot symmetry, explains the research data there is no publication bias.
Analysis of 5. quadrivalent human papillomavirus vaccine I and preventive effect of above of cervical intraepithelial neoplasia meta analysis: a total of 4 articles were included, the total number of 6379, including 3176 in the intervention group and the control group of 3203 people. The research into the heterogeneity test results suggest that P=0.46, I2=0%, explains the heterogeneity Study on the application, fixed effect model, and calculate the relative risk of 0.09, vaccine effectiveness was 91%, CI [0.04,0.21]. icon 4.3.2.2 (a) showed that the forest map completely on the left side of the center line with diamond intersecting line, Z=5.57 (P < 0.00001), indicated that quadrivalent human papillomavirus vaccine for cervical intraepithelial neoplasia grade I and above have a preventive role. The 4.3.2.2 (b) funnel plot symmetry is good, there is no data of publication bias.
6. human papilloma virus vaccine of cervical intraepithelial neoplasia grade II and above the preventive effect of meta: a total of 11 articles were included in the experiment. A total of 75490 people. Among them 37727 in the intervention group and the control group of 37763 people. Such as 4.4.1 (a) into the study of heterogeneity test showed that P < 0.00001, I2=82% that shows significant heterogeneity between the studies and application of random effect model, and calculate the relative risk of 0.07, vaccine effectiveness was 93%, CI [0.02,0.22]. icon 4.4.1 (a) showed that the forest map completely on the left side of the center line with diamond intersecting line, Z=4.73 (P < 0.00001), showed that human papilloma virus vaccines have a preventive effect on CIN II and above. The incidence of 4.4.1 (b) the funnel plot symmetry is good, that does not exist on information publication bias.
7. two price of HPV vaccine for cervical intraepithelial neoplasia grade CIN and preventive effect of more than 6 articles were included, the total number of 53471, including 26733 in the intervention group and 26738 in the control group. Test results indicate that the heterogeneity of P < 0.00001, I2=87% included, indicating that there exist obvious heterogeneity the study, using a random effects model, and calculate the relative risk of 0.09, vaccine effectiveness was 91%, CI [0.042,0.38]. icon 4.4.2.1 (a) showed that the forest map completely on the left side of the center line with diamond intersecting line, Z=3.32 (P=, 0.0009) showed that the two price of human papillomavirus vaccine prevention the role of cervical intraepithelial neoplasia grade II and above. The 4.4.2.1 (b) funnel plot symmetry is good, there is no data of publication bias.
Analysis of preventive effect of 8. quadrivalent HPV vaccine for cervical CIN + II: a total of 5 articles were included, the total number of 22019, including 10994 in the intervention group and the control group of 11025 people. The research into the heterogeneity test results suggest that P=0.84, I2=0%, using fixed effect model, and calculated relative risk was 0.04 that is, vaccine effectiveness was 96%, CI [0.01,0.11]. icon 4.4.2.2 (a) showed that the diamond forest map completely on the left side of the center line, Z=5.96 (P < 0.00001), indicated that quadrivalent human papillomavirus vaccine to prevent cervical intraepithelial neoplasia grade II and above. The 4.4.2.2 (b) funnel plot symmetry well, there is no data of publication bias.
Conclusion:
The 1. human papillomavirus prophylactic vaccine can reduce the risk of persistent infection of HPV16 and HPV18.
The 2. human papillomavirus prophylactic vaccine can reduce the risk of CIN grade I and above the prevalence of cervical lesions.
The 3. human papillomavirus prophylactic vaccine can reduce the risk of the prevalence of CIN class II and above cervix.

【學(xué)位授予單位】：吉林大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2014
【分類號(hào)】：R737.33

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相關(guān)期刊論文 前10條

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