本文選題：宮頸病變 + HPVL1殼蛋白　； 參考：《新疆醫(yī)科大學(xué)》2015年博士論文

【摘要】：目的:研究HPV L1殼蛋白和h TERC基因在新疆維吾爾族和漢族婦女宮頸脫落細(xì)胞中的表達(dá)情況及差異性,探討維吾爾族與漢族宮頸癌發(fā)病機(jī)制的特點(diǎn)及差異性,評價(jià)HPV L1殼蛋白、hTERC基因及HPV L1殼蛋白和hTERC基因聯(lián)合分析對新疆維吾爾族和漢族婦女宮頸病變的診斷價(jià)值。方法:收集2012年9月至2014年3月在新疆維吾爾自治區(qū)人民醫(yī)院婦科門診就診或行宮頸癌機(jī)會性篩查的新疆維吾爾族和漢族婦女病例1160例,所有病例均進(jìn)行TCT和HPV分型檢測,選擇其中HPV感染陽性或TCT陽性或兩項(xiàng)同時(shí)陽性的病例納入研究隊(duì)列。所有納入研究隊(duì)列的病例均行陰道鏡下活檢送病理組織學(xué)檢查,并通過免疫細(xì)胞化學(xué)法檢測宮頸脫落細(xì)胞中HPV L1蛋白的表達(dá)情況,通過F1SH技術(shù)檢測宮頸脫落細(xì)胞中h TERC基因的表達(dá)情況。結(jié)果:1、新疆維吾爾族與漢族婦女TCT結(jié)果的異常率無顯著差異,且其ASCUS、LSIL、HSIL和SCC患者的構(gòu)成比亦無顯著差異;維吾爾族與漢族婦女HPV的陽性率沒有顯著差異,且其高危型HPV感染、混合型HPV感染和低危型HPV感染的構(gòu)成比亦無顯著差異。2、新疆維吾爾族與漢族婦女h TERC基因擴(kuò)增的總陽性率無顯著差異;維吾爾族與漢族婦女NILM組、ASCUS組、LSIL組、HSIL組和SCC組hTERC基因擴(kuò)增的陽性率均沒有顯著差異;維吾爾族與漢族婦女正�；蚵匝装Y組、CIN1組、CIN2組、CIN3組和SCC組hTERC基因擴(kuò)增的陽性率亦均無顯著差異;hTERC基因的表達(dá)率不存在民族差異。維吾爾族與漢族婦女正常或慢性炎癥組/CIN1組和CIN2~+組基因拷貝數(shù)的分布均無顯著差異,且其正�；蚵匝装Y組/CIN1組和CIN2~+組TERC:CEP比例分布亦均無顯著差異,hTERC基因的擴(kuò)增類型不存在民族差異。3、對細(xì)胞學(xué)分組而言,維吾爾族和漢族婦女h TERC基因擴(kuò)增陽性率的大小順序均為:SCC組≈HSIL組㧐LSIL組㧐ASCUS組≈NILM組,隨著細(xì)胞學(xué)分級的升高,各組中hTERC基因的擴(kuò)增陽性率有增加的趨勢;對組織學(xué)分組而言,其大小順序均為:SCC組≈CIN 3組㧐CIN 2組㧐CIN 1組≈正常或慢性炎癥組,隨著宮頸病變惡性程度的增加,各組中hTERC基因的擴(kuò)增陽性率有增加的趨勢,hTERC基因的表達(dá)與宮頸病變的惡性程度呈正相關(guān)。4、新疆維吾爾族與漢族婦女hpvl1殼蛋白的總陽性表達(dá)率無顯著差異,其正常或慢性炎癥組、cin1組、cin2組、cin3組和scc組hpvl1殼蛋白表達(dá)的陽性率均無顯著差異;其nilm組、ascus組、lsil組、hsil組和scc組hpvl1殼蛋白表達(dá)的陽性率亦均無顯著差異。hpvll殼蛋白的表達(dá)率不存在民族差異。5、對于新疆維吾爾族婦女和漢族婦女而言,hpvl1殼蛋白表達(dá)的陽性率在c1n1組為最高,高于正常或慢性炎癥組及其它高病變組;對于不同宮頸病變組而言,hpvl1殼蛋白表達(dá)的陽性率隨宮頸病變惡性程度的增加而降低,呈負(fù)相關(guān);對于不同細(xì)胞學(xué)分級而言,hpvl1殼蛋白表達(dá)的陽性率在lsil組為最高,高于nilm組和ascus組及其他更高級別的細(xì)胞學(xué)分組。而且,自lsil組起,隨著細(xì)胞學(xué)分級的升高,hpvl1殼蛋白表達(dá)的陽性率呈下降的趨勢,呈負(fù)相關(guān)。新疆維吾爾族和漢族婦女宮頸脫落細(xì)胞中hpvll殼蛋白的表達(dá)與宮頸病變的惡性程度均呈負(fù)相關(guān),其可能是宮頸低度鱗狀上皮內(nèi)病變預(yù)后的保護(hù)性因素之一。6、對于hpv感染陽性的新疆維吾爾族婦女與漢族婦女而言,其宮頸脫落細(xì)胞中hpvl1殼蛋白表達(dá)的總陽性率無顯著差異,且其高危型感染者、混合型感染者和低危型感染者中hpvl1殼蛋白表達(dá)的陽性率亦均無顯著差異。維吾爾族和漢族婦女低危型感染者與混合型感染者h(yuǎn)pvl1殼蛋白表達(dá)的陽性率均無顯著差異,高危型感染者h(yuǎn)pvl1殼蛋白表達(dá)的陽性率低于低危型感染者和混合型感染者。7、hpvl1殼蛋白診斷新疆維吾爾族和漢族婦女宮頸高度病變cin2~+時(shí),其適用人群為具有宮頸鱗狀上皮內(nèi)病變的患者,其靈敏度、正確率和陽性預(yù)測價(jià)值較高,特異度和陰性預(yù)測價(jià)值較低,且不存在民族差異。其診斷價(jià)值中等(roc曲線下面積:維吾爾族為0.699,漢族為0.705)。8、hterc基因檢測診斷宮頸高度病變cin2~+時(shí),其適用人群為正�；蚵匝装Y患者及具有宮頸鱗狀上皮內(nèi)病變的患者,其靈敏度、特異度、正確率、陽性預(yù)測價(jià)值和陰性預(yù)測價(jià)值均較高,且不存在民族差異。其診斷價(jià)值較高(roc曲線下面積:維吾爾族為0.875,漢族為0.871)。9、hpvl1殼蛋白聯(lián)合hterc基因檢測診斷宮頸高度病變cin2~+時(shí),其適用人群為具有宮頸鱗狀上皮內(nèi)病變的患者,其靈敏度、正確率和陽性預(yù)測價(jià)值較高,特異度和陰性預(yù)測價(jià)值較低,且不存在民族差異。其診斷價(jià)值中等(roc曲線下面積:維吾爾族為0.706,漢族為0.699)。10、當(dāng)應(yīng)用對象為具有宮頸鱗狀上皮內(nèi)病變的患者時(shí),hpvl1殼蛋白、hterc基因和hpvl1殼蛋白聯(lián)合hterc基因診斷新疆維吾爾族婦女與漢族婦女宮頸高度病變cin2~+的效率為:hterc基因㧐hpvl1殼蛋白聯(lián)合hterc基因≈hpvl1殼蛋白。11、hpvl1/hterc表達(dá)的狀態(tài)隨著宮頸病變程度的升高可排列為hpvl1(-)/hterc(-)、l1(+)/hterc(-)、hpvl1(+)/hterc(+)和hpvl1(-)/hterc(+)。結(jié)論:1、新疆維吾爾族與漢族婦女宮頸脫落細(xì)胞中hterc基因的表達(dá)和hpvl1殼蛋白的表達(dá)沒有民族差異。2、新疆維吾爾族和漢族婦女宮頸脫落細(xì)胞中hterc基因的表達(dá)與宮頸病變的惡性程度均呈正相關(guān),HPV Ll殼蛋白的表達(dá)與宮頸病變的惡性程度均呈負(fù)相關(guān)。3、HPV L1殼蛋白診斷新疆維吾爾族和漢族婦女宮頸高度病變CIN2~+時(shí),其適用人群為具有宮頸鱗狀上皮內(nèi)病變的患者,其靈敏度、正確率和陽性預(yù)測價(jià)值較高,特異度和陰性預(yù)測價(jià)值較低,各項(xiàng)指標(biāo)之間均不存在民族差異,診斷價(jià)值中等;hTERC基因檢測診斷宮頸高度病變CIN2~+時(shí),其適用人群為正�；蚵匝装Y患者及具有宮頸鱗狀上皮內(nèi)病變的患者。其靈敏度、特異度、正確率、陽性預(yù)測價(jià)值和陰性預(yù)測價(jià)值均較高,各項(xiàng)指標(biāo)之間均不存在民族差異,診斷價(jià)值較高;HPV L1殼蛋白聯(lián)合hTERC基因檢測篩查/診斷宮頸高度病變CIN2~+時(shí),其適用人群為具有宮頸鱗狀上皮內(nèi)病變的患者,其靈敏度、正確率和陽性預(yù)測價(jià)值較高,特異度和陰性預(yù)測價(jià)值較低,各項(xiàng)指標(biāo)之間均不存在民族差異,診斷價(jià)值中等。4、當(dāng)應(yīng)用對象為具有宮頸鱗狀上皮內(nèi)病變的患者時(shí),h TERC基因診斷維吾爾族婦女和漢族婦女宮頸高度病變CIN2~+的效率高于HPV L1殼蛋白及HPV L1殼蛋白和hTERC基因聯(lián)合分析。5、HPV L1/hTERC的表達(dá)狀態(tài)隨宮頸病變嚴(yán)重程度的不同而變化,其表達(dá)時(shí)序可能反映了宮頸病變的發(fā)展過程。
[Abstract]:Objective: To study the expression of HPV L1 shell protein and H TERC gene in the cervical exfoliated cells of Uygur and Han women in Xinjiang and to explore the characteristics and differences of the pathogenesis of cervical cancer in Uygur and Han nationality, and to evaluate the combined analysis of HPV L1 shell protein, hTERC gene and HPV L1 shell egg white and hTERC gene for the Uygur nationality in Xinjiang and the Uygur and hTERC genes. Diagnostic value of cervical lesions of Han women. Methods: 1160 cases of Uygur and Han women in Xinjiang from September 2012 to March 2014 at the the Xinjiang Uygur Autonomous Region people's Hospital Department of gynaecologic outpatient or cervical cancer screening were screened in Xinjiang Uygur and Han women. All cases were detected by TCT and HPV typing, of which HPV infection was positive or TCT positive All the two positive cases were included in the study cohort. All the cases included in the cohort were examined by biopsy under colposcopy, and the expression of HPV L1 protein in the exfoliated cells of the cervix was detected by immunocytochemistry and the expression of H TERC gene in the exfoliated cells of the cervix was detected by F1SH. Results: 1. There was no significant difference in the abnormal rate of TCT between the Uygur and Han women, and there was no significant difference in the constituent ratio of ASCUS, LSIL, HSIL and SCC, and there was no significant difference in the positive rate of HPV between Uygur and Han women, and there was no significant difference in the proportion of the high-risk HPV infection, the mixed HPV infection and the low risk HPV infection,.2, the Xinjiang dimension. There was no significant difference in the total positive rate of H TERC gene amplification between the Han and Han women. There was no significant difference in the positive rate of hTERC gene amplification between the Uygur and Han women NILM group, ASCUS group, LSIL group, HSIL group and SCC group, and the positive and chronic inflammation group of Uygur and Han women, CIN1 group, CIN2 group, CIN3 group and SCC group amplification gene amplification. There was no significant difference in sex ratio. There was no national difference in the expression rate of hTERC gene. There was no significant difference in the distribution of gene copies between /CIN1 and CIN2~+ groups in normal or chronic inflammatory groups of Uygur and Han women, and there was no significant difference in the proportion of TERC:CEP in the normal or chronic inflammation group between the /CIN1 group and the CIN2~+ group, and the amplification of the hTERC gene. There was no national difference.3. For the cytological group, the positive rates of H TERC gene amplification in Uygur and Han women were all: SCC group HSIL group? LSIL group? ASCUS group NILM group. With the increase of cytological classification, the positive rate of hTERC gene amplification in each group was increasing; for histological grouping, the size of the group was the size of the group. The sequence is: group SCC CIN 3? CIN 2 groups? CIN 1 groups of normal or chronic inflammation group, with the increase of the malignant degree of cervical lesions, the positive rate of hTERC gene amplification in each group is increasing, the expression of hTERC gene is positively related to the malignant degree of cervical lesions, and the total positive of hpvl1 shell protein in Uygur and Han women in Xinjiang There was no significant difference in the expression rate. There was no significant difference in the positive rate of the expression of hpvl1 shell protein in the normal or chronic inflammation group, cin1 group, Cin2 group, CIN3 group and SCC group, and there was no significant difference in the positive rate of hpvl1 shell protein expression in group nilm, ASCUS, LSIL, HSIL and SCC groups. In our women and Han women, the positive rate of hpvl1 protein expression was highest in the c1n1 group, higher than in the normal or chronic inflammation group and in other high pathological groups. The positive rate of hpvl1 shell protein expression decreased with the increase of the malignant degree of cervical lesions and was negatively correlated with different cervical lesions. The positive rate of hpvl1 protein expression was highest in group LSIL, higher than that in group nilm and ascus and other higher grade cytology groups. Moreover, the positive rate of hpvl1 shell protein expression decreased with the increase of cytological classification in group LSIL, and negative correlation was found. Hpvll shell eggs in cervical exfoliative cells of Xinjiang vim and Han women There is a negative correlation between the expression of white and the malignancy of cervical lesions, which may be one of the protective factors for the prognosis of the cervical low-grade intraepithelial lesions,.6. For the Xinjiang Uygur women with positive HPV infection, the total positive rate of the hpvl1 shell protein in the cervical exfoliative cells of the cervix is not significantly different, and the high risk type is also found in the cervical exfoliative cells. There was no significant difference in the positive rate of hpvl1 protein expression in the infected, mixed and low risk infected people. There was no significant difference in the positive rate of hpvl1 shell protein expression between the Uygur and Han women with low risk infection and mixed infection. The positive rate of hpvl1 shell egg white expression in high risk infected people was lower than that of those with low risk. .7, hpvl1 shell protein in the diagnosis of cervical high lesion cin2~+ in Uygur and Han women in Xinjiang. The sensitivity, accuracy and positive predictive value of the patients with cervical squamous intraepithelial lesion were higher, the specificity and negative predictive value were lower, and there was no national difference. The diagnostic value was moderate (RO The area under the C curve: the Uygur nationality is 0.699, the Han is 0.705).8. When the hTERC gene is used to detect the high lesion of the cervix, the application population is the normal or chronic inflammation patients and the patients with cervix squamous intraepithelial lesion, whose sensitivity, specificity, correct rate, positive predictive value and negative predictive value are high, and there are no ethnic groups. The diagnostic value is high (the area under the ROC curve: the Uygur is 0.875, the Han is 0.871).9, and the hpvl1 shell protein combined with the hTERC gene for the diagnosis of cervical high lesion cin2~+, the suitable population is the patient with the cervical squamous intraepithelial lesion, whose sensitivity, accuracy and positive predictive value are higher, the specificity and negative predictive value are higher. The diagnostic value is moderate (the area under ROC curve: Uygur is 0.706, Han is 0.699).10. When applied to patients with cervical squamous intraepithelial lesion, hpvl1 shell protein, hTERC gene and hpvl1 shell protein are combined with hTERC gene to diagnose the cervical high disease of Xinjiang Uygur women and Han women The efficiency of changing cin2~+ is: the hTERC gene? Hpvl1 shell protein combined with the hTERC gene hpvl1 shell protein.11. The state of hpvl1/hterc expression can be arranged as hpvl1 (-) /hterc (-), L1 (+) /hterc (+), hpvl1 (+) and (+)). Conclusion: 1, the cervical exfoliative cells of the Uygur and Han women in Xinjiang There was no national difference between the expression of the protein and the expression of hpvl1 shell protein. The expression of hTERC gene in the cervical exfoliated cells of the Uygur and Han women in Xinjiang was positively correlated with the malignant degree of cervical lesions. The expression of HPV Ll shell protein was negatively correlated with the malignant degree of cervical lesions, and the HPV L1 shell protein was used to diagnose the Uygur and Han nationality in Xinjiang. The sensitivity, accuracy and positive predictive value of the patients with cervical squamous intraepithelial lesion CIN2~+ are high, the specificity and negative predictive value are low, and there is no national difference between the indexes and the diagnostic value is moderate among all the indexes. When the hTERC gene is detected for the diagnosis of the high lesion of the cervix, CIN2~+, The sensitivity, specificity, accuracy, positive predictive value and negative predictive value of the patients with normal or chronic inflammation and squamous intraepithelial lesion of the cervix were higher. There was no national difference between all the indexes and the value of diagnosis was higher. HPV L1 shell protein combined with hTERC gene to detect and diagnose the high disease of the cervix. When the CIN2~+ was changed, the patients with cervical squamous intraepithelial lesion were of high sensitivity, accuracy and positive predictive value, and the specificity and negative predictive value were low. There was no national difference between the indexes, and the diagnostic value was medium.4. When the application object was the patients with cervical squamous intraepithelial lesion, the H TERC base was found. The diagnostic efficiency of CIN2~+ in Uygur women and Han women is higher than that of HPV L1 shell protein and HPV L1 shell protein and hTERC gene to analyze.5. The expression of HPV L1/hTERC varies with the severity of cervical lesions. The expression timing may reflect the development of cervical lesions.
【學(xué)位授予單位】：新疆醫(yī)科大學(xué)
【學(xué)位級別】：博士
【學(xué)位授予年份】：2015
【分類號】：R737.33
，

本文編號：1998846