本文選題：人乳頭狀瘤病毒 + 宮頸癌　； 參考：《新疆醫(yī)科大學(xué)》2015年博士論文

【摘要】：目的:評價(jià)高危型HPV基因型檢測在宮頸癌篩查中的可行性及應(yīng)用價(jià)值。P16/Ki-67細(xì)胞學(xué)雙染在HPV陽性、宮頸不同病變脫落細(xì)胞中的表達(dá)和意義。探討新疆地區(qū)感染HPV16變異體譜系分布及E6、E7、LCR基因突變研究,分析HPV16變異體在宮頸癌及癌前病變發(fā)生發(fā)展中的作用。方法:應(yīng)用高危型HPV基因檢測系統(tǒng),對2014年09月~2015年8月在新疆自治區(qū)人民醫(yī)院住院及門診就診行HC2、TCT檢測、并有病理結(jié)果的564位女性的宮頸細(xì)胞標(biāo)本進(jìn)行HPV基因型檢測,對其中59例HC2陽性患者的液基細(xì)胞學(xué)涂片用免疫細(xì)胞化學(xué)法檢測P16/Ki-67蛋白在宮頸脫落細(xì)胞中的表達(dá)。對HPV16陽性的宮頸癌及癌前病變患者,提取基因組DNA,利用PCR擴(kuò)增HPV16 DNA E6、E7基因及LCR區(qū)核苷酸片段,正反向測序。與HPV16基因序列分析比對,確定HPV16譜系分布,分析核苷酸突變位點(diǎn)。結(jié)果:(1)高危型HPV基因型檢測在診斷CIN2+病變時(shí)優(yōu)于HC2、TCT、Hybr Miax分型檢測,差異具有統(tǒng)計(jì)學(xué)意義(P0.05),不同液基細(xì)胞學(xué)分級及組織病理分級中HR-HPV感染率不同,差異具有統(tǒng)計(jì)學(xué)意義(P0.05),隨細(xì)胞學(xué)及病理學(xué)診斷級別升高,HR-HPV感染率上升(P0.05),HPV16型感染率上升(P0.05)。各級別宮頸病變以HPV16型及合并HPV16型感染為主,HP16型分布在維吾爾族和漢族婦女之間無統(tǒng)計(jì)學(xué)差異(P0.05)。各年齡段高危型HPV的構(gòu)成比無統(tǒng)計(jì)學(xué)差異(P0.05)。高危型HPV基因型檢測對ASCUS分流優(yōu)于HC2。(2)P16/Ki-67細(xì)胞學(xué)雙染檢測診斷CIN2+病變時(shí)具有高靈敏度(92%)和總符合率(78%),P16/Ki-67細(xì)胞學(xué)雙染檢測與組織病理學(xué)結(jié)果符合率較一致(Kappa=0.569,P0.05),在對ASCUS/ASC-H進(jìn)行P16/Ki-67細(xì)胞學(xué)雙染檢測更能發(fā)現(xiàn)宮頸高級別病變(P0.05),不同宮頸病變P16/Ki-67細(xì)胞學(xué)雙染檢測陽性率:炎癥39.13%(9/23)CIN1 20%(2/10),CIN2-3 91.30%(21/23),宮頸癌100%(2/2)差異具有統(tǒng)計(jì)學(xué)意義(P0.05),隨病變程度的加重,P16/Ki-67細(xì)胞學(xué)雙染陽性率呈上升的趨勢。(3)E6基因突變率為80.00%(92/115)主要突變位點(diǎn)T350G(58.78%),T178G(18.47%),E7突變率為54.78%(63/115)主要突變位點(diǎn)A647G(33.33%),T846C(26.98%),LCR突變率為23.48%(27/115),主要突變位點(diǎn)為C24T(74.07%),C13T(25.92%)。維吾爾族婦女與漢族婦女之間比較,維吾爾族T350G突變率顯著高于漢族,漢族A647G、T846C、C24T突變率顯著高于維吾爾族,差異具有統(tǒng)計(jì)學(xué)意義(P0.05)。維吾爾族宮頸癌組T350G突變率顯著高于炎癥組(P0.05),且隨病變嚴(yán)重程度增加突變率上升,漢族T350G、A647G、T846C、C24T突變率炎癥組、宮頸病變組顯著高于宮頸癌組(P0.05),維吾爾族C24T突變率炎癥組顯著高于宮頸癌組(P0.05),差異均具有統(tǒng)計(jì)學(xué)意義(P0.05)。新疆漢族人中感染的HPV16主要為亞洲型,新疆維吾爾族感染的HPV16主要為歐洲型。結(jié)論:高危型HPV感染是宮頸癌前病變和宮頸癌的主要致病因素;宮頸各級別病變中以HPV16型及合并HPV16型感染為主;隨細(xì)胞學(xué)及病理學(xué)診斷級別升高HR-HPV感染率上升;高危型HPV基因型檢測對ASCUS診斷分流優(yōu)于HC2。P16/Ki-67細(xì)胞學(xué)雙染陽性率隨著宮頸病變程度加重呈上升趨勢;P16/Ki-67細(xì)胞學(xué)雙染檢測可以有效對ASCUS及HPV陽性者進(jìn)行診斷分流,具有臨床應(yīng)用價(jià)值。HPV16E6、E7突變可能與宮頸病變進(jìn)展有關(guān),T350G突變可能是維吾爾族宮頸癌高發(fā)的原因之一;新疆漢族人中感染的HPV16型主要為亞洲型,新疆維吾爾族感染的HPV16型主要為歐洲型。
[Abstract]:Objective: To evaluate the feasibility and application value of high risk HPV genotyping in screening cervical cancer and its value of.P16/Ki-67 cytology in HPV positive and cervical diseased cells. The distribution of HPV16 variants in Xinjiang area and the mutation of E6, E7, LCR gene and HPV16 variant in cervical cancer and cancer were analyzed. Methods: the role of high risk HPV gene detection system was used to detect the HC2, TCT test and HPV genotypes of 564 women's cervical cells in the hospital of Xinjiang Autonomous Region People's Hospital in Xinjiang Autonomous Region People's Hospital in August 2014, and 59 cases of HC2 positive patients with liquid based cytology. The expression of P16/Ki-67 protein in cervix exfoliated cells was detected by immunocytochemical method. Genomic DNA was extracted from HPV16 positive cervical cancer and precancerous lesions, HPV16 DNA E6, E7 gene and LCR region nucleotide fragment were amplified by PCR, and the sequence analysis of HPV16 gene was compared to determine the HPV16 lineage distribution and analysis of nucleoside. Acid mutation sites. Results: (1) high risk HPV genotypes were superior to HC2, TCT, Hybr Miax typing in the diagnosis of CIN2+ lesions, and the difference was statistically significant (P0.05). The rate of HR-HPV infection in different liquid based cytological classification and histopathological classification was different, the difference had the significance of total count (P0.05), and the diagnostic grade of cytology and pathology increased, H. The rate of R-HPV infection increased (P0.05) and the rate of HPV16 type infection increased (P0.05). There was no statistical difference between the Uygur and the Han women (P0.05) in all levels of cervical lesions (P0.05). The composition of high-risk HPV in all ages was less than that of the Han and Han women (P0.05). The high risk type HPV genotypic detection of ASCUS shunt (P0.05). High sensitivity (92%) and total coincidence rate (78%) were superior to HC2. (2) P16/Ki-67 cytological double staining for diagnosis of CIN2+ lesions. The coincidence rate of double staining and histopathology of P16/Ki-67 cytology was consistent (Kappa=0.569, P0.05). In ASCUS/ASC-H, double staining of P16/Ki-67 cytology was more capable of detecting high grade cervical lesions (P0.05). The positive rate of P16/Ki-67 cytology double staining for cervical lesions: 39.13% (9/23) CIN1 20% (2/10), CIN2-3 91.30% (21/23), and 100% (2/2) of cervical cancer (P0.05), with the aggravation of the lesion, the positive rate of double staining of P16/Ki-67 cytology was upward trend. (3) E6 gene mutation rate was 80% (92/115) main mutation site T350G (58). .78%), T178G (18.47%), E7 mutation rate is 54.78% (63/115) major mutation site A647G (33.33%), T846C (26.98%), LCR mutation rate is 23.48% (27/115), the main mutation site is C24T (74.07%), C13T (25.92%). Uygur women and Han women compared to the Han, the Uygur T350G mutation rate is significantly higher than the Han, the Han A647G, significant mutation rate is significant Higher than Uygur, the difference was statistically significant (P0.05). The mutation rate of T350G in Uygur cervical cancer group was significantly higher than that in the inflammatory group (P0.05), and the mutation rate increased with the severity of the lesion, the Han T350G, A647G, T846C, C24T mutation rate in the inflammatory group, the cervical lesion group was significantly higher than the cervical cancer group (P0.05), and the Uygur C24T mutation rate inflammation group showed a significant difference. The difference was statistically significant (P0.05) higher than the cervical cancer group (P0.05). The infection of HPV16 in Xinjiang Han people was mainly Asian type and the HPV16 of Xinjiang Uygur infection was mainly European type. Conclusion: high risk HPV infection is the main cause of cervical cancer and precancerous lesion and cervical cancer in all levels of the cervix with HPV16 and HPV16 HR-HPV infection rate increased with cytological and pathological diagnosis level, and high risk HPV genotyping was superior to HC2.P16/Ki-67 cytology with double staining of ASCUS diagnostic shunt as the degree of cervical lesions increased; double staining of P16/Ki-67 cytology could be used to diagnose and shunt of ASCUS and HPV positive patients. With the clinical value of.HPV16E6, E7 mutation may be associated with the progression of cervical lesions. T350G mutation may be one of the reasons for the high incidence of cervical cancer in Uygur nationality; the HPV16 type of infection in Xinjiang Han people is mainly Asian type, and the HPV16 type of Xinjiang Uygur infection is mainly European type.

【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

【參考文獻(xiàn)】

相關(guān)期刊論文 前10條

1 帕提曼·米吉提;唐努爾·阿布力米提;古扎麗努爾·阿不力孜;李華;;careHPV初篩及TCT分流法在新疆宮頸癌篩查中的應(yīng)用[J];新疆醫(yī)科大學(xué)學(xué)報(bào);2015年04期

2 張媛媛;路玲;古扎麗努爾·阿不力孜;李華;朱明s，

本文編號：1891365