摘要
宫颈病变包括慢性宫颈炎、宫颈湿疣、宫颈上皮内瘤变、宫颈原位癌、宫颈浸润癌等。其中宫颈癌是常见的妇科恶性肿瘤之一，严重威胁妇女的健康。对宫颈癌发病机理的深入研究已揭示高危型HPV是导致宫颈癌的重要原因。目前虽然对高危型HPVE6、E7在宫颈癌发病机制中的作用的进行了深入的研究，并针对宫颈癌的以E6、E7为靶子的重组病毒载体治疗疫苗进行了研究，但对E7在各类宫颈病变中的表达情况国内外未见报道。
目的：探讨HPV16E7在各类宫颈病变中的表达作用机制，为临床宫颈癌前病变及早期宫颈癌的诊断提供经济、有效的方法。探讨E7在各类宫颈病变中尤其是在宫颈癌的表达的影响因素，为临床上应用HPV16E7疫苗预防、治疗宫颈癌提供理论依据。
方法：采用免疫组化方法对10例慢性宫颈炎、10例宫颈湿疣、45例宫颈上皮内瘤变、20例宫颈浸润癌、10例正常宫颈标本行HPV6／11、CMV、HSV-Ⅱ、HPV16E7、Rb及E2F1的测定。用原位杂交行HPV16CDNA的测定。
结果：HPV6／11在宫颈尖锐湿疣组阳性表达率明显增高，P＜0.05=。HPV16CDNA，HSV-Ⅱ及CMV在宫颈癌及宫颈上皮内瘤变中的阳性表达率均增高，P＜0.05。随病变进展HPV16CDNA表达增加，与宫颈癌及宫颈上皮内瘤变呈正相关，P＜0.01。HPV16CDNA、HSV-Ⅱ、CMV在宫颈癌中的阳性表达率分别为65％，25％，30％。但HPV16CDNA在宫颈癌及宫颈上皮内瘤变中的阳性表达率明显高于HSV-Ⅱ、CMV的表达，P＜0.05。HPV16E7在不同类型宫颈组织中的表达特点相似于HPV16CDNA，且与HPV16CDNA呈正相关，P＜0.01。以HPV16CDNA检验结果为标准，HPV16E7的灵敏度为79.4％，特异度为81.1％，阳性预测
硕士论文
值为96.40k。在宫颈癌及宫颈上皮内瘤变时，HPV16E7在HPV16合并
HSV一11及CMV感染时阳性表达率高于单纯HPV16感染时的表达。Rb
在宫颈炎症、宫颈湿疵、宫颈上皮内瘤样病变组的阳性表达率增高P<
0.05。EZFI则在宫颈癌及HSIL组的阳性表达率增高，且EZFI的阳性表
达率和HPV16E7呈正相关P<0.05。
结论:HPv16是引起宫颈癌的主要病因。HPv6/11是引起宫颈尖锐
湿庆的主要病因。HPV16E7在宫颈病变中异常表达，且在一定程度上可
以反映HPV16的感染程度。HPV16E7与EZFI的结合是在被HPV感染
的细胞转录中的一个重要事件，导致肿瘤发生。HSV一11及CMV在宫颈
癌的发生发展过程中与HPV有一定的协同作用。
cervical lesions include chronic cervicitis.cervicao cordyloma.all kinds of precancerous.cervical carcinoma in situ,cervical invase carcinoma etc. Among of which cervical carcinoma is one of familiar gynecologic malignancies which treaten women' s healthy.. The studies on mechanism of the cervical carcinoma have shown that high-risk HPV is main reasion for cervical carcinoma. At present .although the function of high-risk HPV E6 E7 in the cervical carcinoma has been study, and the recombinant vector vaccines which is taken E6 E7 as targets for cervical carcinoma has also been research..the situation of the E7' s expression has not been reported at home and abroad.
Objective: To study the HPV16 E7 expression in various lesions,and the function mechanism of HPV16 E7 in cervical carcinomas and precancerous, in order to offer an ecomomic valid method which can be used for clinical diagnosis of precancerous and earlier carcinomas. Further study the factors which effect on the expression of the E7 in various cervical lesions,particularly in carcinoma, in order to provide the theories basis for clinical E7 vaccine's application to prevent and therapy carcinomas.
Method: Detected the HSV- Ⅱ, CMV, HPV6/11, Rb, E2F1, HPV16E7 of 10 nomal cervix. 10 chronic cervicitis ,10 cervical condyloma ,45 CINs and 20 cervical carcinoma by Immunohistochemistry, detected HPV16CDNA by in situ hybridization.
Result: Cervical condyloma has a great higher HPV6/11 infection rate. Cervical carcinoma and CINs has a great higher HPV16CDNA.,HSV-Ⅱ,
CMV infection rate than nomal cervix., chronic cervicitis , cervical condyloma. P<0.05. the expresion of HPV16CDNA increases following the development of cervical lesions, the expresion of HPV16CDNA and Cervical carcinoma, CINs has positive correlation. P<0. 01. The expresion rate of HPV16CDNA.,
HSV-Ⅱ, CMV in cervical carcinoma is 65%, 25%, 30% respectively , Cervical carcinoma CINs has a great higher HPV16CDNA infection rate than than that of HSV- Ⅱ, CMV, P<0.05. .Cervical carcinoma and CLN Ⅱ Ⅲ has great higher HPV16E7 expression rates than other groups. P<0.05. the expresion of HPV16E7 is the same as the expresion of HPV16CDNA in the various cervical lesions .and the expresion of HPV16E7 and HPV16CDNA has positive correlation. P<0. 01. Standarded by the result of HPV16CDNA ,the sensitivity specificity and positive prevision of HPV16E7 is 79.4% 81.1% . 96.4% respectively. rvical carcinoma CINs, when HPV16 infection was emerged with HSV- Ⅱ, CMV, the expression rates of HPV16E7 are higher than that of HPV16E7 when only HPV16 was infective, the expression rate of Rb increases in chronic cervicitis, cervical condyloma ,CINs .the expression rate of E2F1 increases in cervical carcinoma and HSILs .and the expresion of HPV16E7 and E2F1 has positive correlation. P<0. 05.
Conclusion: HPV16 is main reason for the cervical carcinoma . HPV6/11 is main reason for the cervical condyloma .The expression of HPV16E7 in the various cervical lesions is abnormal. HPV16E7 may reflect the seriousness of HPV16 infection to some extent. HPV16E7 and E2F1 combined which is the important case during the cell transmission cause the carcinoma' s generation.. HSV-Ⅱ, CMV and HPV16 can act together to cervical carcinoma' s generation.
引文
[1] Food Nutrition and the Prevention of Cancer:a global perspective First published 1997 by AICR 301-308
[2] 高进 《肿瘤学基础与研究方法》人民卫生出版社，1999
[3] 郭天棋 人乳头瘤病毒感染与宫颈癌《中国实用妇科与产科杂志》2001 11 17(11)：641-642
[4] Guo WD etal. Corrolation of cervical cancer mortality with reproductive and dietary factors and serum markers in china Int J epidermiol 1994 23;1127-1132
[5] Schmauz,R, etal. Multiple infections in cases of cervical cancer from a high-incidence, area in tropical. Africa Int. J Cancer, 1989. 43:805
[6] Reeres W C Quiroz E.Prevalence of sexual transmitted diseases in high risk women in the Republic of Panama Sex Tran Pis198714:89
[7] 刘树范 浅析巴氏五类法与TBS描述性诊断报告方式 《中国实用妇科与产科杂志》2003年3月，第19卷 第3期135-137
[8] 钱德英 阴道镜在宫颈癌诊断中的应用《中国实用妇科与产科杂志》 2003年3月，第19卷 第3期137-138
[9] Meisels A. Fortin R.Roy M, condylomatous lesions of the cervix, Ⅱ. cytologic, colposcopic and histopathlolgic study Acta Cytol, 1997, 21:379-390
[10] Ricard RM. Amodified terminology for cervical interaepithial neoplasia Obstet Gynecol, 199075:131-133
[11] 陈乐真主编《妇产科诊断病理学》人民军医出版社
[12] Friedrich.SK, Glubas, Eidtmann H. et al Over expression of P53 and prognosis in breast cancer, Cancer 1993 54(24) 6321
[13] 郝敏 石一复 异位子宫内膜间质细胞分泌催乳素的体外研究，中华妇产科杂志2000年第35卷第9期 527
[14] 王伯沅，李玉松，黄高晟等主编《病理学技术》 人民卫生出版社，2000
[15] Bosch FX. Manos MM, Munoz N, et al. Prevalence of Human Papillomavirus in cervical cancer:a World Perspective.J of the National Cancer Institute, 1995;87:796-802
[16] Turek LP. The structure, function, and regulation og papillomaviral genes in infection and cervical cancer. Adv Virus Res, 1994, 44:305
[17] 刘秉文，陈俊杰，主编．《医学分子生物学》中国协和医科大学生出版社，231．
[18] Sun Gwan Hwang, Human Papillomavirus Type 16 E7 Binds to E2F1 and Activates E2F1-driven Transcription in a Retinoblastoma Protein-independent Manner* J. Biol. Chem., Vol. 277, Issue 4, 2923-2930, January 25, 2002
[19] Manos MM,et al. HPV and cervical neoplasia:a prevalent case-control study.Papillomavirus Workshop, Seattle 1991,108
[20] Morrison EAB et al.Human papillomavirus infection and other risk Factors for cervical neoplasia: a case-control study. Int J Canceun 1991,49:6