HPV及相关基因甲基化在宫颈癌中的研究进展

HPV联合宫颈细胞学筛查后大大提高了宫颈癌前病变的检出率,但它预测宫颈癌发生的价值相对较低。近年,肿瘤相关基因的甲基化已在许多癌症中被确认,对HPV及宫颈癌相关基因甲基化的研究也日益增多。对生物标记物的甲基化分析,使预测宫颈癌的发生和区分病变的严重程度有了新的方法。现将HPV及宫颈癌相关基因甲基化的研究进展作一综述。     

高危型HPV负荷量与宫颈癌及其前期病变关系的研究

目的:探讨高危型HPV负荷量与宫颈癌及其前期病变的关系。方法:对2005年1月至2006年12月于本院行宫颈癌筛查的1221例患者临床资料进行统计分析,观察高危型HPV负荷量和宫颈癌及其前期病变的关系,并用ROC曲线分析,确定HC-Ⅱ法检测高危型HPV-DNA判断宫颈病变≥CINⅡ理想的RLU/CO界值。结果:1221例患者组织学诊断为慢性宫颈粘膜炎667例,CIN407例(其中CINⅠ109例、CINⅡ～Ⅲ298例),宫颈癌147例。慢性宫颈炎、CINⅠ、CINⅡ～Ⅲ和宫颈癌患者高危HPV-DNA负荷量的中位数分别为32.58,58.16,103.83和173.68。根据ROC曲线,统计结果中各可能切点的灵敏度和特异度,发现确定预测≥CINⅡ宫颈病变最佳RLU/CO值为3.155,该点灵敏度88%,特异度57%,Youden指数0.446。结论:高危型HPV负荷量与宫颈癌及其前期病变存在明显相关性,预测≥CINⅡ宫颈病变高危HPV负荷量最佳值为3.155。     

含HPV16型反义E7基因的腺相关病毒骨架质粒pUF1-E7AS的构建及鉴定

目的:构建含HPV16型反义E7基因的腺相关病毒骨架质粒pUF1- E7AS并鉴定,探讨腺相关病毒介导的反义E7基因技术用于治疗早期宫颈癌的可能性。方法:使用RT -PCR法扩增全长HPV16型E7基因,利用基因重组法将目的片段反向插入腺相关病毒骨架质粒pUF1并酶切鉴定。结果:RT PCR法扩增全长315bp的HPV16型E7基因,装入pGEM -Teasy载体进行测序,经NCBI数据库blast检索为100%的符合,经基因重组获得含HPV16型反义E7基因的腺相关病毒骨架质粒pUF1 E7AS,AccⅠ和KpnⅠ双酶切鉴定pUF1 E7AS。结论:含HPV16型反义E7基因的腺相关病毒骨架质粒pUF1 E7AS可成功构建。     

p16和CDH1基因异常甲基化在宫颈组织中的表达及其意义

目的:分析宫颈癌和宫颈上皮内瘤样病变(cervical intraepithelial neoplasia, CIN)组织中p16和CDH1基因异常甲基化的变化,评价该指标在宫颈癌中的意义。方法:用甲基化特异性聚合酶链反应法(methylation-specific PCR,MSP)检测CINⅠ40例、CINⅡ～Ⅲ40例、宫颈癌40例组织中p16和CDH1基因的异常甲基化。取正常宫颈组织20例作为对照。结果:(1)p16和CDH1甲基化在正常组未见表达;(2)p16、CDH1甲基化阳性率:CINⅡ、Ⅲ组明显高于CINⅠ组,差异有统计学意义(22．4%vs 2．5%,P＜0．05; 35．0%vs 5．0%,P＜0．05),宫颈癌组高于CINⅡ、Ⅲ组,但差异无统计学意义(40．0% vs 22．4%,P＞0．05;57．5% vs 35．0%,P＞0．05);宫颈癌组高于相应CINⅠ组,差异有统计学意义(40．0% vs 2．5%,P＜0．05;57．5% vs 5．0%,P＜0．05);(3)p16和CDH1甲基化总阳性率(任何一个基因出现甲基化即为阳性):CINⅡ、Ⅲ组明显高于CINⅠ组,差异有统计学意义(40．0% vs 5．0%,P＜0．05),宫颈癌组高于CINⅡ、Ⅲ组,差异有统计学意义(70．0% vs 40．0%,P＜0．05)。结论:p16和CDH1基因启动子区异常甲基化与宫颈癌的生物学行为相关,它可能有助于宫颈癌的早期辅助诊断和治疗。     

TGF-α、EGF-R与HPV在宫颈癌组织中的表达及意义

转化生长因子 ａ（transforming growth factor al-pha,ＴＧＦ－ａ）和表皮细胞生长因子受体（ｅｐｉｄｅｒｍａｌｇｒｏｗｔｈ　ｆａｃｔｏｒ　ｒｅｃｅｐｔｏｒ,ＥＧＦ－Ｒ）与肿瘤的发生发展有关,为研究它们与宫颈癌发生的关系,我们对宫颈癌组织中的ＴＧＦ－ａ、ＥＧＦ－Ｒ和人乳头瘤病毒（ＨＰＶ）进行了检测。１资料与方法１．１临床资料收集我院和西京医院病理科活检和手术切除的宫颈癌６６例,其中鳞癌 级 １６例, 级 ３６例,级１４例。宫颈上皮内瘤变（ＣＩＮ）２５例（ＣＩＮ１１０例,ＣＩＮ２ ９例,ＣＩＮ３ ６例）,以慢…     

人半翼基因及HPV感染与宫颈癌发生发展的关系

人半翼（human wings apart-like，hWAPL）基因是最近几年来发现的一个仅在宫颈癌组织中特异性高表达的基因，具有癌基因的特性。抑制其表达，会导致宫颈癌癌细胞的死亡。人乳头瘤病毒（human papilloma virus，HPV）是公认的宫颈癌主要致病因子，其致癌基因E6和E7可使hWAPL基因高表达，阻断E6和E7的作用使hWAPL基因表达降低。综述hWAPL基因异常表达及宫颈HPV感染在宫颈癌发生发展中的作用，以及二者之间的关系。     

HPV在宫颈癌及癌前病变诊断中的意义

目的;探讨入乳头瘤病毒(HPV)在慢性宫颈炎,宫颈上皮内瘤变(CIN)以及在浸润性宫颈癌(ICC)中的表达,旨在提高宫颈癌及癌变前的诊断率。方法:将207例患者分为5组,宫颈上皮内瘤变(CIN)41例CINⅡ组38例;CINⅢ组35例;浸润性宫颈癌(ICC)组43例,慢性宫颈炎患者作为对照组50例。采用原位杂交技术(HC)方法检测其HPV表达。结果:HPV总检阳性出率为44.9%,在慢性宫颈炎(对照组)、CINⅠ～CINⅢ组以及ICC组中的阳性检出率分刖为22.0%、36.6%、50.0%、57.1%和65.1%。HPV感染与CIN及ICC关系密切;慢性宫颈炎、CINⅠ～Ⅱ组HPV显著低于CINⅢ和ICC,差异达到显著水平(P<0.05)。结论:检测高危HPV是早期诊断CINⅢ及ICC的一个重要辅助方法,在宫颈癌及癌变前诊断中具有重要意义和应用价值。     

HPV亚型在宫颈疾病中的分布特点

目的:探讨HPV亚型在宫颈疾病谱中,即从正常宫颈(慢性宫颈炎)、宫颈上皮内瘤变(CINⅠ、CINⅡ和CINⅢ)到宫颈癌连续发展中的分布特点。方法:回顾分析2005年6月～2008年6月在我院妇科因宫颈疾病就诊的189例患者HPV亚型检测的结果。结果:HPV总感染率56.1%(106/189),复合感染率22.6%(24/106)。正常者HPV感染率19.1%(12/63),检测到的HPV亚型主要是HPV52,58,53,16和33。CINⅠ者HPV感染率57.9%(22/38),最常见的HPV亚型是HPV52,其次是HPV58,16,33和18。CINⅡ者HPV感染率70.5%(31/44),HPV52,16,58,33和18等亚型最常见。CINⅢ者HPV感染率89.3%(25/28),HPV亚型以HPV16,52,58,31,33为主。宫颈癌患者,HPV阳性率100%(16/16),HPV16检测率最高,其次是HPV18,52,58和33。结论:宫颈疾病谱中最常见的高危型HPV亚型是HPV16。不同宫颈病变中HPV亚型感染的差异可能反映了其潜在转归能力,同时提示临床医师应关注宫颈疾病患者高危HPV亚型情况。     

人类疱疹病毒6型及人乳头瘤病毒16型感染与宫颈癌发生、发展关系的研究

目的 :研究人类疱疹病毒 6型 (hHV 6 )及人乳头瘤病毒 16型 (hPV 16 )感染与宫颈癌发生、发展的关系。方法 :应用巢式多聚酶链反应 (nested PCR)检测hHV 6及多聚酶链反应 (PCR)检测hPV 16在 16份正常宫颈、2 0份宫颈炎症、6份宫颈上皮内瘤样病变 (CIN)Ⅰ～Ⅱ级及 34份宫颈癌组织中的感染情况。结果 :宫颈癌组织中hHV 6DNA阳性率为 6 1.76 % (2 1/34) ,明显高于正常组、炎症组及CINⅠ～Ⅱ级组 (P <0 .0 1)。宫颈癌组织中hPV 16DNA阳性率为 76 .4 7% (2 6 /34) ,明显高于正常组的 12 .5 0 %和炎症组的15 .0 0 % (P <0 .0 1)。 2 1份hHV 6DNA阳性组织中的hPV 16DNA也全部阳性 ,二者在宫颈癌组织中呈高度一致性。随着宫颈癌临床期别的增加 ,hHV 6和hPV 16DNA阳性率均呈递减趋势 ,但差异不显著 (P >0 .0 5 )。结论 :hHV 6感染与宫颈癌的发生密切相关 ,可能是宫颈癌的致病因子 ,作为“促进子”(promoter)与hPV 16协同促使宫颈癌进展。     

人半翼基因及HPV感染与宫颈癌发生发展的关系

人半翼(human wings apart-like,hWAPL)基因是最近几年来发现的一个仅在宫颈癌组织中特异性高表达的基因,具有癌基因的特性.抑制其表达,会导致宫颈癌癌细胞的死亡.人乳头瘤病毒(human papilloma virus,HPV)是公认的宫颈癌主要致病因子,其致癌基因E6和E7可使hWAPL基因高表达,阻断E6和E7的作用使hWAPL基因表达降低.hWAPL基因异常表达及宫颈HPV感染在宫颈癌发生发展中的作用,以及二者之间的关系.     

外阴癌中HPV感染与p53、MDM2表达的关系

目的 :探讨HPV6/ 11、16/ 18在外阴癌组织中的感染情况及与p5 3、MDM2蛋白表达的关系。方法 :用原位杂交法 (ISH)检测HPV6/ 11、16/ 18在 30例外阴癌、2 1例外阴上皮内瘤变 (VIN)及 10例外阴正常皮肤组织中的表达。同时用免疫组化SP法检测p5 3、MDM2蛋白的表达。结果 :HPV6/ 11、16/ 18在外阴癌、VIN中的阳性表达率分别为 60 % (18/30 )、33.33% (10 / 30 ) ,4 2 .86% (9/ 2 1)、2 8.5 7% (6/ 2 1) ,正常对照组没有表达。p5 3、MDM2蛋白在外阴癌、VIN、正常对照组中的阳性表达率分别为 63.33% (19/ 30 )、4 0 .0 0 % (12 / 30 ) ,4 7.62 %(10 / 2 1)、5 2 .38% (11/ 2 1) ,0 % (0 / 10 )、0 % (0 / 10 )。HPV6/ 11的表达在外阴癌组、VIN组与正常组差异有显著性 (P <0 .0 5 ) ,外阴癌组HPV16/ 18表达与正常组差异有显著性 (P <0 .0 5 )。外阴病变各组p5 3、MDM2与正常组差异有显著性 (P <0 .0 5 )。结论 :HPV6/ 11、HPV16/ 18、p5 3、MDM2蛋白在外阴组织的不同病变中表达均差异有显著性 ,在外阴癌的发生发展中HPV感染、p5 3突变和MDM2表达可能起一定的作用     

Methylation of HPV16 genome CpG sites is associated with cervix precancer and cancer

Objective.

Invasive cervix cancer (ICC) is the second most common malignant tumor in women. Human papillomavirus 16 (HPV16) causes more than 50% of all ICC and is a major cause of cervix intraepithelial neoplasia (CIN). DNA methylation is a covalent modification predominantly occurring at CpG dinucleotides. Such epigenetic modifications are associated with changes in DNA-protein interactions and gene activation. This study examined the association of viral and host genomic methylation patterns and cervix neoplasia.

Methods.

Exfoliated cervical lavage samples positive for HPV16 from women with and without cytomorphic changes of infection (n = 46), CIN2 (n = 12), and CIN3+ (n = 27) were used to interrogate the methylation patterns of the HPV16 L1 gene and upstream regulatory region (URR), five host nuclear genes (TERT, RARB, DAPK1, MAL, and CADM1), and mitochondrial DNA (mtDNA). DNA isolated from exfoliated cervicovaginal cells was treated with bisulfite, specific regions of the viral and host genome were PCR amplified and CpG methylation was quantified using EpiTYPER and pyrosequencing.

Results.

Methylation at 14 of the tested CpG sites within the HPV16 L1 region were significantly higher in CIN3+ compared to HPV16 genomes from women without CIN3+. In contrast, 2/16 CpG sites in HPV16 URR, 5/5 in TERT, 1/4 in DAPK1 and 1/3 mtDNA, and 2/5 in RARB were associated with increased methylation in CIN3+.

Conclusions.

These results indicate that increased methylation of CpG sites in the HPV16 L1 ORF is associated with CIN3+ and, thus, may constitute a potential biomarker for precancerous and cancerous cervix disease.     

Coexistent squamous cell carcinoma and adenoid basal carcinoma in the uterine cervix and infection with human papillomavirus (HPV 31)

ObjectiveAdenoid basal carcinoma (ABC) is an uncommon neoplasm of the uterine cervix. ABC can be accompanied by carcinoma in situ or invasive carcinoma. Most cases are discovered accidentally during radical hysterectomy. ABC is associated with a high risk of human papillomavirus infection (HPV), most often HPV 16 infection.Case reportWe present a rare case of an 86-year-old Taiwanese married woman who suffered from bloody vaginal discharge and occasional lower abdominal pain and received cervical biopsy. The pathological report revealed squamous cell carcinoma (SCC) of the uterine cervix. After radical hysterectomy, bilateral salpingo-oophorectomy, and bilateral pelvic and para-aortic lymph node dissection, the final pathological report revealed SCC coexisting with ABC, and both of the components were infected by HPV 31. After receiving radiotherapy, she maintained outpatient department follow-up.ConclusionA literature review revealed that this was a rare case of combined ABC–SCC associated with HPV 31 infection. In this case, the ABC component did not affect the tumor stage because it was confined to the cervix. However, we must avoid overestimating the clinical stage because the ABC component is thought to be a benign lesion.     

Ki-67、PCNA及HPV在宫颈癌和宫颈上皮内瘤变的表达及意义

目的:研究Ki-67,增殖细胞核抗原(PCNA)在早期宫颈癌(IA~IIA期高分化)、宫颈上皮内瘤变(CINI、CINII、CINIII)及慢性宫颈炎中的表达,及其与HPV感染的关系,探究3者联合应用的诊断价值。方法:应用免疫组织化学S-P法检测宫颈病变中Ki-67、PCNA抗原的表达,PCR反应检测HPV感染,结合临床病理特点分析。结果:慢性宫颈炎、CIN、宫颈鳞癌中Ki-67阳性表达率分别为33.33%、89.19%、100%。PCNA阳性表达率分别为66.67%、97.30%、100%。HPV阳性率分别是13.33%、54.05%、1000%。CINI和CINII/III中Ki-67阳性表达率分别为85.00%、94.12%;PCNA阳性表达率分别为95.00%、100.00%。HPV阳性率分别是30%、82.35%。CIN和宫颈癌中的Ki7、PCNA及HPV的阳性表达与宫颈炎相比,差异均有显著性(P<0.05)。Ki-67及PCNA过表达率在CINII/III组与CINI组间差异显著(P<0.05)。HPV阳性率在CINII/III与CINI之间差异显著(P<0.01)。Ki-67及PCNA表达与HPV感染有相关性(P<0.05)。结论:Ki-67、PCNA抗原过表达与CINII/III和早期宫颈癌显著相关。Ki-67、PCNA表达与HPV感染率相关,联合检测宫颈组织中Ki-67、PCNA的过表达及HPV感染,有助于判断细胞的增殖活性,可作为诊断早期宫颈癌和CINII/III的标记物。     

宫颈病变细胞中hTERC、c-myc基因的表达及临床意义

目的:检测各级别宫颈上皮内瘤变、宫颈癌患者端粒酶(hTERC)和c-myc基因的表达,探讨二者与宫颈癌发生发展的相关性。方法:采用FISH技术检测193例宫颈病变及52例宫颈癌患者中hTERC基因,c-myc基因的扩增情况,比较分析两种基因表达与CIN级别及宫颈癌临床病理特征的关系。结果:随宫颈病变级别加重,hTERC基因阳性扩增率呈逐渐增高趋势,组间有显著统计学差异(χ2=148.353,P=0.000)。c-myc基因随宫颈病变级别的加重,阳性率逐渐增高,组间有显著统计学差异(χ2=110.128,P=0.000)。c-myc基因阳性率随分化程度的加重而升高,G3阳性率明显高于G1/G2(χ2=6.054,P=0.014),hTERC基因则无显著差异。结论:hTERC基因,c-myc基因可作为鉴别宫颈低度癌前病变和高度癌前病变的重要辅助指标,c-myc基因可能是揭示宫颈癌进展,分化程度的重要指标。     

The relationship between single nucleotide polymorphisms in estrogen-metabolizing genes CYP1A1,CYP17,COMT and estrogen receptor alpha and the risk of endometrial adenocarcinoma among the Chinese women

<正>Objective:To explore whether polymorphisms of the genes responsible for catechol estrogen(CE)formation via estrogen biosynthesis(CYP17)and hydroxylation (CYP1A1)and CE inactivation(COMT)and ERa are associated with an elevated risk for en- dometrial adenocarcinoma in Chinese women.Methods:A multigenic case-control study was conducted,eighty-seven endometrial adenocarcinoma patients and ninety controls were recrui- ted.PCR-RFLP assays were used to determine the genotypes of estrogen-metabolizing genes and ERa gene.Results:The endometrial adenocarcinoma risk associated with individual susceptibili- ty genotypes varied among the six polymorphic sites and was the highest for CYP17,followed by CYP1 A1 Ile-Val,CYP1A1 MspI,COMT,ERa XhaI and ERa PvuII.Multivariate logistic regres- sion showed the CYP1A1 MspI genotype was the most significant determinant for endometrial adenocarcinoma development and was associated with a 3.61 fold increase in risk(95% confi- dence interval,1.73～7.55).Furthermore,a trend of increasing risk for developing endometrial adenocarcinoma was found in women harboring higher numbers of high-risk genotypes.Conclu- sion:The CYP1A1,CYP17 and ERa XbaI genotypes are related to the susceptibility of endome- trial adenocarcinoma,they may be useful markers for predicting endometrial adenocarcinoma susceptibility.The allele encoding for low acticity COMT,ERa PvuII may not be a genetic risk factor for endometrial adenocarcinoma.     

Hypermethylation of two consecutive tumor suppressor genes, BLU and RASSF1A, located at 3p21.3 in cervical neoplasias

OBJECTIVES: Although initiated by human papillomavirus (HPV), cervical carcinogenesis demands other cofactors to shape its natural course. Epigenetic effects such as DNA methylation, are considered to contribute to carcinogenesis process. METHODS: The methylation status of BLU and RASSF1A, as well as the HPV infection status, were assessed in a full spectrum of cervical neoplasia, including 45 low-grade squamous intraepithelial lesions (LSIL), 63 high-grade squamous intraepithelial lesions (HSIL), 107 squamous cell carcinomas (SCC), 23 adenocarcinomas (AC), and 44 normal control tissues. RESULTS: The BLU was methylated in 76.9% of SCC, 57.4% of HSIL, 20.0% of LSIL and 12.5% of normal tissues (P<0.001). The RASSF1A was methylated in 15% of SCC, 17.5% of HSIL, but not in LSIL or normal tissues (P<0.001). In AC, 43.5% of patients showed BLU methylation and 26.1% RASSF1A methylation, significantly higher than the corresponding control frequencies of 12.5% (P=0.005) and 0% (P=0.001), respectively. There was an insignificant trend toward loss of BLU methylation with advancing clinical stages of SCC (84.8%, 67.7%, and 63.6% in stages I, II, and III/IV, respectively; P=0.08). Patients with LSIL infected with high-risk HPV showed a higher rate of BLU methylation than those without HPV (38.8% vs 9.1%, respectively; P=0.057). The methylation of RASSF1A was inversely related to HPV infection in patients with HSIL/SCC (P=0.003). CONCLUSIONS: These results suggest that the methylation of BLU and RASSF1A genes is associated with cervical carcinogenesis, which could be clinically important in the future molecular screening of cervical neoplasia.     

MDR1基因甲基化与新疆维吾尔族、汉族宫颈癌新辅助化疗疗效的相关性

目的:探讨多药耐药基因(MDR1)启动子区的甲基化状态与新疆维吾尔族、汉族宫颈癌新辅助化疗疗效的相关性。方法:采用MassARRY EpiTYPER DNA甲基化分析技术定量分析宫颈鳞癌61例(汉族:39例,维吾尔族:22例)新辅助化疗前后及正常宫颈组织50例(汉族:30例,维吾尔族:20例)中MDR1基因启动子区22个CpG位点的甲基化状态。结果:(1)宫颈癌组的平均甲基化率均低于正常宫颈组,汉族除了CpG-11,CpG-12、13,CpG-23,CpG-30,维吾尔族除了CpG-5,CpG-11,CpG-12、13,CpG-19、20,CpG-22,CpG-23,CpG-25、26、27外,其余CpG单位差异均有统计学意义(P<0.05)。(2)在维吾尔族、汉族化疗前宫颈癌平均甲基化率比较中发现,CpG-5,CpG-7,CpG-8,CpG-19、20,CpG-23,CpG-25、26、27,差异有统计学意义(P<0.05)。(3)宫颈癌新辅助化疗后的平均甲基化率低于化疗前,汉族CpG-7,CpG-8,CpG-12、13,CpG-18,CpG-23及维吾尔族的CpG-7,CpG-8,CpG-12、13,CpG-18,CpG-19、20,CpG-25、26、27,CpG-30差异有统计学意义(P<0.05)。(4)新辅助化疗耐药组的平均甲基化率低于敏感组,汉族CpG-2、3、4及维吾尔族CpG-6,CpG-7,CpG-8,CpG-12、13,CpG-19、20,CpG-23,CpG-30差异有统计学意义(P<0.05)。结论:MDR1基因启动子区部分CpG岛的异常甲基化与宫颈癌的新辅助化疗疗效密切相关,且在维吾尔族、汉族之间存在一定差异。     

p27~(kip1)和p57~(kip2)在宫颈癌组织中的表达及其预后意义

目的:探讨细胞周期调控抑制因子p27~(kip1)和p57~(kip2)在宫颈癌发生发展中的作用及预后意义。方法:采用免疫组化二步法检测p27~(kip1)和p57~(kip2)在48例宫颈癌(宫颈癌组)、13例宫颈上皮内瘤变(CIN组)和15例正常宫颈组织(正常组)中的表达。结果:p27~(kip1)和p57~(kip2)在宫颈癌组中的阳性表达率分别为25·00%和20·83%,显著低于正常组和CIN组(P<0·01,P<0·01),而后两组比较差异无统计学意义(P>0·05)。p27~(kip1)表达与宫颈癌病理分化程度显著相关(P<0·01);p57~(kip2)表达与宫颈癌病理分化程度及肿瘤大小有关(P<0·05,P<0·05);两者均与临床分期、组织学类型及淋巴结转移无关(均P>0·05)。p27~(kip1)与p57~(kip2)表达呈极显著正相关(r=0·621,P<0·01)。Kaplan-Meier单因素分析宫颈癌患者生存时间与p27~(kip1)及p57~(kip2)阳性表达有关(P<0·05,P<0·01)。结论:p27~(kip1)和p57kip2的低表达或缺失可能在宫颈癌发生发展中起重要作用,可能与预后不良有关。     

宫颈癌染色体微卫星不稳定性与人乳头瘤病毒感染状态分析

目的 分析宫颈癌组织染色体微卫星不稳定性与人乳头瘤病毒(HPV)感染状态并探讨其与临床病理参数的关系。方法 2001年7月至2003年1月中国医科大学第二临床学院及辽宁省肿瘤医院应用PCR-聚丙烯酰胺凝胶一硝酸银银染技术，检测60例宫颈癌组织3p染色体3个位点微卫星不稳定性与HPV感染状态。结果 23例宫颈癌组织存在微卫星不稳定(38．3％)，微卫星不稳定性与分期、组织学类型及病理分级有关，与HPV感染无关。结论 微卫星不稳定性是一个独立于HPV感染之外的因素，在宫颈癌尤其腺癌的发展过程中起重要作用，并与宫颈癌预后有关，