宫颈癌患者血清TNF-α、STNFR水平及其与临床关系的研究

目的：探讨肿瘤坏死因子-α(TNF-α)、可溶性肿瘤坏死因子受体(STNFR)与宫颈癌发生、发展及淋巴转移的关系。方法：用双抗体夹心ELISA法检测宫颈癌42例和宫颈上皮内瘤变(CIN)14例血清TNF-α和STNFRⅠ、STNFRⅡ,并与正常34例对照。结果：宫颈癌患者血清TNF-α、STNFRⅠ、STNFRⅡ以及CIN患者STNFRⅠ、STNFRⅡ水平较正常对照组明显增高(P＜001);Ⅱ期宫颈癌患者血清STNFRⅠ、STNFRⅡ水平与Ⅰ期患者相比,差异无显著性;宫颈癌有淋巴转移组患者血清STNFRⅠ、STNFRⅡ水平明显高于无淋巴转移组(P＜00001);经相关分析STNFRⅠ、STNFRⅡ在宫颈癌、宫颈癌淋巴转移组、宫颈癌无淋巴转移组及正常对照组均呈正相关关系,仅CIN组无明显正相关。结论：TNF-α、STNFR与宫颈癌的发生发展有关,STNFR可能是判断宫颈癌是否发生淋巴转移较好的监测指标,对判断预后有重要价值。     

子宫颈上皮癌前病变及子宫颈癌的细胞核

目的探讨宫颈上皮癌变过程中的细胞生物学特征及其变化规律,为临床诊治提供依据.方法收集125份宫颈组织行病理检查,按病变程度不同分为,正常宫颈上皮11份、宫颈上皮内瘤变Ⅰ级(CINⅠ)22份、宫颈上皮内瘤变Ⅱ级(CINⅡ)17份、宫颈上皮内瘤变Ⅲ级(CINⅢ)13份和宫颈鳞癌55份(其中高、中、低分化宫颈鳞癌分别为13、19、23份),以及宫颈腺癌7份.组织切片分别行福根(Feulgen)染色,并以计算机检测其DNA平均倍体值(DMP)、DNA指数(DI)、核面积,打印DNA倍体直方图.结果(1)随病变程度增高,DMP、DI和核面积测定值均依次逐渐增高,正常宫颈上皮与CINⅠ、CINⅡ3者间比较,除正常宫颈上皮与CINⅡ的DI和核面积、CINⅠ与CINⅡ的核面积比较,差异有显著性(P＜0.05)外,其余差异均无显著性(P＞0.05);而宫颈癌与CINⅠ、CINⅡ比较,差异均有极显著性(P＜0.01);高、中、低分化宫颈鳞癌3者间比较,差异也均无显著性.(2)官颈不同病变的DNA倍体直方图各有特点,超5倍体(5C)细胞在CINⅢ病变组织中开始增多,5C、7C和9C细胞在鳞癌病变组织中显著增加.结论宫颈上皮癌变是一个渐进的、由量变到质变的过程.CINⅢ是非癌到癌的变化阶段.     

子宫颈上皮内瘤变端粒酶活性的研究

目的探讨端粒酶激活在宫颈癌变过程中的意义及其作为病情监测方法和预测宫颈上皮内瘤变(CIN)结局的可能性.方法采用端粒重复序列扩增-聚合酶链反应(PCR-TRAP)方法检测了64例CIN患者、21例宫颈癌患者、20例慢性宫颈炎患者及15例正常宫颈妇女宫颈脱落细胞、宫颈活组织检查(活检)组织的端粒酶活性.结果正常宫颈、慢性宫颈炎、CINⅠ级(CINⅠ)、CINⅡ级(CINⅡ)、CINⅢ级(CINⅢ)及宫颈癌患者的宫颈脱落细胞端粒酶的阳性表达率分别为20.0%、25.0%、62.5%、60.0%、82.4%及61.9%;对应的活检组织端粒酶的阳性表达率分别为26.7%、30.0%、50.0%、45.0%、96.4%及95.2%;随着宫颈病变的进展,端粒酶阳性表达率呈逐渐增高趋势(X2细胞=16.28、X2组织=36.98,P均＜0.05).CINⅠ、CINⅡ端粒酶阳性表达率比较,差异无显著性(P细胞=0.24、P组织=0.25);CINⅢ端粒酶阳性表达率高于CINⅠ、CINⅡ(P细胞=0.03、P组织=0.000012);CINⅢ与宫颈癌活检组织端粒酶阳性表达率比较,差异无显著性(P=0.05);宫颈脱落细胞与宫颈活检组织的端粒酶检测结果的对应性良好(X2=46.4,P＜0.05).结论端粒酶激活与宫颈癌变的进程有关,宫颈脱落细胞端粒酶活性检测可以作为CIN病情检测、处理及预后估计的辅助指标.     

子宫颈癌组织中水通道蛋白8和bcl-2蛋白的表达及其相关性

目的 探讨水通道蛋白(AQP)8、bcl-2蛋白在宫颈癌组织中的表达及其相关性.方法 采用免疫组化Envision二步法检测AQP8和bcl-2蛋白在74例宫颈癌(其中鳞癌46例、腺癌28例)、34例宫颈上皮内瘤变(CIN)和15例正常宫颈组织中的表达情况,并分析两者的相关性.结果 AQP8和bcl-2蛋白主要在CIN异型细胞和宫颈癌细胞的细胞质内表达,AQP8蛋白在宫颈鳞癌、腺癌、CIN和正常宫颈组织中的阳性表达率分别为98%、61%、71%和53%,鳞癌高于腺癌、CIN和正常宫颈组织,差异有统计学意义(P＜0.01);腺癌与CIN、正常宫颈组织比较,CIN与正常宫颈组织比较,差异均无统计学意义(P＞0.05).bcl-2蛋白在宫颈鳞癌、腺癌、CIN和正常宫颈组织中的阳性表达率分别为74%、71%、53%和20%,鳞癌与腺癌组织比较,差异无统计学意义(P＞0.05);鳞癌、腺癌高于CIN、正常宫颈组织,CIN也高于正常宫颈组织,差异均有统计学意义(P＜0.01).AQP8和bcl-2蛋白在宫颈癌组织中的表达呈明显正相关(rs=0.463,P=0.000).结论 AQP8和bcl-2蛋白在宫颈癌组织中的表达呈明显正相关,AQP8蛋白表达上调可能与宫颈癌的发生、发展有一定的关系.     

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。     

CD1a和E-cadherin在宫颈上皮内瘤变中的表达

目的:探讨CD1a和E-cadherin与宫颈癌发生发展的关系及作为早期癌变生物学指标的可能性。方法:采用免疫组化SP法检测CD1a和E-cadherin在同期56例宫颈上皮内瘤变、56例宫颈鳞癌和15例正常宫颈组织中的分布及表达。结果:(1)CD1a+朗格汉斯细胞在正常宫颈、CIN和宫颈癌各组中数量逐渐减少,两两比较有显著差异(P0.01);CIN中该细胞数量随病变严重程度减少,CINⅠ和CINⅡ、CINⅠ和CINⅢ组之间两两比较有显著差异(P0.05),而CINⅡ与CINⅢ组间无显著差异(P0.05);(2)E-cadher-in在正常宫颈、CIN和宫颈癌各组中的阳性表达率及强度逐渐下降,两两比较有显著差异(P0.05);在CIN中阳性表达率及表达强度随病变严重程度呈下降趋势,CINⅠ和CINⅡ、CINⅠ和CINⅢ之间两两比较有显著差异(P0.05),而CINⅡ和CINⅢ之间无显著差异(P0.05);(3)宫颈组织中CD1a+朗格汉斯细胞的细胞数与E-cadherin的阳性表达率及强度呈正相关(r=0.912,P0.05)。结论:CD1a+朗格汉斯细胞与E-cadherin可能在宫颈癌的发生、发展过程中起重要作用。     

分析人雄激素受体基因判断子宫颈癌及子宫颈上皮内瘤变组织的克隆状态

目的　通过分析人雄激素受体 (humanandrogenreceptor,HUMARA)基因 ,检测宫颈癌及宫颈上皮内瘤变 (CIN)组织的X染色体失活方式 ,从而判断其克隆状态。方法　对 2 6例宫颈浸润性癌 (宫颈癌组 )、31例CIN(CIN组 )及 33例正常宫颈 (正常宫颈组 )组织标本 ,提取其DNA ,经甲基化敏感性限制性核酸内切酶HhaⅠ消化后 ,对HUMARA基因片段行PCR扩增并电泳 ,通过观察电泳条带判断其克隆状态。结果　HUMARA基因的杂合率为 89%。宫颈癌组、CIN组及正常宫颈组组织的单克隆率分别为 92 %、38%和 10 % ,宫颈癌组分别与CIN组及正常宫颈组比较 ,差异均有极显著性 (P <0 0 0 1) ,CIN组与正常宫颈组比较 ,差异有显著性 (P =0 0 12 )。宫颈癌组中 ,临床分期Ⅰ、Ⅱ、Ⅲ期组织的单克隆率分别为 6 / 7、90 % (9/ 10 )及 7/ 7,两两比较 ,差异均无显著性 (P >0 0 5 )。CIN组中 ,CINⅠ、Ⅱ、Ⅲ组织的单克隆率分别为 2 0 % (2 / 10 )、38% (3/ 8)及 6 3% (5 / 8) ,呈逐级增高趋势 ,但各级CIN间比较 ,差异均无显著性 (P >0 0 5 )。结论　宫颈癌是癌细胞克隆性增殖的结果。对单克隆状态的CIN应给予积极干预或严密随访。HUMARA基因分析可能成为研究宫颈癌发生机制的一种分子生物学检测手段。     

人染色体端粒酶基因的扩增率与宫颈癌前病变和宫颈癌的研究

目的:探讨人染色体端粒酶基因(hTERC)扩增率与宫颈癌前病变及宫颈癌的关系.方法:应用荧光原位杂交技术(FISH)检测宫颈上皮内瘤变(CIN)组108例(CIN Ⅰ 39例、CINⅡ37例、CINⅢ32例),宫颈癌组24例和正常对照组33例,共165例宫颈脱落细胞中hTERC基因的表达情况.结果:CINⅡ、CINⅢ和...     

宫颈癌发生中细胞凋亡与p53基因蛋白及HPV感染的相关性

目的探讨子宫颈癌发生中细胞凋亡与p53基因蛋白表达及高危型人乳头样病毒(HPV)感染的关系.方法检测对象为正常宫颈鳞状上皮(NE)41例、重度非典型增生(SD)41例、原位癌(CIS)37例、早期浸润癌(MIC)31例、大细胞非角化型浸润癌(IC)40例共计190例手术切除福尔马林固定、石蜡包埋的组织标本.凋亡细胞的检出使用TDT-mediateddUTP-biotinnickendlabeling(TUNEL)方法,p53基因蛋白表达采用单克隆抗体免疫组织化学ABC染色方法,HPV16、18型E6DNA感染使用PCR方法进行检测.结果TUNEL标记率从NE到CIS组呈现有意义地减少(P＜0.01);在SD、CIS组,p53基因蛋白超表达者TUNEL标记率呈现有意义的低值(P＜0.05);高危型HPV感染与宫颈癌的发生有关,与细胞凋亡、p53基因蛋白表达未呈现直接的相关性改变.结论细胞凋亡参与宫颈癌发生的早期过程,其与p53基因蛋白超表达有关.     

人宫颈癌脱落细胞端粒酶活性检测的意义

目的 研究宫颈上皮内瘤样病变(CIN )和宫颈癌脱落细胞端粒酶激活的意义。方法 采用端粒酶PCR-ELISA法检测13例CIN和17例宫颈癌脱落细胞端粒酶活性,并与相应的组织标本中端粒酶活性相比较,11例正常宫颈脱落细胞作为对照。结果8例(61.54％)CIN、14例(82.35％)宫颈癌脱落细胞表达端粒酶活性,正常宫颈无端粒酶活性,CIN、宫颈癌及正常宫颈脱落细胞端粒酶活性平均值分别为0.328±0.192、1.329±0.259和0.039±0.084,三组间端粒酶表达率和量存在显著差异。CINⅠ、Ⅱ、Ⅲ级之间端粒酶活性无明显差异。CIN及宫颈癌组织中端粒酶活性和相应脱落细胞一致。结论 端粒酶的激活是宫颈癌的早期改变,在宫颈癌发生发展过程中起重要作用;宫颈脱落细胞和组织中端粒酶活性可能成为宫颈癌早期诊断、预后判断和肿瘤浸润的标记物。     

HSP70在子宫颈鳞癌中的表达及与P53、c-myc表达的关系

目的 :探讨热休克蛋白 70 (heatshockprotein 70 ,HSP70 )在宫颈鳞癌组织中的表达 ,以及它与抑癌基因p5 3、原癌基因c myc表达之间的关系。方法 :采用免疫组化SABC法检测正常宫颈上皮组织、癌前病变宫颈上皮组织和浸润性宫颈鳞癌组织中HSP70、P5 3蛋白、c myc蛋白的表达 ,并分析其相互关系。结果 :HSP70在正常宫颈上皮组织、癌前病变宫颈组织和浸润性宫颈鳞癌组织中的免疫组化记分呈递增趋势 ,两两相比差异有显著性。HSP70免疫组化记分随鳞癌组织分化程度降低而升高。浸润性宫颈鳞癌中P5 3蛋白阳性组和c myc蛋白阳性组HSP70组织化学记分分别高于P5 3阴性组和c myc阴性组。结论 :HSP70表达与宫颈鳞癌发生发展有关 ,且与较低分化程度有关。HSP70可能通过与P5 3蛋白和c myc蛋白之间某种相互作用参与宫颈鳞癌的发生发展     

子宫颈上皮内瘤变及子宫颈鳞癌中增殖细胞核抗原和C-myc基因过度表达及其临床意义

目的：研究增殖细胞核抗原（ＰＣＮＡ）及Ｃ－ｍｙｃ基因过度表达在子宫颈上皮内瘤变（ＣＩＮ）及子宫颈鳞癌中的变化及其临床意义。方法：用免疫组化方法检测ＣＩＮ及子宫颈鳞癌手术标本石蜡包埋切片中的ＰＣＮＡ及Ｃ－ｍｙｃ基因蛋白变化并分析子宫颈癌临床病理资料。结果：从正常子宫颈、ＣＩＮ到子宫颈鳞癌，ＰＣＮＡ含量及Ｃ－ｍｙｃ阳性表达呈增高趋势。ＣＩＮⅢ及子宫颈鳞癌的ＰＣＮＡ标记指数（ＰＣＮＡＬＩ）及Ｃ－ｍｙｃ阳性表达明显高于正常子宫颈及ＣＩＮⅠ－Ⅱ，并且Ｃ－ｍｙｃ基因阳性表达与ＰＣＮＡ大量出现呈正相关。ＰＣＮＡＬＩ及Ｃ－ｍｙｃ阳性表达随细胞分化程度而增加。子宫颈鳞癌分期及有无淋巴结转移对ＰＣ－ＮＡＬＩ及Ｃ－ｍｙｃ阳性表达差异无显著性。结论：检测ＣＩＮ及子宫颈鳞癌中ＰＣＮＡ数量及Ｃ－ｍｙｃ基因表达可了解宫颈癌的发生、发展，早期发现癌前病变及估计肿瘤的恶性潜能。     

The possible role of p53 and bcl-2 expression in cervical carcinomas and their premalignant lesions

OBJECTIVE: The purpose of this study was to assess the expression and clinical significance of bcl-2 and p53 in the progression of cervical neoplasias. METHODS: One hundred seventy-one cervical specimens, consisting of normal cervical epithelium (n = 13), lesions with histological features of HPV infection (n = 14), CIN (cervical intraepithelial neoplasia) lesions (n = 63), and cervical carcinomas (n = 81) were examined immunohistochemically in paraffin sections. RESULTS: Twenty-three specimens showed p53 expression [3/20 (15%) CIN III, 18/63 (29%) ISCC (invasive squamous cervical carcinoma), and 2/18 (11%) adenocarcinomas] while 63 cases expressed the bcl-2 gene [10/13 (77%) normal, 0/14(0%) condylomas, 6/23 (26%) CIN I, 9/20 (45%) CIN II, 15/20 (75%) CIN III, 18/63 (29%) ISCC, and 5/18 (28%) adenocarcinomas]. The expression of bcl-2 was found to increase in direct relation to the grade of CIN (P = 0.02) whereas such a trend was not observed for p53. p53 was not detected in normal or premalignant lesions (except 3 out of 20 cases of CIN III). There was no significant correlation between the expression of p53 and the histological type of cervical carcinoma, even though expression of p53 was higher in ISCC than in adenocarcinomas (29% vs 11%, respectively). In cervical cancer patients, expression of bcl-2 was correlated to a greater than 5-year survival (P < 0.01) while no prognostic significance of p53 expression was found. CONCLUSION: Evaluation of bcl-2 expression may provide additional and independent prognostic information for the clinical course of the disease and therefore to be developed as a prognostic indicator for cervical cancer.     

Expression of bcl-2 and bax in cervical intraepithelial neoplasia and invasive squamous cell carcinoma of the uterine cervix

Bcl-2 protein together with the pro-apoptotic protein bax, are thought to function by forming homo- and heterotypic dimers which control the progression to apoptosis. In this immunohistochemical study we investigated the expression of bcl-2 and bax apoptosis related proteins in cervical intraepithelial neoplasia and invasive squamous cell carcinoma of the uterine cervix. Twenty-four cervical intraepithelial neoplasias grade 1-2 (CIN I/II), 38 grade 3 (CIN III), and 53 invasive squamous cell carcinomas (ISCC) were investigated by immunohistochemical staining for bcl-2 and bax protein. Bcl-2 immunoreactivity was found in five of the 24 CIN I/II cases (20.8%), 18 of 38 CIN II cases (47.4%) and nine of 53 ISCC cases (17%). The positivity for CIN III was significantly higher than for CIN I/II or ISCC (p=0.0351 and p=0.0018, respectively). The percentage of bax immunopositivity was somewhat higher in CIN III than in CIN I/II but this slight difference was not statistically significant. Correlation of the immunostaining results with tumor grade revealed a significant difference for bcl-2 which was more frequently immunopositive in well-differentiated tumors than in poorly-differentiated tumors. There was no significant relation between bax expression and tumor differentiation. Our results suggest that alterations of bcl-2 and bax expression may occur as a relatively early event in cervical tumorigenesis.     

Twist2和E-cadherin在宫颈鳞癌中的表达及意义

目的：研究Twist2与E-cadherin在宫颈上皮内瘤样变（CIN）及宫颈鳞状细胞癌中的表达情况,探讨其在宫颈癌变过程中的作用及意义。方法：应用蛋白质免疫印迹（Western blot）和免疫组织化学法检测Twist2、E-cadherin在正常宫颈组织（对照组）、CINⅠ组、CINⅡ～Ⅲ组、宫颈鳞癌组中的表达情况。结果：Twist2和E-cadherin在4组中阳性表达率比较差异有统计学意义（χ2=48.163,P=0.000;χ2=43.169,P=0.000）。宫颈鳞癌Twist2、E-cadherin的阳性表达率在不同分化程度、临床分期、有无淋巴结转移组间差异有统计学意义（P＜0.05）,在不同年龄间差异无统计学意义（P＞0.05）。Twist2与E-cadherin在宫颈鳞癌组织中的表达呈负相关（r=-0.401,P=0.003）。对照组、CIN组、宫颈鳞癌组间Twist2、E-cadherin的相对表达量差异有统计学意义（F=652.225,P=0.000;F=299.112,P=0.000）。结论：Twist2、E-cadherin可能共同参与了宫颈鳞状细胞癌的恶性转化过程,联合检测Twist2与E-cadherin有助于判断宫颈癌的恶性程度及其预后。     

The role of p53, Bcl-2 and Ki-67 in premalignant cervical lesions and cervical cancer

PURPOSE: The aim of this study was to determine the role of p53, Bcl-2 and Ki-67 expression in the carcinogenesis of cervical carcinoma and aggressiveness of cervical intraepithelial neoplasia (CIN). METHODS: The pathology specimens of 63 patients with a diagnosis of normal squamous epithelium (22 cases), CIN I (14), CIN II (5), CIN III (8) and squamous cell carcinoma (14) were evaluated immunohistochemically for the expression of p53, Bcl-2 and Ki-67 in paraffin sections. RESULTS: The expression of p53 and Ki-67 increased proportionally to the grade of CIN and cervical cancer, but only the increase of p53 expression was statistically significant (p = 0.002). There was no significant correlation between Bcl-2 expression and premalignant and malignant cervical lesions. CONCLUSION: p53 expression may have a role in the carcinogenesis of squamous cell cervical carcinoma whereas Bcl-2 expression has no role. Ki-67 expression can not be used in determining the aggressiveness of CIN lesions.     

新疆地区维汉妇女宫颈病变组织中Survivin与p16~(INK4a)表达的研究

目的:探讨新疆地区维汉妇女宫颈疾病及其癌变组织中Survivin蛋白与p16INK4a蛋白的表达及意义。方法:采用免疫组化SP法,检测240例新疆地区维汉妇女宫颈病变组织中Survivin蛋白和p16INK4a蛋白的表达。维汉妇女各120例,依据病理诊断结果分为4组,非瘤变组(正常及慢性炎症组)30例,CINⅠ组30例,CINⅡ～Ⅲ组30例,宫颈鳞癌组30例。结果:宫颈病变组织中Survivin与p16INK4a蛋白在维、汉族之间的表达差异无显著性(P>0.05);随着宫颈病变程度的上升,不同组别之间Survivin与p16INK4a蛋白的表达有显著差异(P<0.05),但在CINⅡ～Ⅲ组与宫颈鳞癌组之间的表达无统计学意义(P>0.05)。结论:Survivin蛋白和p16INK4a蛋白表达与宫颈疾病及其癌变的发生关系密切,呈正相关;Survivin蛋白和p16INK4a蛋白在新疆地区维汉妇女宫颈病变及其癌变中表达不存在民族差异。     

Increased expressions of claudin-1 and claudin-7 during the progression of cervical neoplasia

OBJECTIVES: Claudin proteins represent a large family of integral membrane proteins crucial for tight junction formation and function and they have been shown to be expressed differently in various cancers. We investigated whether the expressions of claudin-1 and claudin-7 are associated with the progression of uterine cervical neoplasia. METHODS: We analyzed 89 formalin-fixed paraffin embedded cervical tissues that included 10 normal cervical epithelium, 19 low-grade squamous intraepithelial lesion (LSIL), 20 high-grade squamous intraepithelial lesion (HSIL), 20 invasive squamous cell carcinoma (ISCC) without lymph node (LN) metastasis, and 20 ISCC with LN metastasis. The expressions of claudin-1 and claudin-7 were determined by immunohistochemistry. RESULTS: The expressions of claudin-1 and claudin-7 were undetectable in normal cervical squamous epithelium, but had variable staining in the basal layer of normal endocervical glands. The expressions of both proteins, mainly as membranous staining, gradually increased in accordance with the progression from LSIL to HSIL and ISCC (both P values are <0.001) and were detected in all cases of ISCC. CONCLUSIONS: These results suggest that claudin-1 and claudin-7 may play a significant role in tumor progression of cervical neoplasia and may represent useful markers for malignant transformation of cervical squamous cells. Further studies would likely result in the development of novel approaches for early detection and therapy for this disease.