宫颈癌组织中MCM5和P16~(INK4A) mRNA的表达及其临床意义

目的:检测宫颈癌组织中微小染色体维持蛋白-5(minichromosome maintenance protein 5,MCM5)与P16INK4AmRNA的表达,并探讨其在宫颈癌中的临床意义。方法:采用实时荧光定量PCR(real-time PCR)检测40例宫颈鳞状细胞癌、15例低度宫颈上皮内瘤变(CINⅠ)、20例高度宫颈上皮内瘤变(CINⅡ-Ⅲ)中MCM5和P16INK4AmRNA的相对表达量,并以20例正常宫颈组织作为对照,分析其与宫颈癌临床病理特征的关系。结果:(1)随着宫颈病变程度的加重,MCM5和P16INK4AmRNA的表达量逐渐增高。宫颈癌组织中MCM5和P16INK4AmRNA的表达量分别是正常宫颈组织的(3.026±1.210)倍和(2.540±0.718)倍,差异具有统计学意义(P0.05)。宫颈癌组织中MCM5 mRNA的表达量明显高于CINⅠ、CINⅡ-Ⅲ(P0.05),CINⅠ、CINⅡ-Ⅲ中MCM5 mRNA的表达量均显著高于正常宫颈组织,差异具有统计学意义(P0.05),而CINⅠ与CINⅡ-Ⅲ比较差异无统计学意义(P0.05);宫颈癌组织中P16INK4AmRNA的表达量为正常宫颈组织的(2.54±0.86)倍,差异有统计学意义(P0.05),亦显著高于CINⅠ,差异具有统计学意义(P0.05),但与CINⅡ-Ⅲ比较差异无统计学意义(P0.05)。(2)在宫颈癌组织中,MCM5 mRNA的表达量与肿瘤的临床期别、分化程度显著相关(P0.01),但与患者的年龄无关(P0.05);P16INK4AmRNA的表达量与肿瘤的临床期别、年龄均无关(P0.05),但与肿瘤的分化程度相关(P0.01)。结论:MCM5、P16INK4A的高表达可能在宫颈癌的发展中起重要作用。MCM5基因检测有助于区分癌前病变和宫颈癌,有望成为宫颈癌肿瘤增生的新标志物。P16INK4A的检测在宫颈病变筛查中具有重要意义,有助于CIN的分级并预测转归,从而提高宫颈癌筛查率。     

p16和bcl-2在宫颈上皮瘤样病变及宫颈癌中的表达

目的探讨p16和bcl-2表达产物在宫颈上皮瘤样病变及宫颈癌中表达的意义。方法对正常宫颈鳞状上皮、宫颈上皮内瘤变(CIN)和宫颈癌组织共69例,采用免疫组织化学EliVision法,对宫颈癌变过程中p16和bcl-2蛋白进行研究,将结果进行统计分析。结果p16蛋白在CIN中的表达高于正常宫颈上皮(P<0.01),在宫颈癌中的表达也高于正常宫颈上皮(P<0.01),且高于CIN中的表达(P<0.05);bcl-2蛋白在CIN中的表达高于正常宫颈上皮(P<0.01),在宫颈癌中的表达也高于正常宫颈上皮(P<0.01),但与CIN中表达无差异。p16和bcl-2两种蛋白在CIN和宫颈癌中的表达无明显差异。结论p16和bcl-2蛋白的表达与宫颈癌的发生有关,提示这两种蛋白有可能作为高危人群早期筛查的一种免疫组化指标。     

宫颈鳞癌演进过程P16INK4a及Hh-Gli信号通路相关蛋白表达及其相关性研究

探讨P16^INK4a及Sonic hedgehog(Hh-Gli)信号通路蛋白在宫颈癌及癌前病变(CIN)中的表达相关性及其意义．采用Western-blot方法检测HPV16阳性及HPV18阳性宫颈癌细胞系P16^INK4a及Hh-Gli信号通路蛋白Smo、Ptch及Gli表达．免疫组化检测组织芯片P16^INK4a、Shh、Smo、Ptch及Gli表达,包括20例正常宫颈、18例癌旁组织、54例CIN及28例宫颈鳞癌组织．分析P16^INK4a与Hh-Gli信号通路蛋白间表达相关性及与临床病理因素的关系．结果显示P16^INK4a、Smo、Ptch及Gli蛋白在HPV16及HPV18阳性宫颈癌细胞系中表达无显著差异(P>0.05)．P16^INK4a、Shh、Smo、Ptch及Gli蛋白在宫颈癌中表达强度显著高于癌旁及正常组织(P<0.05),在CINⅠ与正常组织间差异不显著(P>0.05)．P16^INK4a、Shh、Smo及Gli蛋白,在CINⅠ、CINⅡ与CINⅢ之间均有显著性差异(P<0.05)．相关分析显示,CINⅡ-CINⅢ中P16^INK4a与Shh和Smo蛋白表达正相关,浸润癌中P16^INK4a与Shh、Smo和Gli蛋白正相关．结论认为,P16^INK4a及Hh-Gli信号通路异常激活与宫颈癌发生及演进密切相关,且二者间具有相关性．Hh-Gli信号通路的激活可能是Shh配体增高调控Smo高表达而上调Gli蛋白所致．     

TGF-β1对人正常胎盘滋养层细胞表达E-钙粘素的调节

E-钙粘素是在胚胎发育中最早表达的分子之一,它可以与Catenin家族成员形成钙粘素/Catenin复合物参与多种细胞功能,对于胚胎植入和胎盘发生具有重要作用.通过RT-PCR、免疫组织化学、细胞粘附分析等方法,在人正常妊娠和输卵管妊娠母胎界面上,发现E-钙粘素主要定位于绒毛细胞滋养层细胞和滋养层细胞柱,从滋养层细胞柱近端向远端,其蛋白质水平逐渐降低.正常胎盘组织中E-钙粘素水平在妊娠早期较高,妊娠中期直至分娩期均维持低水平.在体外培养的人正常胎盘细胞滋养层细胞系(NPC细胞)中,转化生长因子β(TGFβ1)显著上调E-钙粘素蛋白和mRNA的表达,并呈现时间和剂量依赖性,同时,TGFβ1促进NPC细胞之间的粘附.上述结果表明,胎盘中存在E-钙粘素的旁分泌调节机制,E-钙粘素可通过调节滋养层细胞粘附而参与细胞侵润的有节制调控.     

细胞衰老和凋亡相关蛋白表达在宫颈鳞癌变中的意义

目的:许多细胞周期调控因子和衰老相关标志物如p14ARF、p15INK4b、p16INK4a和p53在G1细胞周期阻滞和癌基因诱导的衰老中意义重大。这些关键的调节蛋白在多种恶性肿瘤中经常发生突变或是缺失。在本研究中将探讨这些因子在宫颈癌发生中的意义。方法:在本研究中在正常宫颈上皮、宫颈上皮内瘤变和宫颈鳞癌中,应用免疫组织化学方法检测p14ARF、p15INK4b、p16INK4a、Bcl-2、p53表达,并分析它们的表达与宫颈癌变的相关性。结果:p16INK4a在正常宫颈鳞状上皮10%(2/20)表达阴性,在大部分CIN和宫颈鳞癌中表达阳性,其中在85%(17/20)CIN和75%(15/20)鳞癌中呈弥漫性强阳性表达,CIN和宫颈鳞癌中的阳性表达率显著高于正常上皮(P0.01),CIN和宫颈鳞癌的间表达率无显著差异。p15INK4b在正常宫颈鳞状上皮中65%(13/20)表达弱阳性,在100%(20/20)CIN和95%(19/20)宫颈鳞癌中表达弥漫性阳性,各组之间阳性表达率无显著性差异(P0.05)。p14ARF在40%(8/20)正常宫颈上皮细胞中表达呈弱阳性(1+),在宫颈鳞癌中表达呈弥漫性强阳性90%(18/20),在45%(9/20)CIN中表达阳性,各组之间阳性表达率无显著性差异(P0.05)。Bcl-2在20%(4/20)正常宫颈上皮表达呈弱阳性,在18/20CIN中其表达强度和比率均增加,阳性表达率为90%(18/20),Bcl-2在鳞癌中700%(14/20)呈强阳性和弥漫阳性,CIN和宫颈鳞癌中的阳性表达率显著高于正常上皮(P0.01),CIN和宫颈鳞癌的间表达率无显著差异。P53免疫组化染色显示在正常宫颈上皮为表达为20%(4/20),在大多数CIN25%(5/20)和鳞癌中核阳性85%(17/20),在鳞癌中的阳性表达率显著高于正常宫颈上皮和CIN病变(P0.05)。结论:宫颈鳞癌变涉及包括细胞凋亡和细胞衰老在内的多种信号分子表达异常,这些分子可能在宫颈鳞癌发生发挥重要作用并在宫颈癌早期诊断中有重要意义。     

宫颈癌患者血浆中E-钙黏着蛋白基因启动子区的甲基化状态

肿瘤细胞可以释放DNA进入患者的血浆/血清中,并可作为无创伤性诊断肿瘤的标记物。采用甲基化特异性聚合酶链式反应(MS-PCR)结合亚硫酸盐测序法对151例宫颈癌患者血浆和对应的30例组织中E-钙黏着蛋白基因启动子区甲基化状态进行检测,并与化学发光法检测患者血清的鳞状上皮癌抗原(SCC)相比较,发现此方法的灵敏度为40.39%,特异性为100%,正确性为49.72%,血浆和组织的符合率为76.67%。宫颈炎、子宫肌瘤和正常人的血浆中均未检测到甲基化状态的存在。随着临床分期和组织学分级的增加,E-钙黏着蛋白基因甲基化的检出率也在逐渐增加,与SCC结果相比,MS-PCR方法在早期和恶性度高的宫颈癌中的诊断效果良好。使用E-钙黏着蛋白基因作为分子标记可以对宫颈癌患者进行无创伤性早期诊断和预后的评估。     

c-fos和c-jun在宫颈癌、CIN及宫颈炎中的表达及意义

目的:检测c-fos蛋白和c-jun蛋白在宫颈癌、CIN以及宫颈炎组织中的表达,并探讨其意义.方法:免疫组织化学S-P法检测23例宫颈癌、11例CINⅢ、13例CINⅡ、20例CINⅠ、10例宫颈炎组织标本中c-fos和c-jun蛋白的表达.结果:①c-fos蛋白在宫颈癌、CINⅢ、CINⅡ和CINⅠ以及宫颈炎中的表达分别为82.6%(19/23)、65.2%(7/11)、46.2%(6/13)、35.0%(7/20)、0.0%(0/10);②c-jun蛋白在宫颈癌、CINⅢ、CINⅡ、CINⅠ以及宫颈炎中的阳性表达率分别为78.3%(18/23)、54.5%(6/11)、38.5%(5/13)、30.0%(6/20)、0.0%(0/10);③c-fos和c-jun在宫颈癌、宫颈癌前病变、宫颈炎中的表达均有显著差异(H=0.000,P＜0.05);经秩相关检验分析,c-fos和c-jun在宫颈炎、宫颈癌前病变、宫颈癌中的表达呈正相关(r=0.581,P=0.000).结论:c-fos和c-jun蛋白的表达可能与宫颈癌前病变、宫颈癌的发生密切相关,两者可能在宫颈癌的发生过程中起一定的协同作用.     

E-钙粘素及相关蛋白的研究进展

E-钙粘素介导上皮细胞的同型相互作用,在形态发生、信号转导、细胞极性及组织细胞完整性的维持中起着重要作用。E-钙粘素介导的黏附功能紊乱将导致细胞间粘连松散,与肿瘤侵袭转移密切相关,与肾脏疾病的相关性也越来越受到重视。其相关蛋白在疾病的发生、发展过程中,也起了不可忽视的作用,现就E-钙粘素及相关蛋白的研究进展做一综述。     

E-钙粘素及相关蛋白的研究进展

E-钙粘素介导上皮细胞的同型相互作用,在形态发生、信号转导、细胞极性及组织细胞完整性的维持中起着重要作用。E-钙粘素介导的黏附功能紊乱将导致细胞间粘连松散,与肿瘤侵袭转移密切相关,与肾脏疾病的相关性也越来越受到重视。其相关蛋白在疾病的发生、发展过程中,也起了不可忽视的作用,现就E-钙粘素及相关蛋白的研究进展做一综述。     

共刺激分子B7-H4在宫颈癌中的表达及意义

目的:肿瘤微环境中免疫共刺激分子B7-H4与其配体结合后可提供免疫抑制信号,调控肿瘤组织中的免疫应答。本研究探讨B7-H4、Fas及Caspase-3裂解片段在宫颈鳞状细胞癌中的表达及其与临床病理因素的关系,分析其参与肿瘤免疫逃逸的机制。方法:应用免疫组织化学SP法检测23例正常宫颈上皮、38例宫颈上皮内瘤变(CIN)和132例宫颈鳞状细胞癌组织中B7-H4、Fas及Caspase-3裂解片段的表达水平,分析其与宫颈癌各临床病理因素的相关性。结果:B7-H4在正常宫颈上皮组织中不表达,在CIN组织中微弱表达,在宫颈鳞状细胞癌组织中高表达。B7-H4表达与肿瘤的临床分期、淋巴结转移、原发肿瘤大小和肿瘤浸润深度有关,B7-H4与Fas蛋白表达呈现负相关,与Caspase-3裂解片段存在共表达关系。结论:B7-H4在宫颈鳞状细胞癌中过表达可引起Fas蛋白表达下调和Caspase-3裂解片段增多,抑制肿瘤细胞发生凋亡,参与肿瘤逃避宿主的免疫监视,从而促发宫颈癌的发生和发展。阻断B7-H4通路途径,有望成为宫颈鳞状细胞癌治疗的新靶点。     

E-cadherin 在宫颈上皮内瘤变及宫颈癌中的表达及其与高危型HPV感染的相关性

目的:研究各级宫颈上皮内瘤变(CIN)及宫颈癌组织中E-cadherin的表达及其与高危型人乳头瘤病毒(high risk human papillomavirus,HR-HPV)感染的相关性探讨其在宫颈疾病发生、发展中的意义。方法:选取2008年1月至2014年12月我院收治的150例患者标本并将其分为CINⅠ级组、CINⅡ-Ⅲ级组及宫颈癌组用免疫组化法对E-cadherin的表达情况进行检测并于术前采用PCR-反向点杂交法检测患者高危型HPV感染情况所得结果:进行统计学分析。结果:(1)E-cadherin在CINⅠ级、CINⅡ-Ⅲ级及宫颈癌中的阳性表达率分别为40/50(80.0%),24/50(48.0%)、17/50(34.0%),随疾病的进展E-cadherin的表达明显减少,各组间差异有统计学意义(P0.05)。(2)高危型HPV在CINI级、CINⅡ-Ⅲ级及宫颈癌中的阳性感染率分别为21/50(42.0%)、38/50(76.0%),48/50(96.0%),各组间差异有统计学意义(P0.05)。(3)在CIN和宫颈癌中,HR-HPV阳性组中E-cadherin阳性率39.3%(42/107)低于HR-HPV阴性组中E-cadherin阳性率90.7%(39/43)(P0.05)。结论:E-cadherin的表达下降或缺失可能是HR-HPV导致宫颈癌发生、发展的机制之一。     

Immunohistochemical LRIG3 Expression in Cervical Intraepithelial Neoplasia and Invasive Squamous Cell Cervical Cancer: Association with Expression of Tumor Markers,Hormones, High-Risk HPV-Infection,Smoking and Patient Outcome

The novel biomarker LRIG3 is a member of the LRIG family (LRIG1-3). While LRIG1 has been associated with favorable prognosis and LRIG2 with poor prognosis in invasive cervical cancer, little is known about the role of LRIG3. The aim of this study was to investigate the expression of LRIG3 in invasive cancer and cervical intraepithelial neoplasia (CIN) for possible correlation with other tumor markers, to hormones and smoking, as a diagnostic adjunct in CIN, and prognostic value in invasive cancer. Cervical biopsies from 129 patients with invasive squamous cell carcinoma and 170 biopsies showing low grade and high grade CIN, or normal epithelium were stained for LRIG3 and 17 additional tumor markers. Among other variables the following were included: smoking habits, hormonal contraceptive use, serum progesterone, serum estradiol, high-risk HPV-infection, menopausal status and ten-year survival. In CIN, high expression of the tumor suppressors retinoblastoma protein, p53, and p16, and Ecadherin (cell-cell interaction), or low expression of CK10, correlated to LRIG3 expression. In addition, progestogenic contraceptive use correlated to high expression of LRIG3. In invasive cancer there was a correlation between expression of the major tumor promoter c-myc and high LRIG3 expression. High LRIG3 expression correlated significantly to presence of high-risk HPV infection in patients with normal epithelium and CIN. There was no correlation between LRIG3 expression and 10-year survival in patients with invasive cell cervical cancer. LRIG3 expression is associated with a number of molecular events in CIN. Expression also correlates to hormonal contraceptive use. The results on expression of other tumor markers suggest that LRIG3 is influenced by or influences a pattern of tumor markers in cancer and precancerous cells. Further studies are needed to elucidate if LRIG3 expression might be clinically useful.Key words: LRIG3, cervical cancer, cervical intraepithelial neoplasia, biological markers, human papillomavirus, hormonal contraceptives, smoking     

Positive Surgical Margin,HPV Persistence,and Expression of Both TPX2 and PD-L1 Are Associated with Persistence/Recurrence of Cervical Intraepithelial Neoplasia after Cervical Conization

Objective

To determine the clinicopathologic and immunohistochemical predictors of the persistence/recurrence of cervical intraepithelial neoplasia (CIN) after cervical conization.

Methods

Medical records of 502 patients who received cervical conization treatment of CIN between 2005 and 2012 were reviewed. The clinicopathologic parameters were analyzed using Cox hazard regression. Fifty patients with CIN persistence/recurrence were matched to 50 cases without CIN persistence/recurrence. These 100 cervical specimens were assessed for expression of insulin-like growth factor II messenger RNA (mRNA)-binding protein 3 (IMP3), targeting protein for xenopus kinesin-like protein 2 (TPX2), and programmed cell death-1 ligand-1 (PD-L1) using immunohistochemical staining.

Results

Multivariate analysis found that the independent predictors of CIN persistence/recurrence were positive surgical margin (hazard ratio 5.777, 95% confidence interval 2.334–14.301, p < 0.001) and human papilloma virus persistence for 6 months (hazard ratio 20.685, 95% confidence interval 7.350–57.657, p < 0.001). Co-expression of TPX2 and PD-L1 was significantly higher in CIN persistence/recurrence group than the group without CIN persistence/recurrence (p = 0.013). The depth of glandular involvement (GI) was less than 3mm in about 86.8% (59/68) CIN2-3 lesions, However, No statistically significant associations between GI and persistence/recurrence were observed (P = 0.58).

Conclusion

Positive surgical margin, HPV persistence, and expression of both TPX2 and PD-L1 are associated with persistence/recurrence of cervical intraepithelial neoplasia after cervical conization.     

阴道镜及宫颈活组织检查对早期宫颈上皮内瘤变诊断价值分析

目的:探究阴道镜及宫颈活组织检查对早期宫颈上皮内瘤变(cervicalintraepithelialneoplasia,CIN)的诊断价值。方法:选择2015年3月至2018年5月于我院接受诊治的543例疑似宫颈上皮瘤变患者,分别对其实施阴道镜及宫颈活组织检查,以病理学检测结果为金标准,分别评估两种方式单独检测及联合检测对早期CIN的诊断一致性、灵敏度和特异度,并进行组间对比。结果:(1)543例疑似CIN患者病理诊断早期CIN阳性患者168例,阴性患者375例,诊断率为30.94%;阴道镜对早期CIN诊断发现阳性患者有143例,良性患者有400例,诊断率为26.34%;宫颈活组织检测对早期CIN诊断发现阳性患者有159例,良性患者有384例,诊断率为29.28%;阴道镜联合颈活组织检测对早期CIN诊断发现阳性患者有163例,良性患者有380例,诊断率为30.02%。(2)检测发现,阴道镜对早期CIN诊断一致性为81.77%,灵敏度为60.12%,特异度为91.47%。(3)宫颈活组织对早期CIN诊断一致性为91.71%,灵敏度为83.33%,特异度为95.47%。(4)阴道镜联合宫颈活组织对早期CIN诊断一致性为96.50%,灵敏度为92.86%,特异度为98.13%。(5)联合检测对早期CIN诊断的一致性、灵敏度和特异度均明显优于阴道镜及宫颈活组织单独检测。结论:阴道镜及宫颈活组织检测对早期CIN具有较好的诊断效果,但联合检测诊断准确率更高,适用于早期CIN临床筛查中。     

Alteration in gene expression profile and biological behavior in human lung cancer cell line NL9980 by nm23-H1 gene silencing

Lung cancer is the leading cause of cancer death in both men and women. Tumor metastasis is an essential aspect of lung cancer progression. nm23-H1 is a metastasis suppressor gene. The molecular mechanism by which nm23-H1 suppresses the metastasis is still unclear. Here, we compared the gene expression profile of human large cell lung cancer cell line NL9980 by nm23-H1 gene silencing with that of negative control cells to comprehensively investigate nm23-H1-mediated changes in gene expression of NL9980 cells. Microarray assay revealed that expression of 733-known genes (1.9%, 733/38,500) were altered in response to nm23-H1 gene silencing, including 466 upregulated genes and 267 downregulated. real-time PCR assay of the expression changes indicated that 81.82% (45/55) of verified genes were consistent with that observed in microarray assay. The upregulated genes included MMP-1, -2, SNAI2, CXCL1, 2, 3, PAI-2, while the downregulated genes included cystatin B, TIMP-2, E-cadherin, centrin-2, all of which have been associated with tumor metastasis. Furthermore, we confirmed by Western blot that the expression of MMP-1 and -2 were significantly increased while that of cystatin B was dramatically decreased in NL9980-nm23-H1 silencing cells. The NL9980-nm23-H1 silencing cells exhibited significantly more S phase growth and invasive ability. Thus, silencing of nm23-H1 gene caused metastasis-related gene expression changes in lung cancer cells. The knockdown of nm23-H1 expression may change the lung cancer cells to a more invasive phenotype through alteration in the expression of a set of genes.     

MiR-23a靶向HOXC8在黑龙江省宫颈癌人群中发生的作用分析

目的:研究Mi R-23a靶向HOXC8在黑龙江省宫颈癌人群中发生的作用及机制。方法:采集从2017年1月～2019年1月,于我院确诊为正常宫颈、宫颈上皮内瘤变(CIN)、宫颈癌患者的病变组织各90例。采用逆转录多聚酶联反应(RT-PCR)法分别检测正常宫颈组织、CIN组织、宫颈癌组织中的Mi R-23a表达水平。此外,通过■转染试剂将Mi R-23a模拟物、Mi R-23a抑制物以及空白对照片段转染至宫颈癌细胞Siha中,检测转染后0 h、48 h、72 h时三组Siha细胞的增殖能力情况。另外,以RT-PCR法检测正常宫颈组织、CIN组织、宫颈癌组织中的HOXC8表达水平。结果:宫颈癌组织中Mi R-23a的相对表达量显著高于CIN组织与正常组织,且CIN组织中Mi R-23a的相对表达量显著高于正常组织(均P0.05)。Mi R-23a模拟物组Siha细胞的增殖能力显著优于Mi R-23a抑制物组与空白对照组,且空白对照组Siha细胞的增殖能力明显优于Mi R-23a抑制物组(均P0.05)。宫颈癌组织中HOXC8的相对表达量显著高于CIN组织与正常组织,且CIN组织中HOXC8的相对表达量显著高于正常组织(均P0.05)。结论:Mi R-23a可能是通过靶向下调HOXC8基因的表达,进一步促进了宫颈癌的发生、发展,这为临床宫颈癌的防治提供了新的靶点,值得临床重点关注。     

Prevalence and Predictors of Colposcopic-Histopathologically Confirmed Cervical Intraepithelial Neoplasia in HIV-Infected Women in India

Background

Prevalence estimates of cervical intraepithelial neoplasia (CIN) among HIV-infected women in India have been based on cervical cytology, which may have underestimated true disease burden. We sought to better establish prevalence estimates and evaluate risk factors of CIN among HIV-infected women in Pune, India using colposcopy and histopathology as diagnostic tools.

Methodology

Previously unscreened, non-pregnant HIV-infected women underwent cervical cancer screening evaluation including standardized diagnostic colposcopy by a gynecologist. Histopathologic confirmation was conducted among consenting women with clinical suspicion of CIN. The prevalence of CIN was evaluated by a composite diagnosis based on colposcopy and histopathology results. Multivariable ordinal logistic regression analysis was conducted to determine independent predictors of increasing severity of CIN.

Results

The median age of the n = 303 enrolled HIV-infected women was 30 years (interquartile range, 27–34). A majority of the participants were widowed or separated (187/303, 61.7%), more than one-third (114/302, 37.7%) were not educated beyond primary school, and nearly two-thirds (196/301, 64.7%) had a family per capita income of <1,000 Indian Rupees (∼US$22) per month. Cervical high-risk HPV-DNA was detected in 41.7% (124/297) of participants. The composite colposcopic-histopathologic diagnoses revealed no evidence of CIN in 220 out of 303 (72.6%) women, CIN1 in 33/303 (10.9%), CIN2 in 31/303 (10.2%), CIN3 in 18/303 (5.9%) and 1 (0.3%) woman was diagnosed with ICC. Thus, over a quarter of the participants [83/303: 27.7% (95% CI: 22.7–33.1)] had ≥CIN1 lesions and a sixth [50/303: 16.5% (95% CI: 12.2–21.9)] had evidence of advanced (≥CIN2) neoplastic disease. The independent predictors of increasing severity of CIN as revealed by a proportional odds model using multivariable ordinal logistic regression included (i) currently receiving antiretroviral therapy [adjusted odds ratios (aOR): 2.24 (1.17, 4.26), p = 0.01] and (ii) presence of cervical high-risk HPV-DNA [aOR: 1.93 (1.13, 3.28), p = 0.02].

Conclusions

HIV-infected women in Pune, India have a substantial burden of cervical precancerous lesions, which may progress to invasive cervical cancer unless appropriately detected and treated. Increased attention should focus on recognizing and addressing this entirely preventable cancer among HIV-infected women, especially in the context of increasing longevity due to antiretroviral therapy.     

宫颈癌中端粒酶的表达和高危型人乳头瘤病毒感染

目的:研究不同程度子宫颈病变中高危型人乳头瘤病毒HR-HPV感染和端粒酶活性的表达,以探讨两者在宫颈癌及宫颈上皮内瘤变中的作用及相关性。方法:采用第二代杂交捕获技术检测宫颈脱落细胞HPV-DNA含量,并用免疫组织化学EnVision二步法检测宫颈组织标本中端粒酶的表达。结果:(1)端粒酶阳性表达率在对照组、CINⅠ、CINⅡ、CINⅢ和宫颈癌组分别为10.00%、16.67%、40.00%、70.00%、95.00%,宫颈癌组高于CINⅢ,CINⅢ高于CINⅡ,CINⅡ高于CINⅠ,差异均有统计学意义(x2=4.329,P=0.037;x2=4.327,P=0.038;x2=4.022,P=0.045)。(2)随着宫颈病变级别的增加,高危型HPV的阳性率和病毒负荷量均增高。高危型HPV的阳性率在宫颈癌和CINⅢ组明显高于对照组、CINⅠ及CINⅡ(x2=29.501~7.414,P<0.01)。高危型HPV的病毒负荷量在对照组与其他4组比较,差异均有统计学意义(P<0.05);CINⅠ组分别与CINⅡ、CINⅢ及宫颈癌组比较差异均有统计学意义(P<0.05)。(3)随着宫颈病变级别的增加,高危型HPV的阳性率和端粒酶阳性表达率依次递增,两者有明显的相关性(r=0.943,P<0.01)。结论:高危型HPV感染和端粒酶活性均与宫颈癌前病变及宫颈癌的发生发展密切相关,有望作为子宫颈癌前病变和宫颈癌筛查的监测指标。     

Clonality analysis of archival cervical smears. Correlation of monoclonality with grade and clinical behavior of cervical intraepithelial neoplasia

OBJECTIVE: To establish a polymerase chain reaction (PCR)-based clonality assay for archival cervical smears and examine its value in the detection of cervical intraepithelial neoplasia (CIN) and prediction of its clinical behavior. STUDY DESIGN: Dyskaryotic cells were microdissected from archival cervical smears of 33 cases and subjected to PCR-based clonality analysis of the androgen receptor gene. High-risk HPV subtypes were screened by PCR. RESULTS: Monoclonal patterns were found in 9/9 CIN 3 and 15/21 CIN 2, while polyclonal patterns were observed in the remaining 6 CIN 2 and 3/3 CIN 1. All patients with monoclonal CIN lesions, including 15 CIN 2, showed recurrence of the disease despite treatment. The original CIN 2 and recurrent CIN lesion in each of the 6 examined cases showed the same monoclonal pattern, suggesting a clonal link. In contrast, the patients with polyclonal CIN 1 or 2 became negative and remained disease free. High-risk HPV subtypes were found in all monoclonal CIN lesions, including 9 CIN 3 and 15 CIN 2, and in 4/6 polyclonal CIN 2 but not in CIN 1 lesions. CONCLUSION: Clonality analysis of cervical smears is potentially valuable in the identification of true neoplastic cells and prediction of clinical behavior of CIN 2 lesions.