高危型HPV感染的宫颈CIN在Leep术后的转归临床研究

目的探讨高危型人乳头瘤病毒(HR-HPV)感染的宫颈上皮内瘤变(CIN)在宫颈环形电切术(LEEP)治疗术后的转归。方法对109例高危型HPV感染的CINⅠ～Ⅲ患者进行LEEP治疗,术后6个月再次检测其宫颈HR-HPV的平均负荷量,同时行阴道镜检查及宫颈活检。结果 LEEP术后6个月,CIN患者HR-HPV平均负荷量较治疗前均显著降低(P<0.01)。HR-HPV负荷量转阴率为73.39%(80/109),但各级别CIN HR-HPV转阴率差异无统计学意义(P>0.05)。根据LEEP术后6个月宫颈HPV-DNA负荷量,低度负荷量组8例中,7例为TCT正常者,1例为CIN;中度负荷量组10例中,7例为TCT正常者,3例为CIN;重度负荷量组11例中,7例为TCT正常者,4例为CIN。中、高度HR-HPV病毒负荷组与低度HR-HPV病毒负荷组之间CIN转归存在差异(P<0.05)。结论 LEEP是目前治疗CIN有效的方法,HR-HPV感染的宫颈CIN在LEEP术后,HR-HPV负荷量明显降低,宫颈CIN的转归与持续HR-HPV负荷量的高低密切相关,HC-Ⅱ动态监测HR-HPV负荷量,对术后宫颈CIN预后有指导意义。     

Human papillomavirus types 16 and 18 vaccine (recombinant, AS04 adjuvanted, adsorbed) [Cervarix

Cervarix is a prophylactic vaccine comprised of a mixture of virus-like particles derived from the L1 capsid proteins of human papillomavirus (HPV) types 16 and 18 formulated with the AS04 adjuvant system. It is administered by intramuscular injection as a three-dose vaccine regimen at 0, 1 and 6 months. The vaccine is indicated for the prevention of high-grade cervical intraepithelial neoplasia (CIN 2 and CIN 3) and cervical cancer causally related to HPV types 16 and 18. In randomized, double-blind, phase II or III trials in >19,000 women aged 15-25 years, the HPV 16/18 vaccine showed high efficacy in preventing CIN 2+ associated with HPV 16/18. Cross-protection against new incident or 6-month persistent HPV 45 or HPV 31 infection was also evident. Phase II follow-up was for at least 5.5 years, and the phase III interim analysis was at approximately 15 months after the first vaccine dose. In a bridging study, in adolescent girls aged 10-14 years, the HPV 16/18 vaccine induced twice the already high antibody titres as it did in young women (aged 15-25 years). The immune response in older women (aged 26-55 years) at 24 months in another study was >or= 8-fold higher than antibody levels reported in younger age groups. Anti-HPV 16/18 antibody responses were greater with an AS04-adjuvanted HPV 16/18 vaccine than with an aluminium salt-adjuvanted formulation. The HPV 16/18 vaccine was generally well tolerated and injection-site reactions were the most common vaccine-related adverse events reported.     

高危型人乳头瘤病毒多重感染与宫颈癌及癌前期病变关系的研究

目的 探讨高危型人乳头瘤病毒(HR-HPV)多重感染是否能增加宫颈癌及癌前期病变发生的风险.方法 对病理检查确诊为宫颈癌、癌前期病变和慢性宫颈炎的641例妇女的宫颈细胞标本行HPV基因分型检测,分析HR-HPV多重感染与宫颈癌及癌前期病变的关系.结果 与慢性炎症组比较,低度宫颈上皮内瘤变(CIN I)组、高度宫颈上皮内瘤变(CIN II-III)组、宫颈癌组HR-HPV阳性率明显增高,与CINI组比较,CIN II～11组、宫颈癌组HR-HPV阳性率明显增高,差异有统计学意义(均P<0.01).与慢性炎症组比较,CINⅡ～IlI组的多重感染率增高,差异有统计学意义(P<0.01).宫颈癌发生危险性较高的为HPV-16、-18、-31、-33、45、-53、-58和-59(HPV-16:OR=0.75,95%CI0.16～3.43;HPV-18:OR=2.67,95%CI0.26～26.92;HPV-31:OR:15.00,95%CI0.22～85.20;HPV-33:OR=0.87,95%CI0.25-1.98;HPV-53:OR=0.80,95%C/0.04～14.64;HPV-58:OR=0.53,95%C/0.11~2.62;HPV-59:OR=4.00,95%CI0.43~37.11);CIN II～III发生危险性较高的为HPV-52;CIN I发生危险性较高的为HPV-66、-68、-CP8304.与单独感染比较,未发现HR-HPV多重感染增加宫颈癌发生的风险.结论 HR-HPV多重感染无明显增加宫颈癌及癌前期病变发生的风险.

Abstract：

Objective To investigate whether the presence of multiple high-risk human papillomavirus (HR-HPV) can increase the risk of having cervical carcinoma and precancerous lesion. Methods The cervical samples of 641 women who had histologically verified cervical carcinoma , precancerous lesion or chronic cervicitis were taken for HPV genotype testing. The correlation of multiple HR-HPV and cervical carcinoma or precancerous lesion was amalyzed. Results Compared with chronic cervicitis group, the positivity of HR-HPV in CIN I , CIN II ～ III or carcinoma group was higher, and there was a statistically significant difference(P <0.01). Compared with CIN I group, the positivity of HR-HPV in CIN II ～ III or carcinoma group was higher, and there was a statistically significant difference(P<0. 01 ). Compared with chronic cervicitis group, multiple infection of HR-HPV in CIN II ~ I was higher (P<0.01). HPV-16, -18, -31, -33, -45, -53, -58, and -59 were associated with carcinoma. HPV-52 was CIN II ～ III-associated type and HPV-66, -68, and -cp8304 were associated with CIN I . Compared with single HR-HPV infection, multiple HR-HPV infection cannot increase risk of cervical carcinoma or precancerous lesion. Conclusion The presence of multiple HR-HPV has no increased risk of cervical carcinoma or precancerous lesion.     

Serologic response to human papillomavirus type 16 virus-like particles in Korean women with cervical precancerous and cancerous lesions

The aim of the study was to investigate the seroprevalence to HPV type 16 in Korean women with precancerous and cancerous lesions of the uterine cervix. The cases were 173 Korean women of whom 130 had high-grade cervical intraepithelial neoplasias (CIN), 43 cervical carcinomas and the control group was 106 women showing normal cervical cytology. Serologic assays were performed using HPV-16 VLPs as antigen in an ELISA. Specific antibodies against HPV-16 VLP were detected in 59.2% (77/130) of the patients with high-grade CIN, in 67.4% (29/43) of the patients with cervical cancer and in 20.8% (22/106) of control subjects. No difference of serologic response was found between high-grade CIN and cancer. HPV-16 seropositivity showed the significant association with patients’ age and preoperative HPV DNA infection. Recurrence of high-grade CIN was not affected by the VLP-16 seropositivity. Recurrence of carcinoma showed the borderline association with HPV-16 seropositivity (P=0.06). The association between the cancer recurrence and seropositivity was not found in the logistic regression analysis. Two patients dying of cancer during the follow-up period were both seronegative (P=0.01). In conclusion, serologic testing for HPV-16 VLP antibody provides a disease indicator of cervical lesions and potential prognostic parameter of cervical carcinoma.     

Use of protein-based biomarkers of exfoliated cervical cells for primary screening of cervical cancer

There has been no attempt to apply protein-based markers of exfoliated cervical cells (ECCs) for primary screening of cervical cancer. In the present study, the levels of six tumor-associated protein [TAPs: Sialyl Lewis A (SLeA), Cancer Antigen 15-3 (CA 15-3), p53, heat shock protein (Hsp)70, Hsp27 and squamous cervical carcinoma antigen (SCCA)]and of two human papillomavirus (HPV) viral proteins (HPV16 E7 and HPV16 L1) of ECCs lysates were evaluated by enzyme-linked immunosorbent assays (ELISAs).The wells of 96-well plates were coated with the ECCs lysates from normal, cervical intraepithelial neoplasia (CIN) I, CIN II, CIN III and cancer groups, and candidate proteins were detected by relevant antibodies. SLeA level decreased with increasing severity of lesions, whereas the levels of other candidate proteins increased. SLeA, HPV16 L1 and p53 levels appeared more useful for detecting cervical lesions than the other candidates. The combination of ELISA-SLeA and ELISA-HPV16 L1 could efficiently detect cervical lesions from normal. The combination of ELISA-SLeA and ELISA-p53 could powerfully discriminate cancer from normal with 91.3% sensitivity and 96.7% specificity. The protein levels of ECCs have great potential as biomarkers for primary screening of cervical cancer.     

宫颈上皮内瘤变p16、Rb、Ki-67及高危型HPV的表达

目的研究p16、Rb、Ki-67在宫颈上皮内瘤变(CIN)中的表达,探讨其与HPV感染的关系。方法对121例CIN病变上皮和36例正常上皮行免疫组化染色检测p16、Rb及Ki-67表达情况,其中47例CIN病例用原位杂交法检测高危型HPV感染情况。结果与对照组相比p16、Ki-67在各级别CIN中均有较高表达(P<0.01),且CIN2和CIN3中的表达较CIN1高(P<0.05);同时二者阳性表达均见分层现象。Rb蛋白的阳性率及表达强度从CIN1到CIN3逐渐下调(分别为54.2%、24.4%、21.9%),在对照组与各级别CIN之间差异均有显著性(P<0.01),但CIN2与CIN3之间无差别。CIN1、CIN2及CIN3患者高危型HPV阳性率分别为(71.9%)、(85.3%)和(90.6%),随CIN级别的增加而升高,与对照组相比差异有统计学意义(P<0.01),但不同级别CIN之间差别无统计学意义。结论高危型HPV感染及p16、Ki-67及Rb与宫颈癌前病变发生机制及病变进展相关,联合检测p16蛋白和Ki-67、Rb抗原表达可作为CIN分级诊断的辅助方法。     

Differences on the prevalence of cervical HPV between Lithuania and Belarus

In some countries the cervical cancer incidence and mortality rates are much higher compared to the European average. The differences of HPV and its type prevalence between countries and regions influence cervical cancer incidence and mortality. Regarding the differences in cervical cancer incidence and mortality in Lithuania and Belarus, the aim of this study was to describe HPV infection level and HPVs type distribution among two study groups of patients with moderate or severe cervical intraepithelial neoplasia (CIN2-3) and cervical cancer. Our data shows that 74.2% [95% CI: 63.64÷84.76] of Lithuanian patients with cervical cancer and 85.6% [95% CI: 85.53÷92.85] of the study group with CIN2-3 were HPV positive, while in the study groups of Belarusian patients HPV infection was detected in 92.6% [95% CI, 74.25÷98.71] and 65.4% [95% CI, 44.36÷82.06] cases respectively. HPV 16 was the most prevalent type in Lithuanian as well as in Belarusian patients of the study groups. HPV 18 in Lithuanian patients of the study group with cervical cancer was identified in 10.2% [95% CI: 1.73÷18.67] and in the study group with CIN2-3 — in 2.6% [95% CI: 0.95÷6.15] of cases. HPV 18 was not detected in Belarusian patients of both groups.     

人乳头瘤病毒检测对宫颈病变的诊断价值

目的评价人乳头瘤病毒（HPV-DNA）分型检测对宫颈病变的诊断价值。方法对780例HPV-DNA阳性且病理活检为宫颈癌及宫颈上皮内瘤样病变（CINⅠ-Ⅲ）患者进行手术或物理治疗,治疗后6个月、12个月行HPV-DNA检测及液基薄层细胞学检查。结果780例患者中常见HPV-DNA分型分别为16、52、58、18、33、31型;在CINⅠ患者中,HPV-52、58型检出率最高,在CINⅡ、CINⅢ、原位癌及浸润癌患者中,HPV-16型感染率明显高于其他基因型,差异有统计学意义（P〈0．01）。520例治疗后随访1年,其中432例（83．08％）HPV—DNA感染患者3个月至1年内消退,88例（16．92％）HPV感染未消退,其中细胞学检查为正常或炎症48例（54．55％）,ASC．US14例（15．90％）,LSIL22例（25％）,HSIL4例（4．55％）;HPV持续阳性患者中细胞学检查异常均高于HPV阴性患者。结论宫颈病变患者最常见HPV基因型为16、52、58、18、33、31型,尤其是HPV-16型与高级别上皮内瘤变及宫颈癌密切相关。     

应用原位PCR技术检测宫颈癌和宫颈上皮内瘤变组织中人乳头瘤病毒DNA

目的　探讨原位PCR(isPCR)技术的敏感性及人乳头瘤病毒 (HPV)与宫颈癌和宫颈上皮内瘤变 (CIN)的关系。方法　采用isPCR技术对 66例宫颈癌和 2 5例CIN组织中的人乳头瘤病毒 (HPV)DNA进行检测。结果　 5 2例宫颈癌检测到了HPVDNA ( 78.8% ) ,其中HPV16DNA阳性 4 5例( 78.8% ) ,HPV18DNA阳性 10例 ( 15 .2 % ) ,HPV16、18的DNA均阳性 3例 ,HPV18DNA阳性而HPV16DNA阴性 7例 ,CIN中HPVDNA阳性 13例。结论　isPCR是一种敏感性高、特异性强的方法 ;宫颈癌和CIN的发生与HPV16和HPV 18感染有密切关系。     

高危型HPV型别和分布特点及对LEEP术治疗宫颈鳞状上皮病变的临床价值分析

目的探讨检测高危型人乳头瘤病毒(HPV)型别及分布特点对评估宫颈环形电切术(LEEP术)治疗宫颈鳞状上皮病变预后的意义。方法回顾性分析8704例行HPV检测的女性患者的临床资料,分析其HPV分型检测结果及分布特点,83例行LEEP术的宫颈鳞状上皮病变患者术前及随访HPV感染情况及病理指标。结果8704例女性检测中,HPV阳性926例,占比为10.64%,其中单一亚型感染769例、占比为83.05%,多重亚型感染157例、占比为16.95%。高危型HPV感染率最高的分型依次为:HPV52、16、58、53、33,感染率分别为2.50%(218/8704)、1.75%(152/8704)、1.08%(94/8704)、0.78%(68/8704)、0.57%(50/8704)。926例HPV阳性患者中最终以病理诊断为宫颈鳞状上皮病变CINⅠ~Ⅲ的有235例,其中HPV16阳性89例、占比为37.87%,HPV52阳性70例、占比为29.79%。83例行LEEP术的宫颈鳞状上皮病变患者中,CINⅠ22例,CINⅡ18例,CINⅢ43例,83例术前HPV检测阳性率为100.00%(83/83),17例(20.48%)为HPV多重感染;高危型HPV感染率由高至低分布依次为HPV16、52、58、33、18、53、39、68、56、73;HPV16患者29例,占比为34.94%;HPV52患者14例,占比为16.87%;HPV58患者14例,占比为16.87%;HPV33患者8例,占比为9.64%;HPV18患者7例,占比为8.43%;HPV53患者5例,占比为6.02%;HPV39患者2例,占比为2.41%;HPV68患者2例,占比为2.41%;HPV56患者1例,占比为1.20%;HPV73患者1例,占比为1.20%;其中29例HPV16型病变中CINⅢ22例。83例行LEEP术的宫颈鳞状上皮病变患者术后随访中,检测高危型HPV阳性5例,占比为6.02%(5/83)。4例经病理活检证实有病变残留或复发,发生率为4.82%(4/83),发现病变残留或复发时间为术后3~12个月,其中3例为CINⅢ,1例为CINⅡ;病变残留或复发患者高危型HPV检测阳性占比为100.00%(4/4),其中HPV16型3例,HPV52型1例。结论宫颈鳞状上皮病变以单一的高危型HPV感染为主,主要型别是HPV16、HPV52,宫颈鳞状上皮病变经LEEP术治疗后,高危型HPV检测可有效预测LEEP术后复发或病变残留,通过有效制定随访方案,可及早防治复发或病变残留,值得临床推广应用。     

HPV—DNA亚型联合液基细胞学检测对宫颈癌筛查的临床意义

目的研究HPV—DNA亚型联合液基细胞学检测对宫颈癌筛查的临床意义。方法回顾性分析120例宫颈上皮内瘤变和宫颈癌患者的病历资料,分为接受HPV—DNA亚型检测联合液基细胞学检查的观察组（68例）和仅接受液基细胞学检查的对照组（52例）,观察两组患者中筛查阳性情况以及观察组患者中HPV—DNA哑型的阳性例数。结果观察组检出阳性总例数54例,HPV—DNA-16阳性率79．41％、HPV—DNA-18阳性率67．65％,其中CINⅠ级7例、CINⅡ11例,均明显多于对照组;CINⅢ级17例、宫颈浸润癌20例,与对照组无差异。结论HPV—DNA亚型联合液基细胞学检测对早期发现并诊断宫颈癌有临床意义。     

Human papillomavirus 16 and 18 L1 serology in Korean women with high-grade cervical intraepithelial neoplasia and cervical cancer

We aimed to determine the prevalence of HPV-16/18 antibodies in Korean women with high-grade cervical intraepithelial neoplasia (CIN) and cervical cancer. We conducted the hospital-based case-control study at the university hospital between 2003 and 2006. Cases were 130 high-grade CIN and 43 cervical cancer patients and the control group was 106 women showing normal cervical cytology. Enzyme-linked immunosorbent assays were performed for HPV-16/18 L1 virus-like particles (VLPs) as an antigen. Seropositivity for HPV-16 VLP and HPV-18 VLP was found in 67.4% and 30.2% of cancer patients and 59.2% and 20.0% of high-grade CIN patients, respectively. Seropositivity for HPV-16 with high-grade CIN (OR 6.91; 95% CI 3.74–12.76) and cervical cancer (OR 8.99; 95% CI 3.88–20.84) presented significant associations, as did seropositivity for HPV-18 (high-grade CIN: OR 3.64; 95% CI 1.67–7.95, cervical cancer: OR 6.82; 95% CI 2.52–18.45). Patients with both HPV-16 and 18 seropositivity were 9.38 times (95% CI 2.98–29.51) more likely to have high-grade CIN and 17.05 times (95% CI 4.55–63.87) more likely to have cancer. Both HPV 16 and 18 L1 VLP serology is the clear disease predictors of presence of high-grade CIN and cervical cancer.     

HPV16载量与新疆维吾尔族宫颈癌关系的研究

目的 探讨不同宫颈病变组织中HPV16E6、E7基因载量与新疆维吾尔族宫颈癌前病变进展的关系;评价实时荧光定量PCR(FQ-PCR)检测HPV在临床的应用价值.方法 收集124例宫颈组织(包括宫颈癌和癌前病)和96例宫颈脱落细胞标本,应用实时荧光定量PCR (FQ-PCR)检测早期基因E6、E7和β-肌动蛋白的拷贝数,分析病毒载量.结果 ①β-肌动蛋白阳性标本中,正常对照组、宫颈炎组、CIN组和宫颈癌组HPV16 E6阳性率分别是3.29％、93.3％、75.7％和83.1％;E7阳性率分别是64.8％、86.6％、81％和100％,E6/E7的检出率随宫颈病变严重程度升高,但宫颈癌、CIN、宫颈炎3组之间E6/E7阳性率无显著性差异(x2=0.66,P＞0.05; x2 =0.08,P＞0.05).②HPV16 E6载量(均数±标准差)在正常对照:0.00068±0.00、CINⅠ:1.12±1.98、CINⅡ:0.69±1.02、CIN Ⅲ:3.22±7.86、宫颈癌:2.83±4.59.不同病变组病毒载量分布差异有统计学意义(P＞0.01),与病变严重程度相关(r=0.83,P＜0.01).③HPV16 E7载量(均数±标准差)在正常对照:1.80±5.86、CINⅠ:2220±3894、CIN Ⅱ:11340±21848、CINⅢ:7908±1.02、宫颈癌:9194±20478.各级病变载量分布差异有统计学意义(P＞0.01),与病变严重程度相关(r=0.754,P ＜0.01).结论 采用FQ-PCR检测宫颈组织HPV16 E6/E7结果显示,病毒载量与新疆维吾尔族妇女宫颈病变程度高度相关,其病毒载量可能是预测宫颈病变的理想指标;FQ-PCR方法检测宫颈病变中HPV DNA载量,具有快速、简便、灵敏度高、特异性强等优点,对宫颈癌的普查和治疗有指导意义.     

人乳头瘤病毒16、18与宫颈癌及宫颈上皮内瘤变关系的研究

目的研究人乳头瘤病毒(HPV)16、18型感染与宫颈癌及宫颈上皮内瘤变(CIN)的关系。方法HPV(16、18型)核酸扩增(PCR)荧光检测试剂盒对118例患者宫颈组织中HPV16、18DNA进行检测,其中鳞癌(SCC)37例、腺癌(AUC)16例、CIN 45例(Ⅰ、Ⅱ、Ⅲ级各15例)及正常宫颈组织(NC)20例。结果(1)在SCC中HPVl6阳性率为75.68%,明显高于CIN(35.56%)、AUC(25%)及NC(5%)(P<0.01,P<0.01,P<0.01);CIN中HPV16阳性率明显高于NC(P<0.01);(2)AUC中HPV18阳性率为62.50%,明显高于SCC(8.11%)、CIN(4.44%)、及NC(0.00%)(P<0.01,P<0.01,P<0.01);(3)CINⅡ、Ⅲ级HPV16阳性率明显高于CIN I级(P<0.01,P<0.05);(4)不同分化SCC、AUC相互间HPVl6、18阳性率比较差异无显著性。结论(1)SCC的发生可能和HPVl6感染有关而AUC发生可能和HPVl8感染有关;(2)HPV16感染可能在CINⅠ发展到CINⅢ的过程中起重要作用;(3)SCC、AUC的细胞分化程度和HPV16、18感染无明显关系。     

Epidemiological studies of women under age 30 infected with human papillomavirus

The aim of this paper was to investigate the prevalence of human papilloma virus (HPV) infection in women under 30 years old with cervical intraepithelial neoplasia (CIN) or cervical cancer, in order to provide a basis for cervical cancer prevention and treatment. We recruited 2052 female cases from the education system in Futian District, Shenzhen city, from April 2006 to April 2008, with age ranging from 22 to 60 years old. Secondgeneration hybrid capture test was done for detection of female genital tract HPV and cervical colposcopy for screening CIN or cervical cancer. The prevalence of HPV and cervical precancerous lesions or cervical cancer was evaluated in different age groups of women. The HPV positive rate was 247/2052 (12.00%), and 35/2052 (1.71%) of the cases were⩾CIN I by pathological diagnosis. In the 22–29-year-old age group, there were 291 cases, including 39 HPV-positive cases (13.40%) and one case of pathological diagnosis⩾CIN I (0.34%), and there were 1761 cases in the 30–60-year-old age group, including 208 HPV-positive cases (11.81%) and 34 cases of pathological diagnosis⩾CIN I (1.93%). The HPV-positive rate of 22–29-year-old age group was higher than that of 30–60-year-old age group, but the difference was not significant (χ ² = 0.5967, P = 0.4398); the CIN and cervical cancer detection rate of the former group was lower than that of the latter one, and the difference was not significant either (χ ² = 3.7519, P = 0.0527). The cases in 30–60-year-old age group were divided into five age subgroups, and the HPV-positive rate of the 22–29-year-old age group was compared with the remaining groups, and it was found that the HPV-positive rate of the former group (13.40%) was lower than that of the 40–44-year-old age group (14.70%) but higher than that of the other four groups. Moreover, the difference in the HPV-positive rate between the 22–29-year age group and the 50–60-year-old age group (6.06%) was significant (χ ² = 5.545, P = 0.018), but the difference between the 22–29-year-old age group and each of the other four groups was not significant (P>0.05). In addition, the CIN and cervical cancer detection rate of the 22–29-year-old age group (0.34%) was lower than that of the remaining five groups, and the difference between the 22–29-year-old age group and the 35–39-year-old age group (2.26%), and between 22–29-year-old age group and 40–44-year-old age group (2.30%) was significant (χ ² = 4.446, P = 0.0035; χ ² = 4.525, P = 0.0363, respectively), but the difference between the 22–29-year-old age group and each of other three groups was not significant (P>0.05). Furthermore, 80.00% (28/35) cases of pathological diagnosis⩾CIN I and 90.91% (10/11) lesions of pathological diagnosis⩾CIN II occurred at 35–49 years of age. For many young women below the age of 30 who were infected with high-risk HPV were one-off infections, so it was not appropriate to recommend HPV detection as cervical precancerous lesions or cancer screening program for women less than 30 years old. The prevention and treatment of cervical cancer should be focused on those women more than 35 years of age.     

宫颈电环切除术前后肿瘤坏死因子α及白细胞介素2的变化及意义

目的探讨宫颈电环切除术（LEEP）前后肿瘤坏死因子α（TNF-α）及白细胞介素2（IL-2）等细胞因子的变化及意义。方法采用酶联免疫吸附法（ELISA）测定高危人乳头瘤病毒（HPV）感染的宫颈上皮内瘤变I级（CINI）30例、Ⅱ级（CINII）30例、Ⅲ级（CINⅢ）27例患者LEEP手术前后宫颈局部TNF—α及IL-2的水平。并与25例非HPV感染正常宫颈组织（NCE）相比较。结果LEEP手术前CINI组中TNF-α及IL-2水平与对照组比较．差异无统计学意义（P〉0．05）;LEEP手术前CINⅡ、CINⅢ组中TNF—α及IL-2水平均高于对照组,差异有统计学意义（P〈0．05）;手术后均下降,与手术前比较,差异有统计学意义（P〈0．05）;CINⅡ组手术后TNF-α、IL-2水平及CINⅢ组手术后IL-2水平与对照组比较,差异无统计学意义（P〉0．05）;CINⅢ组手术后TNF-α水平高于对照组,差异有统计学意义（P〈0．05）。CINI、CINⅡ、CINⅢ组HPV病毒转阴率分别为100．0％、93．3％、96．3％,总转阴率为96．6％。结论高危HPV感染的宫颈高度病变中宫颈局部可能存在免疫失衡,LEEP术后免疫失衡有所改善,手术对宫颈局部TNF-α及IL-2水平的影响有限,仍需大样本、多因素的长期追踪。     

液基薄层细胞学和HPV原位杂交在宫颈疾病诊断中的应用

目的探讨液基薄层细胞学(Thin liquid-based cytology test,TCT)、宫颈活检组织学和人乳头状瘤病毒(HPV)原位杂交三种方法在宫颈疾病筛查中的应用价值,指导临床正确应用。方法对403例宫颈疾病患者行TCT检查,对细胞学检查为炎症反应性改变的72例和ASCUS以上病变的227例行阴道镜下宫颈活检组织学检查,根据TCT结果和组织学结果对171例行HPV原位杂交检测。结果TCT与组织学结果的阳性符合率在炎症反应性改变、ASCUS、ASCUS-H、LSIL、HSIL和SCC分别为95.83%(69/72)、14.84%(23/155)、22.73%(5/22)、78.57%(33/42)、100%(3/3)和100%(5/5)。细胞学诊断的级别越高,指导意义越大。将LSIL以上病变作为细胞学阳性诊断,其阳性率为12.41%(72/403);组织学将CINⅠ以上病变作为阳性诊断,阳性率为17.39%(52/299),两者比较无显著性差异(P>0.05)。HPV原位杂交检测171例,阳性率为29.82%(51/171),其慢性炎症伴增生、CINⅠ、CINⅡ-Ⅲ和SCC的HPV感染率分别为14.27%(14/98)、37.93%(22/58)、100%(10/10)和100%(5/5)。高危型16/18亚型的感染在宫颈癌及癌前病变的发生上起着重要的作用。结论无论是TCT检查、组织学检查还是HPV原位杂交检测都各具有优缺点,因此在临床工作中应结合患者的病情及经济承受能力,合理选择、有效结合,以降低漏诊率和过度诊断率。     

电子阴道镜与病理学检查早期诊断宫颈癌

目的探讨采用电子阴道镜与病理细胞学检查早期诊断宫颈癌的临床价值。方法应用电子阴道镜观察具有宫颈病变患者350例，对可疑病例实施官颈电环切活检术158例，并对其细胞学结果与电子图谱作对比分析。结果电子阴道镜发现宫颈上皮内瘤变(CIN)32例，宫颈癌10例，宫颈人乳头瘤病毒(HPV)感染12例，慢性宫颈炎295例，宫颈肌瘤1例；与病理检查比较CIN符合率76．7％，官颈癌与HPV感染病例符合率为100％，慢性官颈炎94．1％。结论对生育年龄的妇女定期行电子阴道境检查，并对可疑病变部位进行电环切活检能够早期而准确地发现宫颈癌及癌前病变。     

宫颈癌组织中CDK1的表达及其与HPV_(16/18)感染的相关性

目的研究CDK1在宫颈癌组织中的表达及其与HPV16/18感染的相关性,以探讨宫颈癌的发生机制,进一步寻找有利于宫颈癌诊断的新的分子标志物,以指导其诊断与预后。方法采用免疫组织化学方法对50例宫颈癌石蜡标本、宫颈上皮内瘤样病变CI NⅠ20例、CI NⅡ~Ⅲ20例、正常宫颈组织20例进行CDK1的检测,同时采用PCR技术检测HPV16/18感染情况。结果①在宫颈癌组织中CDK1的阳性率高于CI N和正常宫颈组织,差异有统计学意义(P<0.05),且CDK1阳性表达率与病理分级有关,差异有统计学意义(P<0.05),CDK1阳性表达率与淋巴结转移、临床分期和年龄分组无关(P>0.05)。②HPV16/18在正常宫颈组织、CI N和宫颈癌中的阳性率逐渐升高,差异有统计学意义(P<0.05),但与年龄、临床分期、病理分级、淋巴结转移无关(P>0.05)。③CDK1与HPV16/18感染无关(rs=0.145,P>0.05)。结论宫颈上皮内瘤样病变及宫颈癌组织中CDK1表达的改变以及HPV16/18感染互相作用,共同影响CI N的发展及宫颈癌的发生。CDK1的异常表达与宫颈癌的恶变程度有关,可作为宫颈癌筛查、预后判断的有利指标。     

宫颈癌组织端粒酶活性与HPV感染的关系

目的探讨宫颈癌组织端粒酶活性与人乳头状瘤病毒(HPV)感染的关系。方法采用原位PCR和原位杂交技术对66例宫颈癌和25例宫颈上皮内瘤变(CIN)组织进行检测。结果宫颈癌组织中端粒酶阳性率为92.4%(61/66),明显高于CIN的32.0%(χ2=33.24,P<0.001)。宫颈癌组织中HPVDNA阳性率为78.8%(52/66),52例HPVDNA阳性组织中51(98.1%)例端粒酶阳性(χ2=11.188,P<0.001)。结论端粒酶活性与HPV感染有密切关系。HPV感染在宫颈癌发生中可能有病因学意义,端粒酶活性增强可能是宫颈癌转化中的重要分子变化。