人乳头状瘤病毒感染与宫颈病变的相关性分析？

目的：分析宫颈上皮内瘤变（ CIN）及宫颈癌（ CC）中人乳头状瘤病毒（ HPV）亚型,探讨HPV感染与宫颈病变的相关性。方法：慢性宫颈炎或液基细胞学异常的妇女检测21种HPV基因亚型和阴道镜下宫颈定位活检,分析2481例CC和CIN患者的HPV感染情况。结果：在2481例CIN和CC患者中,HPV感染率85．0%,HPV感染与宫颈组织学结果有较强的相关性（P〈0．001,Pearson列联系数=0．648）。 CC及CINⅢ、CINⅡ患者以HPV16、18感染最多见,其次见HPV58、33、31、52、45、59、68等亚型。304例患者宫颈感染HPV16、18、58、52、33等亚型后,发生高度鳞状上皮内病变（HSIL）、不明意义的非典型鳞状细胞（ASCUS）及低度鳞状上皮内病变（LSIL）的频率增加,TCT分型与HPV分型有较弱的相关关系（P=0．002,Pearson列联系数=0．322）。细胞学结果提示HSIL、AS-CUS,宫颈组织学诊断以CC、CINIII和CINII为多,TCT分型与组织学分型也有较弱的相关性（ P=0．026,Pearson列联系数=0．172）。结论：HPV16、18、58、33、52、31、45等高危型HPV感染是宫颈癌（ CC）及癌前病变（ CIN）最常见的风险因素。高危型HPV单独或混合感染宫颈后,细胞学检测HSIL、ASCUS及LSIL的发生率增加,细胞学结果与组织学分型的相关性促进了CC和CIN的及时诊治。     

Application of Human Papillomavirus in Screening for Cervical Cancer and Precancerous Lesions

Cervical cancer is a commonly-encountered malignant tumor in women. Cervical screening is particularlyimportant due to early symptoms being deficient in specificity. The main purpose of the study is to assess theapplication value of cervical thinprep cytologic test (TCT) and human papillomavirus (HPV) detection in screeningfor cervical cancer and precancerous lesions. In the study, cervical TCT and HPV detection were simultaneouslyperformed on 12,500 patients selected in a gynecological clinic. Three hundred patients with positive resultsdemonstrated by cervical TCT and/or HPV detection underwent cervical tissue biopsy under colposcopy, andpathological results were considered as the gold standard. The results revealed that 200 out of 12,500 patientswere abnormal by TCT, in which 30 cases pertained to equivocal atypical squamous cells (ASCUS), 80 casesto low squamous intraepithelial lesion (LSIL), 70 cases to high squamous intraepithelial lesion (HSIL) and 20cases to squamous cell carcinoma (SCC). With increasing pathological grade of cervical biopsy, however, TCTpositive rates did not rise. Two hundred and eighty out of 12,500 patients were detected as positive for HPVinfection, in which 50 cases were chronic cervicitis and squamous metaplasia, 70 cases cervical intraepithelialneoplasia (CIN) Ⅰ, 60 cases CIN Ⅱ, 70 cases CIN Ⅲ and 30 cases invasive cervical carcinoma. Two hundred andthirty patients with high-risk HPV infection were detected. With increase in pathological grade, the positive rateof high-risk HPV also rose. The detection rates of HPV detection to CIN Ⅲ and invasive cervical carcinoma aswell as the total detection rate of lesions were significantly higher than that of TCT. Hence, HPV detection is abetter method for screening of cervical cancer at present.     

年轻女性宫颈人乳头瘤病毒感染亚型与宫颈病变的调查

目的：探讨年轻女性（年龄25~35岁）人乳头瘤病毒（HPV）感染亚型与宫颈病变的特点。方法采集1273例患者宫颈上皮细胞标本,采用PCR-反向点杂交法对其进行21种HPV分型的检测。结果1273例年轻女性患者,HPV阳性有130例,检出率为10.2%;单一型感染为115例,包括高危型感染105例,感染率为91.3%,低危型感染10例,感染率为8.7%;最常见高危型是HPV16,共35例,其次为HPV58,共17例;HPV16感染导致宫颈高级别上皮内瘤变10例,低级别上皮内瘤变11例;高危HPV阳性患者,宫颈活检证实为鳞状细胞癌的病例2例,均是HPV16感染。结论年轻女性HPV阳性检出率较高,以单一型感染和高危型感染为主,高危型HPV感染与宫颈高级别上皮内瘤变和宫颈癌的发生密切相关,其中HPV16亚型是导致年轻女性宫颈癌的主要原因。     

Human Papillomavirus Genotype Distribution among Thai Women with High-Grade Cervical Intraepithelial Lesions and Invasive Cervical Cancer: a Literature Review

Infection with high-risk human papillomavirus (HR-HPV) is an essential cause of cervical cancer. Becauseof substantial geographical variation in the HPV genotype distribution, data regarding HPV type-specificprevalence for a particular country are mandatory for providing baseline information to estimate effectivenessof currently implemented HPV-based cervical cancer prevention. Accordingly, this review was conducted toevaluate the HR-HPV genotype distribution among Thai women with precancerous cervical lesions i.e. cervicalintraepithelial neoplasia grade 2-3 (CIN 2-3), adenocarcinoma in situ (AIS), and invasive cervical cancer byreviewing the available literature. The prevalence of HR-HPV infection among Thai women with CIN 2-3 rangedfrom 64.8% to 90.1% and the three most common genotypes were HPV 16 (38.5%), HPV 58 (20.0%), and HPV18 (5.5%). There were high squamous cell carcinoma/CIN 2-3 prevalence ratios in women with CIN 2-3 infectedwith HPV 33 and HPV 58 (1.40 and 1.38, respectively), emphasizing the importance of these subtypes in the riskof progression to invasive cancer among Thai women. Data regarding the prevalence and genotype distributionof HR-HPV in Thai women with AIS remain unavailable. Interesting findings about the distribution of HPVgenotype in cervical cancer among Thai women include: (1) a relatively high prevalence of HPV 52 and HPV58 in invasive squamous cell carcinoma; (2) the prevalence of HPV 18-related adenocarcinoma is almost doublethepreviously reported prevalence, and (3) 75% of neuroendocrine carcinomas are HPV18-positive when takinginto account both single and multiple infections.     

Human papillomavirus DNA in cervical intraepithelial neoplasia detected by in situ hybridisation

Human papillomavirus (HPV) infection was investigated by in situ hybridisation in histological sections from 38 women with abnormal Papanicolaou smears. 13 patients had condylomatous lesions without atypia, 15 cervical intraepithelial neoplasia (CIN) I, 4 CIN II, 3 CIN III and 2 carcinoma in situ (CIS). HPV DNA was detected in 29 cases (78%) (1 specimen was technically inadequate). HPV 16 and 18, and 31, 33 and 35 were both present (67%) in CIN III. HPV 6 and 11 were more frequent in CIN I (56%) and in condylomatous lesions (38%). 31% of the condylomatous lesions without atypia contained HPV 31, 33, and 35 and 31% of those with CIN I were infected with HPV 16 and 18. These data confirm the frequent association of HPV infection with cervical cancer and CIN, and indicate that in situ hybridisation can identify patients with specific types of HPV infection at risk for cervical cancer.     

宫颈高级别病变与HPV感染型别分析

目的探讨HPV在宫颈高级别病变中的感染率及感染型别。方法采用导流杂交法分别检测CINII～Ⅲ30例和宫颈癌患者160例HPV基因型别,比较HPV感染与宫颈病变的关系。结果CINⅡ～III和宫颈癌患者HPV感染率均为90％,且以单型别感染为主,分别为70．37％（19／27）、81．94％（118／144）;在CIN II～Ⅲ中HPV58型、52型感染居多,宫颈癌则以HPV16型、18型感染最常见;无论宫颈鳞癌还是宫颈腺癌,以HPV16型检出率最高。结论HPV16型、18型是宫颈癌的主要致病型,不同病理类型并无HPV型别上的差异;宫颈上皮高级别内瘤变则以HPV58型、52型感染为主;对HPV58型、52型感染者应重视随访。     

p63、CD44v6及HPV16/18在子宫颈癌及癌前病变中的表达及意义

  目的　探讨p63、CD44v6及HPV16/18在不同子宫颈组织病变中的表达及临床病理意义。方法　制作包含有60例子宫颈癌,55例子宫颈上皮内瘤变（CIN）,30例健康人子宫颈上皮的组织芯片,采用免疫组织化学及原位杂交方法检测p63、CD44v6及HPV16／18 在145 例子宫颈病变组织中的表达情况。结果　p63、CD44v6及HPV16／18在子宫颈癌中的表达与CIN和对照组比较差别均有统计学意义（P＜0.05）;HPV16／18在CIN组随着级别增高阳性表达率升高（27.3 %,43.8 %,70.6 %）;p63主要在鳞状细胞癌中表达,在腺癌中不表达;p63阳性率与鳞状细胞癌的分级、临床分期有关;CD44v6的阳性率与肿瘤的病理分级和临床分期有关,并且淋巴结转移病例的阳性率明显高于无转移的病例（P＜0.05）。HPV16／18与p63表达程度相关（P＜0.05）,Cp值为0.49。结论　HPV16／18参与子宫颈鳞状细胞癌的发生和发展,p63可能作为癌基因参与了HPV16／18的致瘤过程,并可作为向鳞状上皮分化的恶性肿瘤的标记之一;CD44v6可以作为判断子宫颈癌远处转移指标之一。     

Development of an in vitro carcinogenesis model of human papillomavirus‐induced cervical adenocarcinoma

Cervical adenocarcinoma (ADC) is the second most common pathological subtype of cervical cancer after squamous cell carcinoma. It accounts for approximately 20% of cervical cancers, and the incidence has increased in the past few decades, particularly among young patients. The persistent infection of high‐risk human papillomavirus (HPV) is responsible for most cervical ADC. However, almost all available in vitro models are designed to study the carcinogenesis of cervical squamous cell carcinoma. To gain better insights into molecular background of ADC, we aimed to establish an in vitro carcinogenesis model of ADC. We previously reported the establishment of an in vitro model for cervical squamous cell carcinoma by introducing defined viral and cellular oncogenes, HPV16 E6 and E7, c‐MYC, and activated RAS to human cervical keratinocytes. In this study, the expression of potential lineage‐specifying factors and/or SMAD4 reduction was introduced in addition to the defined four oncogenes to direct carcinogenesis toward ADC. The cell properties associated with the cell lineage were analyzed in monolayer and organoid cultures and the tumors in mouse xenografts. In the cells expressing Forkhead box A2 (FOXA2), apparent changes in cell properties were observed, such as elevated expression of columnar cell markers and decreased expression of squamous cell markers. Strikingly, the histopathology of tumors expressing FOXA2 resembled cervical ADC, proposing that FOXA2 plays a vital role in dictating the histopathology of cervical cancers.     

Aurora-A在宫颈癌及癌前病变中的表达以及与HPV感染的相关性研究

目的 分析正常宫颈、不同级别宫颈上皮内瘤变(Cervical intraepithelial neoplasia,CIN)和宫颈鳞状细胞癌(Cervical squamous cell carcinoma,SCC)组织中Aurora-A的表达差异,观察其异常表达对宫颈癌变过程的影响及与人乳头瘤病毒(Human papilloma virus,HPV)感染的相关性,了解Aroura-A在CIN与宫颈癌发病机制中的作用。方法 选取已进行宫颈管分泌物高危型HPV检测的宫颈活检或手术标本存档蜡块100例,其中正常宫颈组织20例,CIN1级组织20例、CIN 2级组织20例、CIN 3级组织20例,宫颈癌全部选取的是宫颈鳞状细胞癌组织20例。采用免疫组化方法检测Aurora-A蛋白的表达水平,并分析Aurora-A表达与HR-HPV感染的相关性。结果 Aurora-A在CIN以及宫颈癌中存在高表达(P＜0.05),且其阳性表达率随着宫颈病变程度的加深而增强,两者呈正相关性(r=0.475,P＜0.001);在高级别宫颈上皮内瘤变(CIN2、3)组织中,Aurora-A表达与HPV感染间存在正相关(V=0.591,P＜0.05)。结论 Aurora-A的异常表达可能与宫颈癌的发生发展密切有关,Aurora-A可能作为早期诊断CIN或宫颈癌的重要分子生物学指标,同时也可能是宫颈癌的潜在治疗靶点。     

Attribution of human papillomavirus types to cervical intraepithelial neoplasia and invasive cancers in Southern China

The attribution of individual human papillomavirus (HPV) types to cervical neoplasia, especially intraepithelial lesions, varies ethnogeographically. Population-specific data are required for vaccine cost-effectiveness assessment and type replacement monitoring. HPV was detected from 2,790 Chinese women (444 invasive cervical cancers [ICC], 772 cervical intraepithelial neoplasia [CIN] grade 3, 805 CIN2 and 769 CIN1. The attribution of each HPV type found in multiple-type infections was approximated by the fractional contribution approach. Multiple-type infection was common and correlated inversely with lesion severity (54.7% for CIN1, 48.7% for CIN2, 46.2% for CIN3, 27.5% for ICC). Vaccine-covered high-risk types (HPV16/18) attributed to 59.5% of squamous cell carcinoma, 78.6% of adenocarcinoma, 35.9% of CIN3, 18.4% of CIN2 and 7.4% of CIN1. Distinct features compared to worldwide were a higher attribution of HPV52 and HPV58, and a much lower attribution of HPV45. Inclusion of HPV52 and HPV58 in future vaccines would provide the highest marginal increase in coverage with 11.7% for squamous cell carcinoma, 14.4% for CIN3, 22.6% for CIN2 and 17.7% for CIN1. The attribution of HPV types in southern China is different from elsewhere, which should be considered in prioritizing HPV types for vaccine and screening assay development.     

Carcinogenesis and management of human papillomavirus-associated cervical cancer

Approximately 95% of cervical cancer are caused by human papillomavirus (HPV) infection. Although it is estimated that HPV-associated cervical cancer will decrease with the widespread use of HPV vaccine, it may take time for HPV-associated cervical cancer to be eliminated. For the appropriate management of HPV-associated cervical cancer, it is important to understand the detailed mechanisms of cervical cancer development. First, the cellular origin of most cervical cancers is thought to be cells in the squamocolumnar junction (SCJ) of the uterine cervix. Therefore, it is important to understand the characteristics of SCJ for cervical cancer screening and treatment. Second, cervical cancer is caused by high risk HPV (HR-HPV) infection, however, the manner of progression to cervical cancer differs depending on the type of HR-HPV: HPV16 is characterized by a stepwise carcinogenesis, HPV18 is difficult to detect in precancerous lesions, and HPV52, 58 tends to remain in the state of cervical intraepithelial neoplasia (CIN). Third, in addition to the type of HPV, the involvement of the human immune response is also important in the progression and regression of cervical cancer. In this review, we demonstrate the carcinogenesis mechanism of HPV-associated cervical cancer, management of CIN, and the current treatment of CIN and cervical cancer.

     

HPV不同亚型在宫颈癌前病变及宫颈癌中的分布情况

目的:探讨HPV不同亚型在宫颈癌前病变及宫颈癌中的分布情况。方法:选取我院于2015年1月至2017年1月期间收治的124例宫颈癌患者和宫颈癌前病变患者,其中宫颈癌患者有36例,宫颈癌前病变患者有88例。对所有入选患者的宫颈脱落细胞进行采集,并且进行人乳头瘤病毒检测,观察分析HPV不同亚型在宫颈癌前病变及宫颈癌中的分布情况。结果:共有89例（71.77%）患者检测出HPV阳性,其中宫颈癌患者的阳性检出率为100%,显著高于癌前病变患者中的阳性检出率60.23%（P＜0.05）。宫颈癌患者中HPV18和HPV16亚型的感染率最高,分别为44.44%和47.22%;在88例宫颈癌前病变患者中,低级别型患者的HPV33和HPV52、HPV16亚型感染率最高,分别为9.68%和32.36%、32.36%;高级别型患者的HPV58、HPV52、HPV18、HPV16亚型感染率最高,分别为13.64%、13.64%、22.73%、31.82%。89例HPV感染患者中有9例患者出现多重感染,多重感染率为10.11%,其中三重及以上感染率为3.37%。所有宫颈癌HPV感染患者均为单一感染;癌前病变患者中低级别多重感染率为9.68%,高级别多重感染率为27.27%。结论:宫颈癌患者和宫颈癌前病变患者中均以HPV16和HPV18亚型感染率较高,此外宫颈癌前病变患者中的HPV58和HPV52亚型患者也具有较高的感染率;临床上使用HPV感染检测并针对HPV的综合治疗能够有效预防和控制宫颈癌及其癌前病变的发生,值得广泛推广运用。     

叶酸水平及 HPV16感染对妇女发生宫颈癌变的协同作用研究

目的：探讨叶酸水平、HPV16感染及HPV16 E2和E6 mRNA水平与宫颈癌变的关系,并研究叶酸水平及HPV16感染在宫颈癌变中的协同作用。方法选择新发宫颈炎症（ CI）患者40例、宫颈上皮内瘤样变（ CIN）患者80例（ CINⅠ患者36例,CINⅡ／Ⅲ44例）、宫颈鳞状细胞癌（ SCC）患者48例作为研究对象,采用微生物法测定血清叶酸和红细胞叶酸含量,采用PCR检测宫颈癌组织HPV16的感染情况,采用荧光定量PCR检测宫颈癌组织和叶酸体外干预后Caski宫颈癌细胞中HPV16 E2及E6 mRNA水平,检测不同叶酸浓度对Caski和C33A细胞抑制情况。结果 CINⅠ组、CINⅡ／Ⅲ组和SCC 组HPV16感染率分别与CI 组宫颈组织HPV16感染率比较,差异具有统计学意义（ P＜0．05）。CINⅠ、CINⅡ／Ⅲ、SCC 各组HPV16 E2和E6 mRNA水平与CI组比较差异均具有统计学意义（P＜0．0001）。宫颈癌的严重程度与HPV16 E2和E6 mRNA水平均呈明显正相关性,与血清叶酸和红细胞叶酸含量均呈显著负相关性。叶酸浓度与Caski细胞和C33A细胞的相对抑制率及HPV16 E2和E6 mRNA水平呈明显负相关性。结论叶酸水平低、HPV16感染及HPV16 E2及E6 mRNA低表达均与宫颈癌变有关,补充叶酸明显抑制宫颈癌细胞的增殖,逆转HPV16 E2及E6高表达,提示叶酸水平及HPV16感染在宫颈癌变的过程中具有协同作用。     

宫颈癌患者人乳头瘤病毒感染分布特点

目的:探讨人乳头瘤病毒(HPV)各亚型在广西沿海地区宫颈癌患者中的分布情况,HPV感染与宫颈癌患者的年龄、临床分期、病理类型、分化程度、肿瘤盆腔淋巴结转移及肿瘤的复发的关系。方法:通过凯普导流杂交HPV DNA检测法,对76例宫颈癌患者宫颈脱落细胞进行21种HPV亚型的检测。结果:宫颈癌HPV总阳性率为90.8%。宫颈癌患者HPV阳性各亚型出现的频率排序为:HPV16(56.5%),HPV18、33、58各(7.2%),HPV52、53各(5.8%),HPV31(4.3%),HPV45(2.9%),HPV35、51、56、66、68各(1.4%)。HPV6(5.8%),HPV11、44、43各(1.4%)均合并在高危感染中。HPV感染与临床分期、肿瘤分化程度、肿瘤盆腔淋巴结转移及肿瘤的复发关联无显著性(P>0.05),与年龄密切相关,鳞癌HPV阳性率明显高于腺癌及其它癌,差异有统计学意义(P<0.05)。结论:广西沿海地区妇女宫颈癌患者中以HPV16、18、33、58感染为主要型别。HPV感染与宫颈癌的临床分期、肿瘤分化程度、肿瘤盆腔淋巴结转移及肿瘤的复发无明显相关性,与发病年龄、病理类型有关。     

宫颈鳞状上皮FoxM1及Cdc25B细胞核内蛋白水平与高危型HPV感染的相关性研究

背景与目的：宫颈癌是妇科最常见的恶性肿瘤,人乳头状瘤病毒（human papilloma virus,HPV）与宫颈癌/癌前病变的发生关系密切。宫颈组织活检RNA标本及宫颈癌细胞系中发现HPV 16 E7基因与FoxM1基因表达具有相关性。为发掘辅助诊断宫颈鳞癌及其癌前病变的免疫组织化学（immunohistochemistry,IHC）标志物,分析宫颈组织中高危型HPV感染（high-risk HPV,hrHPV）和转录因子FoxM1及其下游蛋白Cdc25B的细胞核内水平之间的相关性。方法：宫颈活检、锥切及子宫切除组织学标本来自复旦大学附属肿瘤医院病理科资料库（2007—2009年）,用于细胞核FoxM1和Cdc25B蛋白IHC检测,并与23种基因型HPV DNA检测以及P16INK4a（P16）和Ki-67之IHC结果比较。结果：包括22例正常、28例CIN1、50例CIN2/3和40例鳞癌在内共计140例入组。CIN2+中hrHPV感染率100%（90/90）,FoxM1、Cdc25B、P16和Ki-67阳性率分别为100.00%（90/90）、94.44%（85/90）、85.56%（77/90）和97.78%（88/90）,且上述标志物阳性率均随宫颈病变严重程度加剧而上升（Jonckheere-Terpstra检验,P均＜0.000 1）。FoxM1和Cdc25B表达与hrHPV感染、P16和Ki-67阳性率相关（Spearman相关检验,P均<0.000 1）。FoxM1和Cdc25B诊断CIN2+效果佳,曲线下面积（area under curve,AUC）值分别为0.850和0.822。结论：人宫颈鳞状上皮中细胞核FoxM1和Cdc25B蛋白水平与hrHPV感染相关,有望成为诊断与鉴别诊断CIN2+的潜在辅助指标。     

宫颈鳞状细胞癌预测指标的模型建立与分析

目的:通过检测HR-HPV感染、hTERC、c-myc基因扩增和MCM5蛋白在宫颈鳞状细胞癌及不同级别宫颈上皮内瘤变中的水平,筛选宫颈癌相关指标,建立回归模型用以预测宫颈鳞状细胞癌,并评估模型效果。方法:筛选初诊病理确诊宫颈鳞状细胞癌和CIN I、II、III级患者共200例作为研究对象,分别检测HR-HPV感染、hTERC、c-myc基因扩增及MCM5蛋白表达,用Logistic向后逐步回归的方法,筛选宫颈癌相关指标,建立回归模型预测宫颈鳞状细胞癌,并评估模型效果。结果:将HR-HPV负荷量及感染状况、hTERC、c-myc基因扩增和MCM5蛋白表达的检测数据绘制直方图,并进行Logistic向后逐步回归分析,得出hTERC、HR-HPV负荷量、MCM5回归系数分别为0.042、0.061和0.052,P值分别是0.024、0.005、0.005（P＜0.05）,HR-HPV感染状态和c-myc基因P值是0.856和0.682（P＞0.05）,被回归方程排除,提示hTERC（X1)、HR-HPV负荷量(X2)、MCM5(X5）与回归方程存在线性关系,即与宫颈鳞状细胞癌发生有关,由此建立回归模型Logit(P)=-66.283+0.042X1+0.061X2+0.052X5。评估模型拟合优度和预测准确度,H-L检验P值=1(P＞0.05),模型拟合效果好,Cox-Snell R2=0.643,Nagelkerke R2=0.958,模型预测准确度98.5%,模型预测准确性高。结论:由hTERC、HR-HPV负荷量和MCM5蛋白建立的回归模型拟合效果较好,对宫颈鳞状细胞癌的预测准确度较高,hTERC、HR-HPV负荷量和MCM5蛋白联合检测能够用于宫颈鳞状细胞癌的预测评估,对CIN患者的分流管理和预后评估、宫颈鳞癌患者的早期诊断均有较高临床价值。     

P16蛋白在子宫颈上皮内瘤变中表达意义与高危型HPV感染的相关性分析

  目的  研究P16蛋白在宫颈上皮内瘤变（CIN）中表达的意义, 探讨其与高危型人类乳头状瘤病毒（HPV）感染的相关性, 以期用P16蛋白的表达预测CIN进展。  方法  收集大连大学附属医院2009年1月至2011年5月宫颈活检及手术切除标本137例, 免疫组织化学方法检测P16蛋白的表达并评分, HC2方法检测高危型HPV-DNA, 并对数据进行分析。  结果  P16蛋白表达在慢性子宫颈炎伴鳞状上皮化生中均阴性（0/40）, CINⅠ阳性90.91%（20/22）, CINⅡ阳性为95.00%（19/20）, CINⅢ阳性为100.00%（25/25）, 浸润性鳞癌阳性为100.00%（30/30）。在慢性子宫颈炎伴鳞化中高危型HPV阳性1例, CINⅠ12例, CINⅡ14例, CINⅢ22例, 浸润性鳞癌29例。CIN中感染高危型HPV的病例, P16蛋白均呈阳性表达。  结论  P16蛋白可作为区分子宫颈癌及癌前病变与良性反应性增生的标记物, 其表达的分层现象能够很好的反映出CIN的分级, P16蛋白阳性表达的评分有助于区分出有高危发展倾向的CIN。      

维吾尔族妇女宫颈癌发生与EBV及HPV感染的关系

目的:探讨维吾尔族妇女宫颈癌发生过程中EB病毒(Ebstein-Barr virus,EBV)及人乳头瘤病毒(human papillomavirus,HPV)感染的作用及其意义。方法:收集维吾尔族妇女宫颈炎、宫颈内上皮瘤样病变(cervical intraepithelial neoplasja,CIN)Ⅰ/Ⅱ/Ⅲ和宫颈鳞癌患者福尔马林浸泡与石蜡包埋组织标本共178例,提取DNA并采用PCR方法对EBV和HPV DNA进行检测;用免疫组织化学方法检测宫颈癌EBV蛋白表达。结果:病毒DNA检测结果显示,宫颈炎、CINⅠ、CINⅡ～Ⅲ和宫颈癌患者各组HPVDNA检出率依次足2.5%、12.5%、68.0%、96.4%,EBV DNA为0、3.1%、28.0%和69.6%,其中宫颈炎组与CINⅡ～Ⅲ和宫颈癌组问的差异具有统计学意义(P均0.05),但宫颈炎与CINI组间的差异无统计学意义(P0.05)。宫颈病变病理进程不仅伴随着HPV及EBVDNA阳性检出率梯度上升,而且与HPV和EBV双重感染检出率增高呈正相关(r=0.46,X~2=82.50,P0.001)。对宫颈癌组织进行免疫组织化学分析,发现EBV DNA检测阳性标本中EBV蛋白阳性表达检出率为89.7%(34/39),而阴性标本中蛋白表达阳性率为6%(1/17)。结论:维吾尔族妇女宫颈癌的发生与发展可能与HPV和EBV双重感染密切相关。     

应用组织芯片研究HPV6/11、HPV16/18与子宫颈病变的关系

目的 通过检测低危型HPV6/11及高危型HPV16/18在慢性子宫颈炎、子宫颈尖锐湿疣不伴非典型增生、子宫颈鳞状上皮CIN Ⅰ级、子宫颈鳞状上皮CIN Ⅲ级、子宫颈浸润性鳞状细胞癌五种子宫颈病变中的表达情况,探讨HPV与子宫颈病变的相关性、作用机制及其临床意义.方法 应用组织芯片技术,将150例子宫颈病变患者的标本制成组织芯片,用原位杂交法对其进行6/11型及16/18型HPV的测定,应用SPSS 10.0统计软件进行数据分析.结果 低危型HPV6/11在慢性子宫颈炎、子宫颈尖锐湿疣、子宫颈鳞状上皮CIN Ⅰ级、子宫颈鳞状上皮CIN Ⅲ级、子宫颈浸润性鳞状细胞癌中的阳性表达率分别为:13.33%、90%、33.33%、0、0,其中尖锐湿疣组HPV6/11的阳性表达率显著高于其他各组(均P＜0.001);CIN Ⅰ组与CIN Ⅲ及癌比较差异有统计学意义(P=0.001,＜0.05);运用Spearman相关分析表明,HPV6/11在上述五种病变中的阳性表达率与恶性度呈负相关(rs=-0.370,P＜0.001).高危型HPV16/18在慢性子宫颈炎、尖锐湿疣、CIN Ⅰ级、CIN Ⅲ级、鳞状细胞癌中的阳性表达率分别为0、6.67%、10%、56.67%、76.67%,CIN Ⅲ及鳞癌与其他各组间比较均有统计学意义(P＜0.001),但CIN Ⅲ与鳞癌之间无统计学意义(P=0.10);运用Spearman相关分析表明,HPV16/18在上述五种病变中的阳性表达率与恶性度呈正相关(rs=0.628,P＜0.001).结论 低危型HPV6/11主要引起子宫颈尖锐湿疣及CIN Ⅰ;高危型HPV16/18与CIN Ⅲ及子宫颈浸润性鳞癌关系密切,是引起子宫颈CIN Ⅲ及浸润性癌的主要因素.对HPV在子宫颈病变中检测及分型有助于对子宫颈病变的诊断和监测,尤其是对子宫颈癌的预防、早期诊断及早期治疗具有重要意义.     

HPV 16 in multiple neoplastic lesions in women with CIN III

Paraffin embedded material of multiple primary cancers and other hyperplastic tumours from fifteen patients were analyzed by PCR and in situ hybridization for the presence of HPV DNA in the lesions. All patients had also high grade cervical intraepithelial dysplasia (CIN III) and breast carcinomas and were selected from a previous study enrolling 46 women with CIN III and breast carcinomas. HPV 16 was detected by PCR in 8/15 patients (53%), with eleven HPV 16 positive tumours. HPV 16 was detected in two malignant melanomas, one basal cell carcinoma, one squamous cell carcinoma of the vulva, one Bowen disease of the vulva, two high grade vaginal intraepithelial neoplasias, one cancer corporis uteri, one bronchial carcinoma and two lymphomas. Three cases, two high grade vaginal intraepithelial neoplasia and a squamous cell carcinoma of the vulva, were also reported to be positive by in situ hybridization. 5/8 patients (63%) with HPV 16 positive second cancers had also HPV 16 positive breast carcinomas. All fifteen patients with second cancers after CIN III had HPV 16 positive CIN III lesions; 53% of the patients had also a familial cancer history. We assume that HPV 16 may be involved in the development of different second cancers in women with HPV 16 positive CIN III.