人膀胱移行细胞癌HPV—18感染与G1—细胞周期表达的关系

目的：探讨人膀胱移行细胞癌（transitional cell carcinoma,TCC)组织内人乳头瘤病毒18例型（human papillomavirus type 18,HPV-18)DNA与G1－细胞周期素（D1和E）表达之间的关系。方法：用免疫组织化学方法检测57例人膀胱TCC组织（PCR测定29例HPV－18 DNA阳性、28例阴性）及对照组（7例正常膀胱）G1－细胞周期素的表达。结果：细胞周期素D1在癌组织中表达的阳性率71．93％（41／57）;HPV－18DNA阳性组阳性率55．17％（16／29）,阴性组阳性率为89．29％（25／28）,阳性组表达率较阴性组低,两者表达有差异（P＜0．05）;与对照组14．29％（1／7）相比,癌组织表达明显增高（P＜0．05）。细胞周期素E在癌组织中表达阳性率为63．16％（36／57）,在HPV－18DNA阴性（67．86％）和阳性组（58．62％）之间无明显差异（P＞0．05）;与对照组（0％）相比,癌组织表达明显增高（P＜0．05）。结论：G1－期细胞周期素的改变与膀胱移行细胞癌的发生相关。HPV－18DNA与细胞周期素D1表达存在显著的负相关。     

膀胱移行细胞癌胞核DNA含量测定及临床意义

应用显微分光光度计检测膀耽正常粘膜、膀胱乳头状瘤及膀胱移行细胞癌共23倒(正常粘膜3例、乳头状瘤5例及移行细胞癌15例,移行细胞癌分三级,Ⅰ级、Ⅱ级、Ⅲ各5例),其结果显示,正常粘膜上皮细胞和乳头状瘤细胞核及移行细胞癌细胞核Ⅰ、Ⅱ、Ⅲ各组之间胞核DNA含量均值有显著的差别(P<0.05～0.01)。本文通过检测细胞核DNA含量的变化,作者认为对膀胱移行细胞癌的诊断、移行细胞癌分级及判断预后有参考价值。     

膀胱移行细胞癌的HPV-16/18感染与形态学特征

膀胱原发肿瘤的90％以上是移行细胞癌，我实验室的初步研究结果认为其发生可能与HPV－16／18感染相关。本文就108例膀胱移行细胞癌的形态学特征与HPV－16／18感染进行了研究，以期发现膀胱移行细胞癌内HPV－16／18感染形态学的有关特征。1 材料与方法1．1 病例来源 收集中国医学科学院肿瘤医院1996～1998年膀胱移行细胞癌（TCC）石蜡包埋和手术切除标本108例。其病例一般情况如下：膀胱移行细胞癌108例，男性88例，占81．48％，女性20例，占18．52％，男:女＝4：1。最小年龄27岁，最高年龄95岁，平均年龄59．0岁，发病高峰40～70岁，与…     

HPV16/18E6蛋白及HPV18DNA在乳腺导管内乳头状瘤组织中的表达

目的：探讨人乳头状瘤病毒（HPV）18型感染与人乳腺导管内乳头状瘤病因学之间的关系。方法：对柳州地区女性28例乳腺导管内乳头状瘤和5例导管内乳头状瘤恶变材料采用SP法免疫组化染色和原位杂交技术进行HPV16／18E6蛋白及HPV18DNA的检测。结果：乳腺导管内乳头状瘤组中HPV16／18E6蛋白和HPV18DNA的阳性率分别为21．4％和28．6％，多发性组中HPV18 DNA阳性显著高于单发性组（P＜0．04），而导管内乳头状瘤恶变组中HPV18 DNA的阳性率为80．0％，显著高于导管内乳头状瘤组（P＜0．05）。结论：柳州地区女性乳腺导管内乳头状瘤组织中有HPV18DNA感染的存在。HPV18型感染可能涉及乳腺导管内乳头状瘤的发生、发展过程。     

人膀胱移行细胞癌内的16／18型人乳头状瘤病毒感染

目的 探讨人膀胱移行细胞癌与高危型人乳头瘤病毒感染的关系。方法 采用聚合酶链式反应（ＰＣＲ法）检测１１２例膀胱移行细胞组织（包括７５例石蜡包埋组织和３７例手术切除组织）和７例正常膀胱粘膜组织的ＨＰＶ－１６／１８感染率及ＨＰＶ－１６／１８感染与膀胱移行细胞癌病理分极及临床分期的关系。同时检测了２４例膀胱癌病人尿液沉淀中ＨＰＶ阳性率。结果 膀胱移行细胞癌的ＨＰＶ－１６／１８的总感染率为６２．５０％（７     

膀胱移行细胞癌HPV-16/18感染的相关临床病理特征分析

目的　研究膀胱移行细胞癌 (TCC)人乳头瘤病毒 16/18(HPV 16/18)感染的相关临床病理特征。方法　采用PCR法检测 12 3例膀胱TCC组织中HPV 16/18DNA感染情况 ,采用双盲法阅片确定病理特征 ,并收集包括肿瘤数目及术后无瘤生存期在内相关的临床资料 ,应用SPSS 10 .0软件分析所得实验结果。结果　 12 3例TCC组织中HPV 16/18DNA总阳性率达 5 9.3 %( 73 /12 3 ) ,7例正常对照组织内未见有HPV 16/18感染 ,两者有非常显著性差异 ( χ2 =7.2 ,P <0 .0 1) ;TCC多发率为 19.5 % ( 2 4/12 3 ) ,乳头状和浸润性生长为其主要生长方式 ,肿瘤组织内鳞状分化率为 8.9% ( 11/12 3 ) ,凹空细胞出现率为 43 .1% ( 5 3 /12 3 ) ,HPV 16/18DNA仅与凹空细胞出现相关 ( χ2 =18.4,P <0 .0 1) ;Kaplan Meier生存曲线分析发现仅病理分期是独立的预后因子 ,HPV 16/18DNA存在与术后无瘤生存期无关。结论　HPV 16/18感染可能与膀胱TCC发生相关 ;凹空细胞的出现可为提示HPV 16/18感染的指标 ,用于临床诊断有待进一步研究 ;病理分期是独立的预后因子     

人乳头瘤状病毒感染引起喉癌的机制研究

人乳头状瘤病毒（ human papillomavirus,HPV）是一种致瘤病毒,容易感染鳞状上皮与柱状上皮移行区部位,从而引发肿瘤。喉部受到HPV感染后容易引起喉癌的发生。HPV感染喉部后,主要是通过自身整合,激发体内的癌基因及抑制抑癌基因等过程,最终导致喉癌的发生。在喉癌的众多致病因素中,HPV感染是其中较为重要的一个因素。本文阐述HPV的生物学特性及其与喉癌的关系,重点对HPV感染引起喉癌的机制作一综述。     

喉癌病例中HPV感染状态的初步探讨

目的:对喉癌病例中人乳头状瘤病毒（human papillomavirus,HPV）的感染状况进行初步探讨。方法:收集40例新发喉鳞状细胞癌患者（均为广东地区患者）的临床数据及新鲜组织标本,提取DNA,利用Digene HC2 HPV DNA test 试剂盒检测组织标本中的HPV DNA。结果:40例喉癌肿瘤及其癌旁组织标本均为HPV阴性。结论:喉癌病例中HPV感染率低。未来仍需进行进一步大规模HPV感染率的检测。     

人膀胱移行细胞癌 HPV-18感染与 G1-细胞周期素表达的关系

目的：探讨人膀胱移行细胞癌(transitional cell carcinoma,TCC)组织内人乳头瘤病毒18型（human papillomavirus type 18,HPV-18）DNA与G_1-细胞周期素（D1和E）表达之间的关系。方法：用免疫组织化学方法检测57例人膀胱TCC组织（PCR测定29例HPV-18 DNA阳性、28例阴性）及对照组(7例正常膀胱)G_1-细胞周期素的表达。结果：细胞周期素D1在癌组织中表达的阳性率71.93％(41/57);HPV-18 DNA阳性组阳性率55.17％(16/29),阴性组阳性率89.29％（25/28）,阳性组表达率较阴性组低,两者表达有差异(P< 0.05);与对照组14.29％（1/7）相比,癌组织表达明显增高(P< 0.05)。细胞周期素E在癌组织中表达阳性率为63.16％(36/57),在HPV-18 DNA阴性（67.86％）和阳性组（58.62％）之间无明显差异(P >0.05);与对照组(0％)相比,癌组织表达明显增高(P< 0.05)。结论：G_1-期细胞周期素的改变与膀胱移行细胞癌的发生相关。HPV-18 DNA与细胞周期素D1表达存在显著的负相关。     

乳腺癌组织中高危型HPV16、18检测的临床意义

目的:探讨高危型人乳头状瘤病毒(human papillomavirus,HPV)16、18型感染与乳腺癌的关系。方法:通过原位杂交方法检测高危型人乳头状瘤病毒HPV16、HPV18在乳腺癌组织、癌旁组织及正常乳腺组织中的感染情况。结果:HPV16、HPV18在乳腺癌组织中的表达均高于癌旁组织及正常乳腺组织,乳腺癌组织、癌旁组织及乳腺癌患者正常乳腺组织中HPV16的感染率分别为53.3%(32/60)、26.7%(16/60)和25.0%(5/20),在乳腺癌组织中HPV16的感染率与其它两组比较差异有统计学意义（P<0.05）;HPV18的感染率分别为51.7%(31/60)、30.0%(18/60)和20.0%(4/20),在乳腺癌组织中HPV18感染率与其它两组比较差异有统计学意义（P<0.05）;在乳腺癌组织、癌旁组织及乳腺癌患者正常乳腺组织中HPV16和18的共感染率分别为38.3%(23/60)、10.0%(6/60)和10.0%(2/20),乳腺癌组织中HPV16和18的共感染率与癌旁组织及乳腺癌患者正常乳腺组织比较差异有统计学意义（P<0.05）。结论:乳腺癌组织中高危型人乳头状瘤病毒HPV16、HPV18感染率明显高于癌旁乳腺组织及乳腺癌患者正常乳腺组织,HPV16、HPV18感染与乳腺癌的发生、发展可能有一定的关系。     

Newly Established Uterine Cervical Carcinoma Cell Line with Co-amplification of Human Papillomavirus DNA and c-myc Gene

A new human tumor cell line, NCC-c-CX-1 (CX-1), was established from a uterine cervical cancer xenografted in nude mice. This cell line harbored approximately 50 to 100 copies of human papillomavirus (HPV) type 18 DNA per haploid genome, and contained about 16-fold-amplified c-myc gene with rearrangement. These genomic alterations found in CX-1 cells were also present in both primary tumor and xenografted tumor. Histopathologically, original and xenografted tumors were poorly differentiated cancer and were characterized by neuroendocrine features such as positive neuron-specific enolase and chromogranin A by immunohistochemistry and abundant neurosecretory-type granules in the cytoplasm by electron microscopy. However, the established cell line had lost the neuroendocrine features. This cervical cancer cell line may be a useful model for studying cervical carcinogenesis, especially the interaction between HPV and c- myc oncogene.     

Growth Dependence of Human Papillomavirus 16 DNA-positive Cervical Cancer Cell Lines and Human Papillomavirus 16-Transformed Human and Rat Cells on the Viral Oncoproteins

The dependence on human papillomavirus (HPV) Oncoproteins of the growth of cervical cancer cell lines [C4-1, HeLa (both containing HPV 18 DNA), CaSki and SiHa (both containing HPV 16 DNA)], HPV 16-transformed human embryonic kidney cells, and HPV 16-transformed rat brain and 3Y1 cells was examined by using antisense RNA approaches. The cells were transfected with plasmids expressing RNA antisense to the HPV 16 or 18 open reading frames E6E7, together with plasmids expressing the hygromycin B resistance gene, and drug-resistant colonies were scored three weeks later. In all the human cell lines, the efficiency of colony formation was lowered by RNA antisense to the resident HPV type. Some of the rat cell lines responded to the antisense plasmids, but some did not. From a nonresponding rat tumor line (3Y1HP-1T), cell clones with various levels of E7 protein were isolated after transaction with the antisense plasmid, and were examined for anchorageindependent growth in soft agar. The colonies formed by the clones with lower E7 levels tended to be smaller and fewer than those formed by the clones with higher E7 levels. These findings strongly suggest that some of the transformed or cancer phenotypes of cells in vitro are dependent, even after extensive passages and malignant changes, on expression of the oncoproteins of the resident HPV.     

Human Papillomavirus DNA in Squamous Cell Carcinomas of the Respiratory and Upper Digestive Tracts

The prevalence of human papillomavirus (HPV) types 16 and 18in clinical samples of squamous cell carcinomas from respiratoryand upper digestive tracts was studied. HPV DNA of types 16and/or 18 was detected using the polymerase chain reaction (PCR)method in 16 out of 121 cases (13.2%). By Southern blot hybridization,however, only the DNA from a laryngeal and a tonsillar carcinomawas found to hybridize with the whole HPV 16 DNA probe (twoout of 16 HPV DNA-positive cases by PCR, 12.5%). None of theDNAs hybridized with the whole HPV 18 DNA probe. The discrepancyin the results of PCR and Southern blot hybridization methodsseemed to reflect their sensitivity. The possible relation betweenprevalence of HPV DNA and carcinogenesis in respiratory andupper digestive tract is discussed.     

食管癌细胞株Eca109中人乳头瘤病毒(HPV)DNA的检测

应用分子生物学核酸杂交技术,以人乳头瘤病毒HPV6及HPV11型混合探针对食管ECA109鳞癌细胞株进行DNA斑点杂交。检测结果为阳性。为HPV与食管癌关系的研究进一步提供了证据。     

Role of human papillomavirus in the development of urothelial carcinoma

It has been estimated that almost 10% of the worldwide cancer burden is linked to human papillomavirus (HPV) infection. Although the association between HPV and bladder carcinoma has been extensively investigated, data on the role of HPV in bladder carcinogenesis are controversial. The aim of the study was to assess the possible role of human papillomavirus in the development of urothelial bladder carcinomas. Formalin-fixed and paraffin-embedded archival tissue samples were used for DNA extraction. Seventy urothelial bladder carcinoma tissues were screened by nested-polymerase chain reaction (PCR) for HPV DNA with a control group of total 18 cervical tissues with invasive cervical carcinoma and cervical intraepithelial neoplasia III (CIN III). In the study group, we did not find HPV DNA positivity in any of the urothelial carcinomas. In the control group, 15 out of 18 (83.3%) samples were positive for the HPV DNA. These results indicated that there was no association between HPV infection and urothelial carcinomas.     

Detection of High-Risk Human Papillomavirus Genotypes 16 and 18 in Head and Neck Squamous Cell Carcinomas in Jordan

Background: Recently, associations of the human papillomavirus (HPV) with head and neck cancer have become well established. Of particular concern, the severity and pathological outcomes of squamous cell carcinomas are remarkably affected by the genotypes of HPV present in such lesions. This study was conducted to investigate the occurrence of HPV genotypes, particularly high risk 16 and 18, among oral and laryngeal squamous cell carcinomas in Jordan. Methods: During the period of May 2015 to March 2016, we evaluated a total of 108 paraffin-embedded tissue samples, histologically confirmed as SCC, of both oral and laryngeal tumors for the presence of HPV DNA. DNA was extracted using a Zymogen commercial kit. HPV genotypes were detected by nested PCR using consensus primers followed by primer-specific PCR for HPV-16 and HPV-18 genotypes. The genotypes were confirmed by DNA sequencing methods. Results: Sixteen samples were positive for HPV DNA (14.8%) with higher rates in oral tumors compared to their laryngeal counterparts (20% and 6% respectively). The HPV-16 genotype predominated, being detected in 81.3% of the cases as a single infection and in 18.7% in combination with HPV-18. A significant association between the anatomical location and the HPV-16 genotype was observed (p < 0.05). In contrast, no significant associations could be established with tumor grade and gender or age. Conclusions: A relatively high rate of high-risk HPV genotypes, especially HPV 16, is evident in head and neck cancers SCCs in Jordan. Genotyping of HPV might be of considerable value for evaluation of progression.     

Chromosomal Insertion and Amplification of Human Papillomavirus 16 DNA Sequences in a Cell Line of Argyrophil Small Cell Carcinoma of the Uterine Cervix

The chromosomal location of human papillomavirus (HPV) 16 DNA sequences integrated in a cell line derived from argyrophil small cell carcinoma of the uterine cervix was determined by means of fluorescence in situ hybridization (FISH). The HPV 16 DNA sequences were integrated near a fragile site and the location of the c-myc oncogene at 8q24.1. Amplification of the integrated viral sequences resulted in an abnormally banded region. The amplified HPV 16 DNA sequences were also detected in every interphase nucleus by FISH.     

Effect on cancer cells of plasmids that express antisense RNA of human papillomavirus type 18.

Some human squamous cell carcinomas contain DNA of human papillomaviruses (HPV) and express RNA from the E6 and E7 genes. We have examined the effect of plasmids that express antisense RNA of these genes on the growth of the human cancer cell lines HeLa, C4-1, and 1483, which contain HPV type 18 DNA. As controls, the human cancer cell line 183 and the Vero line of monkey kidney cells were used, which do not contain HPV. Plasmids were introduced into the cells by electroporation; cells that contained HPV type 18 accepted the antisense-expressing plasmids at a lower frequency than the cells that lacked HPV. Cell lines were developed from HeLa cells that contained sense- or antisense-expressing plasmids, and lines that contained antisense-expressing plasmids showed slower growth, reduced ability to form colonies in soft agar, and increased serum requirements. The use of antisense HPV RNA might be a suitable approach to gene therapy of HPV-expressing human cancers.     

HPV感染的形态特征及HPV型别与宫颈癌的临床病理联系

目的观察人乳头瘤病毒（HPV）感染的形态学改变,分析挖空细胞形态、HPV型别与宫颈鳞状细胞癌临床病理参数间的联系。方法对594例宫颈鳞状细胞癌进行了形态学观察,按照WHO标准进行组织学分型及分级。运用SPFIO—PCR技术进行HPVDNA扩增,并采用DEIA（DNA enzyme immunoassay）及LiPA（line probe assay）方法进行DNA检测及分型。结果经检测HPVDNA阳性者581例,其中394例具有HPV感染的组织学特点,即出现典型（104例）或不典型（290例）的挖空细胞,检出率为67．8％。36．2％的角化型及72．2％的高分化宫颈鳞状细胞癌中可见典型挖空细胞,而34．0％的非角化型及50．7％的低分化者中无挖空细胞。在HPV型别检测中,以HPV16阳性最多见为453例,其中高、中、低分化者分别为16例、389例及48例;其次为HPV18共43例,其中中分化者32例,低分化者11例;其他高危型HPV按照阳性数多少依次为HPV31、52、59、58、39、45、33、56、66、68、73,分别为17例、12例、12例、11例、6例、5例、5例、3例、2例、1例、1例;低危型HPV包括6及53各1例,且均同时伴有高危型HPV感染。结果显示,HPV16、HPV18阳性者较其他高危型HPV阳性者发病年龄轻;HPV18阳性者较HPV16阳性者分化程度低;HPV18阳性者较HPV16阳性者无挖空细胞病例所占比例较高（分别为48．8％及31．8％）;患者年龄越大FIGO分期越晚。结论挖空细胞形态与宫颈鳞状细胞癌的分化程度密切相关,典型挖空细胞多出现在分化较成熟的癌组织中,而分化较差者常无挖空细胞。HPV16、18是宫颈鳞状细胞癌最重要且最危险的HPV型别。HPV18阳性可能提示宫颈鳞状细胞癌恶性程度高。