高危型人乳头瘤状病毒感染与湖北十堰食管鳞癌发生的关系研究

目的:检测高危型人乳头瘤病毒(human papillomavirus,HPV)在十堰地区食管鳞癌(esophageal squa-mous cell carcinoma,ESCC)组织中的感染率,分析其相关性.方法:收集十堰地区87例食管鳞癌组织和50例对照组食管组织,实时荧光定量PCR法检测组织中HPV16感染率.结果:食管鳞癌组织和对照组食管组织中HPV16的检出率分别为57.5%和36.0%,食管鳞癌组织中HPV16感染率显著高于对照组(P=0.016<0.05).分析食管鳞癌患者年龄、性别、病理分级、大体分型、浸润深度、淋巴结侵犯以及TNM分期与HPV16感染的关系,差异均无统计学意义.HPV16感染与食管鳞癌患者临床特征未见显著相关性.结论:HPV16感染可能是十堰地区食管鳞癌发生的因素之一,针对高危型HPV感染的防治对于该地区食管鳞癌的发生具有重要意义.     

人乳头瘤病毒感染与梅州地区非小细胞肺癌发生的关系

目的 探讨人乳头瘤病毒( HPV)感染与梅州地区非小细胞肺癌(NSCLC)发生的关系.方法应用免疫组织化学SABC法检测43例NSCLC和27例肺良性病变组织中HPV的表达情况.结果HPV在NSCLC和肺良性病变组织中的检出率分别为39.5%和7.4%,差异有统计学意义(P=0.003).结论HPV感染与梅州地区NSC...     

肺鳞癌中人乳头瘤病毒与p53和Rb积聚的关系

目的探讨肺鳞癌组织中人乳头瘤病毒(humanpapillomavirus,HPV)感染与p53蛋白和Rb蛋白表达的关系并分析作用机理。方法采用地高辛标记的HPV-DNA探针,用原位杂交法检测84例肺鳞癌49例支气管黏膜慢性炎标本,组织中的HPV-DNA存在情况,并用免疫组化SABC法检测肺鳞癌组织中p53及Rb蛋白。结果HPV原位杂交阳性信号位于细胞核内,肺鳞癌HPV检出率为48.81%(41/84)、对照组黏膜慢性炎HPV检出率为6.12%(3/49),两组比较差异有统计学意义(P=0)。84例肺鳞癌中31例检出Rb蛋白表达,其中18例HPV阳性,13例HPV阴性,HPV阳性组与阴性组差异无统计学意义(P=0.2588)。84例肺鳞癌中30例检出p53蛋白表达,其中17例HPV阳性,13例HPV阴性,HPV阳性组与阴性组差异无统计学意义(P=0.3634)。结论肺鳞癌与HPV感染关系密切,肺鳞癌组织中也存在p53蛋白积聚,p53蛋白积聚与HPV感染无明显相关性,Rb蛋白积聚与HPV感染无明显相关性。     

维、汉族妇女宫颈鳞癌组织中人乳头瘤病毒基因分型研究

目的:了解维、汉族妇女宫颈鳞癌组织中人乳头瘤病毒(HPV)感染及其基因型的分布情况,并进一步探讨HPV感染及其基因型在维、汉族妇女官颈鳞癌之间的分布是否有差异.方法:采用可检测23种HPV基因型的基因芯片方法分别检测30例维吾尔族宫颈鳞癌组织及30例汉族官颈鳞癌组织的HPV基因型.结果:60例宫颈鳞癌组织中HPV的阳性率为95%(57/60),其中维吾尔族宫颈鳞癌HPV的阳性率为96.6%(29/30),汉族宫颈鳞癌HPV的阳性率为93.3%(28/30),差异无统计学意义(P>0.05).60例宫颈鳞癌组织中共检测到6种HPV基因型,分别为HPV16,56,58,18,68,35,均为高危型感染;其中HPV16最常见,检出率为91.7%(55/60),其次是HPV56,21.7%(13/60);另外,60例宫颈鳞癌中共检测到HPV双基因型重复感染22例,检出率36.7%(22/60).结论:HPV感染与维、汉族妇女宫颈鳞癌关系密切,尤其以HPV16型最有关,其次为HPV56型,并存在一定数量的多亚型重复感染.HPV感染在维、汉族妇女宫颈鳞癌之间无差异.     

食管鳞癌组织HPV的检测及其意义的研究

目的:探讨人乳头状瘤病毒(HPV)与食管鳞癌的相关性,进一步明确人乳头瘤痛毒感染在食管癌病因学中的作用.方法:采用可检测23种HPV基因型的基因芯片和实时荧光定量PCR检测方法检测140例新鲜食管鳞癌组织的HPV型别,同时对照检测85例宫颈鳞癌组织中HPV的感染率.结果:85例宫颈鳞癌组织中HPV的阳性率为95.29%(81/85),共检测到9种HPV基因型,分别为HPV16、18、45、33、58、59、73、31和56,均为高危型感染.其中HPV16最常见,检出率达72.9%(62/85),其次是HPV18为16.5%(14/85),其他7型占28.2%(24/85),HPV双重感染检出率为11.8%(10/85).而在140例食管鳞癌组织中,未检测到任何基因型的HPV.结论:HPV感染似乎可能与高发区食管鳞癌的发生无关.     

原发性肺癌中高危型HPV感染及p53蛋白表达的相关性研究

目的:通过检测高危型人乳头瘤病毒(human papillomavirus,HPV)与p53蛋白在原发性肺癌中的表达情况,探讨高危型HPV感染与p53蛋白表达的相关性及其在原发性肺癌发生和发展中可能的作用。方法:收集2014年4月—2015年6月在新疆医科大学附属肿瘤医院行手术切除的51例原发性肺癌和26例肺良性病变患者的资料,采用第二代杂交捕获法(hybrid capture 2,HC2)检测原发性肺癌和肺良性病变支气管上皮细胞中高危型HPV的感染情况,免疫组织化学法检测原发性肺癌组织和肺良性病变组织中p53蛋白的表达情况。结果:原发性肺癌患者支气管上皮细胞中高危型HPV感染检出率为15.69%,明显高于肺良性病变患者支气管上皮细胞中的0%,差异有统计学意义(P<0.05);原发性肺癌组织p53蛋白的阳性表达率为52.94%,显著高于肺良性病变组织的11.54%,差异有统计学意义(P<0.001)。HPV阳性组中p53蛋白的阳性表达率为75.00%,高于HPV阴性组的48.84%,差异有统计学意义(P<0.05)。结论:HPV感染可能是原发性肺癌发生的危险因素之一,其可能通过使p53失活而促进肺癌的发生和发展。     

E2F-1和survivin蛋白在非小细胞肺癌中的表达及其与HPV感染的相关性研究

背景与目的:人乳头状瘤病毒(human papillomavirus,HPV)与人类多种恶性肿瘤密切相关,而肺癌中亦有HPV的检出引起了众多学者的关注.本实验旨在研究非小细胞肺癌(non-small cell 1ung cancer,NSCLC)中高危HPV感染情况及其与E2F-1和survivin蛋白表达的关系,初步探讨HPV感染可能导致.NSCLC发生、发展的分子机制.方法:特异型PCR检测47例NSCLC和13例肺良性病变组织中是否有HPV16、18DNA存在:免疫组化SP法检测E2F-1和survivin蛋白在肺病变组织中的表达.结果:NSCLC组HPV16、18DNA检出率为42.55%(20/47),明显高于肺良性病变组的7.69%(1/13,P＜0.05).NSCLC组中HPV的感染率与患者的吸烟史、组织学类型及分化程度有关(P＜0.05),而与患者的年龄、性别及淋巴结转移无关(P＞0.05).NSCLC组中E2F-1蛋白表达阳性率为59.57%(28/47),其中64.29%(18/28)呈高表达,显著高于肺良性病变组23.08%(3/13,P＜0.025).NSCLC中survivin蛋白表达阳性率为61.70%(29/47),而肺良性病变组无表达.NSCLC组中E2F-1、survivin蛋白表达呈正相关(r=0.3151,P＜0.05),且两者在HPV阳性组的阳性表达率分别为85.00%(17/20)和80.00%(16/20),均显著高于HPV阴性组的40.74%(11/27)和48.15%(13/27),差异均有统计学意义(P＜0.05).结论:HPV16、18感染在NSCLC的发生中可能有病因学意义,其致癌机制可能与E2F-1和survivin蛋白表达上调有关.     

维、汉族妇女宫颈鳞癌组织中人乳头瘤病毒基因分型研究

目的：了解维、汉族妇女宫颈鳞癌组织中人乳头瘤病毒（HPV）感染及其基因型的分布情况,并进一步探讨HPV感染及其基因型在维、汉族妇女宫颈鳞癌之间的分布是否有差异。方法：采用可检测23种HPV基因型的基因芯片方法分别检测30例维吾尔族宫颈鳞癌组织及30例汉族宫颈鳞癌组织的HPV基因型。结果：60例宫颈鳞癌组织中HPV的阳性率为95%（57/60）,其中维吾尔族宫颈鳞癌HPV的阳性率为96.6%（29/30）,汉族宫颈鳞癌HPV的阳性率为93.3%（28/30）,差异无统计学意义（P〉0.05）。60例宫颈鳞癌组织中共检测到6种HPV基因型,分别为HPV16,56,58,18,68,35,均为高危型感染;其中HPV16最常见,检出率为91.7%（55/60）,其次是HPV56,21.7%（13/60）;另外,60例宫颈鳞癌中共检测到HPV双基因型重复感染22例,检出率36.7%（22/60）。结论：HPV感染与维、汉族妇女宫颈鳞癌关系密切,尤其以HPV16型最有关,其次为HPV56型,并存在一定数量的多亚型重复感染。HPV感染在维、汉族妇女宫颈鳞癌之间无差异。     

肺癌与人乳头状瘤病毒感染和胰岛素样生长因子Ⅱ蛋白表达的相关性及其临床意义

目的:研究肺癌发生、发展中人乳头状瘤病毒(human papillomavirus, HPV)感染的病因学意义以及胰岛素样生长因子Ⅱ(insulin-like growth factor-Ⅱ, IGF-Ⅱ)蛋白的表达,并探讨肺癌发生与这2者之间的相关性.方法:采用PCR和免疫组织化学SP法分别检测68例肺癌组织和12例肺良性病变组织中HPV16/18型DNA﹑高危广谱型HPVE6/E7原癌蛋白和IGF-Ⅱ蛋白的表达水平.结果:肺癌组织的HPV阳性检出率为44.1%,高于肺良性病变组织的8.3%,差异有统计学意义(P＜0.05).HPV感染仅与肿瘤分化程度相关.IGF-Ⅱ蛋白在肺癌组织中的表达水平明显高于肺良性病变组织,且与肿瘤分化程度﹑淋巴结转移和临床分期相关(P<0.05).肺癌组织HPV阳性组与阴性组IGF-Ⅱ蛋白的表达水平差异有统计学意义(P<0.05),HPV阳性组中IGF-Ⅱ蛋白的表达水平较高.结论:高危HPV16/18型感染在肺癌的发生中具有重要的病因学意义,并可能通过整合的HPVE6/E7原癌蛋白促使有丝分裂原IGF-Ⅱ高表达,从而在肺癌的发生、发展中发挥重要作用.     

河南地区食管鳞癌和贲门腺癌与人乳头瘤病毒感染相关性的分析

目的:了解人乳头瘤病毒16型(HPV16)与河南食管癌高发地区食管鳞癌、贲门腺癌发生的关系.方法:利用聚合酶链式反应(PCR)对高发区食管鳞癌组织(44例)、贲门腺癌组织(18例)进行HPV-DNA检测.结果:食管鳞癌及贲门腺癌组织中均检测到HPV16 E6 DNA表达,但食管鳞癌HPV16 E6 DNA表达(84%,37/44)明显高于贲门腺癌(44%,8/18),P<0.01.食管鳞癌及贲门腺癌组织中,高危型HPV16 E6 DNA表达与患者年龄、性别、分化程度、浸润程度,淋巴结转移以及肿瘤分级无相关性,P值均＞0.05.结论:同一地区食管鳞癌和贲门腺癌均有不同程度HPV感染,提示HPV可能是两者共同相关致病危险因素,高危型HPV16感染可能在食管鳞癌和贲门腺癌发生中起重要作用.     

Papillomavirus infection of the lower genital tract: detection of viral DNA in gynecological swabs

A total of 311 smears from the lower genital tract were examined by the filter in situ hybridization method to identify human papillomavirus (HPV) DNA. Of these 311 smears, 229 came from clinically and cytologically negative patients and served as a control group. In this group HPV-DNA was detected in 5 cases (2.2%). Of 82 cytologically positive cases (25 confirmed by histology) 56 (68%) contained HPV-DNA. A high prevalence of HPV 6/11 and absence of HPV 16/18 was found in cases with cytological signs of permissive HPV infection. In mild and moderate dysplasia all viruses occurred at almost the same frequency. In severe dysplasia/carcinoma in situ HPV 16/18 was found 5 times more frequently than HPV 6/11. HPV 16/18 was identified in all 4 invasive cancer cases. Cervical irrigation of colposcopically suspect areas was performed in 15 cytologically and HPV-DNA positive cases using the hydrodynamic filtration method. In 12 cases only the cells obtained from the colposcopically positive areas contained HPV-DNA. The sensitivity and reproducibility of the filter in situ hybridization was shown by: comparing the results obtained by HPV-DNA hybridization using Southern blot analysis of tumor biopsies; analysing the correlation of cytologic diagnosis and presence of HPV-DNA in follow-up examinations, and diagnosing presence or absence of HPV-DNA in parallel filters from the same patients.     

HPV DNA frequency and subset analysis in human breast cancer patients' normal and tumoral tissue samples

Viruses are known to be associated with human malignancies, e.g., Epstein-Barr virus, human papillomavirus (HPV) and human T-cell leukemia virus type I. We conducted a prospective study to define the role of HPV in breast cancer. The malignant and normal breast tissue samples of 50 consecutive breast cancer patients were obtained postoperatively. DNA extracted from all tissues was amplified with the polymerase chain reaction using HPV primers. HPV 11, 16, 18, 33 subtypes were searched in HPV-DNA positive samples. Thirty-seven samples (74%) of tumoral breast tissue expressed HPV-DNA, 16 normal breast tissue samples (32%) were positive as well. There was a significant difference in HPV-DNA positivity between normal and tumoral breast tissue samples. HPV 18 was detected in 20 of the HPV-DNA positive tumoral tissue (54.4%) and in 9 of the HPV-DNA positive normal tissue (56.3%). HPV-33 also was detected in 35 (94.6 %) of the HPV-DNA positive tumoral tissue and in 14 (87.5 %) of the HPV-DNA positive normal tissue samples. HPV DNA was significantly associated with breast tumor tissue compared to normal breast tissue. Additional studies looking at HPV and HPV subtypes are needed to clarify the etiological role of the HPV in breast cancer.     

采用原位杂交法检测生殖系统尖锐湿疣和鳞状细胞癌内乳头瘤病毒的感染

目的　探讨HPV感染与生殖系统尖锐湿疣和鳞状细胞癌的关系。方法　采用HPV6 /11、16 /18原位杂交试剂盒 ,对 5 5例生殖系统不同病变中乳头瘤病毒感染状况进行分析检测。结果　 2 0例生殖系统尖锐湿疣 19例阳性 ,其中 17例为HPV6 /11型 ,2例为HPV16 /18型。 2 0例生殖系统鳞状细胞癌中 ,15例阳性 ,均为HPV16 /18型。 10例正常生殖系统鳞状上皮组织和 5例外阴白斑组织均呈阴性。结论　HPV6 /11多与生殖系统良性疣状病变有关 ,而HPV16 /18感染多见于生殖系统恶性病变。     

新疆和田地区维吾尔族妇女宫颈癌组织中HPVDNA的测定

目的：研究我国宫颈癌高发区新疆和田地区维族妇女宫颈癌发病与人类乳头瘤病毒（HPV）的关系。方法：对50例新疆和田地区维族宫颈癌患组织标本采用PCR（聚合酶联反应）技术,检测HPV－C（总的HPC）,HPV16,HPV18及HPV6／11。结果：HPV－C,HPV16,HPV18及HPV6／11在宫颈癌病人中的检出率分别为80．0％,66．0％,10．0％,0％,HPV16在HPV阳性患者中占的比例为91．4％,鳞癌HPV16阳性率明显地腺癌,而腺癌HPV18检出率明显高于鳞癌（P＜0．05）。HPV在感染率及HPV16阳性率与宫颈癌临床分期及病理分级之间无显著差异。结论：HPV感染与我国宫颈癌高发区新疆维族妇女宫颈癌发有密切关系,其中,HPV16感染在新疆和田地区维族妇女宫颈癌发病中起主要作用,HPV感染与宫颈癌临床全期及病理分级无关。     

Human papillomavirus type 16 and 18 infection is associated with lung cancer patients from the central part of China

Infection with specific high-risk human papillomavirus (HPV) types 16 and 18 have been strongly associated with the genesis of various neoplasms in humans, though such study in lung cancer is limited and the results are controversial. In the present study, we collected and explored 313 fresh lung tumor specimens for the presence of HPV with polymerase chain reaction and non-isotopic in situ hybridization. We found that 44.1% of (138/313) non-small cell lung carcinoma (NSCLC) samples were positive for HPV detection, while 4.2% (4/96) of lung benign controls were positive for HPV 16 and 18 DNA. HPV infection was significant between lung squamous cell carcinoma and adenocarcinoma as well as smoking and non-smoking patients. In HPV-positive lung cancer tissues, abnormal p53 protein accumulation was seen in 97 of the 138 carcinomas (70.3%) and expression of pRb in 54 of the 138 carcinomas (39.1%). There was an obvious relationship between the presence of papilloma viral DNA and abnormal p53 protein accumulation and pRb depletion. Cell proliferation and apoptosis were correlated with HPV infection in NSCLC samples. Our data confirm the high prevalence of HPV in lung carcinomas in the central part of China and suggest the possible mechanism of the carcinogenic role of HPV in these carcinomas.     

青岛地区人乳头状瘤病毒感染亚型与肺鳞状细胞癌的相关性

目的： 检测青岛地区居民肺鳞状细胞癌 (squamous cell carcinoma,SCC)组织人乳头状瘤病毒 (human papillomavirus, HPV) 感染亚型与肺SCC的相关性。方法：收集肺SCC石蜡病理切片196例,提取癌组织和癌旁组织DNA,应用PCR及斑点杂交技术进行HPV基因检测,并对HPV亚型分布及其与肺SCC分级的关系进行分析。结果：在196例标本中,114例(58.16%)存在不同亚型的HPV感染,较癌旁组织14.80%(29/196)明显增高 (P<0.05)。主要为HPV6 (48/196,24.49%)、HPV16 (61/196,31.12%)、HPV18 (4/196, 2.04%) 及HPV58 (1/196,0.51%)4型,HPV6阳性主要存在于低度恶性鳞癌中,HPV16阳性主要发生在中高度恶性鳞癌中。吸烟 (92.98%)和男性 (70.18%)与肺鳞癌HPV感染阳性率正相关 (P<0.05),低龄 (7.89%)与HPV感染负相关 (P<0.05)。结论：HPV感染与肺SCC的形成密切相关,低危型HPV6感染在肺鳞癌发生中的作用值得进一步研究。     

Occurrence of human papillomavirus DNA in primary lung neoplasms.

The occurrence of human papillomavirus (HPV) DNA in primary lung carcinomas and in squamous metaplasia of the bronchus was studied using in situ hybridization techniques and commercially available biotinylated DNA probes to HPV subtypes 6/11, 16/18, and 31/33/35. The authors found HPV DNA in six of 20 cases of squamous cell carcinoma and one of six cases of large cell undifferentiated carcinoma. There were two cases each of the 6/11 serotypes and the 16/18 serotypes and three cases of the 31/33/35 serotypes. Infected cells of the squamous carcinomas uniformly showed koilocytosis. No case of adenocarcinoma, bronchioloalveolar carcinoma, or small cell carcinoma was positive (of 32 cases). Areas of squamous metaplasia in infected tumors showed similar HPV DNA expression in 15% of cases, especially in those with condylomatous atypia. In 5.8% of random bronchial biopsies of squamous metaplasia, HPV DNA was identified. The relationship of HPV infection to the development of upper and lower respiratory tract carcinomas is discussed.     

The genotypes and prognostic significance of human papillomaviruses in cervical cancer

An integrated study on the role of human papillomaviruses (HPV) in cervical cancer has been conducted. Out of a total of 433 cases of cervical cancer, HPV-DNA was detected in 342 (79%) using the polymerase chain reaction (PCR). The incidence of HPV infection was not significantly related to histological types, although a lower incidence was noted in adenocarcinonu cases. The incidence of lymph node (LN) metastasis in adenosquamous carcinoma (55.6%) was significantly higher than in squamous cell carcinoma (SCC) and adenocarcinoma. HPV 16 was detected significantly more often in SCC than in adenocarcinoma. In contrast, HPV 18 was detected more often in adenocarcinoma than in SCC. As a whole, pelvic LN metastases were found in 24.3% of HPV⁺ cases, significantly higher than 11% of HPV^? cases. However, the significant association of HPV-DNA with LN metastasis was only noted in stage I but not stage II. As far as histological types were concerned, the incidence of positive LN was; HPV⁺ SCC >HPV- SCC (p < 0.01), whereas HPV^? adenocarcinoma > HPV⁺ adenocarcinoma (p = 0.12). Genotypes of HPV did not have any effect on nodal status. The presence and types of HPV were not associated with tumor size and distribution of clinical stage. Our results suggest that the prognostic significance of HPV-DNA on nodal status is dependent on histological types while the genotypes of HPV cannot account for prognostic significance in cervical cancer. © 1994 Wiley-Liss, Inc.     

HPV Positive Bronchopulmonary Carcinomas in Women with Previous High-grade Cervical Intraepithelial Neoplasia (CIN III)

A significant higher incidence of some cancers, especially lung cancer, has been found in women with previous HPV-related (human papillomavirus) urogenital and anal neoplasias than in individuals without this particular clinical history. The aim of our study was to investigate whether HPV is present in both CIN III (cervical intraepithelial neoplasia) lesions and bronchopulmonary second primary cancers in women with a clinical history of both diseases. Paraffin-embedded tumour tissue from 75 patients with bronchopulmonary carcinomas was examined using the polymerase chain reaction (PCR) technique and in situ hybridization for the presence of human HPV. In total, 51 primary tumours without metastases, 11 primary tumours with metastases and 13 lymph node metastases without available tissue from primary tumours were analysed. In our study 37/75 primary bronchopulmonary tumours (49%) were identified as HPV positive by the PCR method: 18 cases were purely HPV 16 positive (49%), 12 were purely HPV 6 positive (32%), 5 cases were HPV 16/6 positive (14%), 1 case was HPV 16/11 positive (2%) and 1 case was HPV 16/18 positive (2%). Fourteen metastases were HPV positive, and HPV 16, 11 and 6 were detected in both regional and distant metastases. Two of the HPV 16-positive metastases were brain metastases from two separate HPV 16-positive primary tumours; 35% of the HPV-positive cases were adenocarcinomas, 30% squamous cell carcinomas, 22% oat cell carcinomas, 5% large cell carcinomas, 3% anaplastic carcinoma, 3% low-differentiated carcinoma, and 3% malignant cylindroma. The CIN III lesions from 34 of the 37 HPV-positive bronchopulmonary carcinomas were analysed by PCR. The overall HPV positivity in the CIN III lesions was 74% (25/34 cases): 48% were purely HPV 16 positive, 24% purely HPV 6 positive, 24% HPV 16/6 positive and 4% were HPV 18 positive. Our results indicate that HPV is also involved in the development of bronchopulmonary cancers in women with a history of CIN III lesions.