人乳头瘤病毒、疱疹病毒I型及人巨细胞病毒与口腔鳞癌关系的研究

目的 :研究口腔鳞癌与人乳头瘤病毒 (HPV)、疱疹病毒I型 (HSV -I)和人巨细胞病毒 (HCMV)的关系。方法 :采用斑点杂交和PCR技术检测 32例口腔鳞癌、14例口腔白斑和 10例正常口腔粘膜中HPV1 6 、HSV -I及HCMVDNA。结果 :在正常口腔粘膜、白斑及口腔鳞癌中HPV1 6 、HSV -I及HCMVDNA感染率分别为 0 %、35 7%、5 0 0 % ,40 0 %、5 0 0 %、43 3%和 0 %、14 3%、2 8 1% ,口腔鳞癌及白斑组织中HPV1 6 -DNA的检出率均高于正常口腔 ,且差别具有显著性 (p <0 0 5 ) ;但HSV -I和HCMVDNA在口腔疾患中的检出率与正常比较无显著差别 (p >0 0 5 )。结论 :HPV1 6 感染与口腔鳞癌的发生相关 ;HSV -I和HCMV可能参予口腔鳞癌的发生及发展 ,并且与HPV1 6

阴道微环境与人乳头瘤病毒感染相关性的研究进展

近年,宫颈癌的发病率不但无下降趋势,而且发病年纪日趋年轻化,所以对于宫颈癌的预防不可忽略,早期的筛查和对宫颈癌前病变的干预可以使宫颈癌的发生率降低。宫颈癌及癌前病变的致病因素有很多,主要的致病原因是人乳头瘤病毒(HPV)感染,尤其是高危型人乳头瘤病毒(HP-HPV)的持续感染。对于人乳头瘤病毒感染,阴道微环境的改变与其有一定的相关性,本文对阴道微环境与人乳头瘤病毒(HPV)感染相关性的研究进展进行综述。

Human papillomavirus in upper digestive tract tumors from three countries

AIM: To clarify human papillomavirus (HPV) involvement in carcinogenesis of the upper digestive tract of virological and pathological analyses. METHODS: The present study examined the presence of HPV in squamous cell carcinomas of the oral cavity (n = 71), and esophagus (n = 166) collected from Japan, Pakistan and Colombia, with different HPV exposure risk and genetic backgrounds. The viral load and physical status of HPV16 and HPV16-E6 variants were examined. Comparison of p53 and p16INK4a expression in HPV-positive and HPV-negative cases was also made. RESULTS: HPV16 was found in 39 (55%) oral carcinomas (OCs) and 24 (14%) esophageal carcinomas (ECs). This site-specific difference in HPV detection between OCs and ECs was statistically significant (P < 0.001). There was a significant difference in the geographical distribution of HPV16-E6 variants. Multiple infections of different HPV types were found in 13 ECs, but multiple infections were not found in OCs. This difference was statistically significant (P = 0.001). The geometric means (95% confidence interval) of HPV16 viral load in OCs and ECs were 0.06 (0.02-0.18) and 0.12 (0.05-0.27) copies per cell, respectively. The expression of p16INK4a proteins was increased by the presence of HPV in ECs (53% and 33% in HPV-positive and-negative ECs, respectively; P = 0.036), and the high-risk type of the HPV genome was not detected in surrounding normal esophageal mucosa of HPV-positive ECs. CONCLUSION: Based on our results, we cannot deny the possibility of HPV16 involvement in the carcinogenesis of the esophagus.

HPV 6b L1VIRUS-LIKE PARTICLES ELICIT HUMORAL IMMUNITY IN MICE

Objective.To test whether intramuscular,intranasal,intrarectal and intravagina l administration of HPV6b L 1 virus-like particlescould induce immune response in mice and to as sess whether intra-muscular and mucosal vaccination against HPV is feasible.Me thods.HPV6b L1proteins self-assembled into VLPs in Sf-9cell in vitro.Mic e were immunized on day0and21with50ìg HPV6b L1VLPs intramuscularly,int ranasally,intrarectally and intravagi-nally respectively.Sera were collected for testing IgG titer after a further7days and3months respec-tively.Results .After immunizations,all mice developed significant anti-HPV6b L1antibody titers in serum by7days after the second immunization.The titer of the serum I gG antibody against HPV6b L1VLPs in the intramuscularly immunized group was h igher than that in the intranasally,intrarectally and intravaginally immunized groups respectively,indicating that both muscular and mucosal administration of HPV6b L1VLPs can stimulate a systemic HPV-specific antibody response.Sera of the mice in the in-tramuscularly immunized group still maintained a high tit er of the serum IgG antibody against HPV6b L1VLPs 3months after the immunizat ion.Conclusion.The results demonstrated that the HPV6b L1VLPs maintain stro ng antigenicity.Immu-nization with HPV6b L1VLPs via intramuscular and mucos al routes,without adjuvant ,can elicit spe-cific antibody in sera.These fin dings suggest that the VLPs are able to induce protective antibodies.

Correlation between Load of HPV 16 DNA in Cervical Cancer and HPV 16 DNA in Lymph Nodes

OBJECTIVE To determine the association between viral loadof human papillomavirus 16 (HPV16) DNA in the primary focusof cervical carcinoma and HPV16 DNA in pelvic lymph nodes.METHODS The HPV16 DNA load was measured by fluorescentquantitation polymerase chain reaction (FQ-PCR) in 17 primaryfoci. HPV16 DNA was detected by polymerase chain reaction(PCR) using HPV16 type-specific primers in 296 pelvic lymphnodes which were from 17 cases of cervical cancer.RESULTS The viral load of HPV16 DNA showed statisticallysignificant differences between tumors with a diameter of < 4cm and ≥ 4 cm (P < 0.05). Seven of 17 cervical cancer cases hadHPV16 DNA positive lymph nodes, designated as the positivegroup, while the remaining 10 without positive lymph nodes wasdesignated the negative group. The average load of HPV16 DNAshowed no significant difference between the 2 groups (P > 0.05).The load of HPV16 in the primary lesion was not associated withthat in the lymph nodes. There were 38 HPV16 DNA positivenodes in the total 296 nodes. The rate of positivity of HPV16 DNAin lymph nodes showed statistically significant differences inconsideration of maximum tumor diameter, tumor differentiation,histologic type, depth of myometial infiltration and the metastaticstatus of the nodes, respectively (P < 0.05).CONCLUSION Viral load of HPV16 in the primary cancer focuscorrelated with the quantity of tumor cells in the primary focusbut not with the existence of HPV DNA positive lymph nodes.Detection of HPV DNA may help to find the early metastases thatcannot be evaluated histopathologically, but the prognostic valueof HPV positive lymph nodes needs further examination.

Detection of Human Papillomaviral Infection on Kazakh Patients with Esophageal Squamous Cell Carcinoma in Xinjiang

OBJECTIVE To investigate the detection rate of humanpapilloma virus (HPV) DNA in the Kazakh esophageal carcinoma(EC) patients of Xinjiang.METHODS We detected the prevalence of a HPV gene in tumortissues from 318 esophageal squamous cell carcinoma (ESCC).Tumor tissues were kept in formalin and embedded in paraffin.One hundred seventeen samples used crude cell suspension, whilethe other 201 used the method of DNA extraction with phenol-Tris/chloroform. We analyzed the relevance to EC of Kazakh's inXinjiang.RESULTS In the ESCC samples of Kazakh's in Xinjiang, totaldetection rate for HPV DNA was 64.5% (205/318). The positiverate of HPV in group of crude cell suspensions was 82.9% (97/117)compared with the rate of 53.7% (108/201) in the group of DNAextraction. The results in the two groups showed significantdiffference (x^2 = 5.711, P < 0.05).CONCLUSION HPV DNA infection may be one of the mostimportant factors related to EC of Kazakh's in Xinjiang.

Construction of non-replicating recombinant vaccinia virus expressing HPV16 L1,L2E7 proteins

Objective： To construct a non-replicating vaccinia virus expressing human papillomavirus 16 （HPV16） L1, L2E7 proteins as a candidate vaccine for cervical cancer. Methods： Using vaccinia virus vector, we generated a strain of non-replicating recombinant vaccinia virus vaccine expressing HPV16 L1, L2E7 proteins by homologous recombination and identified by PCR and Westernloting. Results： We demonstrated that the L1, L2E7 gene of HPV16 were integrated into vaccinia genosome and could express L1, L2E7 protein stably when infected the CEF using PCR and Western-blot assay. Conclusion： NTVJL1/L2E7 can express L1, L2E7 protein of HPV16 and can be taken as a candidate vaccine for HPV16-associated diseases.

Etiology and Prevention of Recurrent Condyloma Accuminata

The possible causes of condyloma acuminatarecurrence arc summarized: such as patients with cellularimmune denciencies, physical therapy triggering subclinicalinfective foci, sowing of the virus particles, and insufficienttherapy. Corresponding preventive measures are addressed,including: immunomodulators improving cellular immunity,ensuring the range and depth of physical therapy, and trcatingsexual partners simultaneously.

Fluorescence Quantitative PCR Detected Infection of Condyloma Acuminatum

Objective: Infection of human papillomavirus in condylomaacuminatum (CA) was detected by real time fluorescencequantitative PCR (FQ-PCR) technique. Methods: Specimens of CA-DNA quantification from 94cases were examined by real time FQ-PCR technique and 32cases were compared with the same method after 10-daystreatment. Results: CA-DNA was found in all patients, with an averageof 4.0×10^6 copies/ul. After 10 days of treatment, the averagewas 2.1×10^5 copies/ul. There was a significant difference inthe average amount of CA-DNA before and after thetreatment. Conclusion: Real time FQ-PCR is a good method forexamining CA-DNA amount and it can direct the treatment of CA.

Relationship Between Apoptosis and PCNA Expression of Keratinocytes in Condylomata Acuminata

Objecrive: To investigate the relationship between apoptosis and proliferating cell nuclear antigcn (PCNA)expression of keratinocytes in Condylomata acuminata (CA). Methods: PCNA expression was observed byimmunohistochemistry technique (ABC method) in 51 CAspecimens and 1 normal specimens of foreskin or vaginalmucosae. 55 specimens (40 in the CA group and 15 in thecontrol group) were randomly sampled for in situ labelingof apoptotic cells using the TUNEL method. Results: Positive expression of PCNA in CA and controlgroups were 90.2% and 77.8%, respectively, and theproliferation index in CA group was significantly higherthan that in the control group (P<0.001). The positive rateof apoptosis was 42.5% in the LA group and 53.3% in thecontrol group, and there were no significant differences inthe apoptotic index and apoptosis-proliferation ratiobetween two groups (P>0.05). The proliferation indexshowed a significant negativc correlation with theapoptosis-proliferation ratio (r=-0.62, P=0.01) in the CAgrp. Conclusion: It is suggested that the proliferativeappearance of CA could be due to the imbalance betweencell growth and cell death which is caused by moreproliferation and less apoptosis in keratinocytes.