人乳头瘤病毒黏膜疫苗的研究前景

人乳头瘤病毒( human papillomavirus,HPV)是环状双链DNA病毒,具有高度宿主细胞特异性,主要传播途径是性接触[1].根据感染后诱发病变的不同,嗜黏膜型HPV分为高危型和低危型.低危型HPV感染则与肛门生殖道良性病变和子宫颈鳞状上皮细胞低度病变等疾病有关,高危型HPV感染可引发宫颈癌和肛门癌等疾病.     

HPV L2多肽疫苗的作用机制及其研究进展

早在20世纪70年代,人们就发现人乳头瘤病毒(HPV)感染可以引起人体不同部位的疣状病变,进一步的研究发现,HPV可以通过微小损伤侵入机体表皮和黏膜上皮,潜伏于上皮基底细胞,时机成熟进入角质形成细胞进行增殖,引起皮肤乳头瘤样损害.根据HPV致癌性的不同,可将其分为低危型和高危型.其中,高危型HPV感染与食管癌、喉癌、舌癌等恶性肿瘤的发生有关,尤其是与宫颈癌发生的关系尤为密切[1].     

人类乳头瘤病毒（H^1PV）病毒样颗粒的研究进展

人乳头瘤病毒 ( human papillomavirus,HPV)是一类具有严格宿主范围和组织特异性的 DNA病毒 ,主要感染人的皮肤或粘膜上皮细胞 ,引起感染部位发生良性和恶性病变。根据DNA序列的同源性组织特异性等 ,HPV可分为许多型别。目前发现的人乳头瘤病毒已超过1 0 0型 [1] ,其中感染人生殖道的人乳头瘤病毒有 3 5个型别 [1] ,根据其致瘤性不同分为低危型和高危型两大类。高危 HPV的感染与宫颈癌的发生有十分密切的关系。约 80 %的宫颈癌与四个型别的 HPV感染有关 ,分别是 HPV1 6、1 8、3 1和 45型 ,其中 50 %的宫颈癌与 HPV1 6感染有关 [1]…     

人乳头状瘤病毒基因分型在宫颈组织病变筛查中的应用

宫颈癌是最常见的妇科恶性肿瘤,近年来国内外的研究进一步提示人乳头状瘤病毒(HPV)不同亚型对宫颈上皮细胞的致病力不同,而且存在较大差异.HPV是一种小的双链DNA病毒,可以特异性地感染人皮肤黏膜的鳞状上皮细胞,引起多种良、恶性病变.研究发现99%以上的宫颈癌有HPV感染,HPV是宫颈癌的主要致病因子[1].世界上发现的.HPV已有110余种亚型,其中20余种与宫颈癌密切相关,根据其致癌性分为高危型和低危型两大类.我们研究HPV亚型与宫颈组织病变的相关性,为宫颈癌的筛查防治提供可靠的理论依据.     

人类乳头瘤病毒(H1PV)病毒样颗粒的研究进展

人乳头瘤病毒(human papillomavirus,HPV)是一类具有严格宿主范围和组织特异性的DNA病毒,主要感染人的皮肤或粘膜上皮细胞,引起感染部位发生良性和恶性病变.根据DNA序列的同源性组织特异性等,HPV可分为许多型别.目前发现的人乳头瘤病毒已超过100型[1],其中感染人生殖道的人乳头瘤病毒有35个型别[1],根据其致瘤性不同分为低危型和高危型两大类.高危HPV的感染与宫颈癌的发生有十分密切的关系.约80%的宫颈癌与四个型别的HPV感染有关,分别是HPV16、18、31和45型,其中50%的宫颈癌与HPV16感染有关[1].因此,使用疫苗阻断病毒的感染能有效的减少宫颈癌的发病率.同时还能减少其它一些和HPV相关的肿瘤如:肛门、外阴及扁桃体的肿瘤等.     

乳头瘤病毒感染的免疫学特性

乳头瘤病毒 (Papillomavirus ,PV)是一类高度异质的双链环状小分子DNA病毒 ,具有严格的种属和组织特异性 ,主要感染人类和多种高等脊椎动物皮肤和粘膜组织 ,引起相应部位上皮组织的增生性病变。人乳头瘤病毒 (humanpapillomavirus ,HPV)可分为引起良性增生病变的低危型和与人类多种组织恶性肿瘤 (如宫颈癌、口腔癌、食管癌等 )密切相关的高危型。根据核酸序列同源性 ,HPV可分为 80多型 ,不同型别的HPV引起不同的疾病。HPV 1、2、3、4、7、10、2 6～ 2 9在正常或免疫缺损个体中引起良性疣 ,HPV 5、8、9、12、14、15、17、19～ 2 5、…     

HPV mRNA检测在宫颈癌诊断中的研究

根据国际癌症研究机构(IARC)报道,仅在2012年全世界就有超过25万女性死于宫颈癌,这是女性相关癌症的第四大死因[1].不管是生物学研究还是流行病学研究都已经证实宫颈癌与人乳头瘤病毒(HPV)感染息息相关[2]l.单独的HPV感染可能会引起大约5％的病毒相关的癌症发生,但是却是宫颈癌发病的全部因素[3].目前已经有120多种不同基因型的HPV,根据其临床表现可分为低风险型和高风险型,然而只有少数的HPV能够导致癌症的发生[4].本文就HPV致宫颈癌的发生和HPV的实验室检查以及HPV mRNA的相关进展做一些简要论述.     

国际宫颈腺癌标准和分类:宫颈浸润性腺癌一种新的病理分类

正与2014版WHO分类不同,作者试图根据与病因[即人类乳头瘤病毒(HPV)感染]相关的形态学特征对宫颈腺癌(ECAs)进行分类。该文描述的国际宫颈腺癌标准和分类(IECC标准)将ECAs区分为两种类型,即人乳头状瘤病毒相关性腺癌(HPVA)(高倍可见腺上皮的核分裂和细胞凋亡)和无或有限的HPVA特征的宫颈腺癌[非人类乳头状瘤病毒相关性腺癌(HPVA)],然后根据胞质特点对HPVA进行分类(主要是提供与现有分类方案的连续性)。而透明细     

宫颈人乳头瘤病毒感染的免疫研究进展

人乳头瘤病毒是一种常见的双链闭环DNA病毒,主要引起皮肤黏膜的良恶性增殖性疾病,高危型HPV的持续感染已被证实是宫颈癌发生的必要因素。病毒进入人体后,机体启动固有免疫、细胞免疫、体液免疫来清除病毒。树突细胞、朗格罕氏细胞、自然杀伤细胞等参与抗病毒免疫反应中的抗原提呈、吞噬。T细胞介导的细胞免疫在清除HPV感染中发挥重要的作用。然而,HPV也可以通过多种逃逸机制逃避机体的免疫清除,使得HPV感染持续存在,从而导致宫颈病变。因此,进一步深入明确机体感染HPV后所诱导的固有免疫、细胞免疫、体液免疫等免疫反应及免疫逃逸机制,对于下一步研发新药物、新治疗方法和新疫苗具有重要作用。本文就HPV感染的机体免疫反应变化进行系统性综述。     

人类乳头状瘤病毒感染与头颈部肿瘤的相关性及研究进展

人类乳头状瘤病毒(Human papilomavirus,HPV)是一种致瘤性DNA病毒,具有显著的嗜上皮细胞特性,主要存在于会阴部、尿道、皮肤、喉部、气管及支气管和口腔黏膜.目前已知的HPV型别有100多种,研究发现大约有25型HPV与头颈部肿瘤有关.HPV被公认为一种肿瘤相关病毒,但过往的研究重点放在了HPV与宫颈癌的关系上.近年来,HPV感染与头颈部肿瘤的相关性引起了各国研究者的关注,尤其是与头颈部恶性肿瘤的相关性,但两者相关程度尚未确定.     

Prevalence and genotype distribution of human papillomavirus infection in Harbin,Northeast China

This study aimed to investigate the overall prevalence of human papillomavirus (HPV) infection among women examined at a hospital in Harbin and to evaluate the impact of HPV types on the natural outcome and state of cervical cytology. A total of 2,938 female outpatients from the affiliated hospital of Harbin Medical University were enrolled. Rapid hybridization gene chip and liquid-based cytology tests were used to detect HPV genotypes and cervical cytology. The overall prevalence of HPV in women who came to this hospital was 36.45 %. The majority were infected with a single strain, and the high-risk HPV (HR-HPV) type constituted the largest proportion. HPV16 and 58 were the most common types, while the genotypes of single low-risk HPV (LR-HPV) were not the same in different age groups. HPV53, 16 and 81 were the most common types in multiple HR-HPV infection; HR-HPV16, 33, 81 and LR-HPV 6, 44, 43 were the most common in HR and LR-HPV infection. In total, 44.1 % of the women with HSIL and 44.0 % with ASCUS were positive for HR-HPV16. Multiple HPV infections and single HPV infections had no effect on the natural outcome after half a year. HPV16, 81 and 35 had a better natural outcome, followed by HPV52 and 53, but HPV58, 59 and 18 had a bad outcome after half a year. This is the first study to show that the distribution of HPV types is different in Harbin than it is in other regions. These findings will provide guidance for the vaccination program in this area.     

Evaluation of the detection of human papillomavirus genotypes in cervical specimens by hybrid capture as screening for precancerous lesions in HIV-positive women

Given the frequency and persistence of human papillomavirus (HPV) infection and associated cytological alterations in HIV-1-positive women, the incidence of uterine cervix neoplasm is likely to increase along with patient survival. More appropriate screening programs, which, in addition to Pap smears (PS), also include tests to detect and type HPV, are needed for the early identification of precancerous cervical lesions. This prospective study involved 168 HIV-positive (group A) and 100 HIV-negative women (group B). Cervicovaginal samples were collected for a PS and HPV DNA search. The detected virus was typed as high–intermediate oncogenic risk HPV (HR-HPV) and low-risk HPV (LR-HPV) using hybrid capture (HC) (Murex-Digene) and in-house PCR tests. The HC-detected prevalence of HPV was 111/168 (66%:HR 75.6%) in group A and 15/100 (15%:HR 42.9%) in group B (P < 0.0001). Polymerase chain reaction (PCR) was positive in 91% and 48%, respectively. No significant difference was observed between drug addicts and heterosexual HIV-1-positive women (P = 0.09). HPV was detected in 94% of the 57 HIV-positive women with cytological alterations. HR-HPV was found in 41/49 women with low-grade and 7/8 with high-grade squamous intraepithelial lesions (LSIL and HSIL, respectively). In women with a negative PS, HPV was detected in 57/111 cases (HR 63%) of group A and in 13/98 of group B (6 cases of HR). Of the 54 group A women who underwent biopsy, histology revealed that 41 had LSIL (18 with negative PS, 19 with LSIL, and 4 with HSIL; HR-HPV in 73% and LR-HPV in 17%), nine had HSIL (5 LSIL and 4 HSIL on cytology; HR-HPV in 89% and LR-HPV in 11%), and four were negative (all cytology negative; 3 HR-HPV and 1 LR-HPV). HR-HPV was more frequent as immunodepression worsened. These results show that cytological evaluation alone underestimated histological alterations in 23/50 women (42.6%), whereas the combination of Pap smear and HPV detection reduced this underestimate to 5%. J. Med. Virol. 56:133–137, 1998. © 1998 Wiley-Liss, Inc.     

Overexpression of the proto-oncogene C-jun in association with low-risk type specific human papillomavirus infection in condyloma acuminata

Infection with different types of human papillomavirus (HPV) is associated with neoplasia at different anatomic sites. The “low-risk” HPVs (LR-HPV) are responsible for benign genital lesions such as condyloma acuminata. In order to clarify the tumorigenic mechanism of LR-HPV, the HPV infection status was investigated and the expression of the c-jun proto-oncogene in different HPV-related skin and genital lesions analyzed. Of the 17 condyloma specimens analyzed by Western blotting, 13 cases (76.5%) exhibited overexpression of the c-jun gene. All 13 cases harbored high copy numbers of the LR-HPV genome with an average of 926 copies per cell, whereas the other four cases had an average of 12 copies of LR-HPV per cell (P < 0.001). Further typing of HPV by Southern blotting revealed that HPV-6 and HPV-11 infections predominated in c-jun positive cases. The c-jun protein was detected much less frequently in cervical cancers (three of 29, or 10.3%) and skin warts (one of 10), and was not detected in five genital polyps or in five normal cervical tissues. These findings suggest a type 6/11-specific induction of c-jun gene expression in HPV-related neoplastic lesions. © 1996 Wiley-Liss, Inc.     

Comparison of the AMPLICOR human papillomavirus test and the hybrid capture 2 assay for detection of high-risk human papillomavirus in women with abnormal PAP smear

Infection with human papillomavirus (HPV) is a necessary step in the progression to cervical cancer. Many methods for HPV testing are currently available, mostly developed to detect pools of HPV types. Hybrid Capture 2 (HC2) is one of the most widely used. A new PCR-based assay, the Roche AMPLICOR HPV test, has been recently developed. Both assays recognize a group of 13 HR HPV types contemporaneously. This study evaluated the performance of both methods for detecting high-grade cervical lesions as a part of management for abnormal PAP smears. The study population was composed of 213 women, all referred to colposcopy and histologic diagnosis following an abnormal PAP test. Biopsy-confirmed high-grade cervical intraepithelial neoplasia was used as a gold standard. Overall agreement was 84.9% with a kappa value of 0.6. When comparing the ability to detect moderate cervical intraepithelial neoplasia (CIN2+) and high-grade cervical intraepithelial neoplasia (CIN3+/cancer), AMPLICOR proved slightly more sensitive than HC2, a finding that is important when HPV testing is used in a triage of borderline smear results. Genotyping of discordant results showed a prevalence of LR-HPV types in HC2 positive/AMPLICOR negative samples, and a similar prevalence of HR- and LR-HPV types in AMPLICOR positive/HC2 negative samples. In conclusion, the study shows that the AMPLICOR assay is more sensitive than HC2, which makes it a valid alternative for routine clinical use.     

Analyses of human papillomavirus genotypes and viral loads in anogenital warts

Condylomata acuminata (genital warts) are the most common sexually transmitted viral diseases. These lesions are caused by infection with mucosal human papillomaviruses (HPVs). However, there is limited information on HPV strain distribution involved in the molecular pathogenesis of these lesions. To address this, the strain prevalence and the frequency of multiple HPV infections were determined in wart tissue obtained from 31 patients attending a wart clinic. These lesions were bisected and subjected to parallel DNA and mRNA extractions. HPV-type prevalence and incidence of multiple infections were determined by the Roche Linear Array assay. qPCR compared HPV 6, 11, 16, and 18 viral loads and RT-qPCR measured HPV 6 and 11 E6 genomic expression levels. Seventy-one percent of these samples were infected with multiple HPVs. Only one sample was negative for HPV 6 or 11 DNA. Forty-eight percent of samples were positive for a high risk (oncogenic) HPV. The results show that multiple infections in tissue are frequent and the subsequent analysis of HPV 6 and 11 E6 DNA viral loads suggested that other HPVs could be causing lesions. Further analysis of HPV 6/11 E6 mRNA levels showed that there was no discernable relationship between HPV 6 E6 DNA viral load and relative HPV 6 or 11 E6 mRNA levels thereby questioning the relevance of viral load to lesion causality.     

Increased detection of HPV 16 virus in invasive, but not in early cervical cancers.

Human papilloma virus type 16 (HPV 16) DNA is found in about 50% of cervical squamous cell carcinomas (SCCs), and this association has raised the possibility of a causal role for HPV 16 in cervical carcinogenesis. We have tested this hypothesis by assaying a series of biopsies (n = 119) ranging from normal mucosa to infiltrating SCC with the PCR-technique for the presence of HPV 16 DNA. While HPV 16 DNA was detected in 50% of our cases with invasive SCC, the incidence of HPV 16-positive samples was about 10% in all other biopsies ranging from normal mucosa to cases of carcinoma in situ. HPV 16 therefore appears to be involved in late tumor promotion but not in early tumor development.     

Human Papillomavirus Prevalence and Genotype Distribution among Turkish Women with or Without Cervical Lesion

Context: Human papillomavirus (HPV) infection is the main cause of cervical cancer, but the risk is associated with the various HPV genotypes which may be found in women with or without clinical findings. Aims: We aimed to identify HPV prevalence and genotype distribution in women with or without cervical lesions admitted to Gynaecology and Obstetrics Clinics of one of the largest private hospitals in Istanbul between 2013 and 2017. Subjects and Methods: In the present study, cervical cytobrush samples collected from 2464 women with different cytological conditions, and investigated for the presence of HPV, and the different genotypes. Results were evaluated based on the HPV positivity in different cytological findings, and ages. Furthermore, distribution of high-risk (HR) and low-risk (LR) genotypes in different groups was investigated. Results: Among all participants, 1925 (78.1%) was with the normal cytological condition, 354 (14.4%) with ASC-US; 151 (6.1%) with low-grade squamous intraepithelial lesion (LSIL), and 34 (1.4%) with high-grade squamous intraepithelial lesion (HSIL). Our results showed that 649 out of 2464 patients (26.3%) were positive, and 1815 (73.7%) were negative for the presence of HPV. Among 649 positive patients, 223 (34.3%) were found positive for more than one genotype. HPV 16 was found the most common HR-HPV type in ASC-US and LSIL whereas HPV 18 was the most common in HSIL. HPV 6 was found the most common LR-HPV type in ASC-US and LSIL whereas HPV 11 was the most common in HSIL. 26.9% of women <50 years old, and 22.3% of women ≥50 years old was positive for HPV. The most common HR-HPV genotype was 16 in both groups with (19%) or without (17%) abnormal cytology. Conclusions: We concluded that HPV prevalence and genotype distribution in women with or without clinical findings is an important predictor of cervical cancer.     

A type‐specific study of human papillomavirus prevalence in cervicovaginal samples in three different Spanish regions

Human papillomavirus (HPV) is the most frequent sexually transmitted viral infection. It is necessary to know HPV genotype distribution to identify how many women will be protected by HPV vaccines. During a period of 18 months, we have analyzed 2362 HPV positive reporting data from a secondary demand screening program in three regions in Spain (Cantabria, Leon and Burgos). The study has been conducted using polymerase chain reaction and tube array hybridization covering the 35 HPV genotypes described as affecting anogenital mucosa. There were no significant differences between the three regions according to genotype distribution. The most frequent were HPV16 (19.18%), HPV53 (11.26%) and HPV58 (7.66%). HPV18 was the source of 4.02% of infections. High‐risk HPVs were found in 1863/2362 cases. HPV16 was present in 24.3% of high‐risk infections and HPV18 was found in 5.1%. Uncommon genotypes (<5% of the total prevalence each) were found in 17,9% of the total high‐risk infections (334/1863). Multiple infections were diagnosed in 22% of the cases. The HPV genotype distribution is different from previously published data when multiple types are included in the screening. Both HPV16/18 account for 30% of high‐risk infections in a clinical setting in Spain. The presence of multiple genotypes is very common among the population.