HPV感染对男性的危害与HPV疫苗接种对男性的保护

人乳头瘤病毒（HPV）是全球最常见的性传播病毒之一，可引起男性的生殖器疣、男性不育、口咽癌、肛门癌、阴茎癌等疾病，严重影响了男性的生活质量。目前，HPV疫苗在保护女性健康方面已经取得了巨大成就。近些年来，已有指南推荐男性注射HPV疫苗，并且它的有效性和安全性得到肯定。有研究表明，HPV疫苗对男性特别针对特殊人群具有保护作用。澳大利亚、美国等一些国家已经开展男性HPV疫苗的注射，男性HPV感染及其相关疾病的发病率有所下降。可见，男性接种HPV疫苗的益处已经很明确，提高男性HPV疫苗的覆盖率是一种趋势。     

23296例女性宫颈高危型HPV感染情况分析

目的研究民航总医院就诊女性宫颈高危型人乳头瘤病毒(high risk-human papillomavirus,HR-HPV)感染情况及分型特点。为北京地区预防HPV感染和防治宫颈癌提供科学依据。方法选择2016年10月至2019年4月于民航总医院妇产科就诊并行高危型HPV检测的女性23296例,对其结果进行回顾性分析,分析高危型HPV感染情况,比较不同年龄组、不同亚型HPV感染情况。结果高危型HPV感染率为17.21%。其中单一HPV感染率13.00%,多重HPV感染率4.21%。HPV亚型感染率的前四位依次为HPV52型(感染率3.68%)、HPV16(感染率3.07%)、HPV58(感染率为3.04%)、HPV51(感染率1.89%)。HPV的感染率呈现反抛物线分布,在<20岁的女性中HPV的感染率最高,后逐渐下降,到30~45岁的感染率到达最低点,后逐渐升高,到>60岁到达第二高峰。结论1.本研究HPV感染率总体处于中等感染水平。2.<20岁人群是HPV感染的高危人群,建议在性生活前注射HPV疫苗,可以最有效的阻断HPV感染。3.应重视45岁后患者的HPV感染,尤其是持续性HPV感染,应积极行阴道镜检查,早期发现子宫颈上皮内瘤变及宫颈癌变。     

西安地区女性HPV感染情况及其基因型分布特点研究

目的研究西安市女性HPV感染情况及其基因型分布特点,为HPV疫苗研制和宫颈癌防治提供可靠依据。方法于2016年8月23日-2017年6月20日收集西安市高新医院、凤城医院等8家医院的宫颈脱落细胞标本共1538例,采用人乳头状瘤病毒(HPV)分型检测试剂盒(PCR-膜杂交法)对HPV病毒的DNA进行分型检测,统计并分析HPV整体感染情况、各基因型分布情况及不同年龄组感染情况。结果 1538例标本中HPV阳性共355例,阳性率为23.1%。HPV感染主要是高危型HPV感染,以单一感染为主,多重感染主要是二重感染。共检出18种HPV亚型,其中感染率较高的高危型是16型、39型和52型,低危型是81型和6型。不同年龄组HPV阳性率差异有统计学意义(χ2=13.08,0.01P0.025),其中30岁和60~70岁年龄组女性HPV感染率较高。结论西安市女性HPV感染及其基因型分布与其他地区存在差异,因此有针对性地研制和投放疫苗对降低宫颈癌发生率具有重要意义。     

治疗性HPV DNA疫苗的研究进展

HPV感染与宫颈癌的发生密切相关。治疗性HPV DNA疫苗可以治疗HPV感染,进而阻断由HPV引起的宫颈癌前病变。基于HPV及DNA疫苗的深入研究,研究者通过不同方法来改进治疗性HPV DNA疫苗,以期在不久的将来能应用于临床。     

HPV树突状细胞疫苗研究进展

人乳头瘤病毒(HPV)感染在人群中非常普遍,尚无有效预防和治疗办法.本文概述了以树突状细胞(DC)为基础的HPV疫苗研究现状,包括病毒蛋白及肽段负载的DC疫苗、HPV-DNA、RNA、病毒样颗粒刺激的DC疫苗及肿瘤细胞与DC融合疫苗等,并讨论了其在尖锐湿疣防治中的可能应用.     

HPV L2二代宫颈癌预防性疫苗的研究进展

宫颈癌是女性第二大癌症,全球每年发病50万例.现已证实,高危型人乳头瘤病毒（Human papillomavirus,HPV）的持续感染是宫颈癌的主要病因[1],超过15个HPV基因型与宫颈癌的发病密切相关,其中以HPV16型最为常见.除宫颈癌外,高危型HPV感染还与人体其他器官的恶性肿瘤有关,如喉癌、鼻腔和上颌窦癌和鼻咽癌等[2].因此,研制针对高危型HPV的疫苗是现阶段预防和治疗上述癌症经济、有效的方法.     

HPV与宫颈癌关系及疫苗研究进展

流行病学和病原学研究表明,人乳头瘤病毒(HV)感染是妇女发生宫颈癌重要的原因之一.HPV是无包膜的小型双链环状DNA病毒,不同基因型病毒对细胞的转化能力不同,其中HPV-16、18与子宫颈癌关系最密切.HPV诱发官颈癌的主要机制,是其E6和E7蛋白基因在宫颈细胞中的表达增加,产生的E6和E7蛋白两个癌蛋白分别与抑癌蛋白p53和pRb结合而诱导后两者降解.HPV疫苗包括预防性疫苗和治疗性疫苗两大类.本文对HPV感染与宫颈癌发生的关系、疫苗研究进展进行了系统的阐述.     

HPV与宫颈癌关系及疫苗研究进展

流行病学和病原学研究表明,人乳头瘤病毒（HV）感染是妇女发生宫颈癌重要的原因之一.HPV是无包膜的小型双链环状DNA病毒,不同基因型病毒对细胞的转化能力不同,其中HPV-16、18与子宫颈癌关系最密切.HPV诱发官颈癌的主要机制,是其E6和E7蛋白基因在宫颈细胞中的表达增加,产生的E6和E7蛋白两个癌蛋白分别与抑癌蛋白p53和pRb结合而诱导后两者降解.HPV疫苗包括预防性疫苗和治疗性疫苗两大类.本文对HPV感染与宫颈癌发生的关系、疫苗研究进展进行了系统的阐述.     

治疗性HPV疫苗的研究进展

人乳头瘤病毒(human papillomavirus,HPV)引起包括宫颈癌等在内的多种疾病,如何预防和治疗已为人们所关注.已上市的疫苗主要用于预防HPV的感染,对已感染HPV人群的治疗效果未做进一步研究,而目前临床治疗效果不够理想,因此利用治疗性疫苗通过免疫学方法治疗HPV引起的疾病逐渐成为研究的热点.以HPV E6和E7为靶抗原的治疗性疫苗研究开始较早,研究最为深入,已经取得了一定的进展.同时近年来的研究发现,HPV其他的蛋白如E2、E5、L1和L2等也可作为治疗性疫苗的候选靶抗原,并显示出较好的应用前景.     

北京天坛医院5512例女性HPV感染基因型分析

目的 探讨北京地区女性生殖道人乳头瘤病毒(HPV)感染的基因型分布情况,为预防HPV感染和宫颈疾病防治提供理论依据.方法 使用核酸分子快速导流杂交基因芯片技术,对5512例女性宫颈脱落细胞进行HPV亚型检测.结果 892例患者感染HPV,总感染率为16.2％.居前5位的HPV基因亚型依次为HPV52、58、16、CP8304和HPV53.单一感染664例(24.1％),占所有感染的74.4％(664/892);双重亚型感染175例,占所有感染的19.6％ (175/892);多重亚型感染53例,占所有感染的5.94％(53/892).HPV感染以≤45岁的年轻女性为主(65.4％),≤25岁患者HPV感染率最高(23.2％).结论 HPV52、HPV58、HPV16、CP8304和HPV53感染在北京地区最为常见,总体符合亚洲人群分布规律,同时又具有独特的地域分布特点.     

Cytokine levels in HIV infected and uninfected Indian women: Correlation with other STAs

Host immune status is an important determinant of disease progression. Infections in the genital tract may alter the immunity in the particular site and hence affect the production of local cytokines. We performed this study to determine whether HIV in association with cervical HPV and CT/GC infections influences the production of local cytokines. Cervical secretions from 100 women with or without HIV infection were collected for measuring IL-1β, -6, -10 and -12 concentrations by ELISA. Cervical HPV and CT/GC DNA were detected by HCII test. Significant elevations of IL-6 and IL-10 were observed in patients having HIV infection. Although cervical HPV infection increased the concentrations of both IL-6 and IL-1β but HPV induced abnormal cervical smear was associated only with increased IL-6 concentrations significantly. Double infection had marked relation with IL-6 and IL-10. CT/GC had no direct effect on any of these cytokines but in association with HIV and HPV, these bacterial pathogens elevated the concentrations of IL-6 significantly. Thus, our results suggest that the presence of HIV and other STAs in the genital tract can cause imbalance of local cytokine levels which in turn may facilitate other opportunistic infections.     

Mucosal vaccination with a recombinant Salmonella typhimurium expressing human papillomavirus type 16 (HPV16) L1 virus-like particles (VLPs) or HPV16 VLPs purified from insect cells inhibits the growth of HPV16-expressing tumor cells in mice

Human papillomaviruses, mainly type 16 (HPV16), are responsible for cervical intraepithelial neoplasia, which can lead, in association with other factors, to cervical cancer. Both Salmonella recombinant vaccine strains assembling HPV16 virus-like particles (VLPs) and HPV16 VLPs purified from insect cells are able to induce HPV16 neutralizing antibodies in genital secretions of mice after nasal immunization. Anti-HPV16-specific antibodies in cervical secretions of women may prevent genital infection with HPV16, although this cannot be critically evaluated in the absence of an experimental model for genital papillomavirus infection. Induction of HPV16-specific cell-mediated immunity in the genital mucosa could improve the efficacy of a vaccine and a mucosal route of immunization might be necessary to do so. It has been shown that systemic immunization of mice with purified HPV16 VLPs confers protection against an HPV16-expressing tumor cell challenge through the induction of cytotoxic T-lymphocytes. Using the same C3 tumor model, we show that intranasal immunization of mice with purified HPV16 VLPs in a prophylactic setting also induces anti-tumor immunity. More interestingly, mucosal vaccination of mice with a Salmonella recombinant strain stably expressing HPV16 L1 VLPs also induces anti-tumor immunity in prophylactic as well as in therapeutic settings. Our data suggest that attenuated Salmonella strains expressing chimeric VLPs containing nonstructural viral proteins might be a promising candidate vaccine against cervical cancer by inducing both neutralizing antibodies and cell-mediated immunity.     

女性下生殖道癌临床病理特征与人乳头状瘤病毒型别间的相关性研究

目的：探讨女性下生殖道癌的临床病理与人乳头状瘤病毒（HPV）型别之间的关系。方法：回顾性研究100例下生殖道癌（宫颈癌63例,外阴癌37例）的临床病理特征,并应用PCR技术检测每份标本的HPV状态。结果：在模板内参照阳性的87份中,宫颈癌54份,外阴癌33份,HPV阳性率在宫颈癌中为88．3％,以HPV16型（55．6％）和HPV18型（24．4％）为主,在33例外阴鳞癌中,HPV阳性仅见于基底细胞癌和混疣样癌,阳性率均为83．3％,以HPV16型为主（70．0％）;6例基底细胞样癌中有3例合并宫颈鳞状上皮肿瘤,其中2例宫颈与外阴的肿瘤均为HPV16型阳性;21例角化鳞癌则未检测出HPV－DNA,但有发病年龄高（平均63．3岁）。形态学上角化明显和预后较差等特征。结论：HPV16型和18型在宫颈癌中性阳率较高,而在外阴癌中HPV阳性的意义则因组织学类型而不相同。     

Developing HPV virus-like particle vaccines to prevent cervical cancer: a progress report.

BACKGROUND: the knowledge that sexually transmitted infection with one of a limited number of human papillomaviruses (HPVs) is a central cause of almost all cervical cancers affords the opportunity to prevent this common cancer through anti-viral vaccination. OBJECTIVE: the spectacular success of vaccines in preventing several other viral diseases offers hope that immunoprophylaxis against the relevant HPVs could lead to a major reduction in cervical cancer incidence. RESULTS AND CONCLUSION: the results of preclinical studies and early phase clinical trials of virus-like particle (VLP) based subunit vaccines have been very encouraging. However, unique aspects of papillomavirus biology and genital tract infections, and the lack of sexual a transmission model for papillomavirus, make it far from certain that effective prophylactic vaccination against genital HPV infection will be easily achieved. Future clinical efficacy trials will likely test the hypothesis that parenteral injection of VLPs can induce antibody mediated and type specific protection against genital tract HPV infection and subsequent development of premalignant neoplastic disease.     

Vaccination to protect against infection of the female reproductive tract

Infection of the female genital tract can result in serious morbidities and mortalities from reproductive disability, pelvic inflammatory disease and cancer, to impacts on the fetus, such as infant blindness. While therapeutic agents are available, frequent testing and treatment is required to prevent the occurrence of the severe disease sequelae. Hence, sexually transmitted infections remain a major public health burden with ongoing social and economic barriers to prevention and treatment. Unfortunately, while there are two success stories in the development of vaccines to protect against HPV infection of the female reproductive tract, many serious infectious agents impacting on the female reproductive tract still have no vaccines available. Vaccination to prevent infection of the female reproductive tract is an inherently difficult target, with many impacting factors, such as appropriate vaccination strategies/mechanisms to induce a suitable protective response locally in the genital tract, variation in the local immune responses due to the hormonal cycle, selection of vaccine antigen(s) that confers effective protection against multiple variants of a single pathogen (e.g., the different serovars of Chlamydia trachomatis) and timing of the vaccine administration prior to infection exposure. Despite these difficulties, there are numerous ongoing efforts to develop effective vaccines against these infectious agents and it is likely that this important human health field will see further major developments in the next 5 years.     

Vaccination to protect against infection of the female reproductive tract

Infection of the female genital tract can result in serious morbidities and mortalities from reproductive disability, pelvic inflammatory disease and cancer, to impacts on the fetus, such as infant blindness. While therapeutic agents are available, frequent testing and treatment is required to prevent the occurrence of the severe disease sequelae. Hence, sexually transmitted infections remain a major public health burden with ongoing social and economic barriers to prevention and treatment. Unfortunately, while there are two success stories in the development of vaccines to protect against HPV infection of the female reproductive tract, many serious infectious agents impacting on the female reproductive tract still have no vaccines available. Vaccination to prevent infection of the female reproductive tract is an inherently difficult target, with many impacting factors, such as appropriate vaccination strategies/mechanisms to induce a suitable protective response locally in the genital tract, variation in the local immune responses due to the hormonal cycle, selection of vaccine antigen(s) that confers effective protection against multiple variants of a single pathogen (e.g., the different serovars of Chlamydia trachomatis) and timing of the vaccine administration prior to infection exposure. Despite these difficulties, there are numerous ongoing efforts to develop effective vaccines against these infectious agents and it is likely that this important human health field will see further major developments in the next 5 years.     

Human papillomavirus in exophytic condylomatous lesions on different female genital regions.

Clinically diagnosed exophytic condylomatous lesions on the vulva (20 cases), vagina (5 cases), and cervix (9 cases) were examined pathologically, and human papillomavirus (HPV) types present in those lesions were identified by Southern blot hybridization analysis. All vulvar and vaginal lesions showed typical histopathological features of classical condylomata, and HPV 6 and 11 were found in 15 vulvar and 3 vaginal lesions and in 5 vulvar and 2 vaginal lesions, respectively. In 5 cervical lesions with typical condylomatous changes, HPV 6 or 11 was also detected; however, HPV 16 was found in 2 cases of cervical lesion surrounded by prominent intraepithelial neoplasia, and HPV 31 was found in 2 cases of slightly elevated lesion with intraepithelial neoplasia. These observations suggest that HPV 6 and 11 have the potency to induce the specific pathological changes, condylomatous, in any regions of the female lower genital tract.     

Papillomavirus and cervical cancer: a clinical and laboratory study

It is now widely accepted that HPV types 16, 18, 31, and 33 are associated with the development of high grade intraepithelial neoplasia and malignant lesions in the cervix. On this basis, the identification of HPV types in cervical scrape samples has been advocated as a supplement to cytological screening tests. However, little is known of the distribution of the virus at different sites in the lower female genital tract or of how this distribution may change during the natural course of HPV infection. In this survey, HPV DNA dot hybridizations and, in some instances, Southern blot hybridizations with mixed HPV 6/11 and 16/18 probes were undertaken to detect HPV DNA in cervical scrapes and biopsies of the cervix, vagina, and vulva. A total of 92 women attending a Sydney hospital were screened: 59 of these patients had cervical disease, either invasive cervical carcinoma (CaCx) or cervical intraepithelial neoplasia (CIN), grades I-III. A group of 33 women who lacked evidence of cervical abnormalities served as controls. HPV DNA, predominantly type 16/18, was detected in the cervical biopsies of 96% of the CaCx patients, 80% of the CIN III patients, and 65% of the CIN I-II patients. In contrast only 9% of the cervical biopsies from the control group contained detectable HPV 6, 11, 16, or 18 DNA. A high proportion of the women with cervical abnormalities had evidence of concurrent vaginal and/or vulval papillomavirus involvement. The significance of these findings for routine screening and subsequent management of patients with HPV-associated cervical disease is discussed.     

VAGINAL IMMUNITY IN THE HSV-2 MOUSE MODEL

Herpes simplex virus type 2 (HSV-2) is a sexually transmitted pathogen that infects the genital tract. Efforts to develop vaccines to protect women against this and other sexually transmitted pathogens would be facilitated by a better understanding of the immune mechanisms that protect the female reproductive tract against such infections. Such information would be invaluable in developing vaccine strategies to promote the type and magnitude of immune responses in the genital tract that would effectively protect against infection. This review focuses on recent studies using a progestin-treated adult mouse model to explore mucosal immunity to HSV-2 in the vagina. Evidence indicating a major role for both humoral and T cell immunity is presented.     

Vaginal immunity in the HSV-2 mouse model

Herpes simplex virus type 2 (HSV-2) is a sexually transmitted pathogen that infects the genital tract. Efforts to develop vaccines to protect women against this and other sexually transmitted pathogens would be facilitated by a better understanding of the immune mechanisms that protect the female reproductive tract against such infections. Such information would be invaluable in developing vaccine strategies to promote the type and magnitude of immune responses in the genital tract that would effectively protect against infection. This review focuses on recent studies using a progestin-treated adult mouse model to explore mucosal immunity to HSV-2 in the vagina. Evidence indicating a major role for both humoral and T cell immunity is presented.