乳杆菌与人乳头瘤病毒感染及宫颈病变的相关性

乳杆菌是健康女性阴道内数量最多的菌群,对于维持阴道微生态平衡起着重要的作用。乳杆菌能牢固黏附于阴道黏膜上皮,起到占位性保护作用,并且分泌乳酸,维持阴道的酸性环境,产生H2O2、细菌素、生物表面活性物质等抑菌物质,引起有益的免疫反应,从而抵挡病原微生物的感染,是女性下生殖道重要的微生物屏障。人乳头瘤病毒(HPV)感染是宫颈癌的直接致病因素,而阴道作为宫颈的毗邻器官,其微生态环境对宫颈起着重要的作用。近年来国内外很多学者研究发现以乳杆菌的减少为主的阴道微生态失衡与HPV感染、宫颈癌的发生有密切关系。乳杆菌通过产生各种代谢产物,以及激活机体免疫功能而发挥抵抗HPV感染、抑制肿瘤的作用。本文对乳杆菌与HPV感染及宫颈病变的相关性及其机制进行综述。     

阴道微生物与人乳头瘤病毒感染及宫颈上皮内肿瘤相关性研究进展

人乳头瘤病毒（HPV）感染是宫颈癌前病变或宫颈癌发生的必要条件，阴道微生物多样性的改变可能是造成HPV持续感染继而发生宫颈病变的伴随因素。正常女性阴道微生物多样性较低，仅由少数几种乳酸杆菌（Lactobacillus）构成主要菌群。随着对细菌16SrRNA基因高通量测序技术的应用，越来越多的研究证实阴道菌群中非乳酸杆菌属微生物的多样性增加与HPV感染及宫颈病变存在密切联系。标志性的阴道微生物可能通过多种分子机制与宿主细胞及HPV相互作用，导致阴道局部免疫抑制、慢性炎症的状态，从而造成HPV持续感染及宫颈病变。重建阴道微生态平衡状态尤其是乳酸杆菌为主的阴道菌群是未来HPV感染及相关宫颈病变治疗的新途径。本文就阴道微生物多样性改变与HPV感染及宫颈病变发生的研究观点进行总结归纳。     

阴道微生物与人乳头瘤病毒感染及宫颈上皮内肿瘤相关性研究进展

人乳头瘤病毒(HPV)感染是宫颈癌前病变或宫颈癌发生的必要条件,阴道微生物多样性的改变可能是造成HPV持续感染继而发生宫颈病变的伴随因素。正常女性阴道微生物多样性较低,仅由少数几种乳酸杆菌(Lactobacillus)构成主要菌群。随着对细菌16SrRNA基因高通量测序技术的应用,越来越多的研究证实阴道菌群中非乳酸杆菌属微生物的多样性增加与HPV感染及宫颈病变存在密切联系。标志性的阴道微生物可能通过多种分子机制与宿主细胞及HPV相互作用,导致阴道局部免疫抑制、慢性炎症的状态,从而造成HPV持续感染及宫颈病变。重建阴道微生态平衡状态尤其是乳酸杆菌为主的阴道菌群是未来HPV感染及相关宫颈病变治疗的新途径。本文就阴道微生物多样性改变与HPV感染及宫颈病变发生的研究观点进行总结归纳。     

宫颈阴道菌群的构成特点及其影响宫颈癌发生发展的机制探讨

宫颈阴道菌群种类繁多,一般以乳杆菌为优势菌群。正常宫颈上皮出现上皮内瘤变,并最终进展为宫颈癌的过程中,宫颈阴道菌群也在持续不断的变化。HPV感染是罹患宫颈癌的高危因素,但大多数患者并不会持续感染或发生癌变,菌群的构成和改变可能在其中发挥了重要的作用。本文将对宫颈阴道菌群在宫颈病变不同阶段的特点进行描述,并探讨菌群影响宫颈癌发生发展的可能机制和潜在作用。     

宫颈病变患者治疗前后阴道微生态变化与HPV感染的关系研究进展

宫颈上皮内瘤变(cervical intraepithelial neoplasia,CIN)与宫颈癌(cervical cancer)是威胁女性健康的疾病之一,人乳头瘤病毒(human papilloma virus,HPV)感染是其发生发展的主要因素。阴道菌群、酸碱度及清洁度等因素的改变在宫颈病变的进展过程中发挥至关重要的作用,尤其影响HPV感染、转归及清除。本文将对宫颈病变患者治疗前后阴道微生态变化与HPV感染间的关系进行阐述。     

阴道微生物在宫颈癌中作用机制的研究进展

宫颈癌是妇产科最常见的恶性肿瘤,在2018年全球女性恶性肿瘤数据统计中,宫颈癌的发病率和死亡率处于第4位,有关宫颈癌的研究一直是妇产科学者关注的热点。近年随着微生物组学的展开,阴道微生物群的组成和变动与人乳头瘤病毒（HPV）的侵袭、持续感染及宫颈癌的相关性探讨逐步增多。乳酸杆菌在正常宫颈阴道菌群中占据主导地位,其可以维持阴道微生态的平衡、抑制病原微生物生长以及增强阴道的局部抗感染和抗肿瘤能力,有望成为未来治疗宫颈癌的新策略。目前研究表明,阴道微生物群的异常变化与宫颈癌发生发展有一定的关联,有些阴道细菌通过不同的机制直接或间接发挥作用。就阴道微生物群的抗癌作用机制及其应用于宫颈癌的潜力进行综述。     

阴道微生物多样性与高危型HPV感染的相关性研究

目的:探讨阴道微生物多样性与宫颈高危型HPV(hr HPV)感染的相关性。方法:选取于上海交通大学医学院附属仁济医院体检中心体检或社区募集的68例HPV阴性妇女(正常组)和75例hr HPV感染妇女(感染组)。采用16S rRNA基因扩增技术和二代高通量测序技术分析其阴道微生物组成。结果:两组妇女阴道微生物在门水平,均以厚壁菌门为主要物种,但与正常组(73.23%)相比,感染组(68.77%)所占比例下降。与正常组相比,感染组放线菌门所占比例亦下降,而变形菌门和无壁菌门所占比例明显升高。在种水平,两组均以乳杆菌为主要菌群,其中惰性乳杆菌为优势菌群,在正常组、感染组的比例分别为41.41%、28.03%,其次为阴道加德纳菌。与正常组相比,感染组惰性乳杆菌和阴道加德纳菌所占比例呈下降趋势;而芽孢杆菌、普氏菌、巨球菌、纤毛球菌、链球菌所占比例呈上升趋势。与正常组相比,感染组物种丰富度指数Sobs指数、Ace指数均升高,物种多样性指数Shannon指数升高,Simpson指数降低,差异有统计学意义。利用LEf Se及LDA判别分析两组特征意义的物种,芽孢杆菌、志贺杆菌、海洋杆菌可作为感染组的生物标记物种,乳杆菌、加德纳菌、阴道奇异菌为正常组的生物标记物种。结论:上海地区高危HPV感染女性具有阴道微生物菌群多样性和丰富度增加,乳杆菌水平减少的特点,芽孢杆菌、志贺杆菌和海洋杆菌可作为其生物标记物种,为临床今后从调节阴道微生态角度治疗高危HPV感染提供理论依据。     

阴道微环境与人乳头瘤病毒感染相关性的研究进展

人乳头瘤病毒(HPV)感染是唯一可以明确的导致宫颈癌的致病因子,但HPV感染并不等于已是宫颈癌或者宫颈癌前病变,而提示有一种向宫颈病变发展的可能性。因此,有效的筛查和预防是降低HPV感染及宫颈病变发生的有效措施。宫颈阴道部处于阴道微环境中,正常阴道微环境是由阴道解剖结构、微生物菌群、局部免疫及机体的内分泌调节功能组成,他们之间相互影响,始终处于动态平衡的状态。而当阴道菌群、pH值、局部免疫、雌孕激素水平发生变化,可导致机体对HPV易感性增加,清除力降低。鉴于阴道微环境与HPV感染关系十分密切,本文就HPV感染与阴道微环境相关性进行综述。     

阴道微环境与人乳头瘤病毒感染相关性的研究进展

人乳头瘤病毒(HPV)感染是唯一可以明确的导致宫颈癌的致病因子,但HPV感染并不等于已是宫颈癌或者宫颈癌前病变,而提示有一种向宫颈病变发展的可能性。因此,有效的筛查和预防是降低HPV感染及宫颈病变发生的有效措施。宫颈阴道部处于阴道微环境中,正常阴道微环境是由阴道解剖结构、微生物菌群、局部免疫及机体的内分泌调节功能组成,他们之间相互影响,始终处于动态平衡的状态。而当阴道菌群、pH值、局部免疫、雌孕激素水平发生变化,可导致机体对HPV易感性增加,清除力降低。鉴于阴道微环境与HPV感染关系十分密切,本文就HPV感染与阴道微环境相关性进行综述。     

阴道内环境与HPV感染

阴道内环境是女性微生态系统中一个重要而复杂的组成部分，由阴道正常解剖结构、阴道内的微生物菌群、机体内分泌调节功能以及阴道局部粘膜免疫系统四部分构成。近来研究表明，阴道内环境紊乱与宫颈人乳头瘤病毒(Human papilloma virus,HPV)感染密切相关，且HPV 感染又可进一步加剧阴道内环境紊乱，共同促进宫颈上皮内瘤变(cervical intraepithelial neoplasia,CIN)和宫颈癌(cervical cancer,CC)的发生。     

微小RNA与宫颈癌

宫颈癌是最常见的恶性肿瘤之一,高危人乳头状瘤病毒（HPV）感染是宫颈癌发生的必要因素。微小RNA（miRNA）是一类内源性非编码的小RNA,参与了许多病毒致病和肿瘤发生过程。利用实验生物学及生物信息学方法对与肿瘤相关的miRNA进行研究是当前研究的热点。其中,在宫颈癌中目前已发现若干miRNA（如miR-21,-143,-146a,-199a等）的异常表达。综述miRNA与宫颈癌发生发展关系的研究。     

微小RNA与宫颈癌

宫颈癌是最常见的恶性肿瘤之一,高危人乳头状瘤病毒（HPV）感染是宫颈癌发生的必要因素。微小RNA（miRNA）是一类内源性非编码的小RNA,参与了许多病毒致病和肿瘤发生过程。利用实验生物学及生物信息学方法对与肿瘤相关的miRNA进行研究是当前研究的热点。其中,在宫颈癌中目前已发现若干miRNA（如miR-21,-143,-146a,-199a等）的异常表达。综述miRNA与宫颈癌发生发展关系的研究。     

子宫颈癌疫苗的研究进展

子宫颈癌是妇科常见的恶性肿瘤之一。人乳头状瘤病毒（human papilloma virus,HPV）的持续感染与子宫颈癌的发生密切相关。HPV疫苗在预防和治疗宫颈癌方面备受关注。HPV疫苗能激发机体的细胞和体液免疫应答,有效的预防和控制HPV感染,在预防和治疗宫颈癌方面发挥作用。新型预防性HPV疫苗已在多个国家已经上市;多肽疫苗、蛋白疫苗、病毒载体疫苗、DNA疫苗等治疗性疫苗的研究也有新的进展。现对HPV疫苗在预防和治疗子宫颈癌方面的最新研究进展做一综述。     

Accuracy of HPV testing of vaginal smear obtained with a novel self-sampling device

BACKGROUND: Most of women diagnosed as having cervical cancer have not participated in organized cytological screening. Aim. A study was conducted to evaluate the accuracy of human papilloma virus testing by self-collected vaginal samples in comparison to regular cytological screening. The agreement of hybrid capture 2 assay and polymerase chain reaction assay for detection of human papilloma virus DNA in self-collected vaginal samples and clinician-obtained cervical smears was investigated. METHOD: Forty-three women aged 23-58 years admitted for further examination due to previous positive cytology in the organized screening participated in self-collecting of vaginal samples with a novel self-sampling device. During the visit a clinician also collected a cervical smear using a cytobrush. The vaginal samples collected with the self-sampling device were analyzed for high-risk human papilloma virus with the hybrid capture 2 assay technique and the cervical smears were Pap-stained, examined cytologically and after that reanalyzed for human papilloma virus DNA using a polymerase chain reaction assay. RESULT: The vaginal samples were positive for high-risk human papilloma virus in 37% of the cases using hybrid capture 2 assay. Twelve of the 43 Pap smears showed positive cytology (ASCUS-CIN 3), of which 4 showed CIN 2-3. When polymerase chain reaction assay was performed, human papilloma virus DNA was detected in 40% of the glass slides. The agreement between cytology and the two human papilloma virus testing techniques was 67-74% (kappa 0.27-0.45) and the agreement between the two human papilloma virus tests was 70% (kappa 0.36). CONCLUSION: Testing for high-risk human papilloma virus can identify more women at risk of developing cervical cancer than cytology irrespective of the sampling method. Furthermore, offering a self-sampling device for collection of vaginal smear seems to be a useful screening tool for cervical cancer among women not responding to an invitation for smear sampling.     

Invasive carcinoma of the cervix

Cervical cancer remains the second most common cancer worldwide despite becoming a relatively rare disease in developed countries. It is associated with sexual activity with human papilloma virus being the likely causative agent. Cervical screening has proven to be successful in reducing incidence and mortality from cervical cancer. Primary treatment is based on FIGO classification which is a clinical staging. Traditional radical surgery and radiotherapy have undergone recent changes as a result of minimal access surgery and recent trials on the benefit of chemoradiation.The NHS executive document ‘Improving Outcomes in Gynaecological Cancer’ has recommended that all women with cervical cancer more advanced that FIGO stage Ia and all adenocarcinomas should be referred to the specialist gynaecological oncology team at the cancer centres.The role of vaccines against human papilloma virus is currently being evaluated and hopefully will prevent the development of invasive cervical cancer worldwide.     

Role of human papilloma virus testing in cervical cancer prevention

A clear causal relationship has been established between human papilloma virus (HPV) infection and the development of cervical cancer. Genital HPV infection is currently the most common sexually transmitted disease worldwide. The recent 2001 American Society for Colposcopy and Cervical Pathology Consensus Guidelines have included HPV testing for management of women with cervical cytological abnormalities. Clinicians now face the challenge of deciding when to use HPV testing in follow-up of abnormal Pap tests. This article includes updates on HPV, cervical cancer screening, and HPV testing technology. Recommendations for integration of HPV testing into clinical practice are provided.     

The association of sexually transmitted diseases with cervical intraepithelial neoplasia: a case-control study

Thirty-three women with histologically confirmed cervical intraepithelial neoplasia (grades I to III, with one case of microinvasive carcinoma) and 54 women without evidence of the disease were prospectively studied to determine the relationship of genital infection to cervical neoplasia. Demographic and sexual data for patients and control subjects were collected, with standardized clinical and colposcopic evaluation by means of predefined diagnostic categories. Cultures from the cervix were examined for herpes simplex virus, cytomegalovirus, Chlamydia trachomatis, and Neisseria gonorrhoeae. Human papilloma virus infection was identified by characteristic changes of koilocytosis in cytologic or histopathologic specimen. Cultures from the vagina were evaluated for Gardnerella vaginalis, Trichomonas vaginalis, Ureaplasma urealyticum, Mycoplasma hominis, Candida albicans, and other yeasts. Separate Gram strains were prepared from endocervical secretions and from vaginal secretions. More lifetime sexual partners, larger area of transformation zone, evidence of human papilloma virus infection, and altered vaginal flora were observed in women with cervical intraepithelial neoplasia. The association of human papilloma virus infection and altered vaginal flora with cervical intraepithelial neoplasia was independent of sexual experience.     

人乳头瘤病毒16/18型与宫颈癌

人乳头瘤病毒（HPV）16/18型和宫颈癌的关系密切,在宫颈癌发生发展中起重要作用。HPV16最易导致宫颈鳞癌,HPV18最易导致宫颈腺癌。HPV16/18致癌机制主要是通过病毒基因组中致癌蛋白E6,E7与抑癌基因p53和pRb结合,E6抑制p53的活性,E7灭活Rb基因的活性,致肿瘤发生。常用的HPV检测方法有原位杂交法（ISH）、第二代杂交捕获试验（HCⅡ）、聚合酶链反应（PCR）等。针对HPV16/18的预防和治疗性疫苗成为研究热点。综述HPV16/18型和宫颈癌关系研究进展。