宫颈上皮内瘤变的进展预警

宫颈上皮内瘤变(cervical intraepithelial neoplasia,CIN)是宫颈浸润癌的癌前病变。CIN的发生和进展是一个多因素、多水平的过程。大量研究证实高危型人乳头瘤病毒(human papillomavirus,HPV)持续感染是宫颈癌及CIN的重要致病原因之一,其与宫颈癌的发生、发展有着密切的关系。随着分子生物学的发展和测序技术的进步,阴道微生物与HPV在CIN和宫颈癌的协同作用逐渐被认识。而寻找和探索对CIN进展有判断价值的生物标志物,预警CIN的进展已经成为目前宫颈病变研究的一大热点。综述与CIN进展有关的原因、影响因素及标志物等,以期预警CIN的进展,正确分流及规范管理CIN。     

子宫颈癌前病变组织DNA倍体分析与人乳头状瘤病毒亚型检测

宫颈癌是妇女最常见的恶性肿瘤之一，它由宫颈上皮内瘤变（CIN）发展而来，大部分CIN可自然消退，只有一小部分发展为浸润癌。宫颈癌筛查主要依靠细胞学检查，但其对宫颈病变预测的相对特异性较低，单靠细胞学检查不能区分进展性和非进展性病变，因而需要检测其他标志物，如人乳头状瘤病毒（HPV）亚型和DNA倍体等来提高其诊断的特异性。本研究通过检测宫颈癌前病变组织中DNA倍体状态和HPV亚型感染情况，探讨HPV亚型、DNA异倍体在宫颈癌发生过程中的生物学特征以及对宫颈癌早期诊断的意义。     

宫颈上皮内瘤变分子生物学指标的研究进展

宫颈癌是妇科最常见的恶性肿瘤之一,近年来宫颈癌的发病率逐年上升,且有年轻化趋势。宫颈上皮内瘤变（CIN）是由高危型人乳头瘤病毒（HPV）的持续性感染引起的,是宫颈癌的癌前病变,其反映宫颈癌发生发展中的连续过程,从CIN发展为宫颈癌需要较长的时间。在CIN的进展过程中,许多基因结构和功能都会发生变化。近年来的研究发现,在CIN和宫颈癌的组织中存在着一些表达异常的生物学标记物,这些生物学标记物与前驱病变级别和肿瘤是否发生转移相关,将这些基因作为CIN进展的分子生物学标志物进行检测,早期发现和诊断宫颈癌已成为目前研究的热点。综述CIN研究的前沿性分子生物学指标。     

人乳头状瘤病毒疫苗在子宫颈病变预防与治疗中的应用

全世界每年约有近50万妇女罹患宫颈癌，其中80％在发展中国家，对于官颈癌前病变——官颈上皮内瘤变（cervical inlxaepithelial neoplasia，CIN）及宫颈恶性病变的治疗，一直是世界各国特别是发展中国家的重点研究项目之一。如何更好地预防宫颈癌前病变的发生，如何有效地控制癌前病变，以及如何在现有方法基础上更好地治疗已发生的、正在进展的或复发的宫颈病变，依然是有待解决的重要课题。大量的病因学研究已经表明，人乳头状瘤病毒（HPV）感染是宫颈癌发病至关重要的因素，超过2／3的宫颈癌与HPV16或18感染相关。这些事实提示我们，针对HPV的治疗将对CIN及宫颈癌的预防和治疗提供极大的帮助。     

宫颈上皮内瘤变进展及消退的预测

人乳头瘤病毒(human papillomavirus,HPV)感染,特别是高危型HPV感染,是宫颈上皮内瘤变(cervical intraepi-thelial neoplasm,CIN)发生的重要原因,也是其病变发展为宫颈癌的必要条件。然而,大多数HPV感染是暂时的,只有少数感染持续存在并进展为CIN和宫颈癌。HPV感染发展为CIN,再     

生殖道人乳头瘤病毒感染与宫颈病变、宫颈癌相关性研究

目的 了解生殖道人乳头瘤病毒感染与宫颈病变、宫颈癌的关系，以便早期发现和治疗宫颈上皮内瘤样变（CIN）和原位癌。方法 应用TCT液基细胞学薄片检测法对宫颈病变做阴道细胞学分析，对CIN进行分级（Ⅰ、Ⅱ、Ⅲ）鉴定。对高危病人（如ASCUS、CIN、宫颈原位癌）应用基因杂交捕获法（Hybrid Capture，HC-Ⅱ）分型检测HPV，同时用PCR法检测HPV—DNA，进一步做HPV分型鉴定。最后所有病人均进行阴道镜检查及病理组织学诊断。结果 2003年2月～2005年3月将标本送往广州金域医学检验中心进行TCT和HPV检测（HC—H），其中TCT检测1086例，发现不典型鳞状细胞39例、CINⅠ25例、CINⅡ3例、CINⅢ5例，原位癌3例。高危病人（如ASCUS、CIN、宫颈原位癌）进行HC—Ⅱ检测40例，阳性25例（其中原位癌、CINⅢ和CINⅡ均阳性）。结论 HPV感染与宫颈病变，特别是宫颈癌、宫颈癌前病变的发生有明显的相关性，病变越重，HPV的感染率越高。提示宫颈癌的防治重点应放在高危型HPV感染者。     

TERC基因联合阴道镜及HPV检测在早期宫颈病变诊断中的应用

目的：探讨阴道镜、人端粒酶RNA组分（hTERC）基因扩增和人乳头瘤病毒（HPV）分型检测在早期宫颈病变诊断中的临床意义。方法：对经阴道镜初步诊断为宫颈病变的219例患者,应用荧光染色体原位杂交（FISH）技术检测hTERC基因扩增、表面等离子谐振技术（SPR）检测HPV感染情况,并进行统计学分析。结果：①阴道镜诊断宫颈CINⅠ级59例,CINⅡ级76例,CINⅢ级56例,宫颈癌28例,与组织学最终诊断相比较,两种方法有相关性（P＜0.05）。②hTERC基因在宫颈炎性病变、CINⅠ、CINⅡ、CINⅢ及宫颈鳞癌中的阳性扩增率分别为7.9%,10.9%,44.6%,63.2%和82.6%,各组间比较差异有统计学意义（P＜0.000 1）。③132例进行HPV分型检测的患者中,高危亚型感染54例,低危亚型感染29例,阴性49例, HPV阳性患者的感染类型同宫颈上皮内瘤变等级有关（P=0.041 9）。④同时进行hTERC基因及HPV检测患者中,54例HPV高危亚型患者hTERC基因发生异常扩增者33例,29例低危亚型中发生异常扩增7例,组间比较差异有统计学意义（P＜0.01）。结论：阴道镜作为宫颈病变的初诊手段有一定的漏诊和过度诊断;HPV高危亚型感染可能是导致hTERC基因异常扩增的因素之一;hTERC基因扩增和HPV感染与宫颈高级别病变的进展密切相关,可能是导致宫颈癌发生的直接诱因;阴道镜、HPV和hTERC基因联合检查是判断早期宫颈病变进展并做出诊断的有效手段。     

人乳头瘤病毒感染与宫颈疾病关系的研究

研究证实人乳头状瘤病毒（human papillomavirus，HPV）感染是宫颈癌前期病变-宫颈上皮内瘤变（cervical intraepithelial neoplasia，CIN）和宫颈癌的主要病因。目前已经发现了150多种HPV的亚型（也称基因型），其中至少有40多种亚型与宫颈病变有关，根据在宫颈癌发生中的危险性不同，分为高危型（high—risk types，HR—HPV）和低危型（low—risk types，LR—HPV），不同亚型HPV感染的致病性和后果不同。本研究应用凯普快速导流杂交基因芯片分型技术（HybriMax）对沈阳地区1001例妇女的宫颈脱落细胞进行了HPV感染的分型检测分析，     

人乳头瘤病毒亚型检测在宫颈病变分流管理中的意义

宫颈癌在女性肿瘤中位居第二，占癌症患者总数的15％。每年约有371200个新发病例，约200000例死亡。由于经济水平低下以及缺乏宫颈肿瘤普查手段等因素，80％的新发病例发生在发展中国家。现已明确人乳头瘤病毒（HPV）感染是宫颈癌的根本致病因素。研究证实，大多数宫颈上皮内瘤样病变（CIN）伴有HPV感染，90％宫颈癌标本可以检测出HPVDNA。     

宫颈癌前病变和宫颈癌的筛查新进展及面临的新问题

宫颈癌是妇科常见的恶性肿瘤之一。大样本的研究表明,几乎所有宫颈癌及大多数宫颈上皮内瘤变（CIN）都存在人乳头瘤病毒（HPV）感染。HPV DNA检测在宫颈筛查中起着重要的作用,但其如何与细胞学筛查、阴道镜检查及病理组织学检查优化组合,是我们面临的问题。同时HPV检测对高级别宫颈病变治疗的术后随访有重要的价值,能有效提示宫颈病变残留或复发。但HPV的高感染率和宫颈高级别病变相对较低的发病率,仍需我们寻找新的能早期预测真正发生宫颈癌风险的实验室指标。     

Immunohistochemical and molecular study of severe cervical dysplasia associated with HPV-83

BACKGROUND: Based on epidemiological data, infections with specific types of HPV can be classified as high-risk (HR), low-risk (LR) or intermediate-risk (IR) HPV depending on the risk of progression to cervical cancer. CASE: A 70-year-old woman consulted for relapse of abnormal cytology with high-grade squamous intraepithelial lesions (HSIL) associated with HPV-83 infection. Histological examination demonstrated high-grade cervical intraepithelial neoplasia (CIN III) with strong and diffuse staining by the P16(INK4a)-specific antibody. CONCLUSION: This patient's intermediate-risk HPV infection (HPV-83) rapidly progressed to severe cervical intraepithelial neoplasia (CIN III) with strong anti-P16(INK4a) immunolabelling. Analysis of the E6 peptide sequence revealed several mutations in one of the two putative zinc finger regions (AA residues 107-135) associated with p53 binding.     

宫颈癌及上皮内瘤变人乳头瘤病毒基因型的检测

目的:了解宫颈癌及上皮内瘤变人乳头瘤病毒(HPV)的感染率及其基因型的分布。方法:用PCR-RFLP法检测239例宫颈癌及上皮内瘤变患者HPV感染并进行分型。先用PGMY09/11共同引物扩增生殖道粘膜型HPV L1区的高度保守区,然后联合使用RsaⅠ、MseⅠ、PstⅠ和HaeⅢ4个限制性内切酶对阳性PCR产物进行酶切,利用不同的酶切片段鉴定HPV的基因型。结果:在239例宫颈癌及上皮内瘤变患者中共检出205例(85·8%)HPV感染,其中宫颈上皮内瘤变Ⅰ级(CINⅠ)、宫颈上皮内瘤变Ⅱ~Ⅲ级(CINⅡ~Ⅲ)和宫颈癌中HPV感染率分别是66·7%,89·9%和98·3%,差异有统计学意义(P<0·001)。在宫颈癌及上皮内瘤变中共检出22型HPV,其中主要基因型及其感染率分别是HPV16(45·6%)、58(12·1%)和52(6·3%)。结论:宫颈癌及上皮内瘤变中HPV感染的基因型至少可达22型,其中以HPV16、58和52为最常见。     

Human papillomavirus and vaccination in cervical cancer

Cervical cancer is not only the most frequently reported cancer among women, but also the most common female genital tract neoplasm in Taiwan. Early detection is effective, because the development, maintenance and progression of precursor lesions (cervical intraepithelial neoplasia [CIN]) evolve slowly into invasive cancer, typically over a period of more than 10 years. It is now recognized that human papillomavirus (HPV) infection is a necessary cause for over 99% of cervical cancer cases. Advances in the understanding of the causative role of HPV in the etiology of high-grade cervical lesions (CIN 2/3) and cervical cancer have led to the development, evaluation and recommendation of HPV-based technologies for cervical cancer prevention and control. The prevention of HPV infection before the onset of CIN is now possible with recently available prophylactic HPV vaccines, e.g. the quadrivalent Gardasil (Merck & Co., NJ, USA) and bivalent Cervarix (GlaxoSmithKline, London, UK). This review article provides an up-to-date summary of recent studies and available information concerning HPV and vaccination in cervical cancer.     

Association between cervical schistosomiasis and cervical cancer. A report of 2 cases

BACKGROUND: HPV is now considered the most important risk factor for the development of cervical intraepithelial neoplasia (CIN) and cancer. Although CIN and cancer have been previously reported in association with cervical schistosomiasis, those reports failed to control for the potential coexistence of high-risk HPV. CASES: Two women, 1 with high grade CIN and 1 with invasive cervical cancer, were negative for high-risk HPV subtypes. Evidence of cervical and systemic schistosomal infestation was evident in both cases. CONCLUSION: In support of prior published studies, cervical schistosomiasis seems to be a possible risk factor for the development of CIN and cancer. As populations around the world migrate, North American colposcopists need to become aware of this association.     

Colposcopy and cervical intraepithelial neoplasia

Cervical cancer remains a killer. In the UK it is the third most common gynaecological malignancy with approximately 3200 new cases diagnosed each year and over 900 deaths. The NHS Cervical Screening Programme (NHSCSP) aims to reduce the incidence and mortality associated with cervical cancer. Since its introduction in 1988 there has been a 49% reduction in the incidence of cervical cancer in the UK. Our understanding of cervical cancer has increased dramatically since the inception of the NHSCSP and has resulted in the evolution of the screening programme. Human papilloma virus (HPV) is now recognized as pivotal in the development and progression of cervix intraepithelial neoplasia (CIN). The NHSCSP has recently changed to primary HPV testing for the cervical screening programme. Future interventions must consider the need for ongoing population education and vaccination for HPV in order to decrease the incidence of this entirely preventable disease, and the obstetric risks associated with over-treatment.     

Synchronous Ovarian and Cervical Squamous Intraepithelial Neoplasia: An Analysis of HPV Status

In contrast to the strong association between human papillomavirus (HPV) and cervical intraepithelial neoplasia (CIN), the relationship between HPV and squamous epithelial lesions of the ovary is less clear. We report a case of synchronous ovarian and cervical squamous intraepithelial neoplasia. To investigate the possible association between HPV and squamous intraepithelial neoplasia/carcinomain situ(CIS) of the ovary, DNA was extracted from paraffin-embedded tissues including normal cervix, CIN, CIS from both ovaries, and an area of ovarian endometriosis. All samples were positive for HPV 16 E6 except for one of the two samples from the normal cervical squamous epithelium. These results support the hypothesis that HPV may be involved in the development of ovarian squamous intraepithelial neoplasia.     

HPV testing in cervical screening

High-risk human papillomavirus (hrHPV) bearing cervical intraepithelial neoplasia (CIN) is considered, as the real precursor lesion of cervical cancer and persistence of an hrHPV infection is necessary for the progression to cervical cancer. This knowledge warrants the use of hrHPV testing as an adjunct to cervical cytology in population-based screening programmes and for monitoring therapy efficacy of high-grade CIN lesions. Replacement of cytology by hrHPV testing altogether is considered, but for this to be (cost-) effective, accurate information about the specificity of the hrHPV test is required. Additional test systems that can be used to stratify women with a positive hrHPV test are HPV genotyping, viral load analysis and hrHPV mRNA analysis. The need for HPV genotyping of cervical smears is illustrated by the increased risk for high-grade cervical lesions associated with HPV types 16 and 18. In particular, for women who have normal but persistently (>1 year) HPV18-positive smears, endocervical curettage is suggested (evidently considering the age and possible future pregnancies of the respective woman) because HPV18 is associated with glandular lesions in the cervix, which are difficult to detect by cytology.     

Detection and Clinical Management of Cervical Pathology in the Era of HPV

While infection with high-risk (HR) human papillomavirus (HPV) is central to cervical carcinogenesis, natural history studies show that both low- and high-grade cervical intraepithelial neoplasia (CIN) lesions are very early manifestations of HR-HPV infection. Most high- and low-grade lesions are self limited, and only those HR-HPV infections capable of persisting for decades are at risk of progression. Our new understanding of the natural history of HPV associated lesions has dramatically changed cervical cancer screening, classification and management of cervical lesions. As an increasing proportion of women are vaccinated against those oncogenic-HPVs responsible for most cervical cancers, the positive predictive value of cytology and HPV testing for identification of women at risk for cancer will decrease. New biomarkers, capable of identifying those high-grade lesions which are truly at risk of progression and need treatment, will need to be developed to serve as adjuncts to morphology and patient management.     

FHIT在宫颈癌及宫颈上皮内瘤变的表达及意义

目的:探讨在宫颈癌和宫颈上皮内瘤变(cervical intraepithelial neoplasia,CIN)发生中脆性组氨酸三联体(fragile histid ine triad,FHIT)基因表达异常的作用及与HPV感染的关系。方法:用免疫组化法检测67例宫颈癌、42例CINⅢ和35例正常宫颈上皮组织的FHIT的表达。用PCR法检测宫颈癌石蜡组织中的HPV DNA,并用直接测序法或反向核酸杂交法对HPV分型。结果:正常宫颈组织中FHIT基因表达下调率为8.6%,CINⅢ组为28.57%,宫颈癌组为46.27%,差异均有统计学意义(P<0.05)。CINⅢ组FHIT蛋白表达下调率虽比宫颈癌组为低,但组间无统计学差异(P=0.66)。67例宫颈癌病例中,高危型HPV感染阳性者的FHIT表达下降或缺失占55.32%,明显高于无高危型HPV感染者(20%)(P<0.05)。宫颈癌患者的年龄、临床分期、肿瘤组织学分级、肿瘤浸润深度和淋巴结转移与FHIT蛋白表达均无明显相关(P>0.05)。FHIT表达下调或缺失31例宫颈癌患者的5年生存率为77.1%,FHIT正常表达36例的5年生存率为79.3%(P>0.05)。结论:FHIT在宫颈癌及CINⅢ中的表达明显下调,可能与HPV感染协同在宫颈癌的发生中起了重要作用。而FHIT在宫颈癌发展中的作用及与预后的关系,有待大样本的进一步研究。