宫颈高级别病变与HPV感染型别分析

目的探讨HPV在宫颈高级别病变中的感染率及感染型别。方法采用导流杂交法分别检测CINII～Ⅲ30例和宫颈癌患者160例HPV基因型别,比较HPV感染与宫颈病变的关系。结果CINⅡ～III和宫颈癌患者HPV感染率均为90％,且以单型别感染为主,分别为70．37％（19／27）、81．94％（118／144）;在CIN II～Ⅲ中HPV58型、52型感染居多,宫颈癌则以HPV16型、18型感染最常见;无论宫颈鳞癌还是宫颈腺癌,以HPV16型检出率最高。结论HPV16型、18型是宫颈癌的主要致病型,不同病理类型并无HPV型别上的差异;宫颈上皮高级别内瘤变则以HPV58型、52型感染为主;对HPV58型、52型感染者应重视随访。     

HPV病毒负荷量与宫颈病变的关系

目的探讨高危型HPV病毒感染的负荷量与宫颈病变程度的相关性。方法 对在我院宫颈门诊就诊的2751例患者行HPV DNA检测, 其中对971人行阴道镜下活检。结果 不同级别的宫颈病变之间HPV负荷量检测值的分布没有明显的数值界限, 但将病毒负荷分为低剂量组和高剂量组时宫颈病变程度与HPV负荷量显著相关(P＜0.01)。结论 不同程度的宫颈病变之间病毒负荷量的检测值没有明显界限, 病毒感染负荷不能代表病变的严重程度。但是病毒感染的负荷越高可以提示我们患宫颈高度病变的可能性越大。     

宫颈锥切术后HPV检测的临床意义

目的:探讨人乳头瘤病毒(HPV)在宫颈上皮内瘤样病变(CIN)行LEEP、冷刀锥切(CKC)术后的随访价值。方法:回顾分析180例行LEEP锥切、119例行冷刀锥切的CIN患者术前、术后HPV感染情况,观察锥切术后CIN的消失情况。结果:二者手术前后HPV感染率分别为:LEEP组78.3%和7.8%,CKC组64.7%和6.7%,无统计学差异,术后HPV感染率明显降低,术后HPV持续感染者宫颈病变进展率高于HPV转阴者,二者有统计学差异。结论:HPV检测在LE EP、CKC术后可作为随访有效手段。     

宫颈锥切术后HPV检测的临床意义

目的：探讨人乳头瘤病毒（HPV）在宫颈上皮内瘤样病变（CIN）行LEEP、冷刀锥切（CKC）术后的随访价值。方法：回顾分析180例行LEEP锥切、119例行冷刀锥切的CIN患者术前、术后HPV感染情况,观察锥切术后CIN的消失情况。结果：二者手术前后HPV感染率分别为：LEEP组78.3%和7.8%,CKC组64.7%和6.7%,无统计学差异,术后HPV感染率明显降低,术后HPV持续感染者宫颈病变进展率高于HPV转阴者,二者有统计学差异。结论：HPV检测在LE EP、CKC术后可作为随访有效手段。     

人乳头状瘤病毒检测在宫颈癌和宫颈癌前病变筛查中的应用

目的探讨人乳头状瘤病毒(HPV)检测在宫颈癌及宫颈癌前病变筛查中的应用效果。方法选择2014年8月至2015年8月间在海口市中医院检验科行宫颈癌病变检查的220例患者进行宫颈癌筛查,采用二代杂交捕获技术(HC-2)检测HPV感染情况。结果病理检查结果显示,220例患者中,宫颈癌80例(36.4%),宫颈上皮内瘤变(CIN)Ⅰ级40例(18.2%),CINⅡ级~CINⅢ级80例(36.4%)和慢性宫颈炎20例(9.1%)。宫颈癌、CINⅠ级、CINⅡ级~Ⅲ级和慢性宫颈炎患者HPV阳性率分别为100.0%(80/80)、75.0%(30/40)、95.0%(76/80)和30.0%(6/20)。宫颈癌患者HPV DNA水平显著高于CINⅡ~Ⅲ级、CINⅠ级和宫颈炎患者,差异有统计学意义(P<0.05)。CINⅡ~Ⅲ级和CINⅠ级患者HPV DNA水平显著高于宫颈炎患者,差异有统计学意义(P<0.05)。结论HPV检测可作为预测CIN和宫颈癌的重要指标,值得临床推广应用。     

高危型HPV分型和p16蛋白表达在宫颈病变诊断中的临床意义

目的:了解HPV高危型阳性的高级别鳞状上皮内瘤变(high-grade squamous intraepithelial lesion,HSIL)（CIN II-III）、慢性炎症及宫颈癌中HPV感染分型的不同分型和p16在不同组织中的表达情况,并分析其与HPV的相关性。方法:收集海南省人民医院就诊的海南籍宫颈疾病患者,其中包括HPV高危型阳性的HSIL患者100例、HPV高危型阳性慢性宫颈炎和宫颈癌患者各25例和HPV阴性慢性宫颈炎25例,收集宫颈病理组织,进行HPV分型和p16蛋白表达检测。结果:HPV高危型阳性宫颈病变中,检测出全部13种高危型亚型,主要为HPV16（16.67%）、HPV52（15.33%）、HPV58（12.67%）、HPV31（12.0%）,不同宫颈病变HPV分型结果具有高度统一性,差异不具有统计学意义（P=0.999）;HPV阴性慢性宫颈炎症组织、HPV高危型阳性慢性宫颈炎症组织、HSIL组织、宫颈癌组织中p16蛋白表达阳性率分别为12.0%、72.0%、84.0%、100.0%,不同宫颈病变p16蛋白表达差异具有统计学意义（P＜0.001）,随着宫颈病变的进展,p16蛋白表达逐渐增加,p16蛋白表达与宫颈病变的恶性程度具有正相关性。结论:海南籍宫颈病变患者其高危型HPV感染分型分布与目前研究一致,随着宫颈疾病进展加重, p16蛋白表达增加,HPV分型和p16蛋白联合检测对于诊断不同宫颈疾病具有重要价值。     

HPV基因亚型分布及其与CIN的相关性研究

[目的]探讨健康体检妇女HPV基因亚型分布状况,及HPV感染后宫颈上皮内瘤变的发生情况。[方法]2012年5月至2013年10月于深圳市妇幼保健院行健康体检HPV分型检测阳性的妇女,所有研究对象均进行宫颈HPV分型检测、阴道镜检查及宫颈组织活检。[结果]本研究共纳入妇女2578例,年龄18~70岁,病理结果为正常或炎症者1983例,CINⅠ为278例,CINⅡ/Ⅲ为308例,宫颈浸润癌9例。HPV基因亚型构成前5位高危型HPV为HPV52、43、16、58、56;CINⅠ中HPV基因亚型构成前5位依次为HPV52、16、58、56、43,CINⅡ/Ⅲ中HPV基因亚型构成前5位依次为HPV16、58、52、33、18;随着感染HPV亚型增多,CIN构成比升高,差异具有统计学意义（P〈0.01）;高度宫颈上皮内病变（CINⅡ/Ⅲ）以25~44岁年龄段相对多见。[结论]深圳市妇幼保健院健康体检妇女HPV基因亚型分布与其他地域存在差异。不同程度宫颈癌前病变HPV亚型分布可能存在差异,而HPV16、52、58在宫颈病变中均占有重要地位;HPV多重感染者,CIN风险明显增加;25~44岁有性生活妇女应为宫颈癌筛查的侧重点人群。     

高危型HPV感染在宫颈癌前病变、宫颈癌中的临床意义

目的:分析高危型HPV感染在宫颈癌前病变、宫颈癌发生和发展中的关系,为宫颈病变的筛查和HPV疫苗的选择提供理论依据。方法:选择来我院妇科肿瘤中心就诊的1 197例患者作为研究对象,根据病理检查结果将病例分为慢性宫颈炎组（212例）、LSIL组（142例）、HSIL组（484例）和宫颈癌组（359例）,检测各组高危型HPV感染的情况,分析不同组HPV的阳性率及HPV亚型的分布。结果:慢性宫颈炎组 HPV 感染阳性率为9.43%,LSIL组为78.87%,HSIL组为92.15%,宫颈癌组为97.77%,各组间阳性率两两比较差异有统计学意义（P<0.001）。各组中,高危HPV单一感染率均大于多重感染率,差异有统计学意义（P<0.001）。慢性宫颈炎组以HPV52、HPV16、HPV58为主要亚型（阳性率分别为 3.77%、2.83%和 1.41%）,LSIL组以HPV52、HPV16、HPV58为主要亚型（阳性率分别为 23.94%、21.13%和 16.90%）,HSIL组以HPV16、HPV52、HPV58为主要亚型（阳性率分别为33.06%、29.34%和 19.42%）,宫颈癌组以HPV16、HPV58、HPV52为主要亚型（阳性率分别为 65.18%、20.89%和 10.86%）。本地区HSIL及宫颈癌人群感染率最高的5种亚型是HPV16、HPV18、HPV33、HPV52、HPV58。结论:宫颈病变程度越严重,HPV阳性率越高,不同程度宫颈病变HPV感染的亚型分布有差异。高危型HPV检测对本地区宫颈病变的早期筛查及HPV疫苗的接种有重要的指导意义。     

人乳头状瘤病毒感染与宫颈病变的相关性分析？

目的：分析宫颈上皮内瘤变（ CIN）及宫颈癌（ CC）中人乳头状瘤病毒（ HPV）亚型,探讨HPV感染与宫颈病变的相关性。方法：慢性宫颈炎或液基细胞学异常的妇女检测21种HPV基因亚型和阴道镜下宫颈定位活检,分析2481例CC和CIN患者的HPV感染情况。结果：在2481例CIN和CC患者中,HPV感染率85．0%,HPV感染与宫颈组织学结果有较强的相关性（P〈0．001,Pearson列联系数=0．648）。 CC及CINⅢ、CINⅡ患者以HPV16、18感染最多见,其次见HPV58、33、31、52、45、59、68等亚型。304例患者宫颈感染HPV16、18、58、52、33等亚型后,发生高度鳞状上皮内病变（HSIL）、不明意义的非典型鳞状细胞（ASCUS）及低度鳞状上皮内病变（LSIL）的频率增加,TCT分型与HPV分型有较弱的相关关系（P=0．002,Pearson列联系数=0．322）。细胞学结果提示HSIL、AS-CUS,宫颈组织学诊断以CC、CINIII和CINII为多,TCT分型与组织学分型也有较弱的相关性（ P=0．026,Pearson列联系数=0．172）。结论：HPV16、18、58、33、52、31、45等高危型HPV感染是宫颈癌（ CC）及癌前病变（ CIN）最常见的风险因素。高危型HPV单独或混合感染宫颈后,细胞学检测HSIL、ASCUS及LSIL的发生率增加,细胞学结果与组织学分型的相关性促进了CC和CIN的及时诊治。     

Human papillomavirus testing and genotyping in cervical screening

Mass vaccination against human papillomavirus (HPV) genotypes 16 and 18 will, in the long term, reduce the incidence of cervical cancer, but screening will remain an important cancer control measure in both vaccinated and unvaccinated women. Since the 1960s, cytology screening has helped to reduce the incidence of cervical cancer, but has a low sensitivity for high-grade cervical intraepithelial neoplasia (CIN) and requires frequent testing. Several HPV tests have become available commercially. They appear to be more sensitive for high-grade CIN, and may further reduce the incidence of cervical cancer compared with cytology. However, they are associated with an increased frequency of positive tests without underlying CIN, and therefore increase the need for colposcopy and repeated testing. This problem will pose a major challenge for switching from cytology-based to HPV-based screening. The aim of this article is to discuss the role and the use of HPV tests and HPV genotyping in unvaccinated women.     

Differences in human papillomavirus type distribution in high‐grade cervical intraepithelial neoplasia and invasive cervical cancer in Europe

Knowledge of differences in human papillomavirus (HPV)‐type prevalence between high‐grade cervical intraepithelial neoplasia (HG‐CIN) and invasive cervical cancer (ICC) is crucial for understanding the natural history of HPV‐infected cervical lesions and the potential impact of HPV vaccination on cervical cancer prevention. More than 6,000 women diagnosed with HG‐CIN or ICC from 17 European countries were enrolled in two parallel cross‐sectional studies (108288/108290). Centralised histopathology review and standardised HPV‐DNA typing were applied to formalin‐fixed paraffin‐embedded cervical specimens dated 2001–2008. The pooled prevalence of individual HPV types was estimated using meta‐analytic methods. A total of 3,103 women were diagnosed with HG‐CIN and a total of 3,162 with ICC (median ages: 34 and 49 years, respectively), of which 98.5 and 91.8% were HPV‐positive, respectively. The most common HPV types in women with HG‐CIN were HPV16/33/31 (59.9/10.5/9.0%) and in ICC were HPV16/18/45 (63.3/15.2/5.3%). In squamous cell carcinomas, HPV16/18/33 were most frequent (66.2/10.8/5.3%), and in adenocarcinomas, HPV16/18/45 (54.2/40.4/8.3%). The prevalence of HPV16/18/45 was 1.1/3.5/2.5 times higher in ICC than in HG‐CIN. The difference in age at diagnosis between CIN3 and squamous cervical cancer for HPV18 (9 years) was significantly less compared to HPV31/33/‘other’ (23/20/17 years), and for HPV45 (1 year) than HPV16/31/33/‘other’ (15/23/20/17 years). In Europe, HPV16 predominates in both HG‐CIN and ICC, whereas HPV18/45 are associated with a low median age of ICC. HPV18/45 are more frequent in ICC than HG‐CIN and associated with a high median age of HG‐CIN, with a narrow age interval between HG‐CIN and ICC detection. These findings support the need for primary prevention of HPV16/18/45‐related cervical lesions.     

人乳头瘤病毒E6与宫颈癌

宫颈癌的病因与持续感染人乳头瘤病毒(human papillomavirus,HPV)相关.最近的研究表明,HPV E6在宫颈癌的发生过程中发挥重要作用.本文就HPV E6宫颈癌的发生机制及HPV E6蛋白的表达与宫颈癌的临床意义进行综述.     

The role of human papillomavirus type 16 and the fragile histidine triad gene in the outcome of cervical neoplastic lesions

The presence of high-risk human papillomavirus, loss of heterozygosity on chromosome 3p and fragile histidine triad gene expression were assessed as potential markers of cancer and CIN progression in 83 cervical cancers and 74 cervical intraepithelial neoplasia grade 1 lesions. Human papillomavirus type 16 was an indicator of vascular involvement in cancers. Loss of heterozygosity, especially in the fragile histidine triad gene intron 5, was an indicator of high-grade tumours, greater tumour depth and lymph node involvement. Abnormal fragile histidine triad gene expression was more frequent in cervical intraepithelial neoplasia grade 1 lesions with increased risk of disease progression.     

The role of genotype-specific human papillomavirus detection in diagnosing residual cervical intraepithelial neoplasia

We assessed prospectively whether residual cervical intraepithelial neoplasia (CIN) after treatment for high-grade CIN can be predicted by genotype-specific high-risk HPV (HR-HPV) detection in follow-up cervical scrapes. A broad spectrum, highly sensitive SPF(10)-LiPA-PCR HPV detection technique was used on cervical scrapes before large loop excision of the transformation zone (LLETZ), on the LLETZ biopsy and on follow-up scrapes of 90 patients treated for high-grade CIN. HR-HPV was detected in the biopsies of 93% (n = 84) of the patients and in the follow-up scrapes of 48% (n = 43) of the patients. In 12 patients, genotype-specific HR-HPV persistence was detected in both follow-up scrapes. In 10 patients, residual CIN was detected. In 5 of these patients (including all patients with residual CIN 3), the follow-up scrapes showed genotype-specific HR-HPV persistence. In 2 patients, a different HR-HPV was detected, and 3 patients had HR-HPV-negative follow-up scrapes. Conventional cytologic follow-up was abnormal in 13 patients including all 10 patients with residual CIN. The negative predictive value (NPV) of HR-HPV detection on follow-up scrapes was high (94%). Repeat detection of genotype-specific HR-HPV showed a lower sensitivity and NPV than repeat detection of any HR-HPV, but its specificity was higher. Repeat conventional cytologic follow-up showed the highest sensitivity and NPV. In conclusion, the presence of HR-HPV in cervical scrapes after LLETZ for high-grade CIN is a risk factor for the presence of residual CIN. HR-HPV genotype-specific persistence is specifically present in patients with residual CIN 3. However, HR-HPV detection cannot predict or exclude the presence of residual CIN in the individual patient and additional procedures remain necessary.     

High‐risk human papillomavirus DNA load in a population‐based cervical screening cohort in relation to the detection of high‐grade cervical intraepithelial neoplasia and cervical cancer

In a population‐based cervical screening cohort, we determined the value of type‐specific viral load assessment for the detection of high‐grade cervical intraepithelial neoplasia and cervical cancer (≥CIN2). Viral load was determined by type‐specific real‐time PCR in women with single HPV16,‐18,‐31 and ‐33 infections, as determined by GP5+/6+‐PCR. Study endpoints were the detection of cumulative ≥CIN2 or ≥CIN3 within 18 months of follow‐up. High viral loads of HPV16,‐31, and ‐33 were predictive for ≥CIN2 (relative risk of 1.6 (95% CI: 1.3–1.9), 1.7 (95% CI: 1.1–2.7) and 1.9 (95% CI: 1.1–3.1) per 10‐fold change in viral load, respectively). For HPV18, the relative risk was of similar magnitude (1.5, 95% CI: 0.7–3.1), though not significant (p = 0.3). Subsequently, we determined the sensitivities of viral load for ≥CIN2 and ≥CIN3 in HPV DNA‐positive women using viral load thresholds previously defined in a cross‐sectional study. These thresholds were based on the 25th, 33rd and 50th percentiles of type‐specific HPV16,‐18,‐31 or ‐33 viral load values found in women with normal cytology. For all types, combined sensitivities for ≥CIN2 were 93.5%, 88.8% and 77.7% for the 25th, 33rd and 50th percentile thresholds, respectively. Response‐operator‐characteristics (ROC) curve analysis showed that viral load testing on HPV DNA‐positive women in addition to or instead of cytology may result in an increased sensitivity for ≥CIN2, but at the cost of a marked decrease in specificity in relation to cytology. Similar results were obtained when using ≥CIN3 as endpoint. In conclusion, in a cervical screening setting viral load assessment of HPV16, 18, 31 and 33 has no additive value to stratify high‐risk HPV GP5+/6+‐PCR‐positive women for risk of ≥CIN2 or ≥CIN3. © 2008 Wiley‐Liss, Inc.     

人乳头瘤病毒变异株与宫颈疾病

人乳头瘤病毒(HPV)感染是发生宫颈癌的必要条件。根据病毒基因组核苷酸序列,在亚型的基础上可以进一步将HPV分为不同的变异株。HPV变异株的分布与地理位置关系密切。某些特定的HPV变异株感染可能增加发生宫颈癌的风险,其可能的机制是免疫逃逸、改变病毒癌基因的表达等。     

Patterns of persistent HPV infection after treatment for cervical intraepithelial neoplasia (CIN): A systematic review

A systematic review of the literature was conducted to determine the estimates of and definitions for human papillomavirus (HPV) persistence in women following treatment of cervical intra‐epithelial neoplasia (CIN). A total of 45 studies presented data on post‐treatment HPV persistence among 6,106 women. Most studies assessed HPV persistence after loop excision (42%), followed by conization (7%), cryotherapy (11%), laser treatment (4%), interferon‐alpha, therapeutic vaccination, and photodynamic therapy (2% each) and mixed treatment (38%). Baseline HPV testing was conducted before or at treatment for most studies (96%). Follow‐up HPV testing ranged from 1.5 to 80 months after baseline. Median HPV persistence tended to decrease with increasing follow‐up time, declining from 27% at 3 months after treatment to 21% at 6 months, 15% at 12 months, and 10% at 24 months. Post‐treatment HPV persistence estimates varied widely and were influenced by patient age, HPV‐type, detection method, treatment method, and minimum HPV post‐treatment testing interval. Loop excision and conization appeared to outperform cryotherapy procedures in terms of their ability to clear HPV infection. This systematic review provides evidence for the substantial heterogeneity in post‐treatment HPV DNA testing practices and persistence estimates.     

光动力治疗人乳头瘤病毒感染和宫颈上皮内瘤变的临床应用进展

光动力疗法是联合应用光敏剂及其相关光源,利用光动力学反应选择性破坏肿瘤组织的治疗方法.目前光动力疗法作为一种新的疗法已经在HPV感染和CIN的治疗中广泛应用并取得了良好的治疗效果,通过对国内外光动力疗法在治疗HPV感染及CIN的临床应用的综述,可以为进一步深入研究提供理论依据.     

Human papillomavirus genotype in cervical intraepithelial neoplasia grades 2 and 3 of Taiwanese women

We aimed to assess the distribution of human papillomavirus (HPV) genotypes in high‐grade cervical lesions in Taiwan. The study included 1,086 paraffin‐embedded, formaldehyde‐fixed cervical intraepithelial neoplasia (CIN) 2/3 specimens. HPV genotyping was performed using polymerase chain reaction (PCR)‐based methods. Multiple HPV types were validated by E6 type‐specific PCR, direct sequencing and/or real‐time PCR. HPV DNA was detected in 995 (91.6%) specimens, and multiple HPV types were identified in 192 (19.3%) samples. The leading HPV types were HPV16 (24%), HPV52 (20%), HPV58 (20%), HPV33 (13%), HPV31 (8%) and HPV18 (4.6%). Although the leading six types consisted of 87.6%, HPV16 or 18 comprised only 30.9%. The prevalence of different HPV types showed a significant association with age. In women older than 50 yr, HPV16 and 18 comprised 21.3% (83/389), while HPV52, 58 and 33 represented 55.5% (216/389). In women aged less than 50 yr, HPV16 and 18 comprised 32.1% (224/697, p < 0.0001), while HPV 52, 58 and 33 represented 47.9% (334/697, p = 0.02). The distribution of HPV genotypes was compared with previously reported findings for Taiwanese women with cervical cancer (CC). The overall HPV16 positivity rate was significantly higher in CC than in CIN 2/3 (odds ratio: 2.14, 95% CI: 1.91–2.40). In addition, HPV18, 39 and 45 were significantly overrepresented in CC, whereas HPV52, 58, 33, 31, 35, 51 and 53 were underrepresented. We concluded that an effective vaccine against the most common HPV types could prevent a significant proportion of cervical cancer cases that occur in Taiwan.