Risk factors for the progression or persistence of untreated mild dysplasia of the uterine cervix

To identify the factors that may predict the progression or persistence of untreated mild dysplasia of the uterine cervix, we performed a retrospective review of 118 patients with histologically verified mild dysplasia who underwent colposcopic biopsies between January 1999 and December 2003. Regression to normal occurred in 70.3%, progression to moderate dysplasia or worse occurred in 11.0%, and persistence of mild dysplasia occurred in 18.7%. In regression/progression analysis, progression of untreated mild dysplasia was 34.5% (10/29) in patients with high viral loads (> or =100 relative light units/positive control [RLU/PC]) and 4.5% (3/67) in those with low viral loads (1 to <100 RLU/PC) and negative human papillomavirus (HPV) tests (P < 0.001). Women with high viral loads had a 13-fold greater chance of progression of untreated mild dysplasia than those with low viral loads and negative HPV tests (CI: 2.494-95.297; P = 0.0022). Those associated with both positive smear and positive HPV test (12/45 = 26.7%) were at a greater risk of progression of untreated mild dysplasia as compared with those with positive smear and negative HPV (0/17 = 0.0%) or those with negative smear and positive HPV test (1/18 = 5.6%). Those with high viral loads and both with positive smear and positive HPV test should be followed closely because of their increased risk of progression of untreated mild dysplasia.     

Serologic response to human papillomavirus 16 among Australian women with high-grade cervical intraepithelial neoplasia

This study evaluated the detection of human papillomavirus (HPV) 16 antibody in HPV 16-associated cervical intraepithelial neoplasia (CIN) in Australian women. Seroreactivity to HPV 16 L1 virus-like particles was assessed in patients with CIN 2 (n= 169) and CIN 3 (n= 229) lesions previously tested for the presence of HPV DNA. Seropositivity was significantly commoner in women with HPV 16 DNA-positive lesions (98/184) than in women with no HPV DNA in the lesion (15/47) or with HPV of types other than 16 in the lesion (43/167) (P= 0.0004). In addition, seropositivity was observed in 33% (55/169) of women with CIN 2 and 46% (106/229) of women with CIN 3, in keeping with the lower fraction of CIN 2 (57/169) than CIN 3 (127/229) biopsies positive for HPV 16 DNA. HPV 16 seropositivity is most common in women with HPV 16-associated CIN, but many patients with HPV-associated CIN 3 are seronegative, and HPV 16 seropositivity is common in women with CIN associated with other HPV types. Overall, HPV 16 serology is a poor predictor of presence of HPV 16-associated CIN 3 in patient population studied.     

Screening for gynaecological conditions

Well-organised cervical screening programmes have reduced the mortality from cervical cancer by up to 50% in the developed world. Despite the successful development of human papilloma virus vaccines, there is likely to remain a need for cervical screening for the foreseeable future. In contrast, the value of mass screening for ovarian cancer remains unproven, although current screening methods can detect early-stage disease in asymptomatic individuals. Breast screening does appear to be associated with a reduction in mortality in the long term but paradoxically may increase death rates in young women in the short term. Testing for sexually transmitted infections is effective in reducing morbidity but tends to be selective at present because of concerns over the cost and psychosocial implications of general population screening.     

高危型人乳头瘤病毒检测在宫颈癌筛查中的应用价值

目的探讨将HR-HPV检测作为宫颈癌筛查手段的意义和价值。方法2004-12-2005-04对301医院妇产科门诊就诊的1231例患者,进行HPVDNA的杂交捕获法二代(HPV-HCⅡ)和液基细胞学(Thinprepcytol-ogytest,TCT)的检测,作为宫颈癌及其癌前病变的初筛。131例因细胞学异常,或细胞学正常而HPV检测阳性,或细胞学正常HPV阴性、而临床高度怀疑病变的患者行阴道镜下多点活检,结合病理结果进行分析。结果(1)1231例样本中,经TCT检测正常者1077例(87·43%),ASCUS32例(2·60%),ASCUS-H34例(2·76),LSIL73例(5·93%),HSIL15例(1·22%)。131例阴道镜下多点组织活检,病理证实炎症68例(51·91%),CINⅠ20例(15·27%),CINⅡ18例(13·74%),CINⅢ16例(12·21%),浸润癌4例(4·35%),湿疣5例(3·82%)。(2)HPV总感染率34%,HPV阳性者418例,年龄平均(36·93±10·8)岁,HPV阴性者813例,年龄平均(39·68±11·8)岁,HPV阳性组的年龄明显小于HPV阴性组,P<0·01。各病理组HPV感染率分别为:炎症58·82%,CINⅠ80%,CINⅡ72·22%,CINⅢ100%,浸润癌100%,湿疣60%。(3)阴道镜下多点活检结果:TCT和HPV均(-)者,无高度病变的发生;TCT(-)和HPV( )者中,≥CINⅡ的检出率11·1%(1/9),TCT异常和HPV阳性同时存在的病例中,≥CINⅡ的检出率最高40·5%(32/79);仅TCT异常而HPV(-)者13·2%(5/38),且5例均为CINⅡ,无原位癌和浸润癌的发生。结论持续的HR-HPV感染与宫颈病变的演进有关;HR-HPV检测是有价值的辅助诊断技术,与细胞学联合检测,为最佳宫颈癌筛查方案。     

荧光定量聚合酶链反应检测人乳头瘤病毒的实验研究

目的:探讨尖锐湿疣(CA)患者人乳头瘤病毒(HPV)的感染情况及荧光定量聚合酶链反应(FQ-PCR)检测HPV与分型的临床意义。方法:用FQ-PCR测定292例CA患者疣体组织或分泌物的HPV6、11和HPV16、18及HPV-DNA载量。结果:292例CA患者标本中HPV-DNA阳性感染率95.55%,其中HPV6、11型感染率85.62%,HPV16、18型感染率22.95%,HPV6、11型和HPV16、18型混合感染的感染率为13.01%。定量测定结果显示:HPV6、11型患者病毒载量最高1.0×108copies/ml,最低2.8×103copies/ml;HPV16、18型患者病毒载量最高1.0×108copies/ml,最低2.75×104copies/ml。结论:FQ-PCR检测技术具有灵敏、简捷、安全、特异性等的特点,其定量检测的结果可为临床治疗及观察CA患者感染HPV后病情变化提供可靠依据,有较高的临床实用价值。     

子宫颈癌HPV16/18感染与微血管密度和血管内皮生长因子表达的关系

目的 探讨人乳头状瘤病毒16／18（HPV16／18）在子宫颈癌组织中的感染情况及与微血管密度（MVD）和血管内皮生长因子（VEGF）表达的关系。方法 用原位杂交法检测HPV16／18在60例子宫颈癌（鳞癌40例、腺癌20例）、29例宫颈上皮内肿瘤（CIN）和16例正常子宫颈组织中的HPV16／18感染情况；采用免疫组织化学方法（SP）检测VEGF蛋白的表达，并以CD34抗原作为血管内皮细胞标记，测定其微血管密度。结果 HPV16／18在子宫颈鳞癌、腺癌、CIN和正常子宫颈组织中感染率分别为67．50％（27／40）、35．00％（7／20）、68．97％（20／29）、6．25％（1／16）。HPV16／18感染率鳞癌组与腺癌组和正常组比较差异均有显著性意义（均P〈0．01），而鳞癌组与CIN组相比差异无显著性意义（P〉0．05）。随着宫颈病变的进展，MVD逐渐增大，VEGF的阳性表达率渐增高。MVD在以上5种组织间相比差异均有极显著性意义（均P〈0．01）。VEGF在子宫颈鳞癌、腺癌、CIN、正常宫颈组织细胞质中的阳性表达率分别为95．00％（38／40）、100．00％（20／20）、82．80％（24／29）、18．80％（3／16）。病变患者与正常者相比差异有极显著性意义（P〈0．01）。HPV16／18感染与VEGF表达呈正相关（r=0．245，P〈0．05），而与MVD无相关性（r=．04，P〉0．05）；VEGF的表达与MVD无相关性（r=0．01，P〉0．05）。淋巴转移阳性者MVD的表达量较阴性者高（P〈0．05）。结论 在子宫颈癌的发生发展中HPV16／18的感染起一定的作用，MVD与VEGF在子宫颈组织的不同病变中的表达均有差异性，推测VEGF有促进子宫颈癌组织血管形成作用，MVD与子宫颈癌的恶性程度密切相关。HPV16／18感染可能通过促进VEGF的表达而有利于子宫颈癌组织的生长。     

HPV与宫颈癌的研究进展

宫颈癌（cancer of cervix，CaCx）是国内外危及女性生命的高发肿瘤之一，仅次于乳腺癌，人乳头瘤病毒（human papillomavirus，HPV）的感染是宫颈癌发生发展的重要因素，就HPV与多个癌基因、抑癌基因的相互作用和HPV与其他病原微生物的协同作用方面探讨宫颈癌的发病机制以及对HPV的检测方法等研究进行综述。     

Preclinical refinements of a broadly protective VLP-based HPV vaccine targeting the minor capsid protein,L2

An ideal prophylactic human papillomavirus (HPV) vaccine would provide broadly protective and long-lasting immune responses against all high-risk HPV types, would be effective after a single dose, and would be formulated in such a manner to allow for long-term storage without the necessity for refrigeration. We have developed candidate HPV vaccines consisting of bacteriophage virus-like particles (VLPs) that display a broadly neutralizing epitope derived from the HPV16 minor capsid protein, L2. Immunization with 16L2 VLPs elicited high titer and broadly cross-reactive and cross-neutralizing antibodies against diverse HPV types. In this study we introduce two refinements for our candidate vaccines, with an eye towards enhancing efficacy and clinical applicability in the developing world. First, we assessed the role of antigen dose and boosting on immunogenicity. Mice immunized with 16L2-MS2 VLPs at doses ranging from 2 to 25 μg with or without alum were highly immunogenic at all doses; alum appeared to have an adjuvant effect at the lowest dose. Although boosting enhanced antibody titers, even a single immunization could elicit strong and long-lasting antibody responses. We also developed a method to enhance vaccine stability. Using a spray dry apparatus and a combination of sugars & an amino acid as protein stabilizers, we generated dry powder vaccine formulations of our L2 VLPs. Spray drying of our L2 VLPs did not affect the integrity or immunogenicity of VLPs upon reconstitution. Spray dried VLPs were stable at room temperature and at 37 °C for over one month and the VLPs were highly immunogenic. Taken together, these enhancements are designed to facilitate implementation of a next-generation VLP-based HPV vaccine which addresses U.S. and global disparities in vaccine affordability and access in rural/remote populations.