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。     

A phase II study of Hsp-7 (SGN-00101) in women with high-grade cervical intraepithelial neoplasia

OBJECTIVE: Approximately 2 million women worldwide are infected with high-risk human papillomaviruses (HPV), resulting in a substantial risk for the development of invasive lower genital malignancies. This study was undertaken to determine the effects of vaccination with a protein encoding a bacterial heat shock protein fused to sequences from the oncogenic E7 protein of HPV-16 in women with high-grade cervical intraepithelial neoplasia. Endpoints included lesion regression, immune response, and viral clearance. METHODS: Twenty-one women were prospectively entered into an IRB-approved Phase II study. All women had biopsy-proven high-grade cervical intraepithelial neoplasia and persistent post-biopsy lesions visible by colposcopy. Four injections of HPV-16 Hsp E7 fusion protein at a dose of 500 mug were given 3 weeks apart after which Loop Electrosurgical Excision of the Transformation Zone (LLETZ) was performed. Immune parameters were evaluated pre-vaccine and at the time of LLETZ, and HPV testing was performed at intervals before and after LLETZ. Study subjects were followed for 1 year after LLETZ. RESULTS: Seven of 20 women (35%) evaluable for response had complete regression of their intraepithelial neoplasia at the time of LLETZ, 1 (5%) had regression to CIN I, 11 (55%) had stable disease and 1 (5%) had progression due to enlargement of her lesion. Immune responses were seen in 9 of the 17 women tested; 5 of the 7 complete responders had an immune response. Only 5 of 21 women had HPV-16 or -18. HPV clearance was not associated with lesion regression. CONCLUSION: Hsp-7 (SGN-00101), at this dose and schedule induced lesion regression in women with high-grade intraepithelial neoplasia. The fact that regression was correlated with immune response suggests that enhancing the immunogenicity of this vaccine may lead to improvement in the rate of lesion eradication.     

高级别宫颈上皮内瘤变治疗及转归预测因素的研究进展

研究已证实宫颈上皮内瘤变是宫颈癌的癌前病变,2014年世界卫生组织（WHO）改变了既往宫颈上皮内瘤变的3级分类法,将其分为低级别鳞状上皮内病变和高级别鳞状上皮内病变两类,其中宫颈高级别鳞状上皮内病变具有癌变潜能,极易进展,使我国女性的生理及心理健康受到严重威胁。目前,高级别鳞状上皮内病变的常用治疗方式为宫颈冷刀锥切术和环形电切术,一般疗效较好,但仍可能发生术中及术后出血、切口感染、宫颈狭窄、子宫内膜异位症和肠道损伤等并发症。相关研究显示,人乳头瘤病毒（HPV）分型、切缘阳性以及绝经状态与术后病变残留、复发、进展等风险密切相关,对宫颈锥切术后不良结局的预测有助于加强对此类患者的集中管理,提前预防并及时阻断病变进展途径,降低宫颈癌的患病率和死亡率。目前,预防性HPV疫苗的安全性和有效性已得到充分肯定,对减少HPV感染、预防术后疾病复发疗效显著,但宫颈已有病变者术后接种疫苗的作用效果尚待进一步探究。     

Human papillomavirus genotype prevalence in cervical biopsies from women diagnosed with cervical intraepithelial neoplasia or cervical cancer in Melbourne, Australia

Multicenter international phase III clinical trials using multivalent human papillomavirus (HPV) vaccines for cervical cancer (CC) prevention are underway. As HPV immunity is type specific, defining HPV genotype prevalence in different regions to ascertain whether predominant types differ geographically is considerably important prior to vaccine implementation. This study aimed to define HPV genotypes present in CC and high-grade dysplasia among women in Melbourne, Australia. HPV genotype analysis of a cross section of women in Melbourne with cervical dysplasia/cancer was performed. A total of 493 cervical biopsies from patients being treated for moderate (n= 122) or severe (n= 180) cervical intraepithelial neoplasia (CIN II/III) or CC (n= 191) were tested for HPV genotypes using the PGMY09/11 primer system and line blot assay. HPV detection rates were 63.9%, 72.8%, and 86.9% in CIN II, CIN III, and CC biopsies, respectively. The most prevalent HPV genotypes among CC biopsies were HPV-16 (52.9%), HPV-18 (18.3%), HPV-45 (6.3%), HPV-39 (3.1%), and HPV-73 (2.6%). Multiple HPV infections, comprising two to five types, were identified in 14.4% of biopsies, being significantly fewer (5.2%) among CC biopsies (P < 0.0001). These results indicate that the two most prevalent CC-associated HPV genotypes in Australia parallel those described internationally, with type variations thereafter.     

Clinical responses to Cidofovir applied topically to women with high grade vulval intraepithelial neoplasia

OBJECTIVES: Cidofovir is an acyclic nucleoside phosphonate, with broad spectrum anti-viral activity. It has previously been used in a number of clinical settings, including high grade intraepithelial disease in the cervix and low grade vulval disease. This pilot study was set up to assess whether Cidofovir might be useful in treating high grade vulval intraepithelial neoplasia. METHODS: Women with high grade non-cervical anogenital intraepithelial neoplasia were treated with a topical formulation of 1% Cidofovir in Unguentum Merck. Safety, side effects, clinical response and viral status were assessed. Clinical response was measured using symptoms, clinical (and photographic) appearance, viral status and histology. RESULTS: 12 women with high grade vulval, vaginal or perianal intraepithelial neoplasia were recruited, 10 of whom completed follow up. Diseased tissue underwent ulceration in the majority of cases, with no effect seen on neighbouring normal skin. Four women had complete regression of disease, with resolution of long standing symptoms as well as histological and viral clearance. Three women had a partial response. Two women did not respond, and one woman made a complete symptomatic response but was found to have invasive disease at final biopsy. CONCLUSION: These complete responses, in women with long standing disease, together with preservation of normal tissue, suggest that topical treatment with Cidofovir may have a place in the therapeutic armamentarium of high grade vulval intraepithelial neoplasia.     

Efficacy of imiquimod 5% cream for persistent human papillomavirus in genital intraepithelial neoplasm

ObjectiveTo assess the clinical response to imiquimod 5% cream in patients with persistent human papillomavirus (HPV) infection after treatment of genital intraepithelial neoplasia.Materials and MethodsImiquimod 5% cream was applied to treat 76 women with persistent HPV after surgical therapy for cervical or vaginal intraepithelial neoplasia (CIN or VAIN). One sachet of cream was placed in the cervical os and vagina with an applicator twice weekly for 8 weeks. Repeated HPV evaluation and Papanicolaou (Pap) smear and/or biopsy were performed 3 months following treatment completion.ResultsIn total, 58 of the 76 patients (76.3%) were clear of HPV infection and had normal Pap smears after administration of imiquimod cream. Although atypia or mild dysplasia was noted in 15 of the 18 patients (83.3%) with persistent HPV infection after imiquimod cream treatment, the degree of severity was noticeably less than the initial diagnosis in most of these patients. Persistent HPV positivity was observed in 12 of the 64 patients (18.8%) with CIN and 6 of the 12 patients (50.0%) with VAIN.ConclusionTopical imiquimod 5% cream may be beneficial in most cases of genital intraepithelial neoplasia, especially CIN, with persistent HPV following surgical treatment.     

阴道上皮内瘤变28例临床分析

目的: 探讨阴道上皮内瘤变(VAIN)的临床特点、危险因素、诊治及预后。方法: 回顾性分析北京协和医院2005-2011年住院收治VAIN病例28例临床资料。其中VAINⅡ7例,VAINⅢ21例。结果: 患者年龄29～76岁(中位年龄48岁)。绝经21例(75%)。26例(93%)无临床症状。25例(89%)病变位于阴道顶端。27例进行超薄液基细胞学涂片(TCT)检查异常。23例人乳头瘤病毒(HPV)检测阳性。15例有子宫切除术史,其中因宫颈上皮内瘤变(CIN)和宫颈癌切除子宫10例。子宫切除术后至诊断VAIN时间：宫颈疾病平均3.1年,非宫颈疾病8.8年。不同级别VAIN在年龄、子宫切除原因、目前及既往合并宫颈疾病、TCT结果差异无统计学意义。28例全部进行手术治疗,3例术后复发。结论: HPV病毒感染、宫颈病变、宫颈病变或宫颈癌行子宫切除术史是VAIN的危险因素;细胞学-阴道镜-组织病理学适用于VAIN的诊断及随诊;宫颈病变切除子宫治疗后应密切随访,尤其是术后3年内应警惕VAIN。　　     

Can local application of imiquimod cream be an alternative mode of therapy for patients with high-grade intraepithelial lesions of the vagina?

The aim of the present study was to assess the local application of imiquimod cream 5% as an alternative mode of therapy for high-grade vaginal intraepithelial neoplasia (VAIN 2/3). Positive human papillomavirus (HPV) patients with multifocal high-grade VAIN (2/3) not involving the vaginal vault in hysterectomized patients took part in this study. The treatment consisted of vaginal application of the cream under colposcopic guidance. Following management, biopsies were obtained from the previously recorded lesions. p53 expression was recorded prior and after therapy. Seven patients with VAIN 2/3 took part in this study. Six patients (86%) were positive for high-risk HPV type while three (43%) women who were positive for p53 nuclei prior to therapy were found to be negative following treatment. After treatment, 86% of the patients were found to have either HPV infection or low-grade VAIN. During follow-up, two patients (28.5%) were managed by vaginectomy, one for persistent and one for recurrent high-grade VAIN. Currently, from the five patients that are followed, three have simple HPV infection and two, VAIN 1. Imiquimod cream 5% might represent an alternative although not permanent method of management in young, HPV-positive women with multifocal high-grade lesions of the vagina (VAIN 2/3).     

Recurrent high-grade cervical lesion after primary conization is associated with persistent human papillomavirus infection in Norway

Objective

This retrospective registry-based study aimed to assess the human papillomavirus (HPV)-type distribution in primary and recurrent high-grade cervical intraepithelial neoplasia (CIN2 +), and to discriminate pre-existing from newly-acquired infections.

Methods

Cervical specimens from 58 women (median age (Q1–Q3): 37.6 (31.7–44.9)) who underwent primary (1998–2003) and repeat conizations were confirmed as CIN2 + during expert pathology review. HPV testing was performed using PCR MP-TS123 Luminex for 16 HPV types. Molecular HPV16 E6 and HPV18 LCR DNA sequencing was performed on specimens with persistent HPV16/18.

Results

All 58 paired cones were HPV positive; 49 had CIN3 + in the primary cone. Forty-seven (95.9%) women with primary CIN3 + and recurrent CIN2 + had persistent high-risk (hr) HPV infection, of which 74.5% were HPV16/18. Two women had probable newly-acquired HPV16/52/56 and HPV39 infections. One woman with persistent HPV52 also had a probable new HPV16 E6 variant in the recurrent CIN2 +. Median time delay (Q1–Q3) between conizations was 2.0 years (1.1–4.0), being shorter for women older than 40 years: 2.6 years (1.1–3.7) than for women younger than 40 years: 6.0 years (2.0–8.7). Primary conization histology revealed CIN3, cervical adenocarcinoma in situ and microinvasive carcinomas in 43 (87.8%), 5 (10.2%) and 1 (2.0%) women, respectively. Primary HPV16- and HPV18-infected CIN3 + had a shorter delay between conizations: 1.8 years (1.2–4.4) and 2.2 years (0.4–NE), respectively, compared to HPV33-: 3.8 years (3.3–7.8) or other HPV type-infected: 8.2 years (6.0–NE) CIN3 +.

Conclusions

Routine post-conization hr-HPV DNA testing together with cervical cytology may provide a better prediction for potential recurrent disease. Further, primary prevention through adolescent vaccination may prevent CIN2 + and its recurrence.     

人乳头瘤病毒L1壳蛋白在筛查宫颈鳞状上皮内病变中的应用

目的:探讨人乳头瘤病毒(HPV)L1壳蛋白筛查HPV阳性妇女宫颈脱落细胞中宫颈鳞状上皮内病变的应用价值。方法:选取2012年5月至2014年12月就诊于温州市人民医院的妇女212例,收集宫颈脱落细胞并行HPV L1壳蛋白检测、HPV DNA分型、TCT(液基细胞学)及阴道镜下活检,比较HPV阳性妇女的宫颈脱落细胞中HPV L1壳蛋白的表达情况。结果:212例细胞学标本中HPV L1壳蛋白阳性率为33.9%,其中未见上皮内病变/恶性细胞组(NILM)、无明确诊断意义的鳞状上皮细胞病变组(ASCUS)、低度鳞状上皮内病变组(LSIL)、不能排除高度鳞状上皮内病变组(ASC-H)、高度鳞状上皮内病变组(HSIL)中阳性率分别为47.1%、35.1%、54.2%、29.2%、16.1%,各组比较差异有统计学意义(P0.05);两两比较,HSIL组与LSIL组和NILM组比较,差异均有统计学意义(P均0.005);进行数据合并后,LSIL/ASCUS组与ASC-H/HSIL组比较差异有统计学意义(P=0.001)。178例宫颈细胞学异常患者中,宫颈低级别病变和宫颈高级别病变的HPV L1壳蛋白阳性率比较,在ASCUS组(P=0.000)、LSIL组(P=0.004)中均有差异,在ASC-H组(P=0.127)、HSIL组(P=0.515)中均无差异。HPV 16/18感染患者的HPV L1壳缺失同宫颈高级别病变有更紧密的关系(P=0.003)。结论:子宫颈脱落细胞HPV L1壳蛋白检测在HPV阳性妇女的子宫颈病变筛查中具有一定的价值,可能成为一种合适的分流方法。     

Neoplasia intraepitelial vulvar: Cribado en población de riesgo

BackgroundPatients with cervical intraepithelial neoplasia (CIN) are more likely to develop lesions caused by the human papilloma virus (HPV) in other locations of the lower genital tract (including the vulva). Vulvoscopy is not included in the follow-up of women with CIN. It is proposed to study the efficiency of including vulvoscopy in follow-up. An analysis is also performed on incidence of high-grade vulvar dysplasia, as well as the influence of protective and risk factors analysed.Material and methodsThe study included 95 patients with a diagnosis of CIN in the cone biopsy piece. All the information relative to their socio-demographic and clinical characteristics was collected and included, performing of the vulvoscopy as well as the biopsy.Results and conclusionsThe mean age of the patients was 40 years. Just under two-thirds (62.1%) of them were or had been smokers (more than half of those had quit smoking at the time of the study). Only 21.1% said they were not using a barrier method. Although 78.9% of those studied were or had been users of hormonal contraception, only 8 out of the 95 continued using it. Most (88 out of the 95 women) were vaccinated against HPV. No high-grade vulvar dysplasia was diagnosed. The modification in the lifestyle after the diagnosis of the cervical disease, the transience of the HPV infection, and the greater susceptibility of the cervical epithelium to this, are indicated as the most probable causes of the discordance between the expected prevalence of vulvar disease and the effective rate found within the studied population.     

Cervical cancer prevention in the era of prophylactic vaccines: a preview for gynecologic oncologists

OBJECTIVE: The recent approval of a vaccine to prevent HPV infection is an important advance in cervical cancer prevention. This article is intended to provide gynecologic oncologists with a comprehensive background in modern cervical cancer prevention strategies. METHODS: We describe and contrast the quadrivalent and bivalent vaccines. More established cervical cancer prevention strategies are reviewed, with comments on the impact of HPV vaccination. Clinical guidance is provided for use of the approved quadrivalent vaccine. Safety and side effects of both vaccines are reviewed and future questions and challenges are explored. RESULTS: It is vitally important that both vaccinated and unvaccinated women continue to fully engage in cervical cancer prevention, including cervical cancer screening, follow-up of abnormal screens, and treatment of premalignant lesions. A quadrivalent virus-like particle vaccine has now been approved for use in girls and women ages 9 to 26. A bivalent vaccine may be available soon. Vaccine efficacy in clinical trials has been outstanding, with 100% protection against HPV-type-specific cervical intraepithelial neoplasia (CIN) II and III. CONCLUSIONS: Comprehensive cervical cancer protection now includes prophylactic vaccination for girls and young women in addition to screening and treatment of premalignant changes. Gynecologic oncologists will continue to play an important role in promoting optimal prevention practices.     

HPV亚型在宫颈疾病中的分布特点

目的:探讨HPV亚型在宫颈疾病谱中,即从正常宫颈(慢性宫颈炎)、宫颈上皮内瘤变(CINⅠ、CINⅡ和CINⅢ)到宫颈癌连续发展中的分布特点。方法:回顾分析2005年6月～2008年6月在我院妇科因宫颈疾病就诊的189例患者HPV亚型检测的结果。结果:HPV总感染率56.1%(106/189),复合感染率22.6%(24/106)。正常者HPV感染率19.1%(12/63),检测到的HPV亚型主要是HPV52,58,53,16和33。CINⅠ者HPV感染率57.9%(22/38),最常见的HPV亚型是HPV52,其次是HPV58,16,33和18。CINⅡ者HPV感染率70.5%(31/44),HPV52,16,58,33和18等亚型最常见。CINⅢ者HPV感染率89.3%(25/28),HPV亚型以HPV16,52,58,31,33为主。宫颈癌患者,HPV阳性率100%(16/16),HPV16检测率最高,其次是HPV18,52,58和33。结论:宫颈疾病谱中最常见的高危型HPV亚型是HPV16。不同宫颈病变中HPV亚型感染的差异可能反映了其潜在转归能力,同时提示临床医师应关注宫颈疾病患者高危HPV亚型情况。     

宫颈癌及癌前病变组织中Notch1及HPV16 E6/E7表达的研究

目的 探讨Notch1受体和人乳头瘤病毒16感染在宫颈癌前病变和宫颈癌发生发展中的作用。方法 采用免疫组化SP法检测18例宫颈上皮内瘤变（cervical intraepithelial neoplasia,CIN）和35例宫颈癌标本中Notch1受体及HPV16E6/E7蛋白的表达,以34例正常宫颈组织及慢性宫颈炎组织作为对照。比较各组间Notch1及HPV16E6/E7表达的差异,并分析Notch1与HPV16E6/E7表达的关系。结果 Notch1蛋白在细胞胞浆、胞核及胞膜中表达,HPV16E6/E7在细胞核中表达。从对照组到CIN组到宫颈癌组,Notch1及HPV16E6/E7的表达均逐渐增强（P〈0.01）。Notch1的阳性表达与宫颈癌不同分期、分化程度、淋巴结是否转移无关（P〉0.05）。在宫颈癌组中Notch1与HPV16E6/E7的表达均呈正相关性（P〈0.01）。结论 Notch1表达与HPV16E6/E7感染可能与CIN及宫颈癌的发生密切相关,两者在宫颈癌的发病机制中可能协同发挥作用。     

In situ hybridization analysis of HPV DNA in cervical precancer and cervical cancers from China

Summary A series of 103 cervical biopsies derived from 103 women during July 1958 to September 1963 from Beijing, China were investigated with in situ hybridization for the presence of HPV6, 11, 16, 18, 31 and 33 DNA. The mean age of the patients was 46.1 + 10.6 years with a range of 24–74 years. Morphological features of HPV infection were found in 80 (77.7%) biopsies. Invasive cervical cancer was diagnosed in 43 biopsies and cervical intraepithelial neoplasia CIN I, CIN II and CIN III in 9, 9, and 27 cases, respectively. A total of 63.1% (65/103) of the lesions had morphological features of HPV infections associated with CIN or invasive carcinomas. Altogether, 31.1% (32/103) of the biopsies were shown to contain HPV DNA. Of the cases showing HPV morphology, 43.1% were HPV DNA positive. HPV16 (30/32) was the most frequent type, followed by HPV11 and 18, whereas no lesions with HPV6, 31 or 33 were found. A total of 19/43 (44.2%) of the invasive carcinomas contained HPV DNA. HPV DNA positivity and the grade of CIN showed a statistically significant correlation (P=0.0011). Our study demonstrated the presence of HPV in cervical lesions among Chinese women in the late 1950's and early 1960's when a single sexual partner was the rule and also supports the concept that HPV has as an important etiological role in cervical cancer, the highest risk being associated with HPV type 16. The applicability of in situ hybridization in retrospective assessment is emphasized.     

Results of a phase II randomized,double-blind,placebo-controlled trial of Polyphenon E in women with persistent high-risk HPV infection and low-grade cervical intraepithelial neoplasia

Objective

In vitro data and pilot data suggest that green tea catechins may possess chemopreventive activity for cervical cancer and precursor lesions. We conducted a randomized, double-blind, placebo-controlled trial of Polyphenon E (decaffeinated and enriched green tea catechin extract) in women with persistent human papillomavirus (HPV) infection and low-grade cervical intraepithelial neoplasia (CIN1) to evaluate the potential of Polyphenon E for cervical cancer prevention.

Methods

Ninety-eight eligible women were randomized to receive either Polyphenon E (containing 800 mg epigallocatechin gallate) or placebo once daily for 4 months. The primary study outcome was oncogenic HPV clearance and clearance of CIN1.

Results

Polyphenon E was shown to be acceptable, safe and well tolerated. There was no difference in the response rate by treatment allocation. Complete response, defined as negative for high-risk HPV and normal histopathology, was noted in 7 (17.1%) and 6 (14.6%) women in the Polyphenon E and placebo arms, respectively. Progression, defined as persistent oncogenic HPV with histopathologic evidence of progression, was more common in the Polyphenon E group than in the placebo group [6 (14.6%) vs. 3 (7.7%)].

Conclusion

Based on the largest randomized placebo-controlled trial of a green tea extract for HPV related cervical disease, we conclude that 4 months of Polyphenon E intervention did not promote the clearance of persistent high-risk HPV and related CIN1. Further studies may be necessary to better delineate the risk factors for persistent HPV infection and biology of the disease to facilitate the evaluation of chemopreventive strategies.     

A Review of the Impact and Effectiveness of the Quadrivalent Human Papillomavirus Vaccine: 10 Years of Clinical Experience in Canada

Publicly funded administration of the quadrivalent HPV (qHPV) vaccine in school-aged girls was implemented for all Canadian provinces and territories between 2007 and 2009. However, the impact of female qHPV vaccination in Canada has yet to be evaluated. This systematic literature review of studies published between September 1, 2006 and September 1, 2016 looked at real-world evidence related to the effects of qHPV vaccination on prevalence of HPV infection and disease in Canada over the past decade. PubMed was searched for studies published between September 1, 2006 and September 1, 2016. Studies were eligible if one or more of the following outcomes were assessed in individuals receiving the qHPV vaccine though public immunization programs: HPV infection, anogenital warts (AGW), HPV-associated lesions of the anogenital tract. A “pre-public vaccination program” or “unvaccinated” reference group was required. Key HPV conference abstracts were also reviewed. We identified seven eligible studies representing five Canadian provinces. Results reported indicated that the prevalence of HPV types 6, 11, 16, and 18 was lower in qHPV-vaccinated than unvaccinated individuals (1.5% vs. 11.0%, respectively), whereas non–vaccine-covered genotypes were comparable across vaccination status. Risk of AGW incidence decreased by up to 45% in vaccinated cohorts; incidence of cervical intraepithelial neoplasia 2?+?was significantly reduced by up to 86% in the post-vaccine era. On the basis of these findings, HPV vaccination programs constitute a successful and effective public health initiative.     

四价HPV疫苗预防宫颈癌、HPV感染相关疾病Meta分析

目的：评价四价人乳头瘤病毒（HPV）疫苗预防宫颈癌及HPV相关感染与疾病的有效性与安全性。方法：计算机检索Cochrane图书馆、MEDLINE,EMBASE,NGC和CBM,纳入所有关于四价HPV疫苗的随机对照试验（RCT）,2名研究者独立提取数据并进行方法学质量评估。试验数据的统计分析采用Cochrane协作网提供的RevMan 4.2软件。结果：共纳入5项RCT,包括23 617例女性,Meta分析结果显示：与安慰剂相比,预防性四价疫苗明显降低与HPV6,11,16和18型相关的Ⅱ/Ⅲ级宫颈上皮内瘤样变、原位癌及Ⅱ/Ⅲ级外阴、阴道上皮内瘤样变和外生殖器疣的发病率。主要不良反应较轻微,严重不良反应在疫苗组和安慰剂组保持均衡。结论：四价HPV疫苗对预防相关类型HPV所致宫颈癌及外生殖器病变安全有效。     

四价HPV疫苗预防宫颈癌、HPV感染相关疾病Meta分析

目的：评价四价人乳头瘤病毒（HPV）疫苗预防宫颈癌及HPV相关感染与疾病的有效性与安全性。方法：计算机检索Cochrane图书馆、MEDLINE,EMBASE,NGC和CBM,纳入所有关于四价HPV疫苗的随机对照试验（RCT）,2名研究者独立提取数据并进行方法学质量评估。试验数据的统计分析采用Cochrane协作网提供的RevMan4．2软件。结果：共纳入5项RCT,包括23617例女性。Meta分析结果显示：与安慰剂相比,预防性四价疫苗明显降低与HPV6,11,16和18型相关的Ⅱ,Ⅲ级宫颈上皮内瘤样变、原位癌及Ⅱ／Ⅲ级外阴、阴道上皮内瘤样变和外生殖器疣的发病率。主要不良反应较轻微。严重不良反应在疫苗组和安慰剂组保持均衡。结论：四价HPV疫苗对预防相关类型HPV所致宫颈癌及外生殖器病变安全有效。