HPV infections in retinoblastoma: a systematic review

BackgroundRetinoblastoma is the most common primary intraocular malignancy in children less than 4 years. Retinoblastoma (RB) contains about 3%–5% of all childhood cancers. Recent studies demonstrated that interacting between RB tumor suppressor and oncoproteins of DNA tumor viruses such as human papillomavirus (HPV). The objective of the current systematic review study was to present conducted studies in the field of HPV infection and its possible role in retinoblastoma.MethodsFor this systematic review, all relevant original research studies were assessed by searching in electronic databases include PubMed, Embase, Scopus, Google Scholar, and Web of Science by using relevant keywords. The study was designed based on the PRISMA criteria. All publications with English literature and original researches are considered for screening.ResultsConducted search results lead to 4070 studies. The title and abstract screening lead to 11 studies. Data extraction was performed on 8 included studies. The prevalence of the HPV was ranged from 0 to 69%, and HPV genotype 16 and 18 were the most detected types. The most used method for the detection of the viruses was PCR, and the most assessed sample was formalin‐fixed, paraffin‐embedded tissue blocks.ConclusionThe association between HPV and retinoblastoma is still inconsistent. The prevalence of the HPV in RB was ranged from 0 to 69%, which indicates a wide range and highlights the importance of further investigation for more accurate statistical of HPV prevalence in RB. Thus, further worldwide studies of larger sample sizes of cohorts should be investigated to clarify this uncertainty.     

Intervention to Increase Human Papillomavirus Vaccine Initiation Rates in Adolescent Males

The objective of this quality improvement project was to increase human papillomavirus (HPV) vaccine initiation rates among males aged 11 to 21 years old. A multipronged strategy was implemented at a pediatric practice, including an electronic medical record prompt, educational presentation, and monthly e-mail updates to providers. Deidentified HPV vaccine initiation rate data were collected, and a paired 2-sample t test evaluated differences in prepost vaccine initiation rates. HPV vaccine initiation rates increased by 6.5% during the project period. The medical record prompt was identified as most effective by 75% of participating providers. Small gains can be made to improve HPV vaccine initiation rates among adolescent males.     

HPV阳性患者心理焦虑状况调查与分析

目的探讨人乳头瘤病毒(HPV)阳性患者不同心理焦虑状态的程度和特点,为心理评估、治疗及协调医患关系作基础。方法在宫颈病变普查中,通过Zung氏焦虑自评表(SAS)和病人一般资料问卷对其中90例HPV阳性患者进行心理焦虑状态测评。结果不同年龄、职业、文化程度及HPV持续阳性时间不同患者焦虑状况不同;30岁以上妇女、本科及以上学历、公务员患者焦虑状态较重,患病时间越长其焦虑值越大。结论Zung氏焦虑自评表和病人一般资料问卷能够发现不同的HPV阳性患者具有不同心理焦虑状态及其特征,为制定医疗方案和心理干预提供依据。     

Role of human papillomavirus in oropharyngeal squamous cell carcinoma: A review

Human papillomavirus (HPV) has been implicated in the pathogenesis of a subset of oropharyngeal squamous cell carcinoma. As a result, traditional paradigms in relation to the management of head and neck squamous cell carcinoma have been changing. Research into HPV-related oropharyngeal squamous cell carcinoma is rapidly expanding, however many molecular pathological and clinical aspects of the role of HPV remain uncertain and are the subject of ongoing investigation. A detailed search of the literature pertaining to HPV-related oropharyngeal squamous cell carcinoma was performed and information on the topic was gathered. In this article, we present an extensive review of the current literature on the role of HPV in oropharyngeal squamous cell carcinoma, particularly in relation to epidemiology, risk factors, carcinogenesis, biomarkers and clinical implications. HPV has been established as a causative agent in oropharyngeal squamous cell carcinoma and biologically active HPV can act as a prognosticator with better overall survival than HPV-negative tumours. A distinct group of younger patients with limited tobacco and alcohol exposure have emerged as characteristic of this HPV-related subset of squamous cell carcinoma of the head and neck. However, the exact molecular mechanisms of carcinogenesis are not completely understood and further studies are needed to assist development of optimal prevention and treatment modalities.     

第二代杂交捕获法检测宫颈人乳头瘤病毒感染的初步研究

目的:探讨人乳头瘤病毒与宫颈癌及癌前期病变的相关性.方法:选取2004年12月～2005年7月我院妇科宫颈病门诊妇女1689例,取宫颈刷出物同时作宫颈薄层液基细胞学涂片与HPV-DNA检测,HPV-DNA检测方法是第二代杂交捕获法,可一次检测13种高危型HPV病毒,分析HPV感染与宫颈癌及癌前期病变的关系.结果:HPV-DNA检出率随宫颈癌变程度加重呈趋势性升高,1689例病人中高危型HPV检出率为25.16%(425/1689),宫颈癌及癌前期病变中为90.35%(234/259).结论:高危型HPV是诱发宫颈癌及癌前期病变的重要病因学因素.第二代杂交捕获法可作为宫颈癌的一种筛查方法.     

无锡地区妇女宫颈HPV感染及基因型别分析

目的 对疑似人乳头瘤病毒(HPV)感染的970例妇女进行HPV基因分型检测,以探讨其临床意义.方法 用专用官颈刷采取妇女宫颈的脱落细胞,采用基因芯片法检测970例HPV临床样本,并进行基因分型.结果 970例样本中,HPV感染390例,阳性率40.2%.共检出12种HPV亚型,检出感染单一HPV亚型260例(26.8%),感染两种亚型以上130例(13.4%).低危型主要为HPV6、11,高危型主要为HPVl6、33、52、58、18等.结论 无锡地区妇女宫颈HPV感染率较高,感染亚型主要是6、11型.HPV基因分型检测对于生殖道感染以及子宫颈癌的早期发现以及预防和治疗具有重要意义.     

Genital infection with human papillomavirus in adolescents

Human papillomavirus (HPV) infection is one of the most common sexually transmitted infections in adolescents. Such infection is associated with substantial health risks and is unpredictable in its resolution. Genital warts are the most common clinical manifestations of genital HPV infections. Most genital warts are caused by low-risk HPV types (notably HPV-6 and -11). The majority of genital HPV infections are latent or subclinical. Although the outcome of a genital HPV infection is variable, the infection is usually transient and complete resolution is common. However, persistent infections with high-risk HPV types (notably HPV-16 and -18) are associated with the development of cervical intraepithelial dysplasia (CIN), which may progress to cervical cancer. Genital warts, generally diagnosed in the clinic, can be treated with imiquimod, podofilox, podophyllin, liquid nitrogen, bichloroacetic or trichloroacetic acid, or surgery. Cervical cytology screening is an ideal screening test for subclinical HPV infection with resultant CIN. Annual cervical cytology screening should begin approximately 3 years after initiation of sexual intercourse but no later than age 21 years. Because of the high rate of regression of low-grade squamous intraepithelial lesions (LSIL) in adolescents, the cytologic study should be repeated within 6 to 12 months. Colposcopy should be reserved for persistent LSIL. Patients with high-grade squamous intraepithelial lesions (HSIL) should be referred for colposcopy and biopsy. Confirmed HSIL should be treated with cryotherapy, laser therapy, or loop electrosurgical excisional procedure. The use of therapeutic vaccines is still experimental. HPV infection can be prevented, to a certain extent, by delaying the initiation of sexual activity, limiting the number of sexual partners, and using latex condoms. Several viruslike particle candidate vaccines are under development for the prevention of HPV. These vaccines have been proven safe, well tolerated, highly immunogenic, and highly efficacious. Such vaccines are urgently needed and ultimately may be an important preventive measure.     

HPV vaccination with Gardasil®: a breakthrough in women’s health

Human papillomavirus (HPV) represents one of the most common sexually transmitted infections. Although infection is often self-limited, a percentage of women with HPV infection will go on to develop cervical precancerous or cancerous lesions. It is estimated that HPV16 is responsible for approximately half of all cervical cancers worldwide. Several studies have tested vaccines directed against specific HPV types, namely types 6, 11, 16 and 18. This paper reviews these studies, particularly focusing on a quadrivalent (type 6, 11, 16 and 18) HPV L1 virus-like particle vaccine under investigation in Phase III trials at present. Data indicate that this vaccine, referred to as Gardasil^®, can prevent precancerous cervical lesions and early in situ cervical cancers with few adverse effects, and the vaccine has been approved by the FDA for this indication. Another vaccine, HPV16 L1, directed solely against HPV16, has also been demonstrated to be effective (at present, follow-up has been for up to 48 months) in providing protection against persistent infection with this viral strain and preventing HPV16-related cervical intraepithelial neoplasia 2/3, while producing minimal adverse effects in recipients. Given the lack of a pharmacological intervention that can eradicate HPV in infected individuals and the prevalence of cervical cancer secondary to HPV infection across the world, the HPV vaccine represents a significant breakthrough in women’s health.     

流式荧光杂交法检测人乳头瘤病毒的临床应用

目的探讨流式荧光杂交法检测人乳头瘤病毒(HPV)的临床应用价值。方法采集苏州地区1 406例妇科就诊患者宫颈脱落细胞,用流式荧光杂交技术检测HPV基因型,并对HPV感染率、基因亚型和年龄分布等进行分析。结果检出HPV感染576例(40.97%),其中单一亚型感染392例(27.88%),多重亚型感染184例(13.09%);采用流式荧光杂交法可同时检测26种HPV基因亚型,最常见的亚型为HPV-6、11、16、52、58等;单纯HPV低危亚型感染117例,占阳性病例的20.31%,高危亚型感染365例(63.37%);50～59岁年龄组HPV感染率最高(52.24%),30～39岁年龄组感染率最低(34.02%);并且,随年龄增加低危亚型感染率逐步降低,高危亚型感染率却呈明显上升趋势。结论本地区妇科患者中HPV感染率较高,流式荧光杂交法是检测HPV感染的有效方法,开展HPV分型检测对宫颈病变的防治意义重大。     

孕期人乳头状瘤病毒感染的结局分析

目的:探讨人乳头状瘤病毒(human papillomavirus,HPV)的感染分型及母婴垂直传播情况。方法:对2011年1月—2012年12月在复旦大学附属中山医院青浦分院产科门诊就诊的500例孕妇的宫颈脱落细胞进行HPV-DNA分型检测,并对HPV阳性孕妇分娩的新生儿的口咽部和生殖器黏膜细胞进行HPV-DNA分型检测,分析HPV亚型感染状况。结果:500例孕妇中HPV阳性者102例,感染率20.40%;感染HPV最常见的亚型为HPV16(4.2%)、HPV52(2.20%)、HPV33(1.80%)、HPV58(1.80%)、HPV18(1.60%)、HPV39(1.20%)。HPV阳性孕妇中,单型别感染88例(86.27%);多重型别感染14例(13.73%),其中二重感染11例,三重感染3例。母婴HPV垂直传播7例(6.86%)。25~30岁年龄段孕妇HPV感染率较高,不同孕期孕妇HPV感染率差异无统计学意义(P0.05)。结论:孕期HPV感染以HPV16型为主,并可母婴垂直传播;妊娠期妇女早期筛查对降低宫颈癌发病率和新生儿感染率非常必要。     

Cervical cancer screening:A never-ending developing program

With the term “oncological screening”, we define the overall performances made to detect early onset of tumors. These tests are conducted on a population that does not have any signs or symptoms related to a neoplasm. The whole population above a certain age, only one sex, only subjects with a high risk of developing cancer due to genetic, professional, discretionary reasons may be involved. Screening campaigns should be associated, when risk factors that can be avoided are known, with campaigns for the prevention of cancer by means of suitable behavior. The goal of cancer screening cannot however be limited to the diagnosis of a greater number of neoplasms. Screening will be useful only if it leads to a reduction in overall mortality or at least in mortality related to the tumor. Screening should then allow the diagnosis of the disease at a stage when there is a possibility of healing, possibility that is instead difficult when the disease is diagnosed at the appearance of signs or symptoms. This is the reason why not all campaigns of cancer screening have the same effectiveness. In Italy, every year there are about 150000 deaths due to cancer. Some of these tumors can be cured with a very high percentage of success if diagnosed in time. Cervical cancer can be diagnosed with non-invasive tests. The screening test used all over the world is Papanicolaou (Pap) test. This test may be carried out over the entire healthy population potentially exposed to the risk of contracting cancer. Public health has begun the screening campaigns in the hope of saving many of the approximately 270000 new cases of cancer reported each year. Screening is done following protocols that guarantee quality at the national level: these protocols are subject to change over time to reflect new realities or to correct any errors in the system. A simplified sketch of a possible route of cancer screening is as follows: (1) after selecting the target population, for example all women between 25 and 64 years (in the case of monitoring of cervical cancer), an invitation letter with the date and time of the appointment, planned according to the acceptance capacity of the hospital, is sent to all individuals; (2) an examination, which depending on the individual and the type of cancer to be monitored, for example, can be a Pap smear, is performed and the patient can go home; (3) once available the results of examinations, if negative, they shall be communicated to the person concerned that will be notified by mail and will be recalled for a second test at a few years of distance, in the case of non-negativity, instead, the patient is contacted by telephone and informed of the need to carry out further examinations: it is said that the patient is in the “phase two” of the screening pathway; (4) in phase two, reached by only a small portion of the interested parties (usually less than 3%-5%), more in-depth tests are carried out, which, depending on the individual and the type of cancer, can be: cytological and colposcopic examinations, the removal of a fragment of tissue (biopsy) and subsequent histological examination, additional tests such as ultrasound, radiography, or others such as computerized tomography, magnetic resonance imaging, positron emission tomography, etc., in case of negativity, the concerned person will be called for new control tests at a a few years of distance, in case of non-negativity, it will be proposed instead an oncologic therapeutic plan and/or surgery to treat the diagnosed tumor; and (5) once the treatment plan is completed, the individual enters the follow-up protocol, which is monitored over time to see if the tumor has been completely removed or if instead it is still developing. Cervical cancer is undoubtedly the most successful example of a cancer screening campaign. Paradoxically, its effectiveness is one of the strongest reasons to criticize the usefulness of vaccination against human papillomavirus (HPV) in countries where the screening service with Pap test is organized in an efficient manner. Cervical cancer screening protocols are directed to sexually active women aged 25-64 years: they provide the Pap test performed by examining under a microscope or by staining with a specific “thin prep” the material taken from the cervix with a small spatula and a brush. It is recommended to repeat the test every two or three years. It is important to emphasize that women vaccinated against HPV must continue the screening with Pap test. Although some screening programs (e.g., Pap smears) have had remarkable success in reducing mortality from a specific cancer, any kind of screening is free from inherent limitations. The screening methods are in fact applied to large parts of the apparently healthy population. In particular, the limits for certain cancers may be as obvious as to prohibit the introduction of an organized screening program. Potential limitations of organized screenings are basically of two types: organizational and medical. The limits of organizational type relate to the ability of a program to recruit the whole target population. Although well organized, a screening program will hardly be able to exceed a coverage of 70%-80% of the target population, and in fact the results of the current programs are often much smaller. The limits of medical type are represented by the possibility of reducing the overall mortality, or specific mortality, using a specific screening campaign.     

健康教育在宫颈人乳头瘤病毒感染患者中的作用

目的探讨健康教育在妇科宫颈人乳头瘤病毒(human papillomavirus,HPV)感染患者中的作用。方法将100例宫颈液基细胞学检测结果正常且高危型人乳头瘤病毒检测为阳性的患者随机分成2组:对照组和健康教育组。对健康教育组实施不同形式的健康教育,对照组采用简单的问答式回答。评估2组患者在焦虑、HPV相关知识回答正确率、随访率及随访中HPV转阴率中存在的差异。结果对照组焦虑情绪明显高于健康教育组(P<0.05),健康教育组在HPV相关知识综合掌握率、随访率中评分明显优于对照组(P<0.05)。结论重视HPV感染患者的健康教育,提高患者对自身疾病的认识,可促进患者疾病的顺利康复。健康教育还可以让更多患者随诊,并减少随诊中高危患者的丢失,从而减少宫颈癌的发生。     

HPV分型联合TCT检测在宫颈疾病中的诊断价值

目的探讨人乳头瘤病毒(HPV)分型、液基薄层细胞学(TCT)技术及二者联合检测在宫颈疾病中的诊断价值。方法回顾性分析257例患者行HPV分型检测及TCT检查的检查结果数据,以病理检查结果作为阳性诊断金标准并进行分析。结果 257例患者中82例病理检查结果为阳性。HPV分型、TCT及二者联合检测筛查的灵敏度分别为89.02%、75.61%、71.95%;特异度分别为56.57%、72.57%、88.00%;阳性预测值分别为48.99%、56.36%、73.75%;诊断准确度分别为66.93%、73.54%、82.88%。二者联合检测的特异度、阳性预测值、诊断准确度都明显高于二者单独检测,差异有统计学意义(P0.05)。高危型HPV检出率为42.03%,其中HPV-16检出率最高,检出率为16.73%。结论 HPV分型和TCT联合检测能够提高检出的阳性符合率,建议二者联合应用于宫颈疾病的筛查。     

The performance of the HPV16 real-time PCR integration assay

OBJECTIVES: Integration of high risk human papillomavirus (HPV) into the host genome leads to viral oncogene deregulation predisposing to neoplastic progression. Integration can be detected from pap smear or biopsy and use as marker of progressive disease. DESIGN AND METHODS: We have previously developed a highly sensitive real-time PCR method to determine HPV integration frequency and viral load of HPV16 in clinical samples. The test is accurate and sensitive detecting approx. 50 copies of integrated HPV in the sample. RESULTS: We found that a tenfold excess of episomal form to integrated form interferes with the test, regardless the amount of viral DNA. The same was true with background DNA more than 1500 ng in reaction. CONCLUSIONS: Overall, this method is reproducible and suitable for high-throughput screening of clinical samples, but excess episomal copies might mask the integrated form.     

Papillomavirus-like particle based vaccines: cervical cancer and beyond

Non-infectious human papillomavirus-like particles (VLP), composed of the L1 major capsid protein, are under active development as vaccines to prevent cervical cancer. They would presumably function primarily by generating virion-neutralising antibodies against the genital human papillomavirus (HPV) types that are the principal cause of most cervical cancers. Early phase clinical studies indicate that the VLP vaccines are well tolerated and able to consistently induce high titres of virus type-specific neutralising antibodies. Two types of second-generation VLP-based subunit vaccines with therapeutic implications, both related and unrelated to papillomavirus infection, are in preclinical development. One type seeks to induce cell-mediated immune responses, especially cytotoxic lymphocytes (CTL), against non-structural papillomavirus proteins, proteins of other viruses, or tumour associated antigens. The target antigen is incorporated into the VLPs as a fusion protein of L1 or the L2 minor capsid protein. In mouse models, this approach has generated potent CTL responses after low dose vaccination in the absence adjuvant. The second type of therapeutic VLP-based vaccine seeks to generate autoantibodies to self-antigens. The display of self polypeptides in the context of the highly ordered array of repetitive elements on the papillomavirus VLP surface abrogates the ability of the humoral immune system to functionally distinguish between foreign and self. High titre and high avidity auto-reactive IgG antibodies have been induced to both soluble (TNF-α) and cell surface (CCR5) central self-antigens. Vaccines based on this approach could potentially be effective alternatives to monoclonal antibody (mAb)-based therapies for a variety of disease targets.     

The use of sinecatechins (polyphenon E) ointment for treatment of external genital warts

The skin is an attractive target for gene therapy because it is easily accessible and shows great potential as an ectopic site for protein delivery in vivo. Genetically modified epidermal cells can be used to engineer three-dimensional skin substitutes, which when transplanted can act as in vivo ‘bioreactors’ for delivery of therapeutic proteins locally or systemically. Although some gene transfer technologies have the potential to afford permanent genetic modification, differentiation and eventual loss of genetically modified cells from the epidermis results in temporary transgene expression. Therefore, to achieve stable long-term gene expression, it is critical to deliver genes to epidermal stem cells, which possess unlimited growth potential and self-renewal capacity. This review discusses the recent advances in epidermal stem cell isolation, gene transfer and engineering of skin substitutes. Recent efforts that employ gene therapy and tissue engineering for the treatment of genetic diseases, chronic wounds and systemic disorders, such as leptin deficiency or diabetes, are reviewed. Finally, the use of gene-modified tissue-engineered skin as a biological model for understanding tissue development, wound healing and epithelial carcinogenesis is also discussed.     

人乳头状瘤病毒核酸检测试剂盒用于宫颈癌及癌前病变筛查的临床价值

目的分析人乳头状瘤病毒(HPV)杂交捕获-化学发光法核酸检测试剂盒(DH3)用于宫颈癌及癌前病变筛查的临床价值。方法收集480例妇科门诊妇女宫颈脱落细胞样本,分别采用DH3、TCT和HPV-PCR检测,对TCT≥ASC-US者行阴道镜下病理检测,以病理学结果为金标准,分析DH3诊断价值。结果病理学结果显示,正常者370例(77.08%),良性病变者(≤CINⅠ)59例(12.29%),高危者(≥CINⅡ)51例(10.63%);TCT、HPV-PCR和DH3诊断阳性率分别为26.04%、32.08%和27.08%;DH3与TCT检测一致率为94.79%(P0.01),与HPV-PCR检测一致率为93.13%(P0.01);DH3灵敏度98.18%,特异度87.57%,阳性预测值70.13%,阴性预测值99.39%,准确率为90%,检出高危型(≥CINⅡ)的ROC曲线面积Z=0.887(95%CI为0.785~0.918,P0.01)。结论 DH3试剂盒与TCT、HPV-PCR在检出HPV宫颈癌及癌前病变具有高度一致性,灵敏度、特异度和准确率高,操作便捷,临床筛查意义显著。     

苏州地区妇女宫颈人乳头状瘤病毒基因分型的研究

目的探讨苏州地区妇女宫颈感染人乳头状瘤病毒（HPV）的基因型分布及其临床意义。方法采用基因扩增结合基因芯片技术对4 862例宫颈上皮细胞标本进行23种HPV基因分型检测。结果宫颈上皮细胞HPV阳性率为31.74%（1543/4 862）。其中,一重感染、多重感染的阳性率分别为21.43%（1 042/4 862）、10.30%（501/4 862）。前7位高危型HPV分别为16、58、52、33、18、56、31型,占59.09%,而低危型HPV分别为11、6、43型,占23.70%。结论基因扩增结合基因芯片技术可应用于宫颈细胞HPV分型检测。     

基因芯片检测技术在女性生殖道HPV分型感染中的应用

目的探讨女性生殖道人乳头瘤病毒（HPV）各种基因分型感染的情况。方法采用HPV分型基因芯片检测系统,同时检测5种低危型HPV亚型和18种高危型HPV亚型。结果测定250例标本中HPV阳性92例（36．8％）,20～35岁的年龄阶段检出率最高（占总阳性数73．9％）,其中感染单一亚型57例（61．9％）,感染2种亚型28例（30．4％）,感染3种亚型及以上7例。低危型主要为HPV6、11,其次为43;高危型主要为16、18、33、35、45、31、58等亚型。结论基因芯片对于检测HPV的多种型别和HPV多型别混合感染具有重要意义,可为HPV感染和宫颈癌的防治提供重要依据。