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HPV infections and flat penile lesions of the penis in men who have sex with men 与男性发生性行为的男性的HPV感染和阴茎扁平病变
IF 3.2 Pub Date : 2019-12-01 DOI: 10.1016/j.pvr.2019.100173
Ward P.H. Van Bilsen , Alexandra Kovaleva , Maaike C.G. Bleeker , Audrey J. King , Sylvia M. Bruisten , Wilma Brokking , Henry J.C. De Vries , Chris J.L.M. Meijer , Maarten F. Schim Van Der Loeff

Background

Flat penile lesions (FPL) in heterosexual men are thought to play a role in the transmission of HPV. We investigated the association between FPL and penile HPV, and explored determinants of FPL in men who have sex with men (MSM).

Methods

In 2015–2016, MSM were recruited based on HIV and penile HPV status in a previous cohort. MSM self-completed a questionnaire. Peniscopy was performed after application of acetic acid to visualize FPL. Penile physician-collected samples were tested for HPV-DNA using the highly sensitive SPF10-PCR DEIA/LiPA25 system. HPV viral load (VL) was determined using a quantitative type-specific (q)PCR targeting the L1-region. Presence of HPV and HIV, HPV VL and circumcision status were compared between MSM with and without FPL.

Results

We included 116 MSM, of whom 59/116 (51%) MSM were HIV-positive and 54/116 (47%) had FPL. A penile HPV infection was present in 31/54 (57%) MSM with FPL and 34/62 (55%) MSM without FPL (p = 0.8). There was no difference between MSM with and without FPL regarding presence of penile HPV infection, HPV VL, HIV status or circumcision status (p > 0.05 for all).

Conclusion

Among MSM in Amsterdam, we found no association between FPL and penile HPV, HPV VL, HIV status or circumcision status.

背景异性恋男性的阴茎扁平病变(FPL)被认为在HPV的传播中起作用。我们调查了FPL与阴茎HPV之间的关系,并探讨了男男性行为者(MSM) FPL的决定因素。方法2015-2016年,在既往队列中根据HIV和阴茎HPV状况招募MSM。男同性恋者自行完成了一份调查问卷。应用醋酸后进行阴茎镜检查,以观察阴道外泌素。使用高灵敏度的SPF10-PCR DEIA/LiPA25系统检测阴茎医生收集的样本的HPV-DNA。HPV病毒载量(VL)采用定量型特异性(q)PCR靶向l1区确定。比较有和无FPL的MSM的HPV和HIV的存在、HPV VL和包皮环切情况。结果纳入116例MSM,其中59/116(51%)为hiv阳性,54/116(47%)为FPL。阴茎HPV感染在31/54(57%)有FPL的MSM和34/62(55%)无FPL的MSM中存在(p = 0.8)。在阴茎HPV感染、HPV VL、HIV状态或包皮环切情况方面,有和没有FPL的MSM之间没有差异(p > 0.05)。结论在阿姆斯特丹的MSM中,我们发现FPL与阴茎HPV, HPV VL, HIV状态或包皮环切状态无关。
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引用次数: 5
Immunotherapy for HPV associated cancer HPV相关癌症的免疫治疗
IF 3.2 Pub Date : 2019-12-01 DOI: 10.1016/j.pvr.2019.100176
Ian H. Frazer , Janin Chandra
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引用次数: 27
Sociodemographic and clinical correlates of human papillomavirus vaccine attitudes and receipt among Wisconsin adolescents 威斯康星州青少年对人乳头瘤病毒疫苗的态度和接受情况的社会人口学和临床相关性
IF 3.2 Pub Date : 2019-12-01 DOI: 10.1016/j.pvr.2019.05.001
Kayla E. Hanson , Huong Q. McLean , Edward A. Belongia , Shannon Stokley , Michael M. McNeil , Julianne Gee , Jeffrey J. VanWormer

Few studies have assessed adolescent human papillomavirus (HPV) vaccine attitudes and whether they are associated with vaccination uptake. This study characterized HPV vaccine attitudes among male and female adolescents, identified factors associated with attitude changes, and examined associations between attitudes and vaccination receipt. Surveys were administered to adolescents aged 15–16 years who had not completed the HPV vaccine series. A modified version of the Carolina HPV Immunization Attitudes and Beliefs Scale (CHIAS) was employed to assess barriers, harms, ineffectiveness, and uncertainties scores. Surveys were available from 108 participants; 63% were male and 33% had initiated the HPV vaccine series at baseline. CHIAS scores significantly decreased (i.e., became more favorable) between baseline and follow-up for barriers (p = 0.01) and uncertainties (p < 0.01). At least one sociodemographic/clinical factor was associated with changes in each score. Attitude changes were not associated with receipt of HPV vaccine, although adolescents with higher baseline harms scores were significantly less likely to receive an HPV vaccine dose (OR = 0.67). Adolescents’ HPV vaccine attitudes slightly improved over a one-year period during which an intervention was implemented. More research is needed to learn how parent and adolescent HPV vaccine attitudes form, and how best to address concerns about vaccine harms.

很少有研究评估青少年对人乳头瘤病毒(HPV)疫苗的态度以及它们是否与疫苗接种有关。本研究描述了男性和女性青少年对HPV疫苗的态度,确定了与态度改变相关的因素,并检查了态度与疫苗接种之间的关系。对未完成HPV疫苗系列接种的15-16岁青少年进行了调查。采用改良版的卡罗莱纳人乳头瘤病毒免疫态度和信念量表(CHIAS)评估障碍、危害、无效和不确定性评分。对108名参与者进行了调查;63%为男性,33%在基线时开始接种HPV疫苗系列。在基线和随访期间,障碍(p = 0.01)和不确定性(p < 0.01)的CHIAS评分显著降低(即变得更有利)。至少有一个社会人口学/临床因素与每个分数的变化有关。态度改变与接受HPV疫苗无关,尽管基线危害评分较高的青少年接受HPV疫苗剂量的可能性显着降低(OR = 0.67)。在实施干预的一年期间,青少年对HPV疫苗的态度略有改善。需要更多的研究来了解父母和青少年对HPV疫苗的态度是如何形成的,以及如何最好地解决对疫苗危害的担忧。
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引用次数: 6
High-throughput screening identifies candidate drugs for the treatment of recurrent respiratory papillomatosis 高通量筛选确定治疗复发性呼吸道乳头状瘤病的候选药物
IF 3.2 Pub Date : 2019-12-01 DOI: 10.1016/j.pvr.2019.100181
Faris Alkhilaiwi , Siddartha Paul , Dan Zhou , Xiaohu Zhang , Feibai Wang , Nancy Palechor-Ceron , Kelli Wilson , Rajarshi Guha , Marc Ferrer , Nazaneen Grant , Craig Thomas , Richard Schlegel , Hang Yuan

Recurrent respiratory papillomatosis (RRP) is a benign neoplasm of the larynx caused mainly by human papillomavirus type 6 or 11 and its standard treatment involves repeated surgical debulking of the laryngeal tumors. However, significant morbidity and occasional mortality due to multiple recurrences occur. Conditional reprogramming (CR) was used to establish a HPV-6 positive culture from an RRP patient, named GUMC-403. High-throughput screening was performed at the National Center for Advanced Technology (NCATS) to identify potential drugs to treat this rare but morbid disease. GUMC-403 cells were screened against the NPC library of >2800 approved drugs and the MIPE library of >1900 investigational drugs to identify new uses for FDA-approved drugs or drugs that have undergone significant research and development. From the two libraries, we identified a total of 13 drugs that induced significant cytotoxicity in RRP cells at IC50 values that were clinically achievable. We validated the efficacy of the drugs in vitro using CR 2D and 3D models and further refined our list of drugs to panobinostat, dinaciclib and forskolin as potential therapies for RRP patients.

复发性呼吸道乳头状瘤病(RRP)是一种主要由6型或11型人乳头瘤病毒引起的喉部良性肿瘤,其标准治疗包括反复手术切除喉部肿瘤。然而,由于多次复发,会发生显著的发病率和偶尔的死亡率。采用条件重编程法(CR)对一名命名为GUMC-403的RRP患者进行HPV-6阳性培养。在国家先进技术中心(NCATS)进行了高通量筛选,以确定治疗这种罕见但病态疾病的潜在药物。GUMC-403 细胞与NPC库中2800种已批准的药物和MIPE库中1900种正在研究的药物进行筛选,以确定fda批准的药物或经过重大研究和开发的药物的新用途。从这两个文库中,我们共鉴定出13种药物在临床可达到的IC50值下对RRP细胞产生显著的细胞毒性。我们使用CR 2D和3D模型验证药物的体外疗效,并进一步将我们的药物清单细化为panobinostat, dinaciclib和forskolin作为RRP患者的潜在治疗药物。
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引用次数: 17
Burden of Human papillomavirus (HPV)-related disease and potential impact of HPV vaccines in the Republic of Korea 韩国人乳头瘤病毒(HPV)相关疾病的负担和HPV疫苗的潜在影响
IF 3.2 Pub Date : 2019-06-01 DOI: 10.1016/j.pvr.2018.12.002
Young-Tak Kim , Beatriz Serrano , Jae-Kwan Lee , Hyunju Lee , Shin-Wha Lee , Crystal Freeman , Jin-Kyoung Oh , Laia Alemany , Francesc-Xavier Bosch , Laia Bruni

Background

We aimed to review the burden and the potential impact of human papillomavirus (HPV) vaccines on HPV-related diseases in the Republic of Korea and to discuss cervical cancer prevention practices in this country.

Methods

Cancer burden statistics were retrieved from GLOBOCAN-2018 and Statistics Korea. HPV disease burden was assessed via systematic review. Vaccine types relative contribution (RC) was estimated using data from an international project using formalin-fixed paraffin-embedded specimens.

Results

Despite a downtrend in cervical cancer in recent years, Korean rates remain high. In contrast, oropharyngeal cancer incidence has gradually increased and other anogenital cancers remain rare.

In Korea, HPV prevalence in general population is around 20%. In cervical cancer, RC of HPVs 16/18 (74.0%) increased to 92.0% when including HPVs 31/33/45/52/58. Limited information was available for other HPV-related cancer sites.

Regarding prevention, since the inclusion of the HPV vaccine into the National Immunization Program, almost half (49%) of the target cohort in 2016 had received the first dose of vaccine. Further, percentage of women screened with pap has increased from 41.1%-2009 to 53.0%-2016.

Conclusions

HPV-related disease burden in Korea is significant. Results suggest that the combination of effective and high coverage HPV vaccination and screening programmes could substantially impact on HPV-related disease in Korea.

背景:我们旨在回顾韩国人乳头瘤病毒(HPV)疫苗对HPV相关疾病的负担和潜在影响,并讨论该国的宫颈癌预防措施。方法癌症负担统计数据来源于GLOBOCAN-2018和韩国统计局。通过系统评价评估HPV疾病负担。使用福尔马林固定石蜡包埋标本的国际项目数据估计疫苗类型相对贡献(RC)。结果尽管近年来宫颈癌发病率呈下降趋势,但韩国的宫颈癌发病率仍然很高。相比之下,口咽癌的发病率逐渐增加,而其他肛门生殖器官癌症仍然罕见。在韩国,HPV在一般人群中的患病率约为20%。在宫颈癌中,当包括hpv 31/33/45/52/58时,hpv 16/18的RC从74.0%增加到92.0%。其他hpv相关癌症部位的信息有限。在预防方面,自将HPV疫苗纳入国家免疫规划以来,2016年几乎一半(49%)的目标队列接受了第一剂疫苗。此外,接受pap筛查的女性比例从2009年的41.1%增加到2016年的53.0%。结论韩国shpv相关疾病负担显著。结果表明,有效和高覆盖率的HPV疫苗接种和筛查规划的结合可能对韩国HPV相关疾病产生重大影响。
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引用次数: 13
Viral genome integration of canine papillomavirus 16 犬乳头瘤病毒基因组整合研究
IF 3.2 Pub Date : 2019-06-01 DOI: 10.1016/j.pvr.2019.02.002
Jennifer Luff , Michelle Mader , Peter Rowland , Monica Britton , Joseph Fass , Hang Yuan

Papillomaviruses infect humans and animals, most often causing benign proliferations on skin or mucosal surfaces. Rarely, these infections persist and progress to cancer. In humans, this transformation most often occurs with high-risk papillomaviruses, where viral integration is a critical event in carcinogenesis. The first aim of this study was to sequence the viral genome of canine papillomavirus (CPV) 16 from a pigmented viral plaque that progressed to metastatic squamous cell carcinoma in a dog. The second aim was to characterize multiple viral genomic deletions and translocations as well as host integration sites. The full viral genome was identified using a combination of PCR and high throughput sequencing. CPV16 is most closely related to chipapillomaviruses CPV4, CPV9, and CPV12 and we propose CPV16 be classified as a chipapillomavirus. Assembly of the full viral genome enabled identification of deletion of portions of the E1 and E2/E4 genes and two viral translocations within the squamous cell carcinoma. Genome walking was performed which identified four sites of viral integration into the host genome. This is the first description of integration of a canine papillomavirus into the host genome, raising the possibility that CPV16 may be a potential canine high-risk papillomavirus type.

乳头瘤病毒感染人类和动物,最常引起皮肤或粘膜表面的良性增生。这些感染很少会持续并发展为癌症。在人类中,这种转化最常发生在高风险乳头瘤病毒中,其中病毒整合是致癌的关键事件。本研究的第一个目的是对犬乳头瘤病毒(CPV) 16的病毒基因组进行测序,CPV 16来自犬转移性鳞状细胞癌的色素病毒斑块。第二个目的是表征多个病毒基因组缺失和易位以及宿主整合位点。利用PCR和高通量测序相结合的方法鉴定了病毒全基因组。CPV16与芯片乳头瘤病毒CPV4、CPV9和CPV12亲缘关系最密切,我们建议将CPV16归类为芯片乳头瘤病毒。完整病毒基因组的组装能够鉴定出E1和E2/E4基因的部分缺失以及鳞状细胞癌中的两个病毒易位。基因组行走确定了病毒整合到宿主基因组的四个位点。这是首次描述犬乳头瘤病毒整合到宿主基因组中,提高了CPV16可能是潜在的犬高危乳头瘤病毒类型的可能性。
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引用次数: 12
Immune deviation and cervical carcinogenesis 免疫偏差与宫颈癌的发生
IF 3.2 Pub Date : 2019-06-01 DOI: 10.1016/j.pvr.2019.03.006
Sigrun Smola

Evidence is emerging that a complex interplay between high-risk human papillomavirus infection, the local microenvironment and the immune system is critical for cervical carcinogenesis. To establish persistence, the virus has to evade or overcome immune control. At the transition from precancer to cancer, however, chronic stromal inflammation and immune deviation build up, which may eventually determine the course of disease. Understanding the molecular basis underlying these pivotal stage-specific changes may help to define new tools for better diagnosis and therapy that are required to efficiently combat human papillomavirus-associated disease.

越来越多的证据表明,高危人乳头瘤病毒感染、局部微环境和免疫系统之间的复杂相互作用对宫颈癌的发生至关重要。为了建立持久性,病毒必须逃避或克服免疫控制。然而,在从癌前病变到癌症的转变过程中,慢性间质炎症和免疫偏差的积累可能最终决定疾病的进程。了解这些关键阶段特异性变化的分子基础可能有助于确定更好的诊断和治疗所需的新工具,以有效地对抗人类乳头瘤病毒相关疾病。
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引用次数: 13
Opportunities to improve immune-based prevention of HPV-associated cancers 改善hpv相关癌症免疫预防的机会
IF 3.2 Pub Date : 2019-06-01 DOI: 10.1016/j.pvr.2019.04.010
Peter L. Stern , Richard BS. Roden

Immunization of adolescent girls with VLP vaccines, made of L1 proteins from the most medically significant high risk HPV types, is a major strategy for prevention of cervical cancer plus other HPV-associated cancers. Maximal population impact, including through herd immunity, requires high vaccination coverage. However, protection of unvaccinated women requires secondary prevention through cytology screening. Unfortunately in countries with the highest incidence/mortality due to cervical cancer HPV vaccination (or cytology screening) is not sufficiently available. Vaccination programme costs and a lack of accessibility of the populations for immunization remain significant hurdles. Several approaches could increase effective implementation of HPV vaccination. 1) Use of a single immunization of the current VLP vaccines. 2) Vaccination bundled with other paediatric vaccines with lower dosage to facilitate delivery, improve coverage and reduce costs through established logistics. 3) Local manufacture with lower cost systems (e.g. bacteria) for VLP or capsomer based vaccine production and utilization of additional protective epitopes (e.g L2) for increasing breadth of protection. However, all the latter need appropriate clinical validation. Gender neutral vaccination and extending routine vaccination strategies to women up to age 30 years in combination with at least one HPV screening test can also hasten impact on cancer incidence.

为少女接种VLP疫苗是预防宫颈癌和其他HPV相关癌症的主要策略,该疫苗由医学上最重要的高危HPV类型的L1蛋白制成。最大程度的人口影响,包括通过群体免疫,需要很高的疫苗接种覆盖率。然而,保护未接种疫苗的妇女需要通过细胞学筛查进行二级预防。不幸的是,在宫颈癌发病率/死亡率最高的国家,人乳头瘤病毒疫苗接种(或细胞学筛查)不足。疫苗接种规划的费用和人口无法获得免疫接种仍然是重大障碍。有几种方法可以提高HPV疫苗接种的有效实施。1)使用当前VLP疫苗的单次免疫。2)与其他剂量较低的儿科疫苗捆绑接种,以通过既定的物流便利交付、提高覆盖率和降低成本。3)本地生产低成本系统(如细菌)用于VLP或基于覆膜体的疫苗生产,并利用额外的保护性表位(如L2)以增加保护的广度。然而,后者都需要适当的临床验证。性别中立的疫苗接种和将常规疫苗接种策略扩展到30岁以下的妇女,并结合至少一项HPV筛查检测,也可以加速对癌症发病率的影响。
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引用次数: 11
Optimising future cervical screening strategies 优化日后子宫颈普查策略
IF 3.2 Pub Date : 2019-06-01 DOI: 10.1016/j.pvr.2019.04.001
Henry Kitchener

The switch from primary cytology to primary high risk papillomavirus (HR-HPV) testing for cervical screening is now being implemented in a number of countries. The advantages of this are to increase screening sensitivity which will save lives, and at the same time to extend screening intervals. The challenge with HR-HPV testing is its relatively poor specificity which means identifying a large number of women who are HR-HPV positive with negative cytology. One way of tackling this is to use early recall, in order to select referral to colposcopy to those women who do not clear the virus over a period of 1-2 years, as done in the recently published English Pilot Study. Another challenge in optimising screening is to recognise that wide coverage with prophylactic vaccination will require fewer screens over the lifetime of vaccinated women to maintain cost-effectiveness. HR-HPV testing allows self sampling which could both encourage more women to be screened and be more convenient for those who do wish to be screened. Cervical cancer prevention which combines vaccination and screening now offers a future in which cervical cancer could become a rarity, but efficient strategies need to be implemented.

目前,一些国家正在实施从宫颈筛查的初级细胞学检测到初级高危乳头瘤病毒(HR-HPV)检测的转变。这样做的好处是提高了筛查的灵敏度,从而挽救了生命,同时延长了筛查间隔。HR-HPV检测的挑战在于其特异性相对较差,这意味着要识别出大量HR-HPV阳性但细胞学阴性的妇女。解决这个问题的一种方法是使用早期回忆,以便选择那些在1-2年内没有清除病毒的妇女进行阴道镜检查,正如最近发表的英国试点研究所做的那样。优化筛查的另一个挑战是认识到广泛覆盖预防性疫苗接种将需要在接种疫苗的妇女一生中减少筛查,以保持成本效益。人乳头瘤病毒检测允许自我抽样,这既可以鼓励更多的妇女接受筛查,也对那些希望接受筛查的妇女更方便。子宫颈癌预防结合了疫苗接种和筛检,未来子宫颈癌可能变得罕见,但需要实施有效的策略。
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引用次数: 7
Knowledge about HPV and vaccination among young adult men and women: Results of a national survey 年轻成年男性和女性关于HPV和疫苗接种的知识:一项全国调查的结果
IF 3.2 Pub Date : 2019-06-01 DOI: 10.1016/j.pvr.2019.03.003
Natália Luiza Kops , Glaucia Fragoso Hohenberger , Marina Bessel , Jaqueline Driemeyer Correia Horvath , Carla Domingues , Ana Goretti Kalume Maranhão , Flavia Moreno Alves de Souza , Adele Benzaken , Gerson Fernando Pereira , Eliana Marcia Wendland

Background

In addition to screening by Pap smears, vaccination against human papillomavirus (HPV) can dramatically reduce cervical cancers caused by the virus. The acceptance of HPV vaccination is directly related to HPV knowledge. This research aimed to evaluate knowledge about HPV and vaccination among men and women aged 16–25 years who use the public health system in Brazil.

Methods

This was a cross-sectional, multicenter study of sexually active young adults recruited from 119 primary care units between 2016 and 2017. All participants answered a face-to-face standardized questionnaire.

Results

Of 8581 participants, the mean percentage of correct answers about HPV and vaccination was 51.79% (95% CI 50.90-52.67), but 75.91% (95% CI 74.13-77.69) had awareness of the HPV vaccination. Women answered a higher proportion of questions correctly than men did (p = 0.0003). Lower education level was the variable that most interfered with knowledge. The best information sources for knowledge were both health professionals and the media (1.33%, 95% CI 1.03-1.70).

Conclusions

The results emphasize the importance of educational programs about HPV and vaccination among young adults, especially in socially disadvantaged populations. These findings can help to increase the vaccination rate in the country and to stimulate public health policies.

背景除了通过子宫颈抹片检查外,接种人类乳头瘤病毒(HPV)疫苗可以显著减少由该病毒引起的宫颈癌。接受HPV疫苗接种与HPV知识直接相关。本研究旨在评估巴西使用公共卫生系统的16-25岁男性和女性关于HPV和疫苗接种的知识。这是一项横断面、多中心研究,从2016年至2017年的119个初级保健单位招募了性活跃的年轻人。所有参与者都回答了一份面对面的标准化问卷。结果在8581名参与者中,正确回答HPV和疫苗接种的平均百分比为51.79% (95% CI 50.90-52.67),但75.91% (95% CI 74.13-77.69)的人知道HPV疫苗接种。女性答对问题的比例高于男性(p = 0.0003)。较低的教育水平是对知识干扰最大的变量。知识的最佳信息来源是卫生专业人员和媒体(1.33%,95% CI 1.03-1.70)。结论研究结果强调了在年轻人中,特别是在社会弱势群体中开展HPV教育和疫苗接种的重要性。这些发现有助于提高该国的疫苗接种率,并刺激公共卫生政策。
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引用次数: 35
期刊
Papillomavirus Research
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