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Whole tissue cervical mapping of HPV infection: Molecular evidence for focal latent HPV infection in humans HPV感染的全组织宫颈图谱:人类局灶性潜伏HPV感染的分子证据
IF 3.2 Pub Date : 2019-06-01 DOI: 10.1016/j.pvr.2019.02.004
Anne Hammer , Maurits NC de Koning , Jan Blaakaer , Torben Steiniche , John Doorbar , Heather Griffin , Else Mejlgaard , Hans Svanholm , Wim GV Quint , Patti E. Gravitt

In this study, we aimed to provide molecular evidence of HPV latency in humans and discuss potential challenges of conducting studies on latency. We analyzed the entire cervix of two women who underwent hysterectomy unrelated to cervical abnormality. The cervices were sectioned into 242 and 186 sets respectively, and each set was tested separately for HPV using the SPF10-PCR-DEIA-LiPA25 system. To identify whether there was any evidence of transforming or productive infection, we used the biomarkers E4 and P16INK4a to stain slides immediately adjacent to HPV-positive sections. HPV was detected in both cervices. In patient 1, 1/242 sets was positive for HPV31. In patient 2, 13/186 sets were positive for HPV18 and 1/186 was positive for HPV53. The infection was very focal in both patients, and there was no sign of a transforming or productive infection, as evaluated by the markers E4 and P16INK4a. Had we only analyzed one set from each block, the probability of detecting the infection would have been 32.3% and 2%, respectively.Our findings support the idea that HPV may be able to establish latency in the human cervix; however, the risk associated with a latent HPV infection remains unclear.

在这项研究中,我们旨在提供人类HPV潜伏期的分子证据,并讨论进行潜伏期研究的潜在挑战。我们分析了两名接受子宫切除术的妇女的整个宫颈,与宫颈异常无关。分别分为242套和186套,分别使用SPF10-PCR-DEIA-LiPA25系统进行HPV检测。为了确定是否存在转化性感染或生产性感染的证据,我们使用生物标志物E4和P16INK4a对紧挨着hpv阳性切片的载玻片进行染色。在两种服务中均检测到HPV。患者1中1/242组HPV31阳性。患者2中HPV18阳性13/186,HPV53阳性1/186。通过标记物E4和P16INK4a评估,两例患者的感染都是局灶性的,没有转化性或生产性感染的迹象。如果每个区只分析一组,检测感染的概率分别为32.3%和2%。我们的研究结果支持HPV可能能够在人类子宫颈中建立潜伏期的观点;然而,与潜伏性HPV感染相关的风险仍不清楚。
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引用次数: 22
Discovery, characterisation and genomic variation of six novel Gammapapillomavirus types from penile swabs in South Africa 来自南非阴茎拭子的六种新型伽玛乳头瘤病毒的发现、特征和基因组变异
IF 3.2 Pub Date : 2019-06-01 DOI: 10.1016/j.pvr.2019.02.005
Alltalents T. Murahwa , Tracy L. Meiring , Zizipho Z.A. Mbulawa , Anna-Lise Williamson

Six novel human papillomaviruses from penile swabs were characterised. Multiple full genome clones for each novel type were generated, and complete genome sizes were: HPV211 (7253bp), HPV212 (7208bp), HPV213 (7096bp), HPV214 (7357), HPV215 (7186bp) and HPV216 (7233bp). Phylogenetically the novel papillomaviruses all clustered with Gammapapillomaviruses: HPV211 is most closely related to HPV168 (72% identity in the L1 nucleotide sequence) of the Gamma-8 species, HPV212 is most closely related to HPV144 (82.9%) of the Gamma-17 species, HPV213 is most closely related to HPV153 (71.8%) of the Gamma-13 species, HPV214 is most closely related to HPV103 (75.3%) of the Gamma-6 species, HPV215 and HPV216 are most closely related to HPV129 (76.8% and 79.2% respectively) of the Gamma-9 species. The novel HPV types demonstrated the classical genomic organisation of Gammapapillomavirusess, with seven open reading frames (ORFs) encoding five early (E1, E2, E4, E6 and E7) and two late (L1 and L2) proteins. Typical of Gammapapillomavirusess the novel types all lacked the E5 ORF and HPV214 also lacked the E6 ORF. HPV212 had nine unique variants, HPV213 had five and HPV215 had four variants. Conserved domains observed among the novel types are the Zinc finger Binding Domain and PDZ domains. A retinoblastoma binding domain (pRB) binding domain in E7 protein was additionally identified in HPV214. This study expands the knowledge of the rapidly growing Gammapapillomavirus genus.

从阴茎拭子中鉴定了六种新型人乳头瘤病毒。每个新类型均获得多个全基因组克隆,全基因组大小分别为:HPV211 (7253bp)、HPV212 (7208bp)、HPV213 (7096bp)、HPV214(7357)、HPV215 (7186bp)和HPV216 (7233bp)。新型乳头瘤病毒在系统发育上均与γ乳头瘤病毒聚集;HPV211与γ -8种的HPV168亲缘关系最密切(L1核苷酸序列同源度为72%),HPV212与γ -17种的HPV144亲缘关系最密切(82.9%),HPV213与γ -13种的HPV153亲缘关系最密切(71.8%),HPV214与γ -6种的HPV103亲缘关系最密切(75.3%),HPV215和HPV216与γ -9种的HPV129亲缘关系最密切(分别为76.8%和79.2%)。新的HPV类型显示了经典的gammapapillomavirus的基因组组织,有7个开放阅读框(orf)编码5个早期(E1, E2, E4, E6和E7)和2个晚期(L1和L2)蛋白。作为典型的γ乳头瘤病毒,新型病毒均缺乏E5 ORF, HPV214也缺乏E6 ORF。HPV212有9个独特的变体,HPV213有5个,HPV215有4个变体。新类型的保守结构域包括锌指结合结构域和PDZ结构域。在HPV214中还发现了E7蛋白的一个视网膜母细胞瘤结合域(pRB)结合域。这项研究扩大了快速增长的伽玛乳头瘤病毒属的知识。
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引用次数: 10
Human papillomavirus 16 sub-lineage dispersal and cervical cancer risk worldwide: Whole viral genome sequences from 7116 HPV16-positive women 全世界人类乳头瘤病毒16亚系扩散和癌症风险:7116例HPV16阳性女性的全病毒基因组序列。
IF 3.2 Pub Date : 2019-06-01 DOI: 10.1016/j.pvr.2019.02.001
Gary M. Clifford , Vanessa Tenet , Damien Georges , Laia Alemany , Miquel Angel Pavón , Zigui Chen , Meredith Yeager , Michael Cullen , Joseph F. Boland , Sara Bass , Mia Steinberg , Tina Raine-Bennett , Thomas Lorey , Nicolas Wentzensen , Joan Walker , Rosemary Zuna , Mark Schiffman , Lisa Mirabello

Background

Human papillomavirus (HPV)16 can be separated into genetic sub-lineages (A1–4, B1–4, C1–4, D1–4) which may have differential cervical cancer risk.

Methods

A next-generation sequencing assay was used to whole-genome sequence 7116 HPV16-positive cervical samples from well-characterised international epidemiological studies, including 2076 controls, 1878 squamous cell carcinoma (SCC) and 186 adenocarcinoma/adenosquamous cell carcinoma (ADC), and to assign HPV16 sub-lineage. Logistic regression was used to estimate region-stratified country-adjusted odds ratios (OR) and 95%CI.

Results

A1 was the most globally widespread sub-lineage, with others showing stronger regional specificity (A3 and A4 for East Asia, B1–4 and C1–4 for Africa, D2 for the Americas, B4, C4 and D4 for North Africa). Increased cancer risks versus A1 were seen for A3, A4 and D (sub)lineages in regions where they were common: A3 in East Asia (OR=2.2, 95%CI:1.0–4.7); A4 in East Asia (6.6, 3.1–14.1) and North America (3.8, 1.7–8.3); and D in North (6.2, 4.1–9.3) and South/Central America (2.2, 0.8–5.7), where D lineages were also more frequent in ADC than SCC (3.2, 1.5–6.5; 12.1, 5.7–25.6, respectively).

Conclusions

HPV16 genetic variation can strongly influence cervical cancer risk. However, burden of cervical cancer attributable to different sub-lineages worldwide is largely driven by historical HPV16 sub-lineage dispersal.

背景:人乳头瘤病毒(HPV)16可分为遗传亚系(A1-4,B1-4,C1-4,D1-4),可能具有不同的宫颈癌症风险。方法:使用下一代测序法对来自特征良好的国际流行病学研究的7116个HPV16阳性宫颈样本进行全基因组测序,包括2076个对照组、1878个鳞状细胞癌(SCC)和186个腺癌/腺鳞状细胞瘤(ADC),并分配HPV16亚系。Logistic回归用于估计区域分层的国家调整优势比(OR)和95%CI。结果:A1是全球分布最广的亚系,其他亚系表现出更强的区域特异性(A3和A4代表东亚,B1-4和C1-4代表非洲,D2代表美洲,B4、C4和D4代表北非)。在A3、A4和D(亚)谱系常见的地区,与A1相比,癌症风险增加:东亚的A3谱系(OR=2.2,95%CI:1.0-4.7);A4在东亚(6.6,3.1-14.1)和北美(3.8,1.7-8.3);和D在北美洲(6.2,4.1-9.3)和南美洲/中美洲(2.2,0.8-5.7),其中D谱系在ADC中也比SCC更常见(分别为3.2,1.5-6.5;12.1,5.7-25.6)。结论:HPV16基因变异对宫颈癌症风险有显著影响。然而,可归因于世界各地不同亚系的宫颈癌症负担在很大程度上是由历史上的HPV16亚系扩散驱动的。
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引用次数: 47
What is needed now for successful scale-up of screening? 为了成功扩大筛查,现在需要做些什么?
IF 3.2 Pub Date : 2019-06-01 DOI: 10.1016/j.pvr.2019.04.011
Silvia de Sanjose, Francesca Holme

Effective screening for pre-cancerous lesions of the cervix is the only protective intervention that can be offered to women that have not had the opportunity to be vaccinated. Elimination goals are being developed so that by 2030, 70% of women aged 35–45 years should have been screened at least once in a lifetime and 90% of all detected lesions should have been treated. These goals focus on a substantial reduction of cervical cancer burden in low- and middle-income countries (LMICs). Scaling-up screening in these settings may be substantially improved by using self-sampling (SS), human papillomavirus (HPV) testing, and managing screened-positive women with accessible treatment. The implementation of these tools requires minimal health information data for traceability, provider training, community education, operational management and quality control. Cost-effective algorithms tailored to country needs can greatly impact the burden of disease in a limited number of years.

对没有机会接种疫苗的妇女进行有效的子宫颈癌前病变筛查是唯一的保护性干预措施。正在制定消除目标,以便到2030年,70%的35-45岁妇女一生中至少接受一次筛查,所有发现的病变中90%应该得到治疗。这些目标的重点是大幅减少低收入和中等收入国家的宫颈癌负担。通过使用自取样(SS)、人乳头瘤病毒(HPV)检测和对筛查阳性妇女进行可获得治疗的管理,这些环境中的扩大筛查可大大改善。实施这些工具所需的可追溯性卫生信息数据、提供者培训、社区教育、业务管理和质量控制最少。根据国家需要量身定制的具有成本效益的算法可以在有限的几年内极大地影响疾病负担。
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引用次数: 27
Effect of vaccination against oral HPV-16 infection in high school students in the city of Cali, Colombia 哥伦比亚卡利市中学生口服HPV-16感染疫苗接种效果
IF 3.2 Pub Date : 2019-06-01 DOI: 10.1016/j.pvr.2019.03.001
Andres Castillo , Julio Cesar Osorio , Adrián Fernández , Fabián Méndez , Liliana Alarcón , Gabriela Arturo , Rolando Herrero , Luis Eduardo Bravo

Introduction

In recent years, an association between HPV-16 and oropharyngeal cancers has been reported. Therefore, it is necessary to evaluate whether vaccination decreases the exposure of HPV-16 in the oral cavity.

Objective

To evaluate the effect of vaccination on oral HPV-16 infection in high school students in the city of Cali, Colombia.

Methods

In this cross-sectional study, HPV-16 DNA was detected in samples from the oral cavity and throat of 1,784 high school students of both genders, aged 14–17 years old, in 21 schools in the city of Cali, Colombia. The number in vaccinated girls were 944 vs., 95 unvaccinated girls and 745 unvaccinated boys.

Results

The HPV exposure percentages were: 0.7% in vaccinated girls, 3.2% in unvaccinated girls and 2.3% in unvaccinated boys. The odds ratio (OR) of detection of HPV-16 in vaccinated versus unvaccinated students was 0.28 (95% CI: 0.07–0.88), representing a 72% reduction in HPV-16 detection in students immunized with two doses. The odds of detection of HPV-16 in unvaccinated male students were 3.6 times those of vaccinated girls (OR = 3.6, 95% CI: 1.21–12.81) and increased to almost eight-fold in boys who had initiated sexual activity (OR = 7.74, 95% CI: 1.53–75.09).

Conclusions

HPV vaccination was associated with the reduction of HPV-16 exposure percentages in the oral and oropharyngeal cavity.

近年来,有报道称HPV-16与口咽癌之间存在关联。因此,有必要评估接种疫苗是否能减少HPV-16在口腔中的暴露。目的评价哥伦比亚卡利市高中生口服HPV-16预防接种的效果。方法在横断面研究中,从哥伦比亚卡利市21所学校的14-17岁男女1784名高中生的口腔和喉咙样本中检测HPV-16 DNA。接种疫苗的女孩为944人,未接种疫苗的女孩为95人,未接种疫苗的男孩为745人。结果接种疫苗的女孩HPV暴露率为0.7%,未接种疫苗的女孩为3.2%,未接种疫苗的男孩为2.3%。接种疫苗的学生与未接种疫苗的学生HPV-16检出率的比值比(OR)为0.28 (95% CI: 0.07-0.88),表明接种两剂疫苗的学生HPV-16检出率降低了72%。未接种HPV-16疫苗的男生的检出率是接种过疫苗的女生的3.6倍(OR = 3.6,95% CI: 1.21-12.81),而在有过性行为的男生中,检出率增加到近8倍(OR = 7.74,95% CI: 1.53-75.09)。结论接种hpv疫苗可降低口腔和口咽腔HPV-16暴露率。
{"title":"Effect of vaccination against oral HPV-16 infection in high school students in the city of Cali, Colombia","authors":"Andres Castillo ,&nbsp;Julio Cesar Osorio ,&nbsp;Adrián Fernández ,&nbsp;Fabián Méndez ,&nbsp;Liliana Alarcón ,&nbsp;Gabriela Arturo ,&nbsp;Rolando Herrero ,&nbsp;Luis Eduardo Bravo","doi":"10.1016/j.pvr.2019.03.001","DOIUrl":"10.1016/j.pvr.2019.03.001","url":null,"abstract":"<div><h3>Introduction</h3><p>In recent years, an association between HPV-16 and oropharyngeal cancers has been reported. Therefore, it is necessary to evaluate whether vaccination decreases the exposure of HPV-16 in the oral cavity.</p></div><div><h3>Objective</h3><p>To evaluate the effect of vaccination on oral HPV-16 infection in high school students in the city of Cali, Colombia.</p></div><div><h3>Methods</h3><p>In this cross-sectional study, HPV-16 DNA was detected in samples from the oral cavity and throat of 1,784 high school students of both genders, aged 14–17 years old, in 21 schools in the city of Cali, Colombia. The number in vaccinated girls were 944 vs., 95 unvaccinated girls and 745 unvaccinated boys.</p></div><div><h3>Results</h3><p>The HPV exposure percentages were: 0.7% in vaccinated girls, 3.2% in unvaccinated girls and 2.3% in unvaccinated boys. The odds ratio (OR) of detection of HPV-16 in vaccinated versus unvaccinated students was 0.28 (95% CI: 0.07–0.88), representing a 72% reduction in HPV-16 detection in students immunized with two doses. The odds of detection of HPV-16 in unvaccinated male students were 3.6 times those of vaccinated girls (OR = 3.6, 95% CI: 1.21–12.81) and increased to almost eight-fold in boys who had initiated sexual activity (OR = 7.74, 95% CI: 1.53–75.09).</p></div><div><h3>Conclusions</h3><p>HPV vaccination was associated with the reduction of HPV-16 exposure percentages in the oral and oropharyngeal cavity.</p></div>","PeriodicalId":46835,"journal":{"name":"Papillomavirus Research","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2019-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.pvr.2019.03.001","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37199998","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 11
Dynamics of genotype-specific HPV clearance and reinfection in rural Ghana may compromise HPV screening approaches 加纳农村地区基因型特异性HPV清除和再感染的动态可能会影响HPV筛查方法
IF 3.2 Pub Date : 2019-06-01 DOI: 10.1016/j.pvr.2018.12.004
Amrei Krings , Gifty Boateng , Priscilla Dunyo , Joseph E. Amuah , Rashid A. Adams , Lois Adunyame , Dinah O. Nkansah , Comfort M. Wormenor , Benjamin T. Hansen , Isaac Gedzah , Richard H. Asmah , Edwin K. Wiredu , Andreas M. Kaufmann

Persistent Human Papillomavirus (HPV) infection is a prerequisite for cervical cancer development. Few studies investigated clearance of high-risk HPV in low-and-middle-income countries. Our study investigated HPV clearance and persistence over four years in women from North Tongu District, Ghana.

In 2010/2011, cervical swabs of 500 patients were collected and HPV genotyped (nested multiplex PCR) in Accra, Ghana. In 2014, 104 women who previously tested positive for high-risk HPV and remained untreated were re-tested for HPV. Cytobrush samples were genotyped (GP5+/6+ PCR & Luminex-MPG readout) in Berlin, Germany. Positively tested patients underwent colposcopy and treatment if indicated.

Of 104 women, who tested high-risk HPV+ in 2010/2011, seven (6,7%; 95%CI: 2.7–13.4%) had ≥1 persistent high-risk‐infection after ~4 years (mean age 39 years). Ninety-seven (93,3%; 95%CI: 86.6–97.3%) had cleared the original infection, while 22 (21.2%; 95%CI: 13.8–30.3%) had acquired new high-risk infections with other genotypes. Persistent types found were HPV 16, 18, 35, 39, 51, 52, 58, and 68. Among those patients, one case of CIN2 (HPV 68) and one micro-invasive cervical cancer (HPV 16) were detected.

This longitudinal observational data suggest that single HPV screening rounds may lead to over-referral. Including type-specific HPV re-testing or additional triage methods could help reduce follow-up rates.

持续的人乳头瘤病毒(HPV)感染是宫颈癌发展的先决条件。很少有研究调查了低收入和中等收入国家的高危HPV清除情况。我们的研究调查了加纳北通古地区妇女的HPV清除和持续时间超过四年。2010/2011年,在加纳阿克拉收集了500名患者的宫颈拭子并进行了HPV基因分型(巢式多重PCR)。2014年,104名此前高危HPV检测呈阳性且未接受治疗的女性重新接受了HPV检测。细胞刷样品进行基因分型(GP5+/6+ PCR &德国柏林的Luminex-MPG读出器。阳性检测的患者接受阴道镜检查,并在必要时进行治疗。在2010/2011年检测高危HPV+的104名妇女中,7名(6.7%;95%CI: 2.7-13.4%)在4年后(平均年龄39岁)有≥1例持续性高危感染。九十七(93年,3%;95%CI: 86.6-97.3%), 22例(21.2%;95%CI: 13.8 ~ 30.3%)有其他基因型的新发高危感染。发现的持续型为HPV 16、18、35、39、51、52、58和68。其中检出1例CIN2 (HPV 68)和1例微侵润性宫颈癌(HPV 16)。这一纵向观察数据表明,单轮HPV筛查可能导致过度转诊。包括特定类型的HPV重新检测或额外的分诊方法可以帮助降低随访率。
{"title":"Dynamics of genotype-specific HPV clearance and reinfection in rural Ghana may compromise HPV screening approaches","authors":"Amrei Krings ,&nbsp;Gifty Boateng ,&nbsp;Priscilla Dunyo ,&nbsp;Joseph E. Amuah ,&nbsp;Rashid A. Adams ,&nbsp;Lois Adunyame ,&nbsp;Dinah O. Nkansah ,&nbsp;Comfort M. Wormenor ,&nbsp;Benjamin T. Hansen ,&nbsp;Isaac Gedzah ,&nbsp;Richard H. Asmah ,&nbsp;Edwin K. Wiredu ,&nbsp;Andreas M. Kaufmann","doi":"10.1016/j.pvr.2018.12.004","DOIUrl":"10.1016/j.pvr.2018.12.004","url":null,"abstract":"<div><p>Persistent Human Papillomavirus (HPV) infection is a prerequisite for cervical cancer development. Few studies investigated clearance of high-risk HPV in low-and-middle-income countries. Our study investigated HPV clearance and persistence over four years in women from North Tongu District, Ghana.</p><p>In 2010/2011, cervical swabs of 500 patients were collected and HPV genotyped (nested multiplex PCR) in Accra, Ghana. In 2014, 104 women who previously tested positive for high-risk HPV and remained untreated were re-tested for HPV. Cytobrush samples were genotyped (GP5+/6+ PCR &amp; Luminex-MPG readout) in Berlin, Germany. Positively tested patients underwent colposcopy and treatment if indicated.</p><p>Of 104 women, who tested high-risk HPV+ in 2010/2011, seven (6,7%; 95%CI: 2.7–13.4%) had ≥1 persistent high-risk‐infection after ~4 years (mean age 39 years). Ninety-seven (93,3%; 95%CI: 86.6–97.3%) had cleared the original infection, while 22 (21.2%; 95%CI: 13.8–30.3%) had acquired new high-risk infections with other genotypes. Persistent types found were HPV 16, 18, 35, 39, 51, 52, 58, and 68. Among those patients, one case of CIN2 (HPV 68) and one micro-invasive cervical cancer (HPV 16) were detected.</p><p>This longitudinal observational data suggest that single HPV screening rounds may lead to over-referral. Including type-specific HPV re-testing or additional triage methods could help reduce follow-up rates.</p></div>","PeriodicalId":46835,"journal":{"name":"Papillomavirus Research","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2019-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.pvr.2018.12.004","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36848608","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 7
HPV16 variant analysis in primary and recurrent CIN2/3 lesions demonstrates presence of the same consensus variant 原发性和复发性CIN2/3病变中的HPV16变异分析表明存在相同的共识变异
IF 3.2 Pub Date : 2019-06-01 DOI: 10.1016/j.pvr.2019.04.008
Pascal van der Weele , Audrey J. King , Chris J.L.M. Meijer , Renske D.M. Steenbergen

Introduction

Recurrent cervical intraepithelial lesions (rCIN2/3) after treatment of CIN2/3 occur in 5–15% of cases. rCIN2/3 can result from incomplete resection of CIN2/3, where the same HPV type and variant remains present. rCIN2/3 could also occur following a new infection with a different HPV variant of the same HPV type as the initial lesion. This study investigates HPV16 consensus variants in paired HPV16 positive scrapes from baseline CIN2/3 and rCIN2/3 lesions.

Methods

Paired HPV16 positive cervical scrapes of women with CIN2/3 at baseline and rCIN2/3 6 or 12 months after treatment were selected for whole-genome amplification and Illumina sequencing. Sequences were compared and nucleotide changes over time were characterized.

Results

From 14 paired samples, 10 had identical consensus variants in baseline CIN2/3 and rCIN2/3. Four paired samples showed one to three nucleotide variations at recurrent disease compared to baseline.

Conclusion

Identical or nearly identical HPV16 consensus variants were found in scrapes of paired HPV16 positive baseline CIN2/3 and rCIN2/3 lesions after treatment, suggesting no need for HPV variant analysis when the same HPV type is found in both lesions. These results argue for either incomplete excision of baseline CIN2/3 or inability of clearance of the original HPV infection.

宫颈上皮内病变复发(rCIN2/3)在CIN2/3治疗后发生在5-15%的病例。rCIN2/3可以由CIN2/3的不完全切除引起,其中相同的HPV类型和变体仍然存在。rCIN2/3也可能发生在与初始病变相同HPV类型的不同HPV变体的新感染后。本研究调查了基线CIN2/3和rCIN2/3病变配对HPV16阳性刮痕中的HPV16共识变异。方法选择治疗6个月或12个月后CIN2/3 和CIN2/3的女性HPV16阳性宫颈刮伤,进行全基因组扩增和Illumina测序。序列比较和核苷酸随时间变化的特征。结果在14个配对样本中,10个在基线CIN2/3和rCIN2/3有相同的共识变异。与基线相比,四个配对样本在复发性疾病中显示一到三个核苷酸变异。结论HPV16基线CIN2/3和rCIN2/3配对病变治疗后,在刮擦中发现相同或几乎相同的HPV16一致变异体,提示在两种病变中发现相同HPV型别时无需进行HPV变异体分析。这些结果表明要么不完全切除基线CIN2/3,要么无法清除原始HPV感染。
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引用次数: 4
Mega Hpv laboratories for cervical cancer control: Challenges and recommendations from a case study of Turkey 巨型Hpv实验室用于宫颈癌控制:来自土耳其案例研究的挑战和建议
IF 3.2 Pub Date : 2019-06-01 DOI: 10.1016/j.pvr.2019.03.002
Murat Gultekin , Mujdegul Zayifoglu Karaca , Irem Kucukyildiz , Selin Dundar , Bekir Keskinkilic , Murat Turkyilmaz

Cervical cancer is the fourth most common cancer among women in the world. It is estimated that one woman dies every 2 min from cervical cancer. Nearly all cervical cancers are preventable by early detection and treatment through screening or HPV vaccination. In 2018, World Health Organization (WHO) made a global call for action toward the elimination of cervical cancer. Cervical cancer screening involves a complex organized program, which begins with a call/recall system based on personal invitation of eligible women, followed by participation in screening, and leading to diagnosis, treatment, and management as appropriate. An effective cervical screening program with high coverage is dependent on each country's infrastructure and human resource capacity. Efforts to develop an effective program is particularly challenging in low and middle income countries (LMIC) where resources are limited. For an effective strategy, Turkey redesigned the country's cervical screening program. The local call/recall system and centralized monitoring system of individual women were re-vamped with an automated evaluation system. The revised screening program includes the use of primary HPV testing with a well-defined protocol outlining the algorithms of management (i.e., screening intervals and referral), a single nationwide centralized diagnostic laboratory, and a sustainable agreement with the HPV diagnostics industry. This system allows for traceable, real-time monitoring of screening visits and specimens. Turkey reports on the first four years of this re-vamped organized program and shares lessons learnt from the implementation of this new program.

子宫颈癌是世界上第四大最常见的女性癌症。据估计,每2 分钟就有一名妇女死于宫颈癌。几乎所有的子宫颈癌都可以通过筛查或HPV疫苗的早期发现和治疗来预防。2018年,世界卫生组织(世卫组织)发出了一项全球行动呼吁,呼吁为消除宫颈癌采取行动。宫颈癌筛查涉及一个复杂的有组织的项目,首先是一个基于个人邀请合格妇女的呼叫/召回系统,然后是参与筛查,并酌情进行诊断、治疗和管理。一个有效的高覆盖率子宫颈筛查方案取决于每个国家的基础设施和人力资源能力。在资源有限的低收入和中等收入国家,制定有效规划的工作尤其具有挑战性。为了采取有效的策略,土耳其重新设计了该国的子宫颈筛查计划。本地呼叫/召回系统和个别妇女的集中监测系统重新配备了自动评价系统。修订后的筛查规划包括使用HPV初级检测,并制定明确的方案,概述管理算法(即筛查间隔和转诊),建立一个全国性的集中诊断实验室,并与HPV诊断行业达成可持续的协议。该系统允许对筛查访问和标本进行可追溯的实时监测。土耳其报告了这一经过改组的有组织方案头四年的情况,并分享了从执行这一新方案中吸取的经验教训。
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引用次数: 19
HPV and skin carcinogenesis HPV和皮肤癌
IF 3.2 Pub Date : 2019-06-01 DOI: 10.1016/j.pvr.2019.04.003
Massimo Tommasino

Epidemiological and biological studies provide several lines of evidence for the involvement of cutaneous beta human papillomaviruses (HPVs), together with ultraviolet (UV) radiation, in the development of cutaneous squamous cell carcinoma. These viruses appear to act with a hit-and-run mechanism, being necessary at an early stage of carcinogenesis and being dispensable for the maintenance of the malignant phenotype. Studies in experimental models show that beta HPVs, mainly via the E6 and E7 oncoproteins, are able to promote proliferation and to circumvent cellular stresses induced by UV radiation. These findings support a model of skin carcinogenesis in which beta HPV-infected keratinocytes remain alive despite the accumulation of UV-induced DNA mutations. In this manner, these cells become highly susceptible to progression towards malignancy. Thus, UV radiation is the main driver of skin cancer development, while beta HPVs act as facilitators of the accumulation of UV-induced DNA mutations.

流行病学和生物学研究提供了几种证据,证明皮肤β人乳头瘤病毒(hpv)与紫外线(UV)辐射参与皮肤鳞状细胞癌的发展。这些病毒似乎以一种“打了就跑”的机制起作用,在癌变的早期阶段是必要的,对于恶性表型的维持是可有可无的。实验模型研究表明,主要通过E6和E7癌蛋白,β - hpv能够促进增殖并规避紫外线辐射诱导的细胞应激。这些发现支持了一种皮肤癌发生的模型,即尽管紫外线诱导的DNA突变积累,β - hpv感染的角质形成细胞仍然存活。以这种方式,这些细胞变得高度容易向恶性肿瘤发展。因此,紫外线辐射是皮肤癌发展的主要驱动因素,而β hpv则是紫外线诱导的DNA突变积累的促进因素。
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引用次数: 47
Impact of HPV vaccination: Achievements and future challenges HPV疫苗接种的影响:成就和未来的挑战
IF 3.2 Pub Date : 2019-06-01 DOI: 10.1016/j.pvr.2019.04.004
Julia M.L. Brotherton
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引用次数: 22
期刊
Papillomavirus Research
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