Human Papillomavirus Viruses

人乳头瘤病毒
  • 文章类型: Journal Article
    牙医可以很好地讨论与人乳头瘤病毒(HPV)相关的口腔健康问题,并向患者推荐HPV疫苗。主要是因为HPV病毒会导致口咽癌。.我们评估了洛杉矶(LA)县牙医关于讨论HPV相关口腔健康问题并向患者推荐HPV疫苗的意见。我们测试了主要患者为成人的牙医与儿童和成人之间的意见是否存在差异。我们将19项调查邮寄给2000年随机抽样的洛杉矶县牙医,以进行这项横断面研究。主要结果变量是7个意见陈述的汇总意见得分。我们进行了描述性的,双变量比较和调整线性回归模型。总的来说,261名牙医完成了调查。大多数人(58.5%)担心如果他们推荐疫苗,他们会失去病人;49%的人认为牙医不适合教育,律师,或就HPV相关问题提供建议;42%的人担心疫苗的安全性;40%的人不愿意推荐疫苗.总样本的平均总结意见评分为21.4±5.4。回归分析显示,主要患者人群仅为成人的牙医与儿童和成人之间的观点没有差异(系数=0.146,p=0.83)。总的来说,有反应的牙医对讨论口腔健康相关的HPV问题和向患者推荐HPV疫苗并不十分有利.此外,与儿童和成人相比,主要患者人群仅为成人的牙医的总体意见相似.
    Dentists are well-positioned to discuss oral health issues related to Human Papillomavirus (HPV) and recommend the HPV vaccine to their patients, mainly because the HPV virus causes oropharyngeal cancers.. We assessed Los Angeles (LA) County dentists\' opinions on discussing HPV-related oral health issues and recommending the HPV vaccine to their patients. We tested if opinions differed between dentists whose primary patient population was only adults versus children and adults. We mailed a 19-item survey to 2000 randomly sampled LA County dentists for this cross-sectional study. The primary outcome variable was a summary opinion score of 7 opinion statements. We ran descriptive, bivariate comparisons and adjusted linear regression models. Overall, 261 dentists completed the survey. A majority (58.5%) worried they would lose patients if they recommended the vaccine; 49% thought dentists were not appropriate to educate, counsel, or advise on HPV-related issues; 42% were concerned about the safety of the vaccine; and 40% did not feel comfortable recommending the vaccine. The mean summary opinion score was 21.4 ± 5.4 for the total sample. Regression analysis showed no differences in opinions between dentists whose primary patient population was only adults versus children and adults (Coefficient = 0.146, p = 0.83). Overall, the responding dentists were not very favorable about discussing oral health-related HPV issues and recommending the HPV vaccine to their patients. Additionally, the overall opinions were similar between dentists whose primary patient population was only adults versus children and adults.
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  • 文章类型: Journal Article
    亚洲的口喉癌(OPCs)占全球负担的42%,占相关死亡的50%以上。在西半球,超过70%的OPC病例涉及人乳头瘤病毒(HPV)。但它在东半球的作用尚不清楚。本研究回顾了OPC流行病学,包括患病率,病因(如无烟烟草和HPV),和他们的互动。在SEAR国家中,印度的HPV相关OPCs发病率最高,为38.4%。虽然大多数非洲国家都没有数据,只有14%的发病率报告。相反,美洲地区是HPV阳性率最高的地区之一,在美国不同州达到65%,而巴西报告的发病率高达38%。在欧盟,英国的HPV相关OPC发病率最高,达到52%。在西太平洋地区,新西兰的发病率最高,高达78%。在东南亚国家,无烟烟草消费量较高,HPV感染率相对较低,表明两者之间存在负相关。根据我们的文献检索,全球最常用的检测方法是p16的免疫组织化学和聚合链式反应。OPCs是全球健康问题,正确的识别和分类至关重要。HPV驱动的癌症有更好的生存率,强调需要根据HPV阳性或HPV阴性癌症的负担对特定问题领域进行重点研究。
    Oropharyngeal cancers (OPCs) in Asia account for 42% of the global burden and over 50% of related deaths. Human papillomavirus (HPV) is involved in over 70% of OPC cases in the Western hemisphere, but its role in the Eastern hemisphere is unclear. This study reviews OPC epidemiology, including prevalence, etiological factors (such as smokeless tobacco and HPV), and their interaction. Among the SEAR countries, India had the highest incidence of HPV-related OPCs at 38.4%, while data were unavailable for most African countries, with only a 14% incidence reported. Conversely, the American region exhibited one of the highest HPV positivity rates, reaching up to 65% in different states of the USA, while Brazil reported an incidence of up to 38%. In the European Union, the UK had the highest incidence of HPV-associated OPC, reaching up to 52%. In the Western Pacific region, New Zealand demonstrated the highest incidence at up to 78%. Smokeless tobacco consumption was higher in SEAR countries, which had a relatively lower incidence of HPV infection, suggesting a negative correlation between the two. Based on our literature search, the most common detection methods used globally are immunohistochemistry for p16 and polymerized chain reaction. OPCs are a global health concern, and proper identification and classification are vital. HPV-driven cancers have better survival rates, emphasizing the need for focused research on specific problem areas based on the burden of HPV-positive or HPV-negative cancers.
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  • 文章类型: Journal Article
    宫颈癌是第四常见的癌症,99%的病例与人乳头瘤病毒(HPV)感染有关。它反映了全球不平等,因为其负担在低收入和中等收入国家最为严重。这项研究的目的是确定三个撒哈拉以南非洲国家年轻女性的HPV疫苗接种覆盖率及其决定因素。来自三个撒哈拉以南非洲国家的人口和健康调查的数据被用于分析。共有4,952名妇女被纳入研究。Stata14用于分析数据。使用多水平混合效应逻辑回归模型确定结果变量的决定因素。在95%置信区间具有p值<0.05的因子被宣布为具有统计学意义。在当前的研究中,约有7.5%的年轻女性接种了针对宫颈癌的HPV疫苗。年龄更小,使用互联网,富裕的经济阶层,发现个人水平的媒体暴露是有利条件,而被雇用与HPV疫苗接种呈负相关。在这三个国家中,只有少数年轻女性接种了HPV疫苗。作者建议增加互联网使用,媒体曝光,和经济水平的年轻女性将提高HPV疫苗接种率。此外,在就业妇女中提高意识也将增加HPV疫苗接种的可能性.
    Cervical cancer is the fourth most common cancer, with 99% of cases linked to human papillomavirus (HPV) infection. It reflects global inequity as its burden is highest in low- and middle-income countries. The aim of this study was to determine the HPV vaccination coverage and its determinant factors among young women in the three sub-Saharan African countries. Data from the Demographic and Health Surveys among three sub-Saharan African countries were used for analysis. A total of 4,952 women were included in the study. Stata 14 was used to analyze the data. The determinants of the outcome variable were identified using a multilevel mixed-effects logistic regression model. Factors with p-values < 0.05 at 95% confidence interval were declared statistically significant. About 7.5% young women were vaccinated for HPV vaccine against cervical cancer in the current study. Younger age, use of internet, rich economic class, and individual-level media exposure were found to be favorable conditions, whereas being employed was negatively associated with HPV vaccination. Only few segments of young women in these three countries got HPV vaccination. The authors recommend that increasing internet use, media exposure, and economic level of young women will increase the HPV vaccination rates. Furthermore, creating awareness among employed women will also increase the possibility of HPV vaccination.
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  • 文章类型: Journal Article
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  • 文章类型: Journal Article
    目的:区分普通型宫颈腺癌(UEA)和原发性卵巢肿瘤的卵巢转移通常具有挑战性,因为有几个重叠的特征。本研究旨在探讨转移性卵巢UEA患者的临床病理特征和预后。
    方法:收集了8例转移性卵巢UEA患者的临床病理信息。还进行了免疫染色。
    结果:大多数患者表现为疑似原发性卵巢肿瘤的附件肿块。所有检查的病例在成对的原发性和转移性肿瘤中均显示p16阳性。5例完成术后化疗或同步放化疗(CCRT)的患者没有复发。相比之下,1例在第一个CCRT周期后拒绝进一步治疗的患者出现卵巢和腹膜转移.一名孤立的卵巢转移患者未接受治疗,并在随访期间发生腹膜转移。
    结论:接受卵巢转移治疗的UEA患者显示出良好的预后。鉴于卵巢转移性UEA可以模拟原发性卵巢交界性肿瘤或粘液性或子宫内膜样型癌,病理学家应该意识到这种不寻常但独特的形态,以避免误诊和不当治疗。
    OBJECTIVE: Distinguishing ovarian metastasis of usual-type endocervical adenocarcinoma (UEA) from primary ovarian tumors is often challenging because of several overlapping features. This study aimed to investigate the clinicopathological characteristics and outcomes of patients with metastatic ovarian UEA.
    METHODS: Clinicopathological information was collected from eight patients with metastatic ovarian UEA. Immunostaining was also performed.
    RESULTS: Most patients presented with adnexal masses that were suspected to be primary ovarian tumors. All examined cases showed block p16 positivity in paired primary and metastatic tumors. Five patients who completed post-operative chemotherapy or concurrent chemoradiotherapy (CCRT) did not experience recurrence. In contrast, one patient who refused further treatment after the first CCRT cycle experienced ovarian and peritoneal metastases. One patient with isolated ovarian metastasis left untreated and developed peritoneal metastasis during follow-up.
    CONCLUSIONS: Patients with UEA who received proper management for ovarian metastases showed favorable outcomes. Given that ovarian metastatic UEA can mimic primary ovarian borderline tumor or carcinoma of the mucinous or endometrioid type, pathologists should be aware of this unusual but distinctive morphology to avoid misdiagnosis and inappropriate treatment.
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  • 文章类型: Letter
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  • 文章类型: Journal Article
    将人乳头瘤病毒(HPV)基因组整合到细胞基因组中是导致病毒癌蛋白E6/E7组成型表达并驱动宫颈癌进展的关键事件。然而,HPV整合模式在相关恶性肿瘤的个案基础上有所不同。下一代测序技术在询问HPV整合位点方面仍然面临挑战。在这项研究中,利用纳米孔长读数测序,我们从宫颈癌细胞系(CaSki和HeLa)和五个组织样本中确定了452和108个潜在的整合位点,分别。基于长的纳米孔嵌合读数,我们能够分析HPV长控制区(LCR)的甲基化状态,控制癌基因E6/E7的表达,并在众多整合体中鉴定转录活性整合体。作为概念的证明,我们在CaSki细胞系的6号染色体上的RUNX2和CLIC5之间鉴定了一个活跃的HPV整合体,由ATAC-SEQ支持,H3K27AcChIP-seq,和RNA-seq分析。敲除活性HPV整合物,通过CRISPR/Cas9系统,显著削弱细胞增殖和诱导细胞衰老。总之,用纳米孔测序鉴定转录活性的HPV整合体可以为针对HPV相关癌症的基因治疗提供可行的靶标。
    Integration of the human papillomavirus (HPV) genome into the cellular genome is a key event that leads to constitutive expression of viral oncoprotein E6/E7 and drives the progression of cervical cancer. However, HPV integration patterns differ on a case-by-case basis among related malignancies. Next-generation sequencing technologies still face challenges for interrogating HPV integration sites. In this study, utilizing Nanopore long-read sequencing, we identified 452 and 108 potential integration sites from the cervical cancer cell lines (CaSki and HeLa) and five tissue samples, respectively. Based on long Nanopore chimeric reads, we were able to analyze the methylation status of the HPV long control region (LCR), which controls oncogene E6/E7 expression, and to identify transcriptionally-active integrants among the numerous integrants. As a proof of concept, we identified an active HPV integrant in between RUNX2 and CLIC5 on chromosome 6 in the CaSki cell line, which was supported by ATAC-seq, H3K27Ac ChIP-seq, and RNA-seq analysis. Knockout of the active HPV integrant, by the CRISPR/Cas9 system, dramatically crippled cell proliferation and induced cell senescence. In conclusion, identifying transcriptionally-active HPV integrants with Nanopore sequencing can provide viable targets for gene therapy against HPV-associated cancers.
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  • 文章类型: Journal Article
    目的:人乳头瘤病毒(HPV)阳性的头颈部鳞状细胞癌(HNSCC)在临床和免疫学上与HPV阴性的HNSCC不同。在这里,我们调查了肿瘤抗原HPVE6/E7和野生型p53特异性T细胞反应的存在,以及免疫检查点阻断对HPV阳性HNSCC患者的影响。
    方法:用HPVE6/E7或野生型p53衍生肽混合物刺激HPV阳性HNSCC患者的外周血单核细胞(PBMC),并使用干扰素-γ酶联免疫吸附斑点测定法进行评估。进行流式细胞术以分析T细胞亚群和表达免疫检查点分子的T细胞的比例。
    结果:23例患者中有22例(95.7%)检测到HPVE6/E7特异性T细胞,而20例患者中有3例(15.0%)检测到野生型p53特异性T细胞。16例患者中有7例(43.8%)表现出野生型p53特异性T细胞反应,使用完整的蛋白质而不是肽确定。免疫检查点阻断增强了20例患者中9例(45.0%)的野生型p53特异性T细胞应答。PBMC的流式细胞术分析显示,免疫检查点阻断后表现出增强的野生型p53特异性T细胞应答的应答者具有显著较高的Ki-67+CD4+T细胞比例,Ki-67+CD8+T细胞,调节性T细胞,PD-1+CD4+T细胞,和TIM-3+CD4+T细胞比非应答者。
    结论:我们的研究结果表明,HPV阳性HNSCC患者的外周血中存在肿瘤抗原特异性T细胞。阻断检查点通路可以增强某些患者的T细胞反应,可能是通过激活的T细胞,Tregs,和/或耗尽的CD4+T细胞。
    OBJECTIVE: Human papillomavirus (HPV)-positive head and neck squamous cell carcinoma (HNSCC) is clinically and immunologically distinct from HPV-negative HNSCC. Herein, we investigated the presence of tumor antigens HPV E6/E7 and wild-type p53-specific T-cell responses, and the impact of immune checkpoint blockade in patients with HPV-positive HNSCC.
    METHODS: Peripheral blood mononuclear cells (PBMCs) from patients with HPV-positive HNSCC were stimulated with HPV E6/E7 or wild-type p53-derived peptide mixture and evaluated using the interferon-γ enzyme-linked immunosorbent spot assay. Flow cytometry was performed to analyze the proportion of T-cell subsets and T cells expressing immune checkpoint molecules.
    RESULTS: HPV E6/E7-specific T cells were detected in 22 (95.7%) of 23 patients, whereas wild-type p53-specific T cells were detected in 3 (15.0%) of 20 patients. Seven (43.8%) of 16 patients exhibited wild-type p53-specific T-cell responses, as determined using whole proteins instead of peptides. Immune checkpoint blockade enhanced wild-type p53-specific T-cell responses in 9 (45.0%) of 20 patients. Flow cytometric analysis of PBMCs revealed that responders exhibiting enhanced wild-type p53-specific T-cell responses following immune checkpoint blockade had a significantly higher proportion of Ki-67+CD4+ T cells, Ki-67+CD8+ T cells, regulatory T cells, PD-1+CD4+ T cells, and TIM-3+CD4+ T cells than non-responders.
    CONCLUSIONS: Our findings indicate that tumor antigen-specific T cells are present in the peripheral blood of patients with HPV-positive HNSCC. Blockade of checkpoint pathways can enhance T-cell responses in certain patients, probably via activated T cells, Tregs, and/or exhausted CD4+ T cells.
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  • 文章类型: Journal Article
    关于亚太地区目前的人乳头瘤病毒(HPV)疫苗接种的文献有限。这项综合文献综述旨在描述香港的HPV疫苗接种计划,印度尼西亚,Japan,韩国,马来西亚,菲律宾,新加坡,台湾,泰国,和越南。Programdescriptions,recommendations,funding,并提取了覆盖率数据。包括25次引用。截至2022年,10个感兴趣的领域中有8个将HPV纳入其针对学龄儿童的国家免疫计划(NIP);预计将于2023年在印度尼西亚全面实施,而越南的NIP不包括HPV。新加坡还包括针对女性(18-26岁)的HPV疫苗接种。HPV疫苗接种计划均不包括男性。在大多数地区(n=7),计划仅包括一种疫苗选择。虽然女性HPVNIP存在于亚太地区,在更广泛的人群中加强国家实施计划的机会仍然存在(例如,男性,追赶队列)以扩大公共卫生影响并在HPV疫苗接种中提供性别平等。
    There is limited literature on current human papillomavirus (HPV) vaccination in the Asia-Pacific region. This integrative literature review was conducted to describe HPV vaccination programs in Hong Kong, Indonesia, Japan, South Korea, Malaysia, the Philippines, Singapore, Taiwan, Thailand, and Vietnam. Program descriptions, recommendations, f unding, and coverage data were extracted. Twenty-five citations were included. As of 2022, eight of the 10 areas of interest include HPV in their national immunization program (NIP) for school-aged girls; full implementation in Indonesia is expected in 2023 whereas Vietnam\'s NIP does not include HPV. Singapore also includes HPV vaccination for women (18-26 years). None of the HPV vaccination programs include males. In most areas (n = 7), programs include only one vaccine option. While female HPV NIPs are present in the Asia-Pacific region, opportunities remain to strengthen NIPs in broader populations (e.g., males, catch-up cohorts) to expand public health impact and provide gender equity in HPV vaccination.
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  • 文章类型: Journal Article
    宫颈阴道微生物组可能有助于人乳头瘤病毒(HPV)相关的宫颈癌发生,但研究受到低分辨率分析方法的限制。使用高分辨率生物信息学管道,我们评估了宫颈阴道菌群与HPV和宫颈上皮内瘤变(CIN)的关系.186名女性的宫颈阴道微生物组通过对16SrRNA区域(V3-V4和V5-V6)进行测序来表征,并用高分辨率ANCHOR管道进行注释。使用Roche-Cobas4800测定法对样品进行HPV基因分型。我们使用逐步前向选择拟合逻辑回归模型,以选择与CIN1相关的物种(存在/不存在),并使用回归系数构建基于线性微生物组的评分。从单独的逻辑回归模型计算基于HPV的评分以检测CIN1+。进行了受试者工作特征曲线分析;比较了得分之间的曲线下面积(AUC)和95%置信区间(CI)。总的来说,66.7%的参与者为HPV阳性。鉴定了77种独特的物种:8种使用V3-V4,48种使用V5-V6,21种共享。通过逐步选择保留了12个物种。微生物组的AUC-,基于HPV的评分为0.7656(95%CI0.6885-0.8426),和0.7529(95%CI0.6855-0.8204),分别。细菌物种可能参与宫颈癌的发生,因为基于微生物和HPV的评分类似于CIN1检测。
    The cervicovaginal microbiome may contribute to human papillomavirus (HPV)-associated cervical carcinogenesis, but studies have been limited by low-resolution analysis methods. Using a high-resolution bioinformatics pipeline, we evaluated the relationship of the cervicovaginal microbiome with HPV and cervical intraepithelial neoplasia (CIN). The cervicovaginal microbiome of 186 women was characterized by sequencing 16S rRNA regions (V3-V4 and V5-V6) and annotated with the high-resolution ANCHOR pipeline. Samples were genotyped for HPV using the Roche-Cobas 4800 assay. We fitted logistic regression models using stepwise forward selection to select species (presence/absence) as correlates of CIN1+ and constructed a linear microbiome-based score using the regression coefficients. An HPV-based score was calculated from a separate logistic regression model to detect CIN1+ . Receiver operating characteristic curve analyses were performed; the area under the curve (AUC) and 95% confidence intervals (CI) were compared between scores. Overall, 66.7% of participants were HPV-positive. 77 unique species were identified: 8 using V3-V4, 48 using V5-V6, and 21 shared. Twelve species were retained via stepwise selection. The AUCs for the microbiome-, and HPV-based scores were 0.7656 (95% CI 0.6885-0.8426), and 0.7529 (95% CI 0.6855-0.8204), respectively. Bacterial species may be involved in cervical carcinogenesis as the microbiome- and HPV-based scores performed similarly for CIN1+ detection.
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