Human Papillomavirus

人乳头瘤病毒
  • 文章类型: Journal Article
    背景:人乳头瘤病毒(HPV)感染是全球癌症负担的重要原因。了解影响男性临床实习生促进HPV疫苗接种意愿的因素对于中国制定有效的公共卫生策略至关重要。
    方法:本研究采用分层随机抽样的方法,在2024年1月至3月期间从中国5个省抽取1,980名男性临床实习生。数据收集了参与者的人口统计学特征,HPV相关的临床经验,和知识。计划行为理论框架,包括态度,主观规范,和感知的行为控制,用于检查影响HPV疫苗推广意愿的因素。进行Logistic回归分析以确定与HPV疫苗推广意愿相关的因素。
    结果:在受访者中,72.29%的人愿意鼓励其他人接种HPV疫苗。影响此意愿的重要因素包括年龄较大(OR=3.065,P≤0.001),家庭月收入较高(OR=1.449,P=0.025),参与HPV相关疾病的诊断和治疗(OR=3.458,P≤0.001),对疫苗的积极态度(OR=13.503,P=0.004),和较强的感知行为控制(OR=2.364,P=0.006)。
    结论:本研究强调了实践经验和针对性教育在促进中国男性临床实习生HPV疫苗接种中的关键作用。加强这一群体的培训和教育对于改善HPV疫苗宣传和支持公共卫生工作以减少HPV相关疾病至关重要。
    BACKGROUND: Human papillomavirus (HPV) infection significantly contributes to the global cancer burden. Understanding the factors influencing male clinical interns\' willingness to promote HPV vaccination is crucial for developing effective public health strategies in China.
    METHODS: This study employed a stratified random sampling method to select 1,980 male clinical interns from five provinces in China between January and March 2024. Data were collected on participants\' demographic characteristics, HPV-related clinical experience, and knowledge. The Theory of Planned Behavior framework, encompassing attitudes, subjective norms, and perceived behavioral control, was used to examine factors influencing the willingness to promote the HPV vaccine. Logistic regression analyses were conducted to identify factors associated with the willingness to promote the HPV vaccine.
    RESULTS: Among the respondents, 72.29% were willing to encourage others to receive the HPV vaccine. Significant factors influencing this willingness included older age (OR = 3.065, P ≤ 0.001), higher monthly household income (OR = 1.449, P = 0.025), participation in the diagnosis and treatment of HPV-related diseases (OR = 3.458, P ≤ 0.001), positive attitude towards the vaccine (OR = 13.503, P = 0.004), and strong perceived behavioral control (OR = 2.364, P = 0.006).
    CONCLUSIONS: This study highlights the critical role of practical experience and targeted education in promoting HPV vaccination among male clinical interns in China. Enhancing the training and education of this group is essential for improving HPV vaccine advocacy and supporting public health efforts to reduce HPV-related diseases.
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  • 文章类型: Journal Article
    高危型人乳头瘤病毒(HR-HPV)持续感染与宫颈癌及鳞状上皮内病变(SIL)的发生发展密切相关。α-9HPV,主要由HR-HPV类型组成,占四川HR-HPV感染的75%。HPV的癌蛋白E6和E7在肿瘤发生和发展中起关键作用。值得注意的是,HPV-35是α-9属中唯一不包括在九价HPV预防性疫苗中的HR-HPV类型。收集来自四川的宫颈细胞样本进行HPV检测和基因分型。在406份HPV阳性样本中,31个HPV-35被检测到,成功扩增并测序了24个HPV-35E6和26个E7,检测到E6中的五个核苷酸突变和E7中的三个核苷酸突变,T232C,E6的T434G(W78R,I145R)和C67T,E7的G84T(H23Y,L28F)是非同义词突变。使用PAML4.8服务器检测HPV-35E6、E7和E6为W78R的阳性选择位点。Phyre2用于预测和分析蛋白质结构,W78R对蛋白质结构有影响。IEDB用于筛选HPV-35病变治疗的表位疫苗靶标,并获得5个HPV-35E6和3个HPV-35E7最潜在的表位,用于治疗疫苗设计的最有潜力的肽是79-91YRYSVYGETLEKQ,45-60FACYDLCIVREGQPY,E6的124-135RFHNIGGRWTGR;3-19GEITTLQDYVLDLEPEA,38-47TIDGPAGQAK,E7和W78R的70-88VQSTHIDIRKLEDLLMGTF主要降低表位亲和力。结论已发现HPV-35E6和E7基因的阳性选择位点中的氨基酸置换影响蛋白质结构并降低抗原表位的总体亲和力。这一观察结果与正选择位点的进化意义一致,这可能会使受感染的细胞对免疫系统的检测更具挑战性,从而为病毒带来优势,从而增强HPV对宿主环境的适应性。HPV-35E6、E7的多态性分析有助于中国四川省α-9HPV数据的富集,这有助于提高临床检测的有效性。此外,本研究结果为HPV相关疾病的防治提供了相关理论基础。
    High-risk human papilloma virus (HR-HPV) persistent infection is closely associated with the development of cervical cancer and squamous intraepithelial lesion (SIL).The α-9 HPVs, which is predominantly composed of HR-HPV types, account for 75% of HR-HPV infection in Sichuan. The oncoproteins E6 and E7 of HPV play a crucial role in tumor initiation and progression. Notably, HPV-35 is the only HR-HPV type within the α-9 genus that is not included in the nine-valent HPV prophylactic vaccine. Cervical cell samples obtained from Sichuan were collected for HPV detection and genotyping. Among the 406 HPV-positive samples, 31 HPV-35 were detected, 24 HPV-35 E6 and 26 E7 were successfully amplified and sequenced, five nucleotide mutations in E6 and three in E7 were detected, T232C, T434G of E6 (W78R, I145R) and C67T, G84T of E7 (H23Y, L28F) were non-synonymy mutation. PAML 4.8 server was used to detect positive selection sites of HPV-35 E6, E7, and E6 is W78R. Phyre2 were used to predict and analyze protein structures, W78R made influences on protein structure. IEDB were used to screen epitopes vaccine target for HPV-35 affection therapy, and 5 HPV-35 E6 and 3 HPV-35 E7 most potential epitopes were obtained, the most potential peptides for therapy vaccine design were 79-91YRYSVYGETLEKQ, 45-60FACYDLCIVREGQPY, 124-135RFHNIGGRWTGR of E6; 3-19GEITTLQDYVLDLEPEA, 38-47TIDGPAGQAK, 70-88VQSTHIDIRKLEDLLMGTF of E7 and W78R mainly decreased the epitopes affinity.Conclusions Amino acid substitution in the positive selection sites of HPV-35 E6 and E7 genes have been found to influence protein structure and to decrease the overall affinity of antigen epitopes. This observation aligns with the evolutionary significance of positive selection site, which may confer advantages to the virus by making infected cells more challenging for the immune system to detect, thereby enhancing HPV\'s adaptability to the host environment. The polymorphism analysis of HPV-35 E6, E7 contributes to the enrichment of α-9 HPV data in Sichuan China, which is instrumental in improving the effectiveness of clinical detection. Furthermore, these findings provide a relevant theoretical foundation for the prevention and treatment of HPV-related diseases.
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  • 文章类型: Journal Article
    目的:本研究旨在调查重庆男性的人乳头瘤病毒(HPV)感染和基因分型,并分析与年龄相关的趋势,为重庆男性的HPV预防和疫苗接种计划提供见解。中国。
    方法:本研究为观察性研究。我们调查了2017年至2022年在重庆两家医院接受HPV筛查的男性患者,共计4381例。18至85岁。使用Hybribio快速基因芯片试剂盒进行HPV基因分型。
    结果:在4,381名男性中,HPV总患病率为14.9%,2022年达到19.3%的峰值。单个HPV感染率为11.5%,多重感染为3.4%。最普遍的基因型是HPV-52、HPV-16和HPV-58。单一高危型HPV感染在36-45岁年龄组达到高峰,而多重高危型HPV感染随年龄增长而减少(P-趋势<0.01)。≤25岁年龄组的患病率为3.7%。单一低危HPV感染也随着年龄的增长而下降(P趋势=0.03)。非单价疫苗覆盖的基因型患病率最高,随着年龄的增长。HPV-16与HPV-52和HPV-58共同感染是常见的。单一HPV感染在尿道炎病例中普遍存在(30.8%),肛门生殖器疣(36.4%),和生殖器疣(26.3%),而多种HPV感染在肛门生殖器疣中显著(18.2%)。
    结论:重庆以单一HPV感染为主,HPV-52,HPV-16,HPV-58,HPV-53和HPV-39是最普遍的基因型。非价疫苗覆盖的基因型的流行率随着年龄的增长而增加。本研究为重庆市制定男性特异性HPV预防策略提供了有价值的见解。
    OBJECTIVE: This study aimed to investigate Human papillomavirus (HPV) infection and genotyping in men from Chongqing and analyze age-related trends to provide insights for HPV prevention and vaccination plans tailored for men in Chongqing, China.
    METHODS: This study is an observational study. We investigated male patients who underwent HPV screening at two hospitals in Chongqing from 2017 to 2022, totaling 4,381 cases, aged 18 to 85. HPV genotyping was conducted using the Hybribio Rapid GenoArray kit.
    RESULTS: Among the 4,381 men, the overall HPV prevalence was 14.9%, peaking at 19.3% in 2022. Single HPV infection was 11.5%, and multiple infection was 3.4%. The most prevalent genotypes were HPV-52, HPV-16, and HPV-58. Single high-risk HPV infection peaked in the 36-45 age group, while multiple high-risk HPV infection decreased with age (P-trend < 0.01). Prevalence in the ≤ 25 age group was 3.7%. Single low-risk HPV infection also decreased with age (P-trend = 0.03). Genotypes covered by the nonavalent vaccine had the highest prevalence, increasing with age. Co-infection of HPV-16 with HPV-52 and HPV-58 was common. Single HPV infections were prevalent in cases of urethritis (30.8%), anogenital warts (36.4%), and genital warts (26.3%), while multiple HPV infections were significant in anogenital warts (18.2%).
    CONCLUSIONS: Single HPV infection was predominant in Chongqing, with HPV-52, HPV-16, HPV-58, HPV-53, and HPV-39 being the most prevalent genotypes. The prevalence of genotypes covered by the nonavalent vaccine increased with age. This study offers valuable insights for developing male-specific HPV prevention strategies in Chongqing.
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  • 文章类型: Journal Article
    背景:先前已经进行了一些观察性或回顾性研究,以探索肺癌与人乳头瘤病毒(HPV)感染之间的可能关联。然而,由于研究设计和HPV检测方法的差异,数据和结论可能存在不一致.目前尚无研究提供确凿证据支持HPV参与肺癌的发生发展。因此,HPV与肺癌之间的关系仍存在争议和不确定.本研究旨在通过系统地进行双向双样本孟德尔随机化(TSMR)分析,探讨HPV感染是否与肺癌风险有因果关系。
    方法:在国际肺癌协会(ILCCO)全基因组关联研究数据集中,我们纳入了11,348例肺癌(LUCA)病例,包括3275例鳞状细胞癌(LUSC)病例,3442例腺癌(LUAD),和15861例控制。使用与HPVE7蛋白相关的遗传变异作为工具变量,我们总结了MRCIEUOpenGWAS数据库中与HPV感染相关的统计数据,其中包括HPV-16E7蛋白和HPV-18E7蛋白。双样本孟德尔随机化(MR)结果表示为比值比(OR)和95%置信区间(CI)。
    结果:基于对来自公共数据库的全基因组关联研究(GWAS)数据的综合分析,我们主要使用逆方差加权(IVW)来估计因果关系,在使用MR-Egger时,加权中位数,简单模式,和加权模式,和其他四种方法作为补充。两个样本的MR分析显示暴露因素(HPV-16E7蛋白和HPV-18E7蛋白)与结果因素(肺癌(LUCA)及其亚型鳞状细胞癌(LUSC)和腺癌(LUAD))之间没有因果关系使用IVW方法进行正向MR分析。HPV-16E7蛋白和LUCA及其亚型LUSC和LUAD;IVW方法结果:[OR]=1.002;95%[CI]:0.961-1.045;p=0.920;[OR]=1.023;95%[CI]:0.966-1.084;p=0.438;[OR]=0.438;[OR]=0.994;95%LUCI=0.927-1.018;[OR]0.9通过反向MR观察到LUCA及其亚型LUSC和LUAD作为暴露因子,和HPV感染(HPV-16E7蛋白和HPV-18E7蛋白)作为结果因素,IVW方法的结果也无效。LUCA和HPV-16E7蛋白和HPV-18E7蛋白;IVW方法结果:[OR]=1.036;95%[CI]:0.761-1.411;p=0.82;[OR]=1.318;95%[CI]:0.949-1.830;p=0.099;LUSC和HPV-16E7蛋白和HPV-18E7蛋白;[OR]0.671-1.8182%我们的结果表明,基因预测的HPV感染与LUCA及其亚型LUSC和LUAD之间没有因果关系。此外,在反向MR分析中,我们未观察到LUCA及其亚型LUSC和LUAD与HPV感染之间存在显著的因果关系.
    结论:我们的发现不支持HPV感染与肺癌之间的遗传关联。
    BACKGROUND: Several observational or retrospective studies have previously been conducted to explore the possible association between lung cancer and human papillomavirus (HPV) infection. However, there may be inconsistencies in the data and conclusions due to differences in study design and HPV testing methods. There are currently no studies that provide conclusive evidence to support the involvement of HPV in the occurrence and development of lung cancer. Therefore, the relationship between HPV and lung cancer remains controversial and uncertain. This study aimed to explore whether HPV infection is causally related to lung cancer risk by systematically performing a two-way Two-Sample Mendelian Randomization (TSMR) analysis.
    METHODS: In the International Lung Cancer Consortium (ILCCO) genome-wide association study dataset, we included 11,348 lung cancer (LUCA) cases, including 3275 squamous cell carcinoma (LUSC) cases, 3442 adenocarcinoma (LUAD) cases, and 15,861 cases of control. Using genetic variants associated with the HPV E7 protein as instrumental variables, we summarized statistics associated with HPV infection in the MRC IEU OpenGWAS database, which included the HPV-16 E7 protein and the HPV-18 E7 protein. Two-sample Mendelian randomization (MR) results are expressed as odds ratios (OR) and 95% confidence intervals (CI).
    RESULTS: Based on a comprehensive analysis of genome-wide association study (GWAS) data from public databases, we mainly used inverse-variance weighted (IVW) to estimate causal relationships, while using MR-Egger, weighted median, simple mode, and weighted mode, and other four methods as supplements. Two-sample MR Analysis revealed no causal relationship between exposure factors (HPV-16 E7 protein and HPV-18 E7 protein) and outcome factors (lung cancer (LUCA) and its subtypes squamous cell carcinoma (LUSC) and adenocarcinoma (LUAD)) in forward MR Analysis using the IVW approach.HPV-16 E7 protein and LUCA and its subtypes LUSC and LUAD by IVW method results: [OR] = 1.002; 95% [CI]: 0.961 - 1.045; p = 0.920; [OR] = 1.023; 95% [CI]: 0.966 - 1.084; p = 0.438; [OR] = 0.994; 95% [CI]: 0.927 - 1.066; p = 0.872); HPV-18 E7 protein and LUCA and its subtypes LUSC and LUAD by IVW method results: [OR] = 0.965; 95% [CI]: 0.914 - 1.019; p = 0.197; [OR] = 0.933; 95% [CI]: 0.834 - 1.043; p = 0.222; [OR] = 1.028; 95% [CI]: 0.945 - 1.118; p = 0.524. It was observed through reverse MR that LUCA and its subtypes LUSC and LUAD were used as exposure factors, and HPV infection (HPV-16 E7 protein and HPV-18 E7 protein) was used as the outcome factors, the results of the IVW method are also invalid.LUCA and HPV-16 E7 protein and HPV-18 E7 protein by IVW method results: [OR] = 1.036; 95% [CI]: 0.761 - 1.411; p = 0.82; [OR] = 1.318; 95% [CI]: 0.949 - 1.830; p = 0.099; LUSC and HPV-16 E7 protein and HPV-18 E7 protein by IVW method results: [OR] = 1.123; 95% [CI]0.847 - 1.489; p = 0.421; [OR] = 0.931; 95% [CI]: 0.660 - 1.313; p = 0.682; LUAD and HPV-16 E7 protein and HPV-18 E7 protein by IVW method results: [OR] = 1.182; 95% [CI] 0.983 - 1.421; p = 0.075; [OR] = 1.017; 95% [CI]: 0.817 - 1.267; p = 0.877.Our results indicate that there is no causal relationship between genetically predicted HPV infection and LUCA and its subtypes LUSC and LUAD. In addition, in the reverse MR analysis, we did not observe a significant causal relationship between LUCA and its subtypes LUSC and LUAD on HPV infection.
    CONCLUSIONS: Our findings do not support a genetic association between HPV infection and lung cancer.
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  • 文章类型: Journal Article
    高危型人乳头瘤病毒(HPV)类型的持续感染可导致HPV感染组织中癌症的发展,包括子宫颈,口咽,肛门,阴茎,阴道,还有外阴.虽然目前的HPV疫苗覆盖了大约90%的宫颈癌,近10%的与疫苗中未包括的HPV类型相关的病例仍未解决,尤其是HPV59。这项研究描述了靶向HPV18/45/59的嵌合病毒样颗粒(VLP)的开发,该颗粒被提议作为目前缺乏商业疫苗的高危HPV型(HPV59)的疫苗候选物。鉴于大多数中和抗体表位位于表面环上,我们设计了在密切相关的HPV18和HPV45之间进行这些回路的战略交换。然后扩展该方法以并入HPV59的表面环,产生H18-45BCEF-59HI嵌合VLP的前导候选构建体,其具有从HPV45交换到HPV18的两个表面环。表征证实,H18-45BCEF-59HI在粒径和形态上与野生型(WT)骨架类型非常相似,如透射电子显微镜(TEM)所证实,高效尺寸排阻色谱法(HPSEC),和分析超速离心(AUC),并且证明了类似的热稳定性,如通过差示扫描量热法(DSC)所证明的。嵌合VLP小鼠的免疫研究评估了其免疫原性,显示H18-45EF-59HI嵌合VLP表现出最佳的交叉中和。此外,当在类似良好生产规范(GMP)的设施中生产时,H18-45BCEF-59HIVLP被选为预防HPV18/45/59感染的有希望的候选疫苗.这项研究不仅为目前的疫苗接种缺口提供了潜在的解决方案,而且为设计针对具有多种亚型或变体的病毒的疫苗提供了基础方法。
    Persistent infection with high-risk human papillomavirus (HPV) types can lead to the development of cancer in HPV-infected tissues, including the cervix, oropharynx, anus, penis, vagina, and vulva. While current HPV vaccines cover approximately 90 % of cervical cancers, nearly 10 % of cases associated with HPV types not included in the vaccines remain unaddressed, notably HPV59. This study describes the development of a chimeric virus-like particle (VLP) targeting HPV18/45/59, proposed as a vaccine candidate for high-risk HPV type (HPV59) currently lacking commercial vaccines. Given that the majority of neutralizing antibody epitopes are located on the surface loops, we engineered a strategic swap of these loops between the closely related HPV18 and HPV45. This methodology was then extended to incorporate surface loops of HPV59, resulting in the lead candidate construct of the H18-45BCEF-59HI chimeric VLP with two surface loops swapping from HPV45 to HPV18. Characterization confirmed that H18-45BCEF-59HI closely resembled the wild-type (WT) backbone types in particle size and morphology, as verified by Transmission Electron Microscopy (TEM), High-Performance Size-Exclusion Chromatography (HPSEC), and Analytical Ultracentrifugation (AUC), and demonstrated similar thermal stability as evidenced by Differential Scanning Calorimetry (DSC). Immunization studies in mice with the chimeric VLPs assessed their immunogenicity, revealing that the H18-45EF-59HI chimeric VLP exhibited optimal cross-neutralization. Additionally, when produced in a Good Manufacturing Practice (GMP)-like facility, the H18-45BCEF-59HI VLP was selected as a promising vaccine candidate for the prevention of HPV18/45/59 infection. This study not only offers a potential solution to the current vaccination gap but also provides a foundational approach for the design of vaccines targeting viruses with multiple subtypes or variants.
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  • 文章类型: Journal Article
    人乳头瘤病毒(HPV)感染是全球流行的性传播感染,其持久性是宫颈癌和癌前病变发展的重要因素。了解HPV的患病率和基因型分布可以帮助实施更有针对性的宫颈癌预防和治疗策略。本研究旨在调查武汉市门诊人群中HPV感染的患病率和基因型分布。中国。
    我们的研究回顾性分析了14,492名门诊妇女的宫颈HPV筛查结果。采用PCR和反向斑点杂交技术对18个高危基因型和10个低危基因型的宫颈阴道感染进行分析。
    门诊女性人群中HPV感染的总体患病率为15.33%,在多种感染中,以单一感染为主,以双重感染为主。HR-HPV和LR-HPV患病率排名前五位的基因型为HPV-52(3.77%),53(1.46%),16(1.31%),58(1.19%),39(1.18%)用于HR-HPV,和HPV-54(1.23%),61(1.08%),81(1.04%),42(0.87%),44(0.70%)为LR-HPV。在25岁以下(22.88%)和56岁以上(24.26%)的女性中观察到两个HPV感染流行高峰。HPV感染的患病率和基因型分布在不同门诊人群中存在差异。HPV单一感染率较高,多重感染,与健康检查人群相比,在妇科门诊人群中观察到的所有年龄段的感染。
    本研究揭示了武汉市不同门诊人群HPV的患病率和基因型分布,这可能为该地区的HPV疫苗接种和宫颈癌预防策略提供指导。
    UNASSIGNED: Human papillomavirus (HPV) infection is a prevalent sexually transmitted infection worldwide, with its persistence being a significant factor in the development of cervical cancer and precancerous lesions. Understanding the prevalence and genotypes distribution of HPV can aid in the implementation of more focused strategies for cervical cancer prevention and treatment. This study aimed to investigate the prevalence and genotype distribution of HPV infection among outpatient-based populations in Wuhan, China.
    UNASSIGNED: Our study retrospectively analyzed the results of cervical HPV screening in 14,492 outpatient women. The cervicovaginal infection of 18 high-risk genotypes and 10 low-risk genotypes were analyzed by PCR and reverse dot hybridization techniques.
    UNASSIGNED: The overall prevalence of HPV infection in the outpatient female population was 15.33%, with a predominance of single infection and a predominance of dual infection among multiple infections. The top five genotypes in terms of prevalence of HR-HPV and LR-HPV were HPV-52 (3.77%), 53 (1.46%), 16 (1.31%), 58 (1.19%), 39 (1.18%) for HR-HPV, and HPV-54 (1.23%), 61 (1.08%), 81 (1.04%), 42 (0.87%), 44 (0.70%) for LR-HPV. Two peaks of HPV infection prevalence were observed among women under 25 years (22.88%) and over 56 years (24.26%). The prevalence and genotype distribution of HPV infection varied among different outpatient populations, with higher rates of HPV single infection, multiple infections, and infection across all ages observed in the gynecology outpatient population compared to the health check-up population.
    UNASSIGNED: This study revealed the HPV prevalence and genotype distribution among different outpatient populations in Wuhan city, which may provide guidance for HPV vaccination and cervical cancer prevention strategies in the region.
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  • 文章类型: Journal Article
    人乳头瘤病毒(HPV)与各种癌症的发展有关,包括头部和颈部,子宫颈,阴道,阴茎,和肛门癌。针对HPV阳性肿瘤的治疗性疫苗的开发对于保护已经感染HPV的个体至关重要。预防肿瘤进展,有效治疗疾病。基于HPV治疗性肽的疫苗通过靶向特异性表位同时使变应性或自身免疫反应的风险最小化而表现出特异性和安全性优势。然而,HPV治疗性基于肽的疫苗通常缺乏免疫原性并且经常不能诱导有效的免疫应答。因此,需要更有效的方法来改善基于HPV肽的疫苗的免疫原性.这里,我们回顾了通过联合治疗和改进的递送策略来提高基于HPV肽的疫苗的免疫原性和治疗效果的相关研究和可能用途.需要进一步的研究来验证联合治疗和递送策略修改作为HPV治疗性肽基疫苗的标准治疗方法的应用。
    Human papillomavirus (HPV) has been linked to the development of various cancers, including head and neck, cervical, vaginal, penile, and anal cancers. The development of therapeutic vaccines against HPV-positive tumors is crucial for protecting individuals already infected with HPV, preventing tumor progression, and effectively treating the disease. The HPV therapeutic peptide-based vaccines demonstrate specificity and safety advantages by targeting specific epitopes while minimizing the risk of allergic or autoimmune reactions. However, HPV therapeutic peptide-based vaccines typically lack immunogenicity and frequently fail to induce effective immune responses. Therefore, there is a need for more effective approaches to improve the immunogenicity of HPV peptide-based vaccines. Here, we review relevant research and possible uses for increasing the immunogenicity and therapeutic efficacy of HPV peptide-based vaccines through combined therapy and improved delivery strategies. Additional research is necessary to validate the application of combination therapy and delivery strategy modifications as standard treatment approaches for HPV therapeutic peptide-based vaccines.
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  • 文章类型: Journal Article
    目的:本研究探讨了Hedgehog通路在宫颈癌[CC]进展过程中在上皮细胞中的作用,为改善目前的CC治疗提供新的见解。
    背景:Hedgehog信号通路的异常激活与CC上皮细胞的恶性转化有关。CC的单细胞图谱和Hedgehog途径在CC进展过程中在上皮细胞中的作用仍有待探索。
    目的:通过应用单细胞RNA测序[scRNA-seq]分析,全面分析CC上皮细胞Hedgehog通路激活的机制及其对肿瘤进展的影响。
    方法:从基因表达Omnibus[GEO]数据库获得scRNA-seq数据,然后用Seurat包处理。应用FindNeighbors和Find-Clusters函数对小区进行聚类。CellMarker数据库用于子组注释。通过FindAllMarkers功能过滤每个细胞亚组中差异表达的基因[DEGs]。使用Clusterprofiler包进行感兴趣的基因集的生物学功能分析。使用AUCell功能来计算Hedgehog途径的评分。通过进行伪时间分析产生上皮细胞亚型中的分化轨迹。最后,蛋白质-蛋白质网络[PPI]用于研究Hedgehog途径与感兴趣的基因集中富集的其他途径之间的相互作用。
    结果:总共对9个主要细胞亚群进行了分类,在CC样品中上皮细胞的比例最高。进一步的分析表明,Hedgehog途径在STYK1和TP73上皮细胞亚型中异常激活。伪时间轨迹分析表明,STYK1+上皮细胞的分化轨迹逐渐转化为防御病毒细胞或转化为增殖细胞,而TP73+上皮细胞最终分化为响应雌激素和病毒诱导的增殖的两个分支。PPI剖析显示Hedgehog通路介入CC上皮细胞的增殖和病毒进程。
    结论:本研究全面分析了CC样本的特征和上皮细胞亚型的分化轨迹,以及Hedgehog途径在CC进程中在上皮细胞中的作用。更重要的是,发现了有效的分子诊断和精确治疗CC的靶基因。
    OBJECTIVE: This study explored the role of the Hedgehog pathway in epithelial cells during cervical cancer [CC] progression, providing new insights for improving current CC treatment.
    BACKGROUND: Abnormal activation of the Hedgehog signaling pathway is associated with the malignant transformation of CC epithelial cells. Single-cell atlas of CC and the role of Hedgehog pathway in epithelial cells during CC progression remain to be explored.
    OBJECTIVE: To comprehensively analyze the mechanism of Hedgehog pathway activation in CC epithelial cells and its impact on tumor progression by applying single-cell RNA sequencing [scRNA-seq] analysis.
    METHODS: The scRNA-seq data were acquired from the Gene Expression Omnibus [GEO] database and then processed with the Seurat package. FindNeighbors and Find- Clusters functions were applied to cluster the cells. The CellMarker database was used for subgroup annotation. Differentially expressed genes [DEGs] in each cell subgroup were filtered by FindAllMarkers function. Biological function analysis for the gene set of interest was performed using Clusterprofiler package. AUCell function was employed to calculate the score of the Hedgehog pathway. The differentiation trajectory in epithelial cell subtypes was generated by performing Pseudotime analysis. Finally, protein-protein network [PPI] was used to investigate the interactions between the Hedgehog pathway and other pathways enriched in the gene set of interest.
    RESULTS: A total of 9 major cell subpopulations were classified and the proportion of epithelial cells was the highest in CC samples. Further analysis revealed that the Hedgehog pathway was abnormally activated in STYK1+ and TP73+ epithelial cell subtypes. Pseudo-time trajectory analysis showed that the differentiation trajectory of STYK1+ epithelial cells gradually transformed into defense-to-virus cells or into proliferation cells, while TP73+ epithelial cells eventually differentiated into two branches of response to estrogen and virus-induced proliferation. PPI analysis showed that the Hedgehog pathway was involved in the proliferation and viral process of epithelial cells in CC.
    CONCLUSIONS: The current study comprehensively analyzed the features of CC samples and differentiation trajectories of epithelial cell subtypes, as well as the role of the Hedgehog pathway in epithelial cells during CC progression. More importantly, effective target genes were discovered for the molecular diagnosis and precise treatment of CC.
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  • 文章类型: Journal Article
    人乳头瘤病毒(HPV)是宫颈癌的主要致病因子。HPV的流行和基因型分布在不同地区有所不同。因此,我们的研究旨在调查惠州市HPV的流行病学,中国。
    在5,325名女性门诊患者中检测到HPV检测,我们专注于整体HPV患病率,基因型分布,HPV基因型与宫颈细胞学的相关性。
    总的HPV患病率为27.53%,HPV52、HPV58、HPV39、HPV16和HPV51为优势基因型,单次感染率为70.80%。HPV感染率呈U型年龄分布,5个年龄组间差异有统计学意义(χ2=50.497,p<0.01),阳性率较高的是30岁以下(34.42%)和60岁以上(34.74%)。在高危HPV(hrHPV)感染中,60.69%涉及NILM,0.99%HSIL。多重hrHPV感染的宫颈病变程度比单一感染的宫颈病变严重(p<0.01)。
    惠州HPV感染率高,广东,单一感染为主。HPV感染呈U型年龄分布。多重hrHPV感染令人担忧,因为它可能会加重宫颈病变。女性应更加重视HPV检测,根据当地HPV类型分布选择更合适的HPV疫苗。
    UNASSIGNED: Human papillomavirus (HPV) is a main pathogenic factor for cervical carcinoma. The prevalence and genotypes distribution of HPV vary in different regions. Thus, our study aimed to investigate the epidemiology of HPV in Huizhou, China.
    UNASSIGNED: HPV tests were detected in 5,325 female outpatients, we focused on the overall HPV prevalence, genotypes distribution, and the correlation of HPV genotypes with cervical cytology.
    UNASSIGNED: The overall HPV prevalence was 27.53%, HPV52, HPV58, HPV39, HPV16 and HPV51 were predominant genotypes with single infection rate of 70.80%. HPV infection rate showed a U-shaped age distribution, statistical differences were observed among 5 age groups (χ2 = 50.497, p < 0.01), and the higher positive rate was aged under 30 (34.42%) and above 60 (34.74%). Among high-risk HPV (hrHPV) infections, 60.69% involved NILM, 0.99% HSIL. The degrees of cervical lesions in multiple hrHPV infections were worse than those in single infection (p < 0.01).
    UNASSIGNED: The HPV infection rate is high in Huizhou, Guangdong, single infection was predominant. HPV infection presented with a U-shaped age distribution. Multiple hrHPV infection was worrying since it may aggravate cervical lesions. Women should pay more attention to HPV detection and choose a more appropriate HPV vaccine according to local HPV type distribution.
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  • 文章类型: Published Erratum
    [这更正了文章DOI:10.3389/fimmu.202.967040。].
    [This corrects the article DOI: 10.3389/fimmu.2022.967040.].
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