Human Papilloma Virus

人乳头瘤病毒
  • 文章类型: Journal Article
    扁平苔藓(LP)是一种慢性,复发性皮肤粘膜炎性疾病,病因不明,已经考虑了几种病毒的潜在作用。这项荟萃分析旨在根据病例对照和横断面研究结果确定HPV与口服LP之间的潜在关联。在PubMed中进行了系统的搜索,WebofScience(SCI),谷歌学者,和Scopus数据库,最后一次更新于2024年3月6日。通过计算R的比值比(OR)和95%置信区间(CI)对汇总的数据进行分析。该荟萃分析中包括了541例病例和413例对照的13项研究。它覆盖了八个国家:印度,伊朗,土耳其,捷克共和国,匈牙利,意大利,马其顿,和英国。在七篇论文中,利用OLP的侵蚀性-萎缩性和非侵蚀性-萎缩性。HPV感染与HPV患者患OLP的风险至少高出两倍有关。取决于使用的是原始数据还是填充/修剪的数据。OR值为3.54[2.01,6.24]和2.10[1.16,3.82],分别。进行这项荟萃分析以确定HPV和OLP之间的关联,并揭示HPV感染至少与HPV患者发展OLP的高风险相关。
    Lichen planus (LP) is a chronic, recurrent mucocutaneous inflammatory disease with unclearly defined etiology, where a potential role of several viruses has been considered. This meta-analysis aimed to determine the potential association between HPV and oral LP based on case-control and cross-sectional study results. A systematic search was performed in PubMed, Web of Science (SCI), Google Scholar, and Scopus databases with the last update on 6 March 2024. Pooled data were analyzed by calculating odds ratios (OR) and 95% confidence intervals (CI) with the metafor package for R. A total of 13 studies on 541 cases and 413 controls were included in this meta-analysis. It covered eight countries: India, Iran, Turkey, Czech Republic, Hungary, Italy, Macedonia, and the UK. In seven papers, the differentiation into the erosive-atrophic type and non-erosive-atrophic type of OLP was utilized. HPV infection was associated with at least a two times higher risk for a person with HPV to have OLP, depending on whether original data or filled/trimmed data were used. The OR values were 3.54 [2.01, 6.24] and 2.10 [1.16, 3.82], respectively. This meta-analysis was performed to identify the association between HPV and OLP and revealed that HPV infection was associated with at least a high risk for a person with HPV to develop OLP.
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  • 文章类型: Journal Article
    背景:HPV被认为是最常见的性传播感染。它负责全世界70%的宫颈癌。HIV感染与HPV感染率增加有关。感染艾滋病毒(WLWH)的女性患宫颈癌的风险是其6倍。本研究旨在评估埃及WLWH与HIV阴性妇女相比的流行率和确定HPV感染的基因型,并确定相关的危险因素。
    方法:这项研究在埃及9个省初级保健中心妇科诊所招募的251名WLWH和268名HIV阴性状态妇女中进行。使用结构化访谈问卷从参与者收集数据,并收集宫颈样本用于HPVDNA检测和基因分型。
    结果:HPV感染的总体患病率为13.5%,感染艾滋病毒阴性的妇女中占3.4%,WLWH中占24.4%。从71%的受感染妇女中分离出基因型16和18以外的HR-HPV。女人的年龄,初婚年龄,终生婚姻数量和药物成瘾是HPV感染的重要预测因素(分别为赔率0.96,0.91,2.06,2.01).
    结论:HPV感染在WLWH中更为普遍。除基因型16和18以外的HR-HPV感染在两组中的感染妇女中最为普遍。年轻的年龄,早期性生活活动,一生中有不止一个性伴侣,药物成瘾是HPV感染的独立预测因子。有一个有其他性伴侣的丈夫与感染密切相关。
    BACKGROUND: HPV is considered the most common sexually transmitted infection. It is responsible of 70% of cervical cancers worldwide. HIV infection is associated with increased rates of HPV infection. Women Living With HIV (WLWH) are 6 times at greater risk of developing cervical cancer. The current study aimed to estimate prevalence and identify genotypes of HPV infection among WLWH in Egypt compared to women with negative HIV status and determine associated risk factors.
    METHODS: The study conducted among 251 WLWH and 268 women with negative HIV status enrolled from gynecological clinics in primary health care centers from nine Egyptian governorates. Data was collected from participants using a structured interview questionnaire and cervical samples were collected for HPV DNA detection and genotyping.
    RESULTS: The overall prevalence of HPV infection was 13.5%, 3.4% among women with HIV negative status and 24.4% among WLWH. HR-HPVs other than genotype 16 and 18 were isolated from 71% of infected women. Woman\'s age, age at first marriage, number of lifetime marriages and drug addiction are significant predictors for HPV infection (odds 0.96, 0.91, 2.06, 2.01 respectively).
    CONCLUSIONS: HPV infection is more prevalent among WLWH. Infection with HR-HPV other than genotype 16 and 18 was the most prevalent among infected women in both groups. Young age, early life sexual activity, having more than one sexual partner during the life time, and drug addiction are independent predictors for HPV infection. Having a husband who has had other sexual partners is significantly associated with infection.
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  • 文章类型: Journal Article
    很少有报道分析口咽癌变中涉及的融合基因,其中人乳头瘤病毒相关肿瘤的发病率相对较低。这项研究的目的是鉴定口咽癌症患者的新型驱动融合基因。该研究纳入了57例被诊断为口鼻咽癌的患者。来自新鲜冷冻标本的RNA测序数据用于通过JAFFA鉴定候选融合基因,arriba,和STAR-Fusion管道。通过直接测序确认候选融合基因。将候选融合基因的表达水平与没有融合基因的肿瘤的表达水平进行比较。最后,使用annoFuse管道对驱动基因进行过滤。此外,VIRTUS管道用于分析肿瘤中是否存在人乳头瘤病毒.我们确定了5个(8.8%)新的潜在驱动框内融合基因,MKNK2::MOB3A,ICMT::RPS6KA3,ATP1B3::GRK7,CSNK2A1::KIF16B,和FGFR3::MAEA,和1个(1.8%)已知的框内融合基因,FGFR3::TACC3,在57例咽癌患者中。我们的结果表明,零星的融合基因可能有助于口咽癌的肿瘤发生。
    Few reports have analyzed the fusion genes involved in carcinogenesis in the oropharynx, where the incidence of human papillomavirus-associated tumors is relatively low. The aim of this study was to identify novel driver fusion genes in patients with oropharyngeal cancer. The study enrolled fifty-seven patients who were diagnosed with oropharyngeal carcinoma. RNA sequencing data from fresh-frozen specimens were used to identify candidate fusion genes via the JAFFA, arriba, and STAR-Fusion pipelines. Candidate fusion genes were confirmed by direct sequencing. The expression level of a candidate fusion gene was compared to that of tumors without fusion genes. Finally, filtering was performed for driver genes using the annoFuse pipeline. In addition, the VIRTUS pipeline was used to analyze the presence of human papillomavirus in the tumors. We identified 5 (8.8 %) novel potential driver in-frame fusion genes, MKNK2::MOB3A, ICMT::RPS6KA3, ATP1B3::GRK7, CSNK2A1::KIF16B, and FGFR3::MAEA, and 1 (1.8 %) known in-frame fusion gene, FGFR3::TACC3, in 57 patients with pharyngeal carcinoma. Our results suggest that sporadic fusion genes may contribute to tumorigenesis in oropharyngeal carcinomas.
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  • 文章类型: Journal Article
    人类乳头瘤病毒(HPV)正在威胁人类健康,因为它在全球范围内以不同程度传播。另一方面,信息传递的速度和范围不断提高,以及与HPV相关的新闻报道数量显着增加,探索媒体新闻报道在病毒传播和控制中的作用从未如此重要。利用一个递减的因素来捕捉媒体对人们行为的影响,本文开发了一个模型,描述了HPV传播与媒体影响的动力学,疫苗接种和恢复。我们通过几何方法获得了平衡点的全局稳定性,并通过敏感性分析进一步产生有效的方法来遏制HPV大流行。有了中心流形理论,我们证明了当R0=1时存在正向分岔。我们的研究表明,除了控制感染和易感人群之间的接触并提高有效的疫苗覆盖率,更好的干预措施是加强媒体报道。此外,我们证明,接触率和媒体报道的影响导致多重流行的感染,当某些条件得到满足,这意味着干预措施需要根据具体情况进行调整。
    The human papillomavirus (HPV) is threatening human health as it spreads globally in varying degrees. On the other hand, the speed and scope of information transmission continues to increase, as well as the significant increase in the number of HPV-related news reports, it has never been more important to explore the role of media news coverage in the spread and control of the virus. Using a decreasing factor that captures the impact of media on the actions of people, this paper develops a model that characterizes the dynamics of HPV transmission with media impact, vaccination and recovery. We obtain global stability of equilibrium points employing geometric method, and further yield effective methods to contain the HPV pandemic by sensitivity analysis. With the center manifold theory, we show that there is a forward bifurcation when R0=1. Our study suggested that, besides controlling contact between infected and susceptible populations and improving effective vaccine coverage, a better intervention would be to strengthen media coverage. In addition, we demonstrated that contact rate and the effect of media coverage result in multiple epidemics of infection when certain conditions are met, implying that interventions need to be tailored to specific situations.
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  • 文章类型: Journal Article
    头颈部鳞状细胞癌的一个子集仅表现为颈部转移性疾病,并且原发不明(SCCUP)。大多数原发性肿瘤最终将被识别,通常在口咽部。在少数情况下,主要网站仍然难以捉摸。这里,我们研究辅助测试的作用,包括突变特征分析(MSA),以帮助识别在这种情况下可能的主要网站。22例颈部SCCUP,收集了10年的时间,通过形态学和病毒状态进行分类;包括通过p16免疫组织化学(IHC)和RT-qPCR检测人乳头瘤病毒(HPV),以及EBER-ISH的爱泼斯坦-巴尔病毒(EBV)测试。进行CD5和c-KIT(CD117)IHC以评估所有病毒阴性病例中可能的胸腺起源。全外显子组测序,其次是MSA,用于鉴定指示皮肤起源的UV特征突变。在22个肿瘤中的12个(54.5%)中发现了HPV,有利于口咽起源,与非角质化肿瘤形态密切相关(Fisher精确检验;p=0.0002)。一个具有不确定形态的肿瘤具有不一致的HPV和p16状态(p16+/HPV-)。所有肿瘤均为EBV阴性。在10个病毒阴性SCCUP中的1个(10%)中鉴定出CD5和c-KIT的弥漫性表达,提示可能是异位胸腺起源而不是转移。紫外线突变特征,表明皮肤起源,在10个(10%)病毒阴性SCCUP中的1个中鉴定。该患者在治疗后3个月出现皮肤耳廓原发性。原发性肿瘤在另外2个临床上变得明显(1个下咽,1下咽/喉)。因此,随访后,6个肿瘤对于可能的起源部位仍然无法分类(27%)。在我们的系列中,大多数颈部的SCCUP与HPV相关,因此可能是口咽部起源。针对可能的胸腺起源的CD5和c-KIT的UV特征突变分析和额外的IHC可能有助于进一步分类病毒阴性未知的原发性。密切下咽粘膜的临床检查也可能有帮助,作为原发性肿瘤的一个子集,后来出现在这个部位。
    A subset of head and neck squamous cell carcinomas present solely as metastatic disease in the neck and are of unknown primary origin (SCCUP). Most primary tumors will ultimately be identified, usually in the oropharynx. In a minority of cases, the primary site remains elusive. Here, we examine the role of ancillary testing, including mutational signature analysis (MSA), to help identify likely primary sites in such cases. Twenty-two cases of SCCUP in the neck, collected over a 10-year period, were classified by morphology and viral status; including human papillomavirus (HPV) testing by p16 immunohistochemistry (IHC) and RT-qPCR, as well as Epstein-Barr virus (EBV) testing by EBER-ISH. CD5 and c-KIT (CD117) IHC was done to evaluate for possible thymic origin in all virus-negative cases. Whole exome sequencing, followed by MSA, was used to identify UV signature mutations indicative of cutaneous origin. HPV was identified in 12 of 22 tumors (54.5%), favoring an oropharyngeal origin, and closely associated with nonkeratinizing tumor morphology (Fisher\'s exact test; p = 0.0002). One tumor with indeterminant morphology had discordant HPV and p16 status (p16+/HPV-). All tumors were EBV-negative. Diffuse expression of CD5 and c-KIT was identified in 1 of 10 virus-negative SCCUPs (10%), suggesting a possible ectopic thymic origin rather than a metastasis. A UV mutational signature, indicating cutaneous origin, was identified in 1 of 10 (10%) virus-negative SCCUPs. A cutaneous auricular primary emerged 3 months after treatment in this patient. Primary tumors became clinically apparent in 2 others (1 hypopharynx, 1 hypopharynx/larynx). Thus, after follow-up, 6 tumors remained unclassifiable as to the possible site of origin (27%). Most SCCUPs of the neck in our series were HPV-associated and thus likely of oropharyngeal origin. UV signature mutation analysis and additional IHC for CD5 and c-KIT for possible thymic origin may aid in further classifying virus-negative unknown primaries. Close clinical inspection of hypopharyngeal mucosa may also be helpful, as a subset of primary tumors later emerged at this site.
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  • 文章类型: Journal Article
    宫颈癌(CC)是女性患者中第四大最常见的癌症。所有类型的宫颈癌的主要原因是人乳头瘤病毒(HPV),预计2018年将有570,000例报告病例。两种HPV株(16和18)占宫颈异常和宫颈癌前病变的70%。CC是30至69岁的印度女性中17%与癌症相关的死亡率的主要原因之一是CC。目前批准的宫颈癌治疗方法的副作用可能危及受这种疾病影响的妇女的生命。因此,益生菌在CC的管理中可能极其重要。关于益生菌及其在癌症诊断中的潜力的大量研究,预防,并进行了治疗。这篇综述描述了免疫系统的增强,促进平衡的阴道微生物组,降低继发感染的风险,对身体有抗炎作用。益生菌有可能减少炎症,从而不利地影响癌细胞生长和转移。在抗生素治疗过程中,它们支持平衡的阴道微生物组。益生菌菌株可以灭活致癌病毒。在绝经后的女性中,使用阴道益生菌有助于减轻更年期泌尿生殖系统综合征(GSM)引起的更年期症状。其他药物的抗肿瘤作用可以通过它们作为潜在的药物来增强,因为它们既能促进有益细菌的生长,又能减少潜在有害细菌的数量。肿瘤的发展和癌细胞的增殖可能受到微生物平衡恢复的间接影响。益生菌可能能够预防和治疗宫颈癌,因为它们似乎具有抗癌特性。为了确定具有抗癌特性的益生菌,可以补充甚至可能取代传统的癌症治疗方法,需要进一步调查,包括精心策划的临床试验。
    Cervical cancer (CC) is the fourth most common cancer among female patients. The primary cause of all types of cervical cancer is human papillomavirus (HPV), which was projected to account for 5,70,000 reported cases in 2018. Two HPV strains (16 and 18) account for 70 % of cervical abnormalities and precancerous cervical cancers. CC is one of the main causes of the 17 % cancer-related death rate among Indian women between the ages of 30 and 69 is CC. The side effects of the currently approved treatments for cervical cancer could endanger the lives of women affected by the illness. Thus, probiotics may be extremely important in the management of CC. Numerous studies on probiotics and their potential for use in cancer diagnosis, prevention, and treatment have been conducted. This review describes the enhancement of the immune system, promotion of a balanced vaginal microbiome, and decreased risk of secondary infections, which have anti-inflammatory effects on the body. Probiotics have the potential to reduce inflammation, thereby adversely affecting cancer cell growth and metastasis. During the course of antibiotic therapy, they support a balanced vaginal microbiome. Oncogenic virus inactivation is possible with probiotic strains. In postmenopausal women, the use of vaginal probiotics helps lessen menopausal symptoms caused by Genitourinary Syndrome of Menopause (GSM). The antitumor effects of other medications can be enhanced by them as potential agents, because they can both promote the growth of beneficial bacteria and reduce the quantity of potentially harmful bacteria. The development of tumors and the proliferation of cancer cells may be indirectly affected by the restoration of the microbial balance. Probiotics may be able to prevent and treat cervical cancer, as they seem to have anticancer properties. To identify probiotics with anticancer qualities that can supplement and possibly even replace traditional cancer treatments, further investigation is required, including carefully planned clinical trials.
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  • 文章类型: Journal Article
    头颈部鳞状细胞癌(HNSCC)是全球最常见的肿瘤之一,人乳头瘤病毒(HPV)感染有助于癌症的发展。传统疗法只能达到有限的效率,尤其是复发或转移性HNSCC。由于免疫景观决定性地影响患者的生存和治疗效果,这项研究全面调查了免疫肿瘤微环境(TME)及其与患者预后的关系,特别关注几种树突状细胞(DC)和T淋巴细胞亚群。因此,56例HNSCC患者的福尔马林固定石蜡包埋肿瘤样本,接受过切除和辅助放疗的人,通过多重免疫组织化学分析DCs的详细表型特征和空间分布,CD8+T细胞,和不同肿瘤区室的T辅助细胞亚群。免疫细胞密度和比例与整个HNSCC队列和不同的HPV或缺氧相关亚组的临床特征相关。浆细胞样DC和T淋巴细胞高度浸润肿瘤基质。在T辅助细胞和CD8+T细胞中,表达程序性细胞死亡蛋白-1(PD-1+)和/或淋巴细胞活化基因-3(LAG-3+)的基质调节性T细胞和上皮内耗尽的CD8+T细胞是主要的表型,表明免疫抑制性TME。HPV相关肿瘤显示I型和II型常规DC(cDC1,cDC2)以及几种CD8T细胞表型(包括耗尽,激活,和增殖T细胞。相反,具有缺氧相关基因特征的肿瘤对这些免疫细胞的浸润减少.通过多元Cox回归,确定了免疫相关的预后因素.由DC和T淋巴细胞的高浸润结合HPV阳性或低缺氧定义的患者簇显示出显著延长的存活。因此,cDC1和CD8+T细胞是局部和远处复发的独立预后因素。这些结果可能有助于实施预测HNSCC患者生存的免疫细胞浸润评分,这种患者分层可能会改善未来个性化放化疗(免疫)治疗的设计。
    Head and neck squamous cell carcinoma (HNSCC) is one of the most common tumor entities worldwide, with human papillomavirus (HPV) infection contributing to cancer development. Conventional therapies achieve only limited efficiency, especially in recurrent or metastatic HNSCC. As the immune landscape decisively impacts the survival of patients and treatment efficacy, this study comprehensively investigated the immunological tumor microenvironment (TME) and its association with patient outcome, with special focus on several dendritic cell (DC) and T lymphocyte subpopulations. Therefore, formalin-fixed paraffin-embedded tumor samples of 56 HNSCC patients, who have undergone resection and adjuvant radiotherapy, were analyzed by multiplex immunohistochemistry focusing on the detailed phenotypic characterization and spatial distribution of DCs, CD8+ T cells, and T-helper cell subsets in different tumor compartments. Immune cell densities and proportions were correlated with clinical characteristics of the whole HNSCC cohort and different HPV- or hypoxia-associated subcohorts. Tumor stroma was highly infiltrated by plasmacytoid DCs and T lymphocytes. Among the T-helper cells and CD8+ T cells, stromal regulatory T cells and intraepithelial exhausted CD8+ T cells expressing programmed cell death protein-1 (PD-1+) and/or lymphocyte-activation gene-3 (LAG-3+) were the predominant phenotypes, indicating an immunosuppressive TME. HPV-associated tumors showed significantly higher infiltration of type I and type II conventional DCs (cDC1, cDC2) as well as several CD8+ T cell phenotypes including exhausted, activated, and proliferating T cells. On the contrary, tumors with hypoxia-associated gene signatures exhibited reduced infiltration for these immune cells. By multivariate Cox regression, immune-related prognostic factors were identified. Patient clusters defined by high infiltration of DCs and T lymphocytes combined with HPV positivity or low hypoxia showed significantly prolonged survival. Thereby, cDC1 and CD8+ T cells emerged as independent prognostic factors for local and distant recurrence. These results might contribute to the implementation of an immune cell infiltration score predicting HNSCC patients\' survival and such patient stratification might improve the design of future individualized radiochemo-(immuno)therapies.
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  • 文章类型: Journal Article
    原发性泪囊肿瘤(PTLS)是一种罕见的眼部附属器肿瘤亚型,有可能危及生命的临床过程。越来越多的证据表明,人乳头瘤病毒(HPV)是这些肿瘤的病原体。在这个回顾性观察病例系列中,我们报告了3例PTLS。所有三个人都接受了最初的泪囊鼻腔吻合术,发现泪囊中有组织肿块。组织学发现分别为上皮性乳头状瘤,上皮性马氏乳头状瘤,和未分化的表皮样癌.PCR评估在第一种情况下确定了HPV血清型6,在第三种情况下确定了16,在第二例中发现高p16表达。这3例PTLS用HPV检测补体36例其他文献中确定,HPV在这些肿瘤的发病机制中进一步发挥作用。眼科医生必须对慢性泪道闭塞症状保持警惕,并在一线治疗失败时诉诸CT扫描和眼眶多普勒超声检查。
    Primary tumors of the lacrimal sac (PTLS) are a rare subtype of ocular adnexa tumors, with potentially life-threatening clinical course. There has been growing evidence of human papilloma virus (HPV) as an etiological agent in these tumors.In this retrospective observational case series, we report three cases of PTLS. All three underwent an initial dacryocystorhinostomy revealing a tissular mass in the lacrimal sac. Histological findings were respectively epithelial papilloma, epithelial Malpighian papilloma, and undifferentiated epidermoid carcinoma. PCR evaluation identified HPV serotype 6 in the first case and 16 in the third, and high p16 expression was found in the second case.These three cases of PTLS with HPV detection complement 36 other cases identified in the literature, further incriminating HPV in the pathogenesis of these neoplasms. Ophthalmologists must remain wary of chronic lacrimal occlusion symptoms, and resort to CT scan and orbital Doppler sonography whenever first-line treatment fails.
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  • 文章类型: Journal Article
    目的:关于阴茎鳞状细胞癌(pSCC)患者的北美队列数据很少。在这里,我们旨在评估各种方法的敏感性,以确定人乳头瘤病毒(HPV)状态,确定高危型HPV阳性的患病率,并评估相关临床病理变量对预后的影响。
    方法:纳入pSCC患者(n=121)在单一机构连续接受部分/全部阴茎切除术(2000-2022)治疗。HPV状态(基于免疫组织化学[IHC],原位杂交[ISH],和泛病毒宏基因组测序[PMS]),组织学特征,并对结果进行了审查。结果事件包括由于疾病和进展导致的死亡。
    结果:大多数患者为白人(105/121,86.8%)。37例(30.6%)高危型HPV阳性,形态学评估的灵敏度为97.3%(95%置信区间[CI],86.2-99.5)用于预测与IHC/ISH/PMS相比的高危HPV状态。与高危HPV阳性患者相比,高危HPV阴性患者的疾病进展更为常见(HR2.74,CI1.12-8.23,P=0.03)。此外,在高危型HPV阴性患者中,患有中度-低分化肿瘤的患者的疾病特异性死亡率增加(32.6%,CI17.1-48.1)与高分化肿瘤(0%)相比。在高危HPV阳性患者中,具有基底细胞形态的患者具有较低的疾病特异性死亡率(0%vs14.4%,CI0.0-33.1)。
    结论:我们在约三分之一的pSCC患者中证实了高危型HPV阳性。仅形态学评估在正确确定HPV状态方面具有很高的敏感性。我们的结果表明,高危HPV状态和形态学特征(高危HPV阴性,高危型HPV阳性pSCC中的基底细胞亚型)可能具有预后价值。
    OBJECTIVE: There is a paucity of data on North American cohorts of patients with penile squamous cell carcinoma (pSCC). Herein, we aimed to assess the sensitivity of various modalities to identify human papillomavirus (HPV) status, determine the prevalence of high-risk HPV-positivity, and evaluate the prognostic impact of relevant clinicopathologic variables.
    METHODS: Patients with pSCC (n = 121) consecutively treated with partial/total penectomy (2000-2022) at a single institution were included. HPV status (based on immunohistochemistry [IHC], in situ hybridization [ISH], and panviral metagenomic sequencing [PMS]), histologic features, and outcomes were reviewed. Outcome events included death due to disease and progression.
    RESULTS: The majority of patients were white (105/121, 86.8%). Thirty-seven (30.6%) were high-risk HPV-positive, and morphologic evaluation had a sensitivity of 97.3% (95% confidence interval [CI], 86.2-99.5) for predicting high-risk HPV status compared to IHC/ISH/PMS. Disease progression was more common among high-risk HPV-negative compared to high-risk HPV-positive patients (HR 2.74, CI 1.12-8.23, P = 0.03). Moreover, among high-risk HPV-negative patients, those with moderate-poorly differentiated tumors had increased disease-specific mortality (32.6%, CI 17.1-48.1) compared to those with well-differentiated tumors (0%). Among high-risk HPV-positive patients, those with basaloid morphology had lower disease-specific mortality (0% vs 14.4%, CI 0.0-33.1).
    CONCLUSIONS: We demonstrate high-risk HPV-positivity in approximately one-third of patients with pSCC. Morphologic evaluation alone had a high sensitivity in correctly determining HPV status. Our results suggest that high-risk HPV status and morphologic features (differentiation in high-risk HPV-negative, and basaloid subtype in high-risk HPV-positive pSCC) may have prognostic value.
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  • 文章类型: Journal Article
    目的我们旨在研究铂类三联诱导化疗对转移性头颈部鳞状细胞癌(HNSCC)在肿瘤人乳头瘤病毒(HPV)状态诊断中的有效性以及循环肿瘤HPVDNA(ctHPVDNA)在诱导化疗期间的临床相关性。方法纳入21例患者。使用优化的数字PCR在一部分患者中纵向定量ctHPVDNA。结果HPV相关的HNSCC患者(N=7)对诱导化疗的反应明显优于HPV无关的HNSCC患者(N=14)(完全或部分反应率,100%vs.36%,P=0.007)。诱导化疗后,与HPV相关的HNSCC患者接受放疗的患者多于与HPV无关的患者(86%vs.36%,P=0.06)。存活患者的中位随访时间为26个月,HPV相关HNSCC患者的两年总生存率为86%,HPV无关HNSCC患者的两年总生存率为43%(P=0.04).在两个病人中,ctHPVDNA水平在第一个周期诱导化疗后急剧下降,但在第二个周期后转为持续升高,表明在第二个周期结束时获得耐药性。诱导化疗后的影像学检查未能鉴定耐药性。在一个病人中,ctHPVDNA逐渐下降,但在诱导化疗后仍可检测到,尽管没有影像学残留疾病。ctHPVDNA在放疗期间变得不可检测。结论HPV相关的HNSCC患者在诊断时存在远处转移,应明确治疗。ctHPVDNA水平反映了实时疾病活动。诱导化疗期间的ctHPVDNA监测可以帮助治疗策略的决策。
    Objectives We aimed to examine the effectiveness of platinum-based triplet induction chemotherapy in metastatic squamous cell carcinoma of the head and neck (HNSCC) at diagnosis in terms of tumor human papillomavirus (HPV) status and the clinical relevance of circulating tumor HPV DNA (ctHPVDNA) during induction chemotherapy. Methods  Twenty-one patients were included. ctHPVDNA was longitudinally quantified using optimized digital PCR in a subset of patients. Results HPV-related HNSCC patients (N=7) had a significantly better response to induction chemotherapy than HPV-unrelated HNSCC patients (N=14) (complete or partial response rate, 100% vs. 36%, P = 0.007). Following induction chemotherapy, more HPV-related HNSCC patients than HPV-unrelated patients received radiotherapy (86% vs. 36%, P = 0.06). With a median follow-up of 26 months in surviving patients, the two-year overall survival was 86% in HPV-related HNSCC patients and 43% in HPV-unrelated HNSCC patients (P = 0.04). In two patients, ctHPVDNA levels drastically decreased after the first cycle of induction chemotherapy but turned to continuous increase after the second cycle, suggesting the acquisition of drug resistance by the end of the second cycle. Radiographic imaging after induction chemotherapy failed to identify the drug resistance. In one patient, ctHPVDNA decreased gradually but remained detectable after induction chemotherapy despite no radiographic residual disease. ctHPVDNA became undetectable during radiotherapy. Conclusion HPV-related HNSCC patients with distant metastasis at diagnosis should be treated definitively. The ctHPVDNA level reflects real-time disease activity. ctHPVDNA monitoring during induction chemotherapy could help the decision-making of the therapeutic strategy.
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