Human papillomaviruses(HPVs) cause virtually all cervical cancers, the second leading cause of death by cancer among women, as well as other anogenital cancers and a subset of head and neck cancers. Approximately half...Human papillomaviruses(HPVs) cause virtually all cervical cancers, the second leading cause of death by cancer among women, as well as other anogenital cancers and a subset of head and neck cancers. Approximately half of women, who develop cervical cancer die from it. Despite the optimism that has accompanied the introduction of prophylactic vaccines to prevent some HPV infections, the relatively modest uptake of the vaccine, especially in the developing world, and the very high fraction of men and women who are already infected, means that HPV-associated disease will remain as a significant public health problem for decades. In this review, we summarize some recent findings on HPV-associated carcinogenesis, such as mi RNAs in HPV-associated cancers, implication of stem cells in the biology and therapy of HPV-positive cancers, HPV vaccines, targeted therapy of cervical cancer, and drug treatment for HPV-induced intraepithelial neoplasias.展开更多
Background: The main objective of this study is to analyse the change in the type of lesions developed by HPV-infected patients after the introduction of the vaccine in three different periods;2002-2006 (years previou...Background: The main objective of this study is to analyse the change in the type of lesions developed by HPV-infected patients after the introduction of the vaccine in three different periods;2002-2006 (years previous to the implementation of the vaccine in Spain), 2009-2011 (shortly after the vaccination) and 2020-2021 (years where the vaccine was well established) at a single hospital. Methods: This is an observational, descriptive, retrospective study based on the review of the results of the biopsies of patients with HPV lesions at a single large tertiary hospital, Hospital Clínico San Carlos, in Madrid, Spain. We have collected the data from three different time periods: 2002-2006, 2009-2011, 2020-2021 to try to understand the potential changes in these lesions after vaccine introduction. Results: In this time we have reviewed the data from 946 women. In these three periods, a decreasing trend in the rate of squamous cell carcinoma was noted, the rate of adenocarcinoma remains stable, and the rate of cervical intraepithelial neoplasia grades 2 - 3 (CIN 2-3) lesions shows an increasing trend. We have also found a change in the mean ages of the patients with these lesions, as this increased in the three lesions caused by HPV after the implementation of the vaccine. Our study indicates that the identification of other high risk serotypes, apart from 16 and 18, as well as those with indeterminate risk, has undergone a progressive increase, increasing from 24.24% and 14.11% respectively in 2002-2006 to 40.42% and 28.34% in 2020-2021. Conclusion: Our study confirms the effectiveness of the vaccines developed so far, against the HPV serotypes they contain. This is demonstrated by the evidence, in our population, of a decrease in the incidence of squamous cell carcinoma in uterine cervix. In parallel, an increase in the mean age of diagnosis has been verified, for both squamous cell carcinoma and its CIN 2-3 precursor lesions, as well as a change in the infective trend of HPV serotypes that are not included in the current vaccines.展开更多
文摘胃癌是全球最常见的恶性肿瘤之一。由于胃癌早期无明显症状,多数患者初诊已达进展期,5年生存率不到30%,总体预后差[1]。2014年癌症基因组图谱(TCGA)提出胃癌分子分型:染色体不稳定(chromosomal instability,CIN)型、微卫星不稳定(microsatellite instability,MSI)型、基因组稳定(genomicalstability,GS)型和EB病毒阳性(EBV+)型。其中,CIN亚型最为常见(50%),具有高频率拷贝数变异(copy number variation,CNV)的非整倍性特征,常伴有TP53突变和大量RTK/RAS基因扩增[2]。CIN是指染色体数目或结构的持续异常,涉及多种分子机制的调控异常,产生非整倍体、染色体重排、驱动基因的缺失或扩增等复杂后果,与肿瘤异质性、不良预后及治疗耐药性相关。CNV是CIN的核心特征之一,特定局灶性扩增或缺失区域可作为胃癌诊断、分型、治疗及预后评估的重要分子标签[3]。因CIN的高度异质性,其在胃癌发生发展中的具体作用和机制尚未完全阐明。近年来胃癌及胃癌前病变的基因组信息不断得到补充完善,因此,本文对CIN在胃癌发生发展中的研究进展进行综述,以期为完善胃癌预防、诊断及治疗等方面提供新思路。
基金supported by a grant from National Cancer Institute R01CA133053Career Development Awards from the Cervical Cancer SPORE NCI P50CA098252+1 种基金the STI CRC NIH U19 AI 113212the UAB Comprehensive Cancer Center Pilot Program Project grant
文摘Human papillomaviruses(HPVs) cause virtually all cervical cancers, the second leading cause of death by cancer among women, as well as other anogenital cancers and a subset of head and neck cancers. Approximately half of women, who develop cervical cancer die from it. Despite the optimism that has accompanied the introduction of prophylactic vaccines to prevent some HPV infections, the relatively modest uptake of the vaccine, especially in the developing world, and the very high fraction of men and women who are already infected, means that HPV-associated disease will remain as a significant public health problem for decades. In this review, we summarize some recent findings on HPV-associated carcinogenesis, such as mi RNAs in HPV-associated cancers, implication of stem cells in the biology and therapy of HPV-positive cancers, HPV vaccines, targeted therapy of cervical cancer, and drug treatment for HPV-induced intraepithelial neoplasias.
文摘Background: The main objective of this study is to analyse the change in the type of lesions developed by HPV-infected patients after the introduction of the vaccine in three different periods;2002-2006 (years previous to the implementation of the vaccine in Spain), 2009-2011 (shortly after the vaccination) and 2020-2021 (years where the vaccine was well established) at a single hospital. Methods: This is an observational, descriptive, retrospective study based on the review of the results of the biopsies of patients with HPV lesions at a single large tertiary hospital, Hospital Clínico San Carlos, in Madrid, Spain. We have collected the data from three different time periods: 2002-2006, 2009-2011, 2020-2021 to try to understand the potential changes in these lesions after vaccine introduction. Results: In this time we have reviewed the data from 946 women. In these three periods, a decreasing trend in the rate of squamous cell carcinoma was noted, the rate of adenocarcinoma remains stable, and the rate of cervical intraepithelial neoplasia grades 2 - 3 (CIN 2-3) lesions shows an increasing trend. We have also found a change in the mean ages of the patients with these lesions, as this increased in the three lesions caused by HPV after the implementation of the vaccine. Our study indicates that the identification of other high risk serotypes, apart from 16 and 18, as well as those with indeterminate risk, has undergone a progressive increase, increasing from 24.24% and 14.11% respectively in 2002-2006 to 40.42% and 28.34% in 2020-2021. Conclusion: Our study confirms the effectiveness of the vaccines developed so far, against the HPV serotypes they contain. This is demonstrated by the evidence, in our population, of a decrease in the incidence of squamous cell carcinoma in uterine cervix. In parallel, an increase in the mean age of diagnosis has been verified, for both squamous cell carcinoma and its CIN 2-3 precursor lesions, as well as a change in the infective trend of HPV serotypes that are not included in the current vaccines.
