ArticleNPJ genomic medicine2021
Recurrent integration of human papillomavirus genomes at transcriptional regulatory hubs.
Article in NPJ genomic medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
49 citing papers in PubMed, 1 synthesis or guideline pooled it, 63 citations in OpenAlex.
- Monogenic etiologies of persistent human papillomavirus infections: A comprehensive systematic review.Genetics in medicine : official journal of the American College of Medical Genetics · 2024Pooled it
- The cervicovaginal microbiome: an emerging determinant of HPV infection and disease.Journal of virology · 2026Review
- Revisiting HPV integration landscapes using telomere-to-telomere human genome reference closes the gaps in HPV integration sites search.Virology journal · 2026Article
- Biology-aligned cervical cancer screening: target-centric biomarkers and next-generation diagnostic platforms.Biomarker research · 2026Review
- The interaction between virus-bound KLF4 and host-bound PARP1 directs the localization of wild-type adeno-associated virus type 2 (wtAAV2) to cellular sites of DNA damage.Journal of virology · 2026Article
- Molecular Mimics: How Viral Genomes Dupe Their Host by Usurping CTCF to Establish Infection.Viruses · 2026Review
- HPV16 E6 oncoprotein promotes microhomology-mediated viral integration by increasing PolΘ protein expression.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- HPV Integration in Head and Neck Cancer: Downstream Splicing Events and Expression Ratios Linked with Poor Outcomes.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026Article
- An Overview of the Mechanisms of HPV-Induced Cervical Cancer: The Role of Kinase Targets in Pathogenesis and Drug Resistance.Cancers · 2026Review
- The immune microenvironment of HPV-associated cancers: from viral oncogenesis to immunotherapy response.Frontiers in immunology · 2026Review
- Challenges in the detection and assembly of virus integration structures in human genomes.Frontiers in oncology · 2026Review
- Association of hepatitis B virus genomes with active chromatin hubs challenges host replication fidelity, leading to DNA damage.Journal of virology · 2025Article
- From Viral Infection to Genome Reshaping: The Triggering Role of HPV Integration in Cervical Cancer.International journal of molecular sciences · 2025Review
- Human papillomavirus genomes associate with active host chromatin during persistent viral infection.PLoS pathogens · 2025Article
- Adeno-Associated Virus 2 (AAV2) - Induced RPA exhaustion generates cellular DNA damage and restricts viral gene expression.PLoS pathogens · 2025Article
- Molecular Mechanisms and Clinical Divergences in HPV-Positive Cervical vs. Oropharyngeal Cancers: A Critical Narrative Review.BMC medicine · 2025Review
- Nuclear keratin 6A upregulates human papillomavirus oncogene expression through TEAD1 interaction.Virology journal · 2025Article
- Generation of a spontaneous murine HPV + oral cancer model with site-specific oncogene insertion using CRISPR-SONIC.Cell & bioscience · 2025Article
- Novel Avenues for the Detection of Cancer-Associated Viral Genome Integrations Using Long-Read Sequencing Technologies.Cancers · 2025Review
- Human Papillomavirus Genomes Associate with Active Host Chromatin during Persistent Viral Infection.bioRxiv : the preprint server for biology · 2025Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Oncogenic human papillomavirus (HPV) genomes are often integrated into host chromosomes in HPV-associated cancers. HPV genomes are integrated either as a single copy or as tandem repeats of viral DNA interspersed with, or without, host DNA. Integration occurs frequently in common fragile sites susceptible to tandem repeat formation and the flanking or interspersed host DNA often contains transcriptional enhancer elements. When co-amplified with the viral genome, these enhancers can form super-enhancer-like elements that drive high viral oncogene expression. Here we compiled highly curated datasets of HPV integration sites in cervical (CESC) and head and neck squamous cell carcinoma (HNSCC) cancers, and assessed the number of breakpoints, viral transcriptional activity, and host genome copy number at each insertion site. Tumors frequently contained multiple distinct HPV integration sites but often only one "driver" site that expressed viral RNA. As common fragile sites and active enhancer elements are cell-type-specific, we mapped these regions in cervical cell lines using FANCD2 and Brd4/H3K27ac ChIP-seq, respectively. Large enhancer clusters, or super-enhancers, were also defined using the Brd4/H3K27ac ChIP-seq dataset. HPV integration breakpoints were enriched at both FANCD2-associated fragile sites and enhancer-rich regions, and frequently showed adjacent focal DNA amplification in CESC samples. We identified recurrent integration "hotspots" that were enriched for super-enhancers, some of which function as regulatory hubs for cell-identity genes. We propose that during persistent infection, extrachromosomal HPV minichromosomes associate with these transcriptional epicenters and accidental integration could promote viral oncogene expression and carcinogenesis.
Identifiers
What Socratic holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.