ArticleVirology2009
Laser capture microdissection of cervical human papillomavirus infections: copy number of the virus in cancerous and normal tissue and heterogeneous DNA methylation.
Article in Virology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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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.
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Who cites it
30 citing papers in PubMed, 58 citations in OpenAlex.
- HPV-Associated Field Cancerization: Molecular Alterations in Histologically Normal Tissues and Implications for Early Detection and Cancer Prevention.Current issues in molecular biology · 2026Review
- The Hallmarks of Cervical Cancer: Molecular Mechanisms Induced by Human Papillomavirus.Biology · 2024Review
- Optimal Papanicolaou Smear Conditions for Manual Microdissection of Single Target Cells.Microorganisms · 2023Article
- Pre-Vaccination Human Papillomavirus Genotypes and HPV16 Variants among Women Aged 25 Years or Less with Cervical Cancer.Pathogens (Basel, Switzerland) · 2023Article
- Detection of Host Cell Gene/HPV DNA Methylation Markers: A Promising Triage Approach for Cervical Cancer.Frontiers in oncology · 2022Review
- Association between oncogenic human papillomavirus type 16 and Killian polyp.Infectious agents and cancer · 2021Article
- Determination of Causative Human Papillomavirus Type in Tissue Specimens of Common Warts Based on Estimated Viral Loads.Frontiers in cellular and infection microbiology · 2020Article
- Whole tissue cervical mapping of HPV infection: Molecular evidence for focal latent HPV infection in humans.Papillomavirus research (Amsterdam, Netherlands) · 2019Article
- Searching HPV genome for methylation sites involved in molecular progression to cervical precancer.Journal of Cancer · 2019Article
- HPV epigenetic mechanisms related to Oropharyngeal and Cervix cancers.Cancer biology & therapy · 2018Review
- Identification of reliable biomarkers of human papillomavirus 16 methylation in cervical lesions based on integration status using high-resolution melting analysis.Clinical epigenetics · 2018Article
- Why Human Papillomavirus Acute Infections Matter.Viruses · 2017Review
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- Article
- Stratification of HPV-induced cervical pathology using the virally encoded molecular marker E4 in combination with p16 or MCM.Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc · 2015Article
- HPV16 methyl-haplotypes determined by a novel next-generation sequencing method are associated with cervical precancer.International journal of cancer · 2015Article
- Detection of Human Papillomavirus Infections at the Single-Cell Level.Intervirology · 2015Article
- New Methods in Tissue Engineering: Improved Models for Viral Infection.Annual review of virology · 2014Article
- Expression of RUNX3 and β-catenin in the carcinogenesis of sporadic colorectal tubular adenoma.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2014Article
- Characterization of HPV DNA methylation of contiguous CpG sites by bisulfite treatment and massively parallel sequencing-the FRAGMENT approach.Frontiers in genetics · 2014Article
Corrections and comments
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Authors and funding
9 authors at 5 institutions in 3 countries.
Funding
Abstract
Research on the pathogenicity of human papillomaviruses (HPVs) during cervical carcinogenesis often relies on the study of homogenized tissue or cultured cells. This approach does not detect molecular heterogeneities within the infected tissue. It is desirable to understand molecular properties in specific histological contexts. We asked whether laser capture microdissection (LCM) of archival cervical tumors in combination with real-time polymerase chain reaction and bisulfite sequencing permits (i) sensitive DNA diagnosis of small clusters of formalin-fixed cells, (ii) quantification of HPV DNA in neoplastic and normal cells, and (iii) analysis of HPV DNA methylation, a marker of tumor progression. We analyzed 26 tumors containing HPV-16 or 18. We prepared DNA from LCM dissected thin sections of 100 to 2000 cells, and analyzed aliquots corresponding to between nine and 70 cells. We detected nine to 630 HPV-16 genome copies and one to 111 HPV-18 genome copies per tumor cell, respectively. In 17 of the 26 samples, HPV DNA existed in histologically normal cells distant from the margins of the tumors, but at much lower concentrations than in the tumor, suggesting that HPVs can infect at low levels without pathogenic changes. Methylation of HPV DNA, a biomarker of integration of the virus into cellular DNA, could be measured only in few samples due to limited sensitivity, and indicated heterogeneous methylation patterns in small clusters of cancerous and normal cells. LCM is powerful to study molecular parameters of cervical HPV infections like copy number, latency and epigenetics.
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