ArticleAmerican journal of cancer research2016
Chronic oxidative stress increases the integration frequency of foreign DNA and human papillomavirus 16 in human keratinocytes.
Article in American journal of cancer research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers, 1 of them a synthesis that pooled it.
What it found
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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.
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Who cites it
29 citing papers in PubMed, 1 synthesis or guideline pooled it, 55 citations in OpenAlex.
- Relationship between GSTM1 and GSTT1 polymorphisms and HPV infection: a systematic review.Molecular biology reports · 2021Pooled it
- Efficacy and safety of an adsorbent and anti-oxidative vaginal gel on CIN1 and 2, on high-risk HPV, and on p16/Ki-67: a randomized controlled trial.Archives of gynecology and obstetrics · 2021Trial
- The cervicovaginal microbiome: an emerging determinant of HPV infection and disease.Journal of virology · 2026Review
- Up-regulation of peroxiredoxin 3 by high-risk human papillomavirus in cervical cancer cells.Archives of medical science : AMS · 2026Article
- Vaginal Adsorbent Gel as a Therapeutic Agent: Is a New Era Beginning for HPV?Journal of clinical medicine · 2025Article
- HPV and HCMV in Cervical Cancer: A Review of Their Co-Occurrence in Premalignant and Malignant Lesions.Viruses · 2024Review
- Emerging paradigms: unmasking the role of oxidative stress in HPV-induced carcinogenesis.Infectious agents and cancer · 2024Review
- Microplastics and Oxidative Stress-Current Problems and Prospects.Antioxidants (Basel, Switzerland) · 2024Review
- Successful Preventive Treatment of Oncogenic Transforming HPV Infections in Low-Grade Cytology (ASC-US/LSIL) Patients with an Adsorptive and Antioxidant Vaginal Gel.Journal of clinical medicine · 2023Article
- The Drivers, Mechanisms, and Consequences of Genome Instability in HPV-Driven Cancers.Cancers · 2022Review
- Pathological Similarities in the Development of Papillomavirus-Associated Cancer in Humans, Dogs, and Cats.Animals : an open access journal from MDPI · 2022Review
- Human papillomavirus and cervical cancer: an insight highlighting pathogenesis and targeting strategies.Virusdisease · 2022Review
- Article
- Proton-induced DNA damage promotes integration of foreign plasmid DNA into human genome.Frontiers in oncology · 2022Article
- Genetic instability and anti-HPV immune response as drivers of infertility associated with HPV infection.Infectious agents and cancer · 2021Review
- An Adsorptive and Antioxidant Vaginal Gel Clears High-Risk HPV- and p16/Ki-67-Associated Abnormal Cytological Cervical Findings: AFrontiers in medicine · 2021Article
- DNA damage in cancer development: special implications in viral oncogenesis.American journal of cancer research · 2021Article
- Oxidative stress markers in patient-derived non-cancerous cervical tissues and cells.Scientific reports · 2020Article
- The Potential of Immune Checkpoint Blockade in Cervical Cancer: Can Combinatorial Regimens Maximize Response? A Review of the Literature.Current treatment options in oncology · 2020Review
- In silico analyzing the molecular interactions of plant-derived inhibitors against E6AP, p53, and c-Myc binding sites of HPV type 16 E6 oncoprotein.Molecular biology research communications · 2020Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cervical cancer is the second most common cancer, and the fourth most common cause of cancer death in women worldwide. Nearly all of these cases are caused by high-risk HPVs (HR HPVs), of which HPV16 is the most prevalent type. In most cervical cancer specimens, HR HPVs are found integrated into the human genome, indicating that integration is a key event in cervical tumor development. An understanding of the mechanisms that promote integration may therefore represent a unique opportunity to intercept carcinogenesis. To begin identifying these mechanisms, we tested the hypothesis that chronic oxidative stress (OS) induced by virus- and environmentallymediated factors can induce DNA damage, and thereby increase the frequency with which HPV integrates into the host genome. We found that virus-mediated factors are likely involved, as expression of E6*, a splice isoform of HPV16 E6, increased the levels of reactive oxygen species (ROS), caused oxidative DNA damage, and increased the frequency of plasmid DNA integration as assessed by colony formation assays. To assess the influence of environmentally induced chronic OS, we used L-Buthionine-sulfoximine (BSO) to lower the level of the intracellular antioxidant glutathione. Similar to our observations with E6*, glutathione depletion by BSO also increased ROS levels, caused oxidative DNA damage and increased the integration frequency of plasmid DNA. Finally, under conditions of chronic OS, we were able to induce and characterize a few independent events in which episomal HPV16 integrated into the host genome of cervical keratinocytes. Our results support a chain of events leading from induction of oxidative stress, to DNA damage, to viral integration, and ultimately to carcinogenesis.
Indexed as
Identifiers
27186429PMC4859882W2408171712What OpenQuestion 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 OpenQuestion graph.