ArticleOncogene2010
The immortalizing and transforming ability of two common human papillomavirus 16 E6 variants with different prevalences in cervical cancer.
Article in Oncogene, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers, 1 of them a synthesis that pooled it.
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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
38 citing papers in PubMed, 1 synthesis or guideline pooled it, 71 citations in OpenAlex.
- Roles of hypoxia inducible factors in viral infection: Are they a potential therapeutic target?Virulence · 2025Pooled it
- Pre-vaccination prevalence of anogenital and oral human papillomavirus in young HIV-infected men who have sex with men.Papillomavirus research (Amsterdam, Netherlands) · 2019Trial
- HPV16 E6 and E7 Genetic Variability in Oral and Anal Samples from HIV-Positive MSM.Pathogens (Basel, Switzerland) · 2025Article
- HPV16 E7 oncoprotein test as a triage strategy for HPV16-positive women in cervical cancer screening: long-term follow-up outcome.Frontiers in oncology · 2023Article
- Genetic diversity of E6, E7 and the long control region in human papillomavirus type 16 variants in Beijing, China.Biochemistry and biophysics reports · 2022Article
- Deep Sequencing of HPV16 E6 Region Reveals Unique Mutation Pattern of HPV16 and Predicts Cervical Cancer.Microbiology spectrum · 2022Article
- HPV16-E6/E7 Oncogene Mutation and p53 Expression among Indonesian Women with Cervical Cancer.Asian Pacific journal of cancer prevention : APJCP · 2022Article
- Generation and characterization of human Fetal membrane and Decidual cell lines for reproductive biology experiments†.Biology of reproduction · 2022Article
- Transcriptome analysis of cervical cancer exosomes and detection of HPVE6*I transcripts in exosomal RNA.BMC cancer · 2022Article
- Molecular insights into the interaction of HPV-16 E6 variants against MAGI-1 PDZ1 domain.Scientific reports · 2022Article
- E6/E7 Functional Differences among Two Natural Human Papillomavirus 18 Variants in Human Keratinocytes.Viruses · 2021Article
- Metabolic Reprogramming in Cancer: Role of HPV 16 Variants.Pathogens (Basel, Switzerland) · 2021Review
- Virus-Host Protein-Protein Interactions between Human Papillomavirus 16 E6 A1 and D2/D3 Sub-Lineages: Variances and Similarities.International journal of molecular sciences · 2020Article
- The D2 and D3 Sublineages of Human Papilloma Virus 16-Positive Cervical Cancer in Guatemala Differ in Integration Rate and Age of Diagnosis.Cancer research · 2020Article
- An epithelial organoid model with Langerhans cells for assessing virus-host interactions.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2019Article
- High frequency of HPV16 European variant E350G among Mexican women from Sinaloa.The Indian journal of medical research · 2018Article
- High-Risk Human Papillomaviral Oncogenes E6 and E7 Target Key Cellular Pathways to Achieve Oncogenesis.International journal of molecular sciences · 2018Review
- HPV-6 Molecular Variants Association With the Development of Genital Warts in Men: The HIM Study.The Journal of infectious diseases · 2017Article
- Functional variants of human papillomavirus type 16 demonstrate host genome integration and transcriptional alterations corresponding to their unique cancer epidemiology.BMC genomics · 2016Article
- Three-dimensional cell culture models for investigating human viruses.Virologica Sinica · 2016Review
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Persistent infection with high-risk human papillomaviruses (HPVs), especially type 16 has been undeniably linked to cervical cancer. The Asian-American (AA) variant of HPV16 is more common in the Americas than the prototype in cervical cancer. The different prevalence is based on three amino acid changes within the E6 protein denoted Q14H/H78Y/L83V. To investigate the mechanism(s) behind this observation, both E6 proteins, in the presence of E7, were evaluated for their ability to extend the life span of and transform primary human foreskin keratinocytes (PHFKs). Long-term cell culture studies resulted in death at passage 9 of vector-transduced PHFKs (negative control), but survival of both E6 PHFKs to passage 65 (and beyond). Compared with E6/E7 PHFKs, AA/E7 PHFKs were significantly faster dividing, developed larger cells in monolayer cultures, showed double the epithelial thickness and expressed cytokeratin 10 when grown as organotypic raft cultures. Telomerase activation and p53 inactivation, two hallmarks of immortalization, were not significantly different between the two populations. Both were resistant to anoikis at later passages, but only AA/E7 PHFKs acquired the capacity for in vitro transformation. Proteomic analysis revealed markedly different protein patterns between E6/E7 and AA/E7, particularly with respect to key cellular metabolic enzymes. Our results provide new insights into the reasons underlying the greater prevalence of the AA variant in cervical cancer as evidenced by characteristics associated with higher oncogenic potential.
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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.