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Pathogens (Basel, Switzerland) May 2024Breast cancer is the most common malignancy in the female sex; although recent therapies have significantly changed the natural history of this cancer, it remains a... (Review)
Review
Breast cancer is the most common malignancy in the female sex; although recent therapies have significantly changed the natural history of this cancer, it remains a significant challenge. In the past decade, evidence has been put forward that some oncogenic viruses may play a role in the development of sporadic breast cancer; however, data are scattered and mostly reported as sparse case series or small case-control studies. In this review, we organize and report current evidence regarding the role of high-risk human papillomavirus, mouse mammary tumor virus, Epstein-Barr virus, cytomegalovirus, bovine leukemia virus, human polyomavirus 2, and Merkel cell polyomavirus in the pathogenesis of breast cancer.
PubMed: 38921749
DOI: 10.3390/pathogens13060451 -
Current Issues in Molecular Biology Jun 2024Human papillomavirus 16 (HPV 16) infection is associated with several types of cancer, such as head and neck, cervical, anal, and penile cancer. Its oncogenic potential...
Bioinformatics Analysis Reveals E6 and E7 of HPV 16 Regulate Metabolic Reprogramming in Cervical Cancer, Head and Neck Cancer, and Colorectal Cancer through the PHD2-VHL-CUL2-ELOC-HIF-1α Axis.
Human papillomavirus 16 (HPV 16) infection is associated with several types of cancer, such as head and neck, cervical, anal, and penile cancer. Its oncogenic potential is due to the ability of the E6 and E7 oncoproteins to promote alterations associated with cell transformation. HPV 16 E6 and E7 oncoproteins increase metabolic reprogramming, one of the hallmarks of cancer, by increasing the stability of hypoxia-induced factor 1 α (HIF-1α) and consequently increasing the expression levels of their target genes. In this report, by bioinformatic analysis, we show the possible effect of HPV 16 oncoproteins E6 and E7 on metabolic reprogramming in cancer through the E6-E7-PHD2-VHL-CUL2-ELOC-HIF-1α axis. We proposed that E6 and E7 interact with VHL, CUL2, and ELOC in forming the E3 ubiquitin ligase complex that ubiquitinates HIF-1α for degradation via the proteasome. Based on the information found in the databases, it is proposed that E6 interacts with VHL by blocking its interaction with HIF-1α. On the other hand, E7 interacts with CUL2 and ELOC, preventing their binding to VHL and RBX1, respectively. Consequently, HIF-1α is stabilized and binds with HIF-1β to form the active HIF1 complex that binds to hypoxia response elements (HREs), allowing the expression of genes related to energy metabolism. In addition, we suggest an effect of E6 and E7 at the level of PHD2, VHL, CUL2, and ELOC gene expression. Here, we propose some miRNAs targeting PHD2, VHL, CUL2, and ELOC mRNAs. The effect of E6 and E7 may be the non-hydroxylation and non-ubiquitination of HIF-1α, which may regulate metabolic processes involved in metabolic reprogramming in cancer upon stabilization, non-degradation, and translocation to the nucleus.
PubMed: 38921041
DOI: 10.3390/cimb46060370 -
Current Oncology (Toronto, Ont.) Jun 2024The rates of cervical cancer screening in Cameroon are unknown and HPV vaccination coverage for age-appropriate youths is reported at 5%.
INTRODUCTION
The rates of cervical cancer screening in Cameroon are unknown and HPV vaccination coverage for age-appropriate youths is reported at 5%.
OBJECTIVES
To implement the mother-child approach to cervical cancer prevention (cervical screening by HPV testing for mothers and HPV vaccination for daughters) in Meskine, Far North, Cameroon.
METHODS
After the sensitization of the Meskine-Maroua region using education and a press-release by the Minister of Public Health, a 5-day mother-child campaign took place at Meskine Baptist Hospital. The Ampfire HPV Testing was free for 500 women and vaccination was free for age-appropriate children through the EPI program. Nurses trained in cervical cancer education conducted group teaching sessions prior to having each woman retrieve a personal sample. Self-collected samples were analyzed for HPV the same day. All women with positive tests were assessed using VIA-VILI and treated as appropriate for precancers.
RESULTS
505 women were screened, and 92 children vaccinated (34 boys and 58 girls). Of those screened, 401 (79.4%) were aged 30-49 years old; 415 (82%) married; 348 (69%) no education. Of the HPV positive cases (101): 9 (5.9%) were HPV 16, 11 (10.1%) HPV 18, 74 (73%) HPV of 13 other types. Those who were both HPV and VIA-VILI positive were treated by thermal ablation (63%) or LEEP (25%).
CONCLUSION
The mother-child approach is an excellent method to maximize primary and secondary prevention against cervical cancer.
Topics: Humans; Uterine Cervical Neoplasms; Female; Cameroon; Adult; Middle Aged; Papillomavirus Vaccines; Early Detection of Cancer; Papillomavirus Infections; Child; Male; Adolescent; Young Adult; Resource-Limited Settings
PubMed: 38920728
DOI: 10.3390/curroncol31060244 -
Cells Jun 2024Recent studies have highlighted neurons and their associated Schwann cells (SCs) as key regulators of cancer development. However, the mode of their interaction with...
Recent studies have highlighted neurons and their associated Schwann cells (SCs) as key regulators of cancer development. However, the mode of their interaction with tumor cells or other components of the tumor microenvironment (TME) remains elusive. We established an SC-related 43-gene set as a surrogate for peripheral nerves in the TME. Head and neck squamous cell carcinoma (HNSCC) from The Cancer Genome Atlas (TCGA) were classified into low, intermediate and high SC score groups based on the expression of this gene set. Perineural invasion (PNI) and TGF-β signaling were hallmarks of SC tumors, whereas SC tumors were enriched for HPV16-positive OPSCC and higher PI3K-MTOR activity. The latter activity was partially explained by a higher frequency of mutation and copy number gain. The inverse association between PI3K-MTOR activity and peripheral nerve abundance was context-dependent and influenced by the mutation status. An in silico drug screening approach highlighted the potential vulnerabilities of HNSCC with variable SC scores and predicted a higher sensitivity of SC tumors to DNA topoisomerase inhibitors. In conclusion, we have established a tool for assessing peripheral nerve abundance in the TME and provided new clinical and biological insights into their regulation. This knowledge may pave the way for new therapeutic strategies and impart proof of concept in appropriate preclinical models.
Topics: Humans; Tumor Microenvironment; Squamous Cell Carcinoma of Head and Neck; Phosphatidylinositol 3-Kinases; Signal Transduction; Peripheral Nerves; Head and Neck Neoplasms; Mutation; TOR Serine-Threonine Kinases; Class I Phosphatidylinositol 3-Kinases; Schwann Cells; PTEN Phosphohydrolase; Gene Expression Regulation, Neoplastic; Tumor Suppressor Protein p53
PubMed: 38920662
DOI: 10.3390/cells13121033 -
Cells Jun 2024Head and neck cancers rank as the sixth most prevalent cancers globally. In addition to traditional risk factors such as smoking and alcohol use, human papillomavirus...
Head and neck cancers rank as the sixth most prevalent cancers globally. In addition to traditional risk factors such as smoking and alcohol use, human papillomavirus (HPV) infections are becoming a significant causative agent of head and neck cancers, particularly among Western populations. Although HPV offers a significant survival benefit, the search for better biomarkers is still ongoing. In the current study, our objective was to investigate whether the expression levels of three PDZ-domain-containing proteins (SCRIB, NHERF2, and DLG1), known HPV E6 cellular substrates, influence the survival of HNSCC patients treated by primary surgery (n = 48). Samples were derived from oropharyngeal and oral cancers, and HPV presence was confirmed by PCR and p16 staining. Clinical and follow-up information was obtained from the hospital database and the Croatian Cancer registry up to November 2023. Survival was evaluated using the Kaplan-Meier method and Cox proportional hazard regression. The results were corroborated through the reanalysis of a comparable subset of TCGA cancer patients (n = 391). In conclusion, of the three targets studied, only SCRIB levels were found to be an independent predictor of survival in the Cox regression analysis, along with tumor stage. Further studies in a more typical Western population setting are needed since smoking and alcohol consumption are still prominent in the Croatian population, while the strongest association between survival and SCRIB levels was seen in HPV-negative cases.
Topics: Humans; Male; Female; Prognosis; Tumor Suppressor Proteins; Middle Aged; Membrane Proteins; Papillomavirus Infections; Papillomaviridae; Aged; Squamous Cell Carcinoma of Head and Neck; Head and Neck Neoplasms; Biomarkers, Tumor; Kaplan-Meier Estimate; Adult
PubMed: 38920638
DOI: 10.3390/cells13121002 -
MSphere Jun 2024James Romero-Masters works in the field of tumor virology, focusing on the role of the human papillomavirus oncogenes in pathogenesis. In this mSphere of Influence...
James Romero-Masters works in the field of tumor virology, focusing on the role of the human papillomavirus oncogenes in pathogenesis. In this mSphere of Influence article, they reflect on how the article "Mouse papillomavirus infection persists in mucosal tissues of an immunocompetent mouse strain and progresses to cancer" impacted them, informing their research strategies, and what it means for the mouse papillomavirus model.
PubMed: 38920397
DOI: 10.1128/msphere.00177-24 -
Frontiers in Oncology 2024The devastating scourge of cervical cancer in Africa is largely due to the absence of preventive interventions, driven by low awareness and poor perception of the...
BACKGROUND
The devastating scourge of cervical cancer in Africa is largely due to the absence of preventive interventions, driven by low awareness and poor perception of the disease in the continent. This work is a preliminary effort toward understanding key social drivers promoting this disease in our immediate environment with a view to mitigating it.
METHOD
Female students of two tertiary health institutions in Azare, northeastern Nigeria, were approached to participate in this cross-sectional descriptive study. A structured self-administered questionnaire was administered to consenting participants and covered questions on their socio-demographics, awareness, perception, and attitude about/toward cervical cancer and its prevention. The responses were scrutinized for coherency and categorized into themes using summary statistics, while a chi-square test was used to determine the association between awareness of cervical cancer and participant age, marital status, religion, screening uptake, and willingness to undergo screen.
RESULTS
Awareness of cervical cancer was recorded among 174/230 (75.7%) respondents who enrolled in this study; 117 (67.2%) knew that it was preventable, but only three (1.3%) respondents had undergone screening. Among the aware participants, 91 (52.3%) and 131 (75.3%) knew that sexual intercourse and multiple sexual partners are risk factors for the disease, respectively. In contrast, knowledge of the etiology was poor; 82 (47.1%) respondents who knew it was preventable had heard about human papillomavirus (HPV), while 72 (41.4%) knew that HPV causes cervical cancer. Most (78%) of the participants expressed willingness to take a human papillomavirus vaccine or undergo screening (84.6%) if made available to them. Awareness was significantly associated with participants' age (p = 0.022) and willingness to undergo screening (p = 0.016).
CONCLUSION
This study revealed discordance between awareness and knowledge about cervical cancer. Educational initiatives reflective of population perception/knowledge of cervical cancer are needed to mitigate the rising incidence of this disease, especially among female healthcare providers.
PubMed: 38919519
DOI: 10.3389/fonc.2024.1415627 -
Frontiers in Microbiology 2024The incidence of oropharyngeal cancer (OPC) is increasing. This study used bibliometric analysis and topic modeling to explore the research trends and advancements in...
OBJECTIVES
The incidence of oropharyngeal cancer (OPC) is increasing. This study used bibliometric analysis and topic modeling to explore the research trends and advancements in this disease over the past 10 years, providing valuable insights to guide future investigations.
METHODS
7,355 English articles from 2013 to 2022 were retrieved from the Web of Science Core Collection for bibliometric analysis. Topic modeling was applied to 1,681 articles from high-impact journals, followed by an assessment of topic significance ranking (TSR). Medical Subject Headings (MeSH) terms were extracted using R and Python, followed by an analysis of the terms associated with each topic and on an annual basis. Additionally, genes were extracted and the number of genes appearing each year and the newly emerged genes were counted.
RESULTS
The bibliometric analysis suggested that the United States and several European countries hold pivotal positions in research. Current research is focused on refining treatments, staging and stratification. Topic modeling revealed 12 topics, emphasizing human papillomavirus (HPV) and side effect reduction. MeSH analysis revealed a growing emphasis on prognosis and quality of life. No new MeSH terms emerged after 2018, suggesting that the existing terms have covered most of the core concepts within the field of oropharyngeal cancers. Gene analysis identified TP53 and EGFR as the most extensively studied genes, with no novel genes discovered after 2019. However, CD69 and CXCL9 emerged as new genes of interest in 2019, reflecting recent research trends and directions.
CONCLUSION
HPV-positive oropharyngeal cancer research, particularly treatment de-escalation, has gained significant attention. However, there are still challenges in diagnosis and treatment that need to be addressed. In the future, more research will focus on this issue, indicating that this field still holds potential as a research hotspot.
PubMed: 38919494
DOI: 10.3389/fmicb.2024.1387679 -
BMC Oral Health Jun 2024Despite the better prognosis associated with human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma (OPSCC), some patients experience relapse and...
BACKGROUND
Despite the better prognosis associated with human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma (OPSCC), some patients experience relapse and succumb to the disease; thus, there is a need for biomarkers identifying these patients for intensified treatment. Leucine-rich repeats and immunoglobulin-like domain (LRIG) protein 1 is a negative regulator of receptor tyrosine kinase signaling and a positive prognostic factor in OPSCC. Studies indicate that LRIG1 interacts with the LIM domain 7 protein (LMO7), a stabilizer of adherence junctions. Its role in OPSCC has not been studied before.
METHODS
A total of 145 patients diagnosed with OPSCC were enrolled. Immunohistochemical LMO7 expression and staining intensity were evaluated in the tumors and correlated with known clinical and pathological prognostic factors, such as HPV status and LRIG1, CD44, Ki67, and p53 expression.
RESULTS
Our results show that high LMO7 expression is associated with significantly longer overall survival (OS) (p = 0.044). LMO7 was a positive prognostic factor for OS in univariate analysis (HR 0.515, 95% CI: 0.267-0.994, p = 0.048) but not in multivariate analysis. The LMO7 expression correlated with LRIG1 expression (p = 0.048), consistent with previous findings. Interestingly, strong LRIG1 staining intensity was an independent negative prognostic factor in the HPV-driven group of tumors (HR 2.847, 95% Cl: 1.036-7.825, p = 0.043).
CONCLUSIONS
We show for the first time that high LMO7 expression is a positive prognostic factor in OPSCC, and we propose that LMO7 should be further explored as a biomarker. In contrast to previous reports, LRIG1 expression was shown to be an independent negative prognostic factor in HPV-driven OPSCC.
Topics: Humans; Oropharyngeal Neoplasms; Male; Female; Middle Aged; Prognosis; LIM Domain Proteins; Biomarkers, Tumor; Carcinoma, Squamous Cell; Aged; Transcription Factors; Membrane Glycoproteins; Adult; Ki-67 Antigen; Hyaluronan Receptors; Tumor Suppressor Protein p53; Papillomavirus Infections; Immunohistochemistry; Aged, 80 and over; Survival Rate
PubMed: 38918827
DOI: 10.1186/s12903-024-04510-4 -
Asian Pacific Journal of Cancer... Jun 2024
Review
Topics: Humans; India; Papillomavirus Vaccines; Health Knowledge, Attitudes, Practice; Papillomavirus Infections; Vaccination; Papillomaviridae; Uterine Cervical Neoplasms; Human Papillomavirus Viruses
PubMed: 38918643
DOI: 10.31557/APJCP.2024.25.6.1857