Human papillomavirus genomics: Understanding carcinogenicity

Tumour Virus Research, Journal Year: 2023, Volume and Issue: 15, P. 200258 - 200258

Published: Feb. 20, 2023

Human papillomavirus (HPV) causes virtually all cervical cancers and many at other anatomical sites in both men women. However, only 12 of 448 known HPV types are currently classified as carcinogens, even the most carcinogenic type - HPV16 rarely leads to cancer. is therefore necessary but insufficient for cancer, with contributing factors including host viral genetics. Over last decade, whole genome sequencing has established that fine-scale within-type variation influences precancer/cancer risks, these risks vary by histology race/ethnicity. In this review, we place findings context life cycle evolution various levels diversity: between-type, within-type, within-host. We also discuss key concepts interpreting genomic data, features genome; events leading carcinogenesis; role APOBEC3 infection evolution; methodologies use deep (high-coverage) characterize within-host variation, opposed relying on a single representative (consensus) sequence. Given continued high burden HPV-associated cancers, understanding carcinogenicity remains important better understanding, preventing, treating attributable infection.

Language: Английский

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HPV oncogenes expressed from only one of multiple integrated HPV DNA copies drive clonal cell expansion in cervical cancer

mBio, Journal Year: 2024, Volume and Issue: 15(5)

Published: April 16, 2024

The integration of HPV DNA into human chromosomes plays a pivotal role in the onset papillomavirus-related cancers. often occurs by linearizing viral E1/E2 region, resulting loss critical early polyadenylation signal (PAS), which is essential for E6E7 bicistronic transcripts and expression E6 E7 oncogenes. Here, we provide compelling evidence that, despite presence numerous integrated copies, virus-host fusion originate from only single HPV16 HPV18 cervical cancers cancer-derived cell lines. host genomic elements neighboring are efficient oncogenes that leads to clonal expansion. RNAs produced use RNA downstream site, almost all involve splicing sequences. In culture, siRNAs specifically targeting portion effectively silenced expression. This, turn, inhibited growth promoted senescence HPV16+ CaSki HPV18+ HeLa cells. Showing site instrumental expansion sheds new light on mechanisms HPV-induced carcinogenesis could be used development precision medicine tailored combat HPV-related malignancies.

Language: Английский

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HPV Infections—Classification, Pathogenesis, and Potential New Therapies

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(14), P. 7616 - 7616

Published: July 11, 2024

To date, more than 400 types of human papillomavirus (HPV) have been identified. Despite the creation effective prophylactic vaccines against most common genital HPVs, viruses remain among prevalent pathogens found in humans. According to WHO data, they are cause 5% all cancers. Even frequent persistent and recurrent benign lesions such as warts. HPVs resistant many disinfectants relatively unsusceptible external conditions. There is still no drug available inhibit viral replication, treatment based on removing or stimulating host immune system. This paper presents systematics HPV differences structure between different genetic types, lineages, sublineages, literature GenBank data. We also present pathogenesis diseases caused by HPV, with a special focus role played E6, E7, other proteins development cancerous lesions. discuss further prospects for infections, including, others, substances that block entry into cells, inhibitors early proteins, some plant origin well new possibilities therapeutic vaccines.

Language: Английский

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Navigating therapeutic strategies: HPV classification in head and neck cancer

British Journal of Cancer, Journal Year: 2024, Volume and Issue: 131(2), P. 220 - 230

Published: April 20, 2024

The World Health Organisation recognised human papillomavirus (HPV) as the cause of multiple cancers, including head and neck cancers. HPV is a double-stranded DNA virus, its viral gene expression can be controlled after infection by cellular promoters. In cancer cells, genome detected either integrated into host genome, episomal (extrachromosomal), or mixture episomal. Viral integration requires breakage both DNA, rate correlates with level damage. Interestingly, patients HPV-positive cancers generally have good prognosis except for group fully who show worst clinical outcomes. Those present lowered genes limited infiltration cytotoxic T cells. An impediment to effective therapy applications in clinic sole testing positivity without considering status. This review will discuss potential determinant response therapies highlight field novel therapeutic avenue that would reduce burden improve patient survival.

Language: Английский

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Roles of human papillomavirus in cancers: oncogenic mechanisms and clinical use

Signal Transduction and Targeted Therapy, Journal Year: 2025, Volume and Issue: 10(1)

Published: Jan. 24, 2025

Abstract Human papillomaviruses, particularly high-risk human have been universally considered to be associated with the oncogenesis and progression of various cancers. The genome papillomaviruses is circular, double-stranded DNA that encodes early late proteins. Each proteins crucial significance in infecting epithelium host cells persistently supporting viral integrating into cells. Notably, E6 E7 proteins, classified as oncoproteins, trigger incidence cancers by fostering cell proliferation, hindering apoptosis, evading immune surveillance, promoting invasion, disrupting balance cellular metabolism. Therefore, targeting decoding molecular mechanisms which drive carcinogenesis are great necessity better treat papillomaviruses-related applied clinically different facets papillomavirus-related cancers, including prevention, screening, diagnosis, treatment, prognosis. Several types prophylactic vaccines publicly utilized worldwide greatly decreased occurrence benefited numerous people. Although therapeutic developed tested clinically, none them officially approved date. Enhancing efficacy searching for innovative technologies remain critical challenges warrant continuous research attention future.

Language: Английский

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The Relationship Between Cervicovaginal Infection, Human Papillomavirus Infection and Cervical Intraepithelial Neoplasia in Romanian Women

Diseases, Journal Year: 2025, Volume and Issue: 13(1), P. 18 - 18

Published: Jan. 16, 2025

Cervical intraepithelial neoplasia (CIN) is a premalignant cervical condition closely linked to persistent high-risk HPV infection, major risk factor for cancer. This study aims investigate the relationship between cervicovaginal infections, and CIN development in 94 Romanian women with lesions. Comprehensive assessments included genotyping, cytology, colposcopy, histopathology. In 53.20% of cases, vaginal infections were identified, Candida albicans most frequently associated HPV. Histopathology revealed 48.94% low-grade CIN, 42.55% high-grade 8.51% invasive carcinoma. There was strong correlation types (especially 16 18), colposcopic findings, histopathology, age. emphasizes mutual effect infection increasing developing cancer among women. Persistent types, particularly 18, has been confirmed as primary driver progression.

Language: Английский

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Human papillomavirus associated cervical lesion: pathogenesis and therapeutic interventions

MedComm, Journal Year: 2023, Volume and Issue: 4(5)

Published: Sept. 14, 2023

Abstract Human papillomavirus (HPV) is the most prevalent sexually transmitted virus globally. Persistent high‐risk HPV infection can result in cervical precancerous lesions and cancer, with 70% of cancer cases associated types HPV16 18. imposes a significant financial psychological burden. Therefore, studying methods to eradicate halt progression remains crucial. This review comprehensively explores mechanisms underlying HPV‐related lesions, including viral life cycle, immune factors, epithelial cell malignant transformation, host environmental contributing factors. Additionally, we provide comprehensive overview treatment for cancer. Our focus on immunotherapy, encompassing therapeutic vaccines, checkpoint inhibitors, advanced adoptive T therapy. Furthermore, summarize commonly employed drugs other nonsurgical treatments currently utilized clinical practice managing lesions. Gene editing technology undergoing research and, although not yet officially numerous preclinical studies have substantiated its efficacy. it holds promise as precise strategy

Language: Английский

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The human papillomavirus late life cycle and links to keratinocyte differentiation

Journal of Medical Virology, Journal Year: 2024, Volume and Issue: 96(2)

Published: Feb. 1, 2024

Abstract Regulation of human papillomavirus (HPV) gene expression is tightly linked to differentiation the keratinocytes virus infects. HPV late confined cells in upper layers epithelium where capsid proteins are synthesized. As these highly immunogenic, and an immune‐privileged site, this spatial restriction aids immune evasion. Many decades work have contributed current understanding how occurs at a molecular level. This review will examine what known about HPV‐infected lesions dissect intricacies regulation. Future directions for novel antiviral approaches be highlighted.

Language: Английский

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The potential use of therapeutics and prophylactic mRNA vaccines in human papillomavirus (HPV)

Virology Journal, Journal Year: 2024, Volume and Issue: 21(1)

Published: May 31, 2024

Abstract Cervical cancer (CC) and other malignant malignancies are acknowledged to be primarily caused by persistent human papillomavirus (HPV) infection. Historically, vaccinations against viruses that produce neutralizing antibodies unique the virus have been an affordable way manage viral diseases. CC risk is decreased, but not eliminated, HPV vaccinations. Since made available globally, almost 90% of infections successfully avoided. On lesions diseases already present, however, no discernible treatment benefit has shown. As a result, therapeutic vaccines elicit immune responses mediated cells necessary for established cancers. mRNA possess remarkable potential in combating malignancy as result their superior industrial production, safety, efficacy. Furthermore, considering expeditiousness vaccine exhibits promise approach targeting HPV. Given HPV-encoded early proteins, including oncoproteins E6 E7, consistently present HPV-related cancers pre-cancerous crucial functions progression persistence diseases, they serve ideal targets vaccines. The action mechanism vaccines, recent advancements clinical trials, applications highlighted this study, which also offers quick summary state Lastly, we highlight few difficulties with vaccination practice provide our thoughts on further quickly changing sector. It expected will soon produced prevention treatment. Graphical

Language: Английский

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Portable, and ultrasensitive HR-HPV tests based on nucleic acid biosensors

Frontiers in Cellular and Infection Microbiology, Journal Year: 2024, Volume and Issue: 14

Published: Feb. 28, 2024

Cervical cancer is the third most common threatening women’s health globally, and high-risk human papillomavirus (HR-HPV) infection main cause of cervical worldwide. Given recurrent nature HR-HPV infection, accurate screening essential for its control. Since commonly used polymerase chain reaction (PCR) technique limited by professional equipment personnel, convenient ultrasensitive detection methods are still highly needed. As new molecular methods, nucleic acid amplification-based biosensors have advantages high sensitivity, rapid operation, portability, which helpful point-of-care testing in rural remote areas. This review summarized based on a variety amplification strategies involved improved PCR, loop-mediated isothermal amplification, recombinase hybridization reaction, catalyzed hairpin assembly, CRISPR/Cas systems. In combination with microfluidic technology, lateral flow assays, electrochemical analysis other sensing technologies, throughput, short response time, sensitivity easy operation field. Although there shortcomings, such as cost poor reproducibility, this approach will be suitable on-site or auxiliary clinical diagnosis complex environments areas future.

Language: Английский

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