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British Journal of Cancer Feb 2020The human papillomavirus (HPV) family includes more than 170 different types of virus that infect stratified epithelium. High-risk HPV is well established as the primary... (Review)
Review
The human papillomavirus (HPV) family includes more than 170 different types of virus that infect stratified epithelium. High-risk HPV is well established as the primary cause of cervical cancer, but in recent years, a clear role for this virus in other malignancies is also emerging. Indeed, HPV plays a pathogenic role in a subset of head and neck cancers-mostly cancers of the oropharynx-with distinct epidemiological, clinical and molecular characteristics compared with head and neck cancers not caused by HPV. This review summarises our current understanding of HPV in these cancers, specifically detailing HPV infection in head and neck cancers within different racial/ethnic subpopulations, and the differences in various aspects of these diseases between women and men. Finally, we provide an outlook for this disease, in terms of clinical management, and consider the issues of 'diagnostic biomarkers' and targeted therapies.
Topics: DNA, Viral; Ethnicity; Head and Neck Neoplasms; Human papillomavirus 16; Human papillomavirus 18; Humans; In Situ Hybridization; Papillomaviridae; Papillomavirus Infections; Prevalence; Prognosis; RNA, Viral; Reverse Transcriptase Polymerase Chain Reaction; Risk Factors; Sex Factors; Squamous Cell Carcinoma of Head and Neck
PubMed: 31708575
DOI: 10.1038/s41416-019-0602-7 -
Seminars in Radiation Oncology Oct 2021Human papillomavirus (HPV) is a ubiquitous DNA virus that infects squamous epithelia. Though HPV only encodes 8 genes, it is capable of causing cellular transformation... (Review)
Review
Human papillomavirus (HPV) is a ubiquitous DNA virus that infects squamous epithelia. Though HPV only encodes 8 genes, it is capable of causing cellular transformation and ultimately cancer in host cells. In this article we review the classification of HPV viruses, their genetic structure and life cycle, viral gene biology, and provide an overview of the role of HPV in cancer. We explain how the viral life cycle can lead to integration of viral DNA into the host genome leading to increased cell cycle progression, decreased apoptosis, altered DNA repair, and chromosomal instability. We describe the multifaceted roles of the canonical oncogenes E6 and E7 in promoting tumorigenesis and the important role of other viral genes in regulating cancer development. We also review how the virus actively suppresses innate and adaptive immunity to evade immune detection and promote a pro-tumorigenic microenvironment. The biology presented here will serve as a foundation to the other chapters in this edition and we hope it will incite enthusiasm for continued research on this fascinating virus that causes significant morbidity and mortality worldwide.
Topics: Alphapapillomavirus; Biology; Carcinogenesis; Humans; Neoplasms; Oncogene Proteins, Viral; Papillomaviridae; Papillomavirus E7 Proteins; Papillomavirus Infections; Tumor Microenvironment
PubMed: 34455982
DOI: 10.1016/j.semradonc.2021.02.006 -
Tumour Virus Research Dec 2023The incorporation of HPV DNA testing into cervical screening programs has shown that many HPV-positive women are cytologically normal, with HPV-positivity fluctuating... (Review)
Review
The incorporation of HPV DNA testing into cervical screening programs has shown that many HPV-positive women are cytologically normal, with HPV-positivity fluctuating throughout life. Such results suggest that papillomaviruses may persist in a latent state after disease clearance, with sporadic recurrence. It appears that virus latency represents a narrow slot in a wider spectrum of subclinical and possibly productive infections. Clinical studies, and animal model infection studies, suggested a key role for host immune surveillance in maintaining such asymptomatic infections, and although infections may also be cleared, most studies have used the term 'clearance' to describe a situation where the presence of HPV DNA falls below the clinical detection level. Given our knowledge of papillomavirus immune evasion strategies and the restricted pattern of viral gene expression required for 'basal cell' persistence, the term 'apparent clearance' and 'subclinical persistence' of infection may better summarise our understanding. Subclinical infection also encompasses the lag phase, which occurs between infection and lesion development. This is dependent on infection titre, with multifocal infections developing more rapidly to disease. These concepts can usefully influence patient management where HPV-positivity occurs sometime after the onset of sexual activity, and where vertical transmission is suspected despite a lag period.
Topics: Animals; Humans; Female; Papillomavirus Infections; Human Papillomavirus Viruses; Uterine Cervical Neoplasms; Asymptomatic Infections; Early Detection of Cancer; Papillomaviridae; DNA
PubMed: 37354969
DOI: 10.1016/j.tvr.2023.200268 -
Journal of Medical Virology May 2023Although cervical intraepithelial neoplasia (CIN) lesions are considered to be not randomly distributed across the cervix, but predominantly in the anterior wall, the...
Although cervical intraepithelial neoplasia (CIN) lesions are considered to be not randomly distributed across the cervix, but predominantly in the anterior wall, the clinicopathological etiology remains unknown. Herein, we aimed to elucidate the relationship between quantitatively measured area of CIN2/3 and cervical cancer associated factors by retrospective cohort study. We analyzed 235 consecutive therapeutic conization specimens dissected as a single intact section to determine CIN2/3 area and its correlation with both clinical risk factors including human papillomavirus (HPV) status (single or multiple infection) and uterine position defined by transvaginal ultrasound. Cervical wall was classified into three groups: anterior: (11, 12, 1, and 2 o'clock), posterior (5, 6, 7, and 8 o'clock) and lateral (3, 4, 9, and 10 o'clock). Multiple regression revealed that younger age and HPV16 status were significantly correlated with CIN2/3 area (p = 0.0224 and p = 0.0075, respectively). The Jonckheere-Terpstra test showed a significant trend: CIN2/3 area was highest in the single HPV16 group, followed by the multiple HPV16 group and the non-HPV16 group (p < 0.0001). CIN2/3 area in the anterior wall was statistically significantly larger than the posterior and lateral wall (p = 0.0059 and p = 0.0107, respectively). CIN2/3 area in the anterior wall was significantly greater with anteversion-anteflexion than retroversion-retroflexion (p = 0.0485), whereas CIN2/3 area in the posterior wall was significantly larger with retroversion-retroflexion than anteversion-anteflexion (p = 0.0394). In conclusion, the topographical distribution of CIN2/3 area is closely associated with patient age, high-risk HPV status, especially single HPV16 infection and uterine position.
Topics: Female; Humans; Uterine Cervical Neoplasms; Human Papillomavirus Viruses; Retrospective Studies; Uterine Cervical Dysplasia; Cervix Uteri; Human papillomavirus 16; Papillomavirus Infections; Papillomaviridae
PubMed: 37212300
DOI: 10.1002/jmv.28777 -
Recent Results in Cancer Research.... 2021Human papillomaviruses (HPVs) are small DNA viruses that infect basal epithelial cells and are the causative agents of cervical, anogenital, as well as oral cancers....
Human papillomaviruses (HPVs) are small DNA viruses that infect basal epithelial cells and are the causative agents of cervical, anogenital, as well as oral cancers. High-risk HPVs are responsible for nearly half of all virally induced cancers. Viral replication and amplification are intimately linked to the stratified epithelium differentiation program. The E6 and E7 proteins contribute to the development of cancers in HPV positive individuals by hijacking cellular processes and causing genetic instability. This genetic instability induces a robust DNA damage response and activating both ATM and ATR repair pathways. These pathways are critical for the productive replication of high-risk HPVs, and understanding how they contribute to the viral life cycle can provide important insights into HPV's role in oncogenesis. This review will discuss the role that differentiation and the DNA damage responses play in productive replication of high-risk HPVs as well as in the development of cancer.
Topics: Alphapapillomavirus; DNA Repair; Humans; Oncogene Proteins, Viral; Papillomaviridae; Papillomavirus Infections; Virus Replication
PubMed: 33200365
DOI: 10.1007/978-3-030-57362-1_7 -
Viruses May 2022Papillomaviruses (PV) replicate in undifferentiated keratinocytes at low levels and to high levels in differentiated cells. The restricted replication in... (Review)
Review
Papillomaviruses (PV) replicate in undifferentiated keratinocytes at low levels and to high levels in differentiated cells. The restricted replication in undifferentiated cells is mainly due to the expression of the conserved viral E8^E2 repressor protein, a fusion protein consisting of E8 and the hinge, DNA-binding, and dimerization domain of E2. E8^E2 binds to viral genomes and represses viral transcription and genome replication by recruiting cellular NCoR/SMRT-HDAC3 corepressor complexes. Tissue culture experiments have revealed that E8^E2 modulates long-term maintenance of extrachromosomal genomes, productive replication, and immortalization properties in a virus type-dependent manner. Furthermore, in vivo experiments have indicated that Mus musculus PV1 E8^E2 is required for tumor formation in immune-deficient mice. In summary, E8^E2 is a crucial inhibitor whose levels might determine the outcome of PV infections.
Topics: Animals; DNA-Binding Proteins; Mice; Papillomaviridae; Papillomavirus Infections; Viral Proteins; Virus Replication
PubMed: 35632695
DOI: 10.3390/v14050953 -
Acta Cytologica 2020The association between high-risk genotypes of human papillomavirus (hr-HPV) and cervical cancer is well established. As hr-HPV testing is rapidly becoming a part of... (Review)
Review
The association between high-risk genotypes of human papillomavirus (hr-HPV) and cervical cancer is well established. As hr-HPV testing is rapidly becoming a part of routine cervical cancer screening, either in conjunction with cytology or as primary testing, the management of hr-HPV-positive women has to be tailored in a way that increases the detection of cervical abnormalities while decreasing unnecessary colposcopic biopsies or other invasive procedures. In this review, we discuss the overall utility and strategies of hr-HPV testing, as well as the advantages and limitations of potential triage strategies for hr-HPV-positive women, including HPV genotyping, p16/Ki-67 dual staining, and methylation assays.
Topics: Adult; Cytodiagnosis; Early Detection of Cancer; Female; Genotype; Humans; Middle Aged; Papillomaviridae; Papillomavirus Infections; Triage; Uterine Cervical Neoplasms
PubMed: 30889579
DOI: 10.1159/000496569 -
Viruses Dec 2021Previously, human papillomaviruses were best known for causing diseases in the genital tract, where high-risk types may cause, e.g., cancer of the cervix uteri, while...
Previously, human papillomaviruses were best known for causing diseases in the genital tract, where high-risk types may cause, e.g., cancer of the cervix uteri, while low risk types could cause condylomas [...].
Topics: Head; Head and Neck Neoplasms; Humans; Neck; Papillomaviridae; Papillomavirus Infections; Papillomavirus Vaccines
PubMed: 34960721
DOI: 10.3390/v13122452 -
International Journal of Oncology Sep 2019Human papillomavirus (HPV) is the most common sexually transmitted infection, exhibiting a tropism for the epidermis and mucosae. The link between persistent HPV... (Review)
Review
Human papillomavirus (HPV) is the most common sexually transmitted infection, exhibiting a tropism for the epidermis and mucosae. The link between persistent HPV infection and malignancies involving the anogenital tract as well as the head and neck has been well‑established, and it is estimated that HPV‑related cancers involving various anatomical sites account for 4.5% of all human cancers. Current prophylactic vaccines against HPV have enabled the prevention of associated malignancies. However, the sizeable population base of current infection in whom prophylactic vaccines are not applicable, certain high‑risk HPV types not included in vaccines, and the vast susceptible population in developing countries who do not have access to the costly prophylactic vaccines, put forward an imperative need for effective therapies targeting persistent infection. In this article, the life cycle of HPV, the mechanisms facilitating HPV evasion of recognition and clearance by the host immune system, and the promising therapeutic strategies currently under investigation, particularly antiviral drugs and therapeutic vaccines, are reviewed.
Topics: Antiviral Agents; Humans; Immune Evasion; Life Cycle Stages; Neoplasms; Papillomaviridae; Papillomavirus Infections; Papillomavirus Vaccines
PubMed: 31364734
DOI: 10.3892/ijo.2019.4847 -
Viruses Dec 2022Persistent infection with high-risk human papillomaviruses (HR-HPVs), particularly HPV16 and 18, has long been known to induce cervical cancer progression. However,...
Persistent infection with high-risk human papillomaviruses (HR-HPVs), particularly HPV16 and 18, has long been known to induce cervical cancer progression. However, given that a minority of HPV-infected women develop cancer, analysis of HR-HPV-infected women could help to predict who is at risk of acquiring cervical cancer. Therefore, to improve HR-HPVs detection, we used the FDA-approved cobas 4800 HPV and REBA HPV-ID HPV assays to detect HR-HPVs in colposcopy-derived cervical cells from 303 patients, detecting 72.28% (219) and 71.62% (217) of HR-HPVs positive cases, with HPV16 detection rates of 35.64% (108) and 30.69% (93), respectively. Of the HPV16-positive cases, cobas 4800 and REBA HPV-ID identified 28.81% (51) and 25.42% (45) of the CIN1 cases, and 55% (33) and 50% (30) of the 60 CIN2/3 cases, respectively. HPV-diagnostic concordance was 82.17% overall (kappa = 0.488), 87.45% for HR-HPVs (kappa = 0.689), and 88.33% for CIN2/3 (kappa = 0.51). The HR-HPVs detection rates of these assays were comparable. Our findings reveal that the FDA-approved HR-HPVs detection assay is appropriate for screening women with HR-HPVs infection, and for predicting increased risk of cervical cancer progression. REBA HPV-ID can be used to detect low risk-HPV types in high-grade cervical lesions that are HR-HPV negative as well as in the distribution of HPV types.
Topics: Female; Humans; Uterine Cervical Neoplasms; Uterine Cervical Dysplasia; Human Papillomavirus Viruses; Papillomavirus Infections; Cervix Uteri; Human papillomavirus 16; Early Detection of Cancer; Papillomaviridae; Genotype
PubMed: 36560717
DOI: 10.3390/v14122713