scholarly journals Genetic Predisposition to Persistent Human Papillomavirus-Infection and Virus-Induced Cancers

2021 ◽  
Vol 9 (10) ◽  
pp. 2092
Author(s):  
Helen Espinoza ◽  
Kim T. Ha ◽  
Trang T. Pham ◽  
J. Luis Espinoza
Keyword(s):  
Genetic Variants ◽  
Genome Wide Association Study ◽  
Association Studies ◽  
Hpv Infection ◽  
Human Papillomaviruses ◽  
Sexually Transmitted ◽  
Individual Susceptibility ◽  
Hpv Types ◽  
Genetic And Environmental Factors ◽  
The Individual

Human papillomaviruses (HPVs) are the most common sexually transmitted pathogens worldwide and among the more than 200 identified HPV types, approximately 15 high risk (HR-HPV) types are oncogenic, being strongly associated with the development of cervical cancer, anogenital cancers and an increasing fraction of head and neck squamous cell carcinomas (HNSCC). HPV-associated cervix cancer accounts for 83% of HPV-attributable cancers, and more than two-thirds of those cases occur in developing countries. Despite the high frequency of HPV infections, in most cases, the virus is cleared by the host immune response and only a small proportion of infected individuals develop persistent infections that can result in malignant transformation, indicating that other elements, including biological, genetic and environmental factors may influence the individual susceptibility to HPV-associated cancers. Previous studies have quantified that heritability, in the form of genetic variants, common in the general population, is implicated in nearly 30% of cervical cancers and a large number of studies conducted across various populations have identified genetic variants that appear to be associated with genes that predispose or protect the host to HPV infections thereby affecting individual susceptibility to HPV-associated cancers. In this article, we provide an overview of gene association studies on HPV-associated cancers with emphasis on genome-wide association study (GWAS) that have identified novel genetic factors linked to HPV infection or HPV-associated cancers.

scholarly journals Genetic Polymorphism of Cancer Susceptibility Genes and HPV Infection in Cervical Carcinogenesis

2011 ◽  
Vol 2011 ◽  
pp. 1-8 ◽  
Author(s):  
Osamu Nunobiki ◽  
Masatsugu Ueda ◽  
Eisaku Toji ◽  
Michiko Yamamoto ◽  
Kyoko Akashi ◽  
...  
Keyword(s):  
Cancer Susceptibility ◽  
Association Studies ◽  
Gene Promoter ◽  
Hpv Infection ◽  
Host Susceptibility ◽  
Cervical Carcinogenesis ◽  
Mdm2 Gene ◽  
P53 Codon 72 ◽  
Cancer Susceptibility Genes ◽  
Hpv Types

It is widely accepted that specific human papillomavirus (HPV) types are the central etiologic agent of cervical carcinogenesis. However, a number of infected women do not develop invasive lesions, suggesting that other environmental and host factors may play decisive roles in the persistence of HPV infection and further malignant conversion of cervical epithelium. Although many previous reports have focused on HPV and environmental factors, the role of host susceptibility to cervical carcinogenesis is largely unknown. Here, we review the findings of genetic association studies in cervical carcinogenesis with special reference to polymorphisms of glutathione-S-transferase (GST) isoforms, p53 codon 72, murine double-minute 2 homolog (MDM2) gene promoter 309, and FAS gene promoter -670 together with HPV types including our recent research results.

scholarly journals Papillomavirus can be transmitted through the blood and produce infections in blood recipients: Evidence from two animal models

2019 ◽  
Author(s):  
Nancy M. Cladel ◽  
Pengfei Jiang ◽  
Jingwei J. Li ◽  
Xuwen Peng ◽  
Timothy K. Cooper ◽  
...  
Keyword(s):  
Animal Models ◽  
Hpv Infection ◽  
Human Papillomaviruses ◽  
Viral Dna ◽  
Internal Organs ◽  
Sexually Transmitted ◽  
Potential Source ◽  
Papillomavirus Infection ◽  
Blood Banks ◽  
Gain Access

AbstractHuman papillomavirus (HPV) infections are commonly thought to be strictly sexually transmitted. However, studies have demonstrated the presence of HPV in cancers of many non-sexual internal organs, raising the question as to how the viruses gain access to these sites. A possible connection between blood transfusion and HPV-associated disease has not received much attention. We show, in two animal models, that blood infected with papillomavirus yields infections at permissive sites. Furthermore, we demonstrate that blood from actively infected mice can transmit the infection to naïve animals. Finally, we report papillomavirus infections in the stomach tissues of animals infected via the blood. Stomach tissues are not known to be permissive for papillomavirus infection, although the literature suggests that HPVs may be associated with a subset of gastric cancers. These results indicate that the human blood supply, which is not screened for papillomaviruses, could be a potential source of HPV infection and subsequent cancers.SUMMARYHuman papillomaviruses cause 5% of human cancers. Currently, blood banks do not screen for these viruses. We demonstrate that blood transfused from papillomavirus-infected animals produces infections in recipients. Public health implications are significant if the same is true for humans.DefinitionsLocal papillomavirus infection:An infection initiated by the direct application of virus or viral DNA to the site of infectionIntravenous (IV) papillomavirus infection:An infection resulting from blood-borne delivery of virus or viral DNA to the site of infection.

scholarly journals Virus-like Particle-Based L2 Vaccines against HPVs: Where Are We Today?

Viruses ◽  
2019 ◽  
Vol 12 (1) ◽  
pp. 18 ◽  
Author(s):  
Rashi Yadav ◽  
Lukai Zhai ◽  
Ebenezer Tumban
Keyword(s):  
Amino Acids ◽  
Capsid Protein ◽  
Hpv Vaccine ◽  
Genital Warts ◽  
Human Papillomaviruses ◽  
Target Antigen ◽  
Sexually Transmitted ◽  
Virus Like Particle ◽  
Protective Antibodies ◽  
Hpv Types

Human papillomaviruses (HPVs) are the most common sexually transmitted infections worldwide. Ninety percent of infected individuals clear the infection within two years; however, in the remaining 10% of infected individuals, the infection(s) persists and ultimately leads to cancers (anogenital cancers and head and neck cancers) and genital warts. Fortunately, three prophylactic vaccines have been approved to protect against HPV infections. The most recent HPV vaccine, Gardasil-9 (a nonavalent vaccine), protects against seven HPV types associated with ~90% of cervical cancer and against two HPV types associated with ~90% genital warts with little cross-protection against non-vaccine HPV types. The current vaccines are based on virus-like particles (VLPs) derived from the major capsid protein, L1. The L1 protein is not conserved among HPV types. The minor capsid protein, L2, on the other hand, is highly conserved among HPV types and has been an alternative target antigen, for over two decades, to develop a broadly protective HPV vaccine. The L2 protein, unlike the L1, cannot form VLPs and as such, it is less immunogenic. This review summarizes current studies aimed at developing HPV L2 vaccines by multivalently displaying L2 peptides on VLPs derived from bacteriophages and eukaryotic viruses. Recent data show that a monovalent HPV L1 VLP as well as bivalent MS2 VLPs displaying HPV L2 peptides (representing amino acids 17–36 and/or consensus amino acids 69–86) elicit robust broadly protective antibodies against diverse HPV types (6/11/16/18/26/31/33/34/35/39/43/44/45/51/52/53/56/58/59/66/68/73) associated with cancers and genital warts. Thus, VLP-based L2 vaccines look promising and may be favorable, in the near future, over current L1-based HPV vaccines and should be explored further.

scholarly journals Prevalence of viral sexually transmitted infections and HPV high-risk genotypes in women in rural communities in the Department of La Paz, Bolivia

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Marianela Patzi-Churqui ◽  
Katty Terrazas-Aranda ◽  
Jan-Åke Liljeqvist ◽  
Magnus Lindh ◽  
Kristina Eriksson
Keyword(s):  
High Risk ◽  
Rural Communities ◽  
Sexually Transmitted Infections ◽  
Access To Health Care ◽  
Dried Blood Spots ◽  
Hpv Infection ◽  
La Paz ◽  
Sexually Transmitted ◽  
Hpv Types ◽  
High Risk Hpv

Abstract Background Bolivia has the highest prevalence of cervical cancer in South America and the prevalence of viral sexually transmitted infections (STIs) among people in urban cities is increasing. Little is known about the prevalence of viral STIs in rural communities, which generally have limited access to health care. In order to study the prevalence of viral STIs in rural Bolivia, we recruited women from villages and towns in the Department of La Paz in Bolivia. Methods Three hundred ninety-four female participants were assessed for IgG-antibodies to herpes simplex virus type 2 (HSV-2), human immunodeficiency virus (HIV) and hepatitis B virus (HBV, anti-HBc), as well as for the presence of HBV surface antigen (HBsAg) in dried blood spots. The prevalence of 12 high-risk types of human papillomavirus (HPV) was assessed by qPCR in dried cervicovaginal cell spots from 376 of these women. χ2 test was used to compare variables between the populations and binary logistic regression was used to identify risk factors associated with the positivity of the tests. Results The seroprevalence of HSV-2 was 53% and of HBV 10.3%. HBAg was detected in 15.8% of women with anti-HBV antibodies indicating chronic infection. The frequency of high-risk HPV infection was 27%, with the most prevalent high-risk HPV types being HPV 56, 39 and 31 followed by HPV 16 and 18. Finally, none of the 394 women were seropositive for HIV, and about 64% of the studied population was positive for at least one of the viral infections. Conclusions Women in Bolivian rural communities in La Paz show a high prevalence of HBV, HPV and, in particular, HSV-2. In contrast, none of the women were HIV positive, suggesting that the HIV prevalence in this population is low. The pattern of high-risk HPV types differed from many other countries with a predominance of HPV-types not included in the Gardasil vaccine which was officially introduced in Bolivia in April 2017.

scholarly journals The Agmatine-Containing Poly(Amidoamine) Polymer AGMA1 Binds Cell Surface Heparan Sulfates and Prevents Attachment of Mucosal Human Papillomaviruses

2015 ◽  
Vol 59 (9) ◽  
pp. 5250-5259 ◽  
Author(s):  
Valeria Cagno ◽  
Manuela Donalisio ◽  
Antonella Bugatti ◽  
Andrea Civra ◽  
Roberta Cavalli ◽  
...  
Keyword(s):  
Cell Surface ◽  
Viral Infections ◽  
Human Papillomaviruses ◽  
Sexually Transmitted ◽  
Human Papillomavirus 16 ◽  
Virus Attachment ◽  
Hpv Types ◽  
Heparan Sulfates ◽  
Further Development ◽  
Topical Microbicide

ABSTRACTThe agmatine-containing poly(amidoamine) polymer AGMA1 was recently shown to inhibit the infectivity of several viruses, including human papillomavirus 16 (HPV-16), that exploit cell surface heparan sulfate proteoglycans (HSPGs) as attachment receptors. The aim of this work was to assess the antiviral activity of AGMA1 and its spectrum of activity against a panel of low-risk and high-risk HPVs and to elucidate its mechanism of action. AGMA1 was found to be a potent inhibitor of mucosal HPV types (i.e., types 16, 31, 45, and 6) in pseudovirus-based neutralization assays. The 50% inhibitory concentration was between 0.34 μg/ml and 0.73 μg/ml, and no evidence of cytotoxicity was observed. AGMA1 interacted with immobilized heparin and with cellular heparan sulfates, exerting its antiviral action by preventing virus attachment to the cell surface. The findings from this study indicate that AGMA1 is a leading candidate compound for further development as an active ingredient of a topical microbicide against HPV and other sexually transmitted viral infections.

scholarly journals Induction of the Upstream Regulatory Region of Human Papillomavirus Type 31 by Dexamethasone Is Differentiation Dependent

2003 ◽  
Vol 77 (20) ◽  
pp. 10975-10983 ◽  
Author(s):  
Jennifer L. Bromberg-White ◽  
Ellora Sen ◽  
Samina Alam ◽  
Jason M. Bodily ◽  
Craig Meyers
Keyword(s):  
Life Cycle ◽  
Monolayer Culture ◽  
Regulatory Region ◽  
Hpv Infection ◽  
Human Papillomaviruses ◽  
Host Tissue ◽  
Semisolid Medium ◽  
Glucocorticoid Response ◽  
Hpv Types ◽  
Glucocorticoid Response Elements

ABSTRACT Glucocorticoids have been shown to play a role in the transforming abilities of human papillomaviruses (HPVs), and glucocorticoid response elements (GREs) have been identified in the upstream regulatory regions (URRs) of various HPV types. These findings have made glucocorticoids potential therapeutic targets for HPV infection. We have previously shown that the URR of HPV type 31 (HPV31) is insensitive to induction by the synthetic glucocorticoid dexamethasone (dex) in monolayer culture, despite the identification of three potential GREs in the 5′ region of the URR. Due to the fact that the HPV life cycle is intimately linked to the differentiation of the host tissue, we chose to determine whether the URR of HPV31 was inducible by dex under differentiating conditions. Upon suspension of cells in a semisolid medium of methylcellulose, we found that the URR of HPV31 was inducible by dex. The three GREs appear to play roles as independent repressors of this inducibility. By 5′ deletion analysis, the element(s) responsible for this induction was localized to nucleotides (nt) 7238 to 7557. Furthermore, we found that the region between nt 7883 and 7900 appears to act as a repressor of dex inducibility. These findings indicate that epithelial differentiation has a profound effect on the action of dex on the URR of HPV31, suggesting that glucocorticoids play an important role in the differentiation-dependent life cycle of HPV.

scholarly journals Prevalence of Human Papillomavirus (HPV) infection in women living in remote riverine communities in the Amazonas, Brazil

2019 ◽  
Author(s):  
Marco Antonio Zonta ◽  
Karina Bonilha Roque ◽  
Yara Juliano ◽  
Anne Liljander ◽  
Markus Cavalar ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Human Papillomavirus ◽  
Hpv Infection ◽  
Public Health Services ◽  
Cervical Lesions ◽  
Transmitted Infection ◽  
Sexually Transmitted ◽  
Remote Areas ◽  
Hpv Types ◽  
Crucial Part

Abstract Human papillomavirus (HPV) is the most common sexually transmitted infection worldwide. Since some HPV types are associated with the development of cervical cancer, routine screening for HPV plays a crucial part in cancer prevention programs at global level. In Brazil, the cervical cancer rate is among the highest in the world, in particular in indigenous women living in remote areas with limited access to public health services. The objective of this study was to determine the prevalence of HPV infections and their co-occurrence with cervical lesions in Brazilian women living in isolated riverine communities. Moreover, the association between social environment, sexual activity and prevalence of HPV infection was assessed.

scholarly journals Vaginal microbiota and human papillomavirus infection among young Swedish women

2020 ◽  
Vol 6 (1) ◽  
Author(s):  
Liqin Cheng ◽  
Johanna Norenhag ◽  
Yue O. O. Hu ◽  
Nele Brusselaers ◽  
Emma Fransson ◽  
...  
Keyword(s):  
Human Papillomavirus ◽  
Alpha Diversity ◽  
Hpv Infection ◽  
Cross Sectional Study ◽  
Vaginal Microbiota ◽  
Microbial Composition ◽  
Cross Sectional ◽  
Sexually Transmitted ◽  
Hpv Types ◽  
Oncogenic Hpv

Abstract Human papillomavirus (HPV) infection is one of the most common sexually transmitted diseases. To define the HPV-associated microbial community among a high vaccination coverage population, we carried out a cross-sectional study with 345 young Swedish women. The microbial composition and its association with HPV infection, including 27 HPV types, were analyzed. Microbial alpha-diversity was found significantly higher in the HPV-infected group (especially with oncogenic HPV types and multiple HPV types), compared with the HPV negative group. The vaginal microbiota among HPV-infected women was characterized by a larger number of bacterial vaginosis-associated bacteria (BVAB), Sneathia, Prevotella, and Megasphaera. In addition, the correlation analysis demonstrated that twice as many women with non-Lactobacillus-dominant vaginal microbiota were infected with oncogenic HPV types, compared with L. crispatus-dominated vaginal microbiota. The data suggest that HPV infection, especially oncogenic HPV types, is strongly associated with a non-Lactobacillus-dominant vaginal microbiota, regardless of age and vaccination status.

scholarly journals Sex differences in the prevalence and determinants of HPV-related external genital lesions in young adults: a national cross-sectional survey in Brazil

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Juliana Comerlato ◽  
Natália Luiza Kops ◽  
Marina Bessel ◽  
Jaqueline Driemeyer Horvath ◽  
Bruna Vieira Fernandes ◽  
...  
Keyword(s):  
Young Adults ◽  
Sex Differences ◽  
Smoking Status ◽  
Hpv Infection ◽  
Cross Sectional Survey ◽  
Cross Sectional ◽  
Sexually Transmitted ◽  
Primary Health ◽  
Hpv Types ◽  
Male Sex

Abstract Background External genital lesions (EGL) are the most common sexually transmitted infections (STIs). We aimed to evaluate the prevalence, determinants and sex differences in EGL among young adults from Brazil. Methods Overall, 7694 participants (aged 16 to 25 years) underwent an interview, genital examination and sampling for HPV genotyping. Results The prevalence of EGL was 4.08% (234) and is more frequent in men (5.72%) than women (2.31%) (p <  0.001). Genital lesions were significantly associated with male sex, infection by high-risk and multiple HPV types, having more than two sexual partners in the last year, smoking status and the presence of other STI. While alcohol use was associated with a higher prevalence of EGL in women, same-sex sexual relationship increase the prevalence in men. In the EGL group, 67.79% (p = 0.032) were positive for HPV infection and the types HPV6 and HPV11 were the most prevalent ones. Conclusion The prevalence of EGL in young adults was consistently high, and most cases were associated with genital HPV infection and STIs. Although men have a higher prevalence, both sexes share most genital lesion determinants. The promotion of sexual education and vaccination especially focus in young men, who are usually outside the targets of primary health care programmes, can prevent EGL in Brazilian young adults.

scholarly journals Broad Neutralization Responses Against Oncogenic Human Papillomaviruses Induced by a Minor Capsid L2 Polytope Genetically Incorporated Into Bacterial Ferritin Nanoparticles

2020 ◽  
Vol 11 ◽  
Author(s):  
Fan Yang ◽  
Filipe C. Mariz ◽  
Xueer Zhao ◽  
Gloria Spagnoli ◽  
Simone Ottonello ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Capsid Protein ◽  
Pyrococcus Furiosus ◽  
Neutralizing Antibody ◽  
Hpv Infection ◽  
Cross Reactivity ◽  
Human Papillomaviruses ◽  
Promising Alternative ◽  
Peptide Epitope ◽  
Hpv Types

Cervical cancer remains a global health burden despite the introduction of highly effective vaccines for the prophylaxis of causative human papillomavirus infection (HPV). Current efforts to eradicate cervical cancer focus on the development of broadly protective, cost-effective approaches. HPV minor capsid protein L2 is being recognized as a promising alternative to the major capsid protein L1 because of its ability to induce responses against a wider range of different HPV types. However, a major limitation of L2 as a source of cross-neutralizing epitopes is its lower immunogenicity compared to L1 when assembled into VLPs. Various approaches have been proposed to overcome this limitation, we developed and tested ferritin-based bio-nanoparticles displaying tandemly repeated L2 epitopes from eight different HPV types grafted onto the surface of Pyrococcus furiosus thioredoxin (Pf Trx). Genetic fusion of the Pf Trx-L2(8x) module to P. furiosus ferritin (Pf Fe) did not interfere with ferritin self-assembly into an octahedral structure composed by 24 protomers. In guinea pigs and mice, the ferritin super-scaffolded, L2 antigen induced a broadly neutralizing antibody response covering 14 oncogenic and two non-oncogenic HPV types. Immune-responsiveness lasted for at least one year and the resulting antibodies also conferred protection in a cervico-vaginal mouse model of HPV infection. Given the broad organism distribution of thioredoxin and ferritin, we also verified the lack of cross-reactivity of the antibodies elicited against the scaffolds with human thioredoxin or ferritin. Altogether, the results of this study point to P. furiosus ferritin nanoparticles as a robust platform for the construction of peptide-epitope-based HPV vaccines.

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