scholarly journals The Biological Impact of Genomic Diversity in Cervical Cancer Development

2016 ◽  
Vol 60 (6) ◽  
pp. 513-517 ◽  
Author(s):  
Cristina Mendes de Oliveira ◽  
José Eduardo Levi
Keyword(s):  
Cervical Cancer ◽  
Human Papillomaviruses ◽  
Genomic Variation ◽  
Genomic Diversity ◽  
Etiologic Agents ◽  
Arabic Number ◽  
Disease Associations ◽  
Technical Advances ◽  
Hpv Types ◽  
Cervical Cancer Development

Human papillomaviruses (HPVs) are the etiologic agents of cervical cancer, the unique human neoplasia that has one single necessary cause. The diversity of HPVs is well described, with 200 HPV types existing as distinct taxonomic units and each receiving an Arabic number. On a clinical basis, they are usually grouped by their site of occurrence and disease associations. Those types inhabiting the anogenital mucosa are more intensively studied and further divided into cancer-associated HPVs, which are termed ‘high risk', while those linked to benign proliferative lesions are assigned as ‘low risk'. HPV16 is responsible for approximately 50% of all ICC cases, and paradoxically is one of the most prevalent types among healthy women. Longitudinal studies have shown that when an incidental HPV16 infection becomes persistent it will result in an enhanced risk for the development of high-grade lesions. However, it is unknown why some persistent, HPV16 infections (or infections by other HR-HPV types) progress to CIN3+ while most clear spontaneously. Several epidemiological investigations have focused on cofactors, from the most obvious such as cigarette and other carcinogenic exposures, to coinfections by other STDs such as chlamydia, with no significant findings. Thus, the current focus is on genomic variation from both virus and host. Such studies have been potentialized by the enormous technical advances in nucleic acid sequencing, allowing this relationship to be broadly interrogated. Corroborating subgenomic data from decades ago, an association between HPV16 lineages and carcinogenesis is being revealed. However, this effect does not seem to apply across female populations from different continents/ethnicities, again highlighting a role played by HPV16 adaptation and evasion from the host over time.

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.

scholarly journals The Laboratory Diagnosis of Genital Human Papillomavirus Infections

2005 ◽  
Vol 16 (2) ◽  
pp. 83-91 ◽  
Author(s):  
François Coutlee ◽  
Danielle Rouleau ◽  
Alex Ferenczy ◽  
Eduardo Franco
Keyword(s):  
Cervical Cancer ◽  
High Risk ◽  
Hpv Infection ◽  
Human Papillomaviruses ◽  
High Grade ◽  
Hpv Testing ◽  
Screening Programs ◽  
Detection Techniques ◽  
Hpv Types ◽  
High Risk Hpv

Human papillomaviruses (HPVs) are the etiological agents of several genital cancers, including cancer of the uterine cervix. The detection of HPV infection in genital samples may increase the sensitivity of primary and secondary screenings of cervical cancer. HPV testing may also improve the specificity of screening programs, resulting in the avoidance of overtreatment and cost savings for confirmatory procedures. The major determinants of clinical progression of HPV infection include persistence of HPV infection, involvement of high-risk HPV types, high HPV viral load, integration of viral DNA and presence of several potential cofactors. Signal amplification HPV-DNA detection techniques (Hybrid Capture II, Digene Corporation, USA) are standardized, commercially available, and capable of detecting several high-risk HPV types. They also increase the sensitivity of screening for high-grade lesions in combination with cytology. The sensitivity of these techniques to detect high-grade lesions is higher than that of cytology, but the referral rate for colposcopy is greater. These techniques are approved for the triage to colposcopy of women with cervical smears interpreted as atypical squamous cells of undetermined significance. Triage and screening for cervical cancer using HPV will probably be restricted to women aged 30 years or older because of the high prevalence of infection in younger women. Amplification techniques are ideal for epidemiological studies because they minimize the misclassification of HPV infection status. These techniques can detect low HPV burden infections. Consensus primers amplify most genital types in one reaction, and the reverse hybridization of amplicons with type-specific probes allows for the typing of HPV-positive samples. Consensus PCR assays are currently under evaluation for diagnostic purposes. HPV testing is currently implemented for the clinical management of women.

scholarly journals Glycosylation in Cervical Cancer: New Insights and Clinical Implications

2021 ◽  
Vol 11 ◽  
Author(s):  
Zhiwei Xu ◽  
Yaqin Zhang ◽  
Dickson K. W. Ocansey ◽  
Bo Wang ◽  
Fei Mao
Keyword(s):  
Cervical Cancer ◽  
Cancer Biology ◽  
Molecular Mechanisms ◽  
Human Papillomaviruses ◽  
Altered Expression ◽  
Cervical Cancers ◽  
Variable Sensitivity ◽  
Glycan Profiling ◽  
Hpv Types ◽  
Analytical Approaches

Cervical cancer has become the most frequent female malignancy and presents as a general health challenge in many countries undergoing economic development. Various human papillomaviruses (HPV) types have appeared as one of the most critically identifiable causes of widespread cervical cancers. Conventional cervical cytological inspection has limitations of variable sensitivity according to cervical cytology. Glycobiology has been fundamental in related exploration in various gynecologic and reproductive fields and has contributed to our understanding of cervical cancer. It is associated with altered expression of N-linked glycan as well as abnormal expression of terminal glycan structures. The analytical approaches available to determine serum and tissue glycosylation, as well as potential underlying molecular mechanisms involved in the cellular glycosylation alterations, are monitored. Moreover, cellular glycosylation influences various aspects of cervical cancer biology, ranging from cell surface expressions, cell-cell adhesion, cancer signaling, cancer diagnosis, and management. In general, discoveries in glycan profiling make it technically reproducible and affordable to perform serum glycoproteomic analyses and build on previous work exploring an expanded variety of glycosylation markers in the majority of cervical cancer patients.

scholarly journals Human papillomavirus genotype distribution in Ethiopia: an updated systematic review

2022 ◽  
Vol 19 (1) ◽  
Author(s):  
Awoke Derbie ◽  
Daniel Mekonnen ◽  
Endalkachew Nibret ◽  
Melanie Maier ◽  
Yimtubezinash Woldeamanuel ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
High Risk ◽  
Human Papillomaviruses ◽  
Low Risk ◽  
Scientific Quality ◽  
Genotype Distribution ◽  
Hpv 16 ◽  
Hpv Genotypes ◽  
Hpv Types ◽  
Hpv 18

Abstract Background Cervical cancer is caused by infection with high-risk human papillomaviruses (HR-HPVs). It is one of the leading causes of cancer-related deaths in Ethiopia and globally. To develop efficient vaccination and HPV-based cervical cancer screening approaches, data on genotype distribution of HPVs is crucial. Hence, the study was aimed to review HPV genotype distribution in Ethiopia. Methods Research articles were systematically searched using comprehensive search strings from PubMed/Medline and SCOPUS. Besides, Google Scholar was searched manually for grey literature. The last search was conducted on 18 August 2021. The first two authors independently appraised the studies for scientific quality and extracted the data using Excel sheet. The pooled HPV genotype distribution was presented with descriptive statistics. Results We have included ten studies that were reported from different parts of the country during 2005 and 2019. These studies included 3633 women presented with different kinds of cervical abnormalities, from whom 29 different HPV genotypes with a sum of 1926 sequences were reported. The proportion of high-risk, possible/probable high-risk and low-risk HPVs were at 1493 (77.5%), 182 (9.4%) and 195 (10.1%), respectively. Of the reported genotypes, the top five were HPV 16 (37.3%; 95% CI 35.2.1–39.5%), HPV 52 (6.8%; 95% CI 5.8–8.0%), HPV 35 (4.8%; 95% CI 3.9–5.8%), HPV 18 (4.4%; 95% CI 3.5–5.3%) and HPV 56 (3.9%: 95% CI 3.1–4.9%). Some of other HR-HPV groups include HPV 31 (3.8%), HPV 45 (3.5%), HPV 58 (3.1%), HPV 59(2.3%), and HPV 68 (2.3%). Among the high-risk types, the combined prevalence of HPV 16/18 was at 53.7% (95% CI 51.2–56.3%). HPV 11 (2.7%: 95% CI 2.1–3.5%), HPV 42 (2.1%: 95% CI 1.5–2.8%) and HPV 6 (2.1%: 95% CI 1.4–2.7%) were the most common low-risk HPV types. Conclusions We noted that the proportion of HR-HPV types was higher and HPV 16 in particular, but also HPV 52, HPV 35 and HPV 18, warrant special attention in Ethiopian’s vaccination and HPV based cervical screening program. Additional data from other parts of the country where there is no previous HPV genotype report are needed to better map the national HPV genotypes distribution of Ethiopia.

HPV Detection

2013 ◽  
pp. 196-214
Author(s):  
Aris Spathis ◽  
Stavros Archondakis ◽  
Petros Karakitsos
Keyword(s):  
Cervical Cancer ◽  
Risk Factor ◽  
Patient Management ◽  
Cancer Development ◽  
Human Papilloma Viruses ◽  
Screening Strategies ◽  
Combining Data ◽  
Hpv Types ◽  
Cervical Cancer Development ◽  
Epithelial Lesion

Human papilloma viruses (HPVs) have been acknowledged to be the leading risk factor of cervical intra-epithelial lesion creation (CIN) and cervical cancer development (CxCa), while recently, a vaccine protecting from the most commonly HPV types found in CxCa has been produced and introduced in vaccination schemes across the globe. Many different techniques have been created and utilized in HPV detection and monitoring with a vast amount of them being commercialized and few of them integrated in screening strategies. However, there has been no effort in combining data from all the different techniques and provide efficient patient triaging schemes, since, apart from the obvious increase of patient cost, the amount of data and its interpretation in patient management has been impossible.

scholarly journals Prediction of High-Risk Types of Human Papillomaviruses Using Reduced Amino Acid Modes

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Xinnan Xu ◽  
Rui Kong ◽  
Xiaoqing Liu ◽  
Pingan He ◽  
Qi Dai
Keyword(s):  
Amino Acids ◽  
Cervical Cancer ◽  
Amino Acid ◽  
High Risk ◽  
Protein Sequence ◽  
Human Papillomaviruses ◽  
Prediction Methods ◽  
Structure Information ◽  
Hpv Types ◽  
High Risk Hpv

A human papillomavirus type plays an important role in the early diagnosis of cervical cancer. Most of the prediction methods use protein sequence and structure information, but the reduced amino acid modes have not been used until now. In this paper, we introduced the modes of reduced amino acids to predict high-risk HPV. We first reduced 20 amino acids into several nonoverlapping groups and calculated their structure and physicochemical modes for high-risk HPV prediction, which was tested and compared with the existing methods on 68 samples of known HPV types. The experiment result indicates that the proposed method achieved better performance with an accuracy of 96.49%, indicating that the reduced amino acid modes might be used to improve the prediction of high-risk HPV types.

scholarly journals Whole-Genome Analysis of Human Papillomavirus Type 16 Prevalent in Japanese Women with or without Cervical Lesions

Viruses ◽  
2019 ◽  
Vol 11 (4) ◽  
pp. 350 ◽  
Author(s):  
Yusuke Hirose ◽  
Mamiko Onuki ◽  
Yuri Tenjimbayashi ◽  
Mayuko Yamaguchi-Naka ◽  
Seiichiro Mori ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Large Scale ◽  
Phylogenetic Analyses ◽  
Invasive Cervical Cancer ◽  
Japanese Women ◽  
Genetic Variations ◽  
Human Papillomaviruses ◽  
Cancer Development ◽  
Cervical Lesions ◽  
Cervical Cancer Development

Recent large-scale genomics studies of human papillomaviruses (HPVs) have shown a high level of genomic variability of HPV16, the most prevalent genotype in HPV-associated malignancies, and provided new insights into the biological and clinical relevance of its genetic variations in cervical cancer development. Here, we performed deep sequencing analyses of the viral genome to explore genetic variations of HPV16 that are prevalent in Japan. A total of 100 complete genome sequences of HPV16 were determined from cervical specimens collected from Japanese women with cervical intraepithelial neoplasia and invasive cervical cancer, or without cervical malignancies. Phylogenetic analyses revealed the variant distribution in the Japanese HPV16 isolates; overall, lineage A was the most prevalent (94.0%), in which sublineage A4 was dominant (52.0%), followed by sublineage A1 (21.0%). The relative risk of sublineage A4 for cervical cancer development was significantly higher compared to sublineages A1/A2/A3 (odds ratio = 6.72, 95% confidence interval = 1.78–28.9). Interestingly, a novel cluster of variants that branched from A1/A2/A3 was observed for the Japanese HPV16 isolates, indicating that unique HPV16 variants are prevalent among Japanese women.

scholarly journals Prediction of High-Risk Types of Human Papillomaviruses Using Statistical Model of Protein “Sequence Space”

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Cong Wang ◽  
Yabing Hai ◽  
Xiaoqing Liu ◽  
Nanfang Liu ◽  
Yuhua Yao ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
High Risk ◽  
Statistical Model ◽  
Computational Methods ◽  
Sequence Space ◽  
Protein Sequence ◽  
Human Papillomaviruses ◽  
Hpv Types ◽  
Related Proteins ◽  
Protein Sequence Space

Discrimination of high-risk types of human papillomaviruses plays an important role in the diagnosis and remedy of cervical cancer. Recently, several computational methods have been proposed based on protein sequence-based and structure-based information, but the information of their related proteins has not been used until now. In this paper, we proposed using protein “sequence space” to explore this information and used it to predict high-risk types of HPVs. The proposed method was tested on 68 samples with known HPV types and 4 samples without HPV types and further compared with the available approaches. The results show that the proposed method achieved the best performance among all the evaluated methods with accuracy 95.59% andF1-score 90.91%, which indicates that protein “sequence space” could potentially be used to improve prediction of high-risk types of HPVs.

scholarly journals Promoter Methylation of p16INK4A, hMLH1, and MGMT in Liquid-Based Cervical Cytology Samples Compared with Clinicopathological Findings and HPV Presence

2011 ◽  
Vol 2011 ◽  
pp. 1-5 ◽  
Author(s):  
Aris Spathis ◽  
Evaggelia Aga ◽  
Maria Alepaki ◽  
Aikaterini Chranioti ◽  
Christos Meristoudis ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Promoter Methylation ◽  
Methylation Status ◽  
Cervical Carcinogenesis ◽  
Hpv Dna ◽  
Molecular Events ◽  
Dependent Inactivation ◽  
Clinicopathological Findings ◽  
Hpv Types ◽  
Cervical Cancer Development

Cervical cancer is a common cancer inflicting women worldwide. Even though, persistent infection with oncogenic Human Papillomavirus (HPV) types is considered the most important risk factor for cervical cancer development, less than 5% of women with HPV will eventually develop cervical cancer supporting that other molecular events, like methylation-dependent inactivation of tumor suppressor genes, may cocontribute in cervical carcinogenesis. We analyzed promoter methylation of three candidate genes (p16, MGMT, and hMLH1) in 403 liquid-based cytology samples. Methylation was commonly identified in both benign and pathologic samples and correlated with higher lesion grade determined by cytological, colposcopical, or histological findings, with HPV DNA and mRNA positivity of specific HPV types and p16INK4Aprotein expression. Overall accuracy of methylation is much lower than traditional diagnostic tests ranking it as an ancillary technique with more data needed to identify the exact value of methylation status in cervical carcinogenesis.

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