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 and the Development of Different Cancers

2016 ◽  
Vol 150 (3-4) ◽  
pp. 185-193 ◽  
Author(s):  
Ge Gao ◽  
David I. Smith
Keyword(s):  
Cervical Cancer ◽  
Squamous Cell Carcinomas ◽  
Human Papillomaviruses ◽  
Whole Genome ◽  
Physical Status ◽  
Cervical Cancers ◽  
Mate Pair ◽  
Almost All ◽  
Next Generation Sequencing Ngs ◽  
Generation Sequencing

Human papillomaviruses (HPV) are responsible for the development of almost all cervical cancers. HPV is also found in 85% of anal cancer and in 50% of penile, vulvar, and vaginal cancers, and they are increasingly found in a subset of head and neck cancers, i.e., oropharyngeal squamous cell carcinomas (OPSCC). The model for how HPV causes cancer is derived from several decades of study on cervical cancer, and it is just presumed that this model is not only completely valid for cervical cancer but for all other HPV-driven cancers as well. Next-generation sequencing (NGS) has now provided the necessary tools to characterize genomic alterations in cancer cells and can precisely determine the physical status of HPV in those cells as well. We discuss recent discoveries from different applications of NGS in both cervical cancer and OPSCCs, including whole-genome sequencing and mate-pair NGS. We also discuss what NGS studies have revealed about the different ways that HPV can be involved in cancer formation, specifically comparing cervical cancer and OPSCC.

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 Human papillomavirus genotypes in cervical cancers in Mozambique

2004 ◽  
Vol 85 (8) ◽  
pp. 2189-2190 ◽  
Author(s):  
Pontus Naucler ◽  
Flora Mabota da Costa ◽  
Otto Ljungberg ◽  
Antonio Bugalho ◽  
Joakim Dillner
Keyword(s):  
Cervical Cancer ◽  
Human Papillomavirus ◽  
Case Series ◽  
Cervical Neoplasia ◽  
Consecutive Case ◽  
Substantial Impact ◽  
Cervical Cancers ◽  
Hpv Types ◽  
Oncogenic Hpv

The distribution of human papillomavirus (HPV) types in cervical cancers is essential for design and evaluation of HPV type-specific vaccines. To follow up on a previous report that HPV types 35 and 58 were the dominant HPV types in cervical neoplasia in Mozambique, the HPV types in a consecutive case series of 74 invasive cervical cancers in Mozambique were determined. The most common worldwide major oncogenic HPV types 16 and 18 were present in 69 % of cervical cancers, suggesting that a vaccine targeting HPV-16 and -18 would have a substantial impact on cervical cancer also in Mozambique.

Decreased Expression of EIF4A1 After Preoperative Brachytherapy Predicts Better Tumor-Specific Survival in Cervical Cancer

2014 ◽  
Vol 24 (5) ◽  
pp. 908-915 ◽  
Author(s):  
Shanhui Liang ◽  
Yuqi Zhou ◽  
Yiran Chen ◽  
Guihao Ke ◽  
Hao Wen ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Tissue Microarrays ◽  
Prognostic Indicator ◽  
Staining Intensity ◽  
Altered Expression ◽  
Cervical Cancers ◽  
Kaplan Meier ◽  
Gynecology And Obstetrics ◽  
Before And After ◽  
Altered Expression Pattern

ObjectiveThe aim of this study is to investigate whether EIF4A1, EIF4E, and EIF4G1 can serve as prognostic markers for patients with cervical cancer receiving preoperative brachytherapy.Materials and MethodsTissue microarrays composed of 35 normal cervix samples, 87 cervical cancers treated without preoperative therapy, and 50 pairs of cervical cancer tissues collected before and after preoperative brachytherapy were constructed and evaluated for the expression of EIF4A1, EIF4E, and EIF4G using immunohistochemistry. Immunohistochemical staining was scored by the staining intensity and the percentages of tumor cells. The χ2 test was used to analyze the association between the immunohistochemistry results and clinicopathologic variables. The Kaplan-Meier method was applied to analyze the disease-specific survival.ResultsOverexpression of EIF4A1, EIF4E, and EIF4G1 were detected in 83.9%, 84.7%, and 80.3% of cervical cancers, respectively, all of which were significantly related to advanced International Federation of Gynecology and Obstetrics stage, squamous cell histology, lymph node metastasis, and deep stromal invasion (P < 0.05). The altered expression pattern of EIF4A1 and EIF4E after preoperative brachytherapy was significantly correlated with the cervical cancer response to brachytherapy (P = 0.029 and 0.012, respectively). The decreased expression of EIF4A1 predicted better tumor-specific survival (P = 0.02). The alteration of EIF4A1 was an independent predictor for tumor-specific survival (P = 0.047; hazards ratio, 0.272; 95% confidence interval, 0.076–0.982).ConclusionsOverexpression of EIF4A1, EIF4E, and EIF4G1 were acquired malignant phenotypic features of cervical cancer. EIF4A1 might function as a novel prognostic indicator and a potential therapeutic target for cervical cancer.

scholarly journals Simultaneous Characterization of Somatic Events and HPV-18 Integration in a Metastatic Cervical Carcinoma Patient Using DNA and RNA Sequencing

2014 ◽  
Vol 24 (2) ◽  
pp. 329-338 ◽  
Author(s):  
Winnie S. Liang ◽  
Jessica Aldrich ◽  
Sara Nasser ◽  
Ahmet Kurdoglu ◽  
Lori Phillips ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Rna Sequencing ◽  
Cervical Carcinoma ◽  
Human Papillomaviruses ◽  
Altered Expression ◽  
Dna And Rna ◽  
Cancer Pathogenesis ◽  
Somatic Alterations ◽  
Hpv 18

ObjectiveIntegration of carcinogenic human papillomaviruses (HPVs) into the host genome is a significant tumorigenic factor in specific cancers including cervical carcinoma. Although major strides have been made with respect to HPV diagnosis and prevention, identification and development of efficacious treatments for cervical cancer patients remains a goal and thus requires additional detailed characterization of both somatic events and HPV integration. Given this need, the goal of this study was to use the next generation sequencing to simultaneously evaluate somatic alterations and expression changes in a patient’s cervical squamous carcinoma lesion metastatic to the lung and to detect and analyze HPV infection in the same sample.Materials and MethodsWe performed tumor and normal exome, tumor and normal shallow whole-genome sequencing, and RNA sequencing of the patient’s lung metastasis.ResultsWe generated over 1.2 billion mapped reads and identified 130 somatic point mutations and indels, 21 genic translocations, 16 coding regions demonstrating copy number changes, and over 36 genes demonstrating altered expression in the tumor (correctedP< 0.05). Sequencing also revealed the HPV type 18 (HPV-18) integration in the metastasis. Using both DNA and RNA reads, we pinpointed 3 major events indicating HPV-18 integration into an intronic region of chromosome 6p25.1 in the patient’s tumor and validated these events with Sanger sequencing. This integration site has not been reported for HPV-18.ConclusionsWe demonstrate that DNA and RNA sequencing can be used to concurrently characterize somatic alterations and expression changes in a biopsy and delineate HPV integration at base resolution in cervical cancer. Further sequencing will allow us to better understand the molecular basis of cervical cancer pathogenesis.

scholarly journals Expression of the high-risk human papillomavirus type 18 and 45 E7 oncoproteins in cervical carcinoma biopsies

2005 ◽  
Vol 86 (12) ◽  
pp. 3235-3241 ◽  
Author(s):  
Marc Fiedler ◽  
Sigrun Ressler ◽  
Beatriz Campo-Fernández ◽  
Andreas Laich ◽  
Lars Jansen ◽  
...  
Keyword(s):  
High Risk ◽  
Cervical Carcinoma ◽  
Human Papillomaviruses ◽  
Hpv 16 ◽  
Cervical Cancers ◽  
Hpv Types ◽  
High Level ◽  
E7 Proteins ◽  
High Risk Hpv ◽  
Hpv 18

E7 proteins are major oncoproteins of high-risk human papillomaviruses (HPVs), which play a key role in cervical carcinogenesis. These proteins have been shown to immortalize primary human cells. Due to the absence of antibodies with suitable sensitivity and specificity, little is known about expression of the E7 oncoproteins in naturally infected tissues. Recently, high-level expression of the E7 protein of HPV-16, the most prevalent oncogenic HPV type, was demonstrated in cervical carcinomas by immunohistochemistry; however, approximately 15 additional high-risk HPV types are known to be associated with cervical carcinoma. It is unknown whether the E7 oncoproteins of HPV-18 and -45, the second and third most prevalent HPV types, are expressed in cervical cancers. Using antibodies against HPV-18 and -45 E7 proteins, it is shown here for the first time that the HPV-18 and -45 E7 proteins can be detected in cervical carcinoma biopsies. Together with anti-HPV-16 E7 antibodies, this could create the possibility of detecting E7 oncoproteins in approximately 80 % of all cervical cancers.

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.

Understanding HPV Disease and Prevention: A Guide for School Nurses

2009 ◽  
Vol 25 (4) ◽  
pp. 261-269 ◽  
Author(s):  
Suzy Lockwood-Rayermann ◽  
Susan J. McIntyre
Keyword(s):  
Cervical Cancer ◽  
Sexual Debut ◽  
Cervical Screening ◽  
Hpv Vaccination ◽  
Primary Source ◽  
School Nurses ◽  
Student Health ◽  
Cervical Cancers ◽  
Hpv Types ◽  
Source Of Information

Oncogenic human papillomavirus (HPV) causes 99.7% of all cervical cancers. HPV Types 16 and 18 are responsible for approximately 77% of cases, and peak prevalence occurs in females younger than 25 years of age. The recent implementation of HPV vaccination provides females with the opportunity to prevent infection. School nurses are advocates of student health and often a primary source of information. Therefore, they can play a key role in promoting vaccination prior to sexual debut. They can also promote regular cervical screening postvaccination, which may not be apparent to many students and parents. To deal with such issues, school nurses need a firm understanding of HPV and its role in cervical cancer. A greater understanding of HPV disease and prevention among school nurses, students, and parents may lead to greater reductions in the burden of cervical and other HPV-related diseases.

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.

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