scholarly journals Novel Antigenic Targets of HPV Therapeutic Vaccines

Vaccines ◽  
2021 ◽  
Vol 9 (11) ◽  
pp. 1262
Author(s):  
Ditte Rahbæk Boilesen ◽  
Karen Nørgaard Nielsen ◽  
Peter Johannes Holst
Keyword(s):  
Cervical Cancer ◽  
Head And Neck ◽  
Cytotoxic T Cells ◽  
Expression Patterns ◽  
Hpv Infection ◽  
Therapeutic Vaccines ◽  
Screening Programs ◽  
Associated Lesions ◽  
E6 And E7 ◽  
Hpv Oncoproteins

Human papillomavirus (HPV) infection is the cause of the majority of cervical cancers and head and neck cancers worldwide. Although prophylactic vaccines and cervical cancer screening programs have shown efficacy in preventing HPV-associated cervical cancer, cervical cancer is still a major cause of morbidity and mortality, especially in third world countries. Furthermore, head and neck cancer cases caused by HPV infection and associated mortality are increasing. The need for better therapy is clear, and therapeutic vaccination generating cytotoxic T cells against HPV proteins is a promising strategy. This review covers the current scene of HPV therapeutic vaccines in clinical development and discusses relevant considerations for the design of future HPV therapeutic vaccines and clinical trials, such as HPV protein expression patterns, immunogenicity, and exhaustion in relation to the different stages and types of HPV-associated lesions and cancers. Ultimately, while the majority of the HPV therapeutic vaccines currently in clinical testing target the two HPV oncoproteins E6 and E7, we suggest that there is a need to include more HPV antigens in future HPV therapeutic vaccines to increase efficacy and find that especially E1 and E2 could be promising novel targets.

Human Papillomavirus Selected Properties and Related Cervical Cancer Prevention Issues

2020 ◽  
Vol 26 (18) ◽  
pp. 2073-2086
Author(s):  
Saule Balmagambetova ◽  
Andrea Tinelli ◽  
Ospan A. Mynbaev ◽  
Arip Koyshybaev ◽  
Olzhas Urazayev ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Human Papillomavirus ◽  
Cancer Prevention ◽  
Screening Program ◽  
Hpv Infection ◽  
Cervical Cancer Prevention ◽  
Point Of View ◽  
Prevention Strategies ◽  
Middle Income ◽  
Screening Programs

High-risk human papillomavirus strains are widely known to be the causative agents responsible for cervical cancer development. Aggregated damage caused by papillomaviruses solely is estimated in at least 5% of all malignancies of the human body and 16% in cancers that affect the female genital area. Enhanced understanding of the complex issue on how the high extent of carcinogenicity is eventually formed due to the infection by the Papoviridae family would contribute to enhancing current prevention strategies not only towards cervical cancer, but also other HPV associated cancers. This review article is aimed at presenting the key points in two directions: the current cervical cancer prevention and related aspects of HPV behavior. Virtually all applied technologies related to HPV diagnostics and screening programs, such as HPV tests, colposcopy-based tests (VIA/VILI), conventional and liquid-based cytology, currently available are presented. Issues of availability, advantages, and drawbacks of the screening programs, as well as vaccination strategies, are also reviewed in the article based on the analyzed sources. The current point of view regarding HPV is discussed with emphasis on the most problematic aspect of the HPV family concerning the observed increasing number of highly carcinogenic types. Present trends in HPV infection diagnostics throughout the human fluids and tissues are also reported, including the latest novelties in this field, such as HPV assay/self-sample device combinations. Besides, a brief outline of the related prevention issues in Kazakhstan, the leading country of Central Asia, is presented. Kazakhstan, as one of the post-soviet middle-income countries, may serve as an example of the current situation in those terrains, concerning the implementation of globally accepted cervical cancer prevention strategies. Along with positive achievements, such as the development of a nationwide screening program, a range of drawbacks is also analyzed and discussed.

scholarly journals Current Status of Human Papillomavirus-Related Head and Neck Cancer: From Viral Genome to Patient Care

2021 ◽  
Author(s):  
Haoru Dong ◽  
Xinhua Shu ◽  
Qiang Xu ◽  
Chen Zhu ◽  
Andreas M. Kaufmann ◽  
...  
Keyword(s):  
Human Papillomavirus ◽  
Head And Neck ◽  
Treatment Strategies ◽  
Hpv Infection ◽  
Immune Checkpoint Blockade ◽  
Current Status ◽  
Future Directions ◽  
Sequencing Technologies ◽  
E6 And E7 ◽  
The Continuum

AbstractHuman papillomavirus (HPV) infection identified as a definitive human carcinogen is increasingly being recognized for its role in carcinogenesis of human cancers. Up to 38%–80% of head and neck squamous cell carcinoma (HNSCC) in oropharyngeal location (OPSCC) and nearly all cervical cancers contain the HPV genome which is implicated in causing cancer through its oncoproteins E6 and E7. Given by the biologically distinct HPV-related OPSCC and a more favorable prognosis compared to HPV-negative tumors, clinical trials on de-escalation treatment strategies for these patients have been studied. It is therefore raised the questions for the patient stratification if treatment de-escalation is feasible. Moreover, understanding the crosstalk of HPV-mediated malignancy and immunity with clinical insights from the proportional response rate to immune checkpoint blockade treatments in patients with HNSCC is of importance to substantially improve the treatment efficacy. This review discusses the biology of HPV-related HNSCC as well as successful clinically findings with promising candidates in the pipeline for future directions. With the advent of various sequencing technologies, further biomolecules associated with HPV-related HNSCC progression are currently being identified to be used as potential biomarkers or targets for clinical decisions throughout the continuum of cancer care.

scholarly journals Role of Immune Checkpoint Inhibitors in Cervical Cancer: From Preclinical to Clinical Data

Cancers ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 2089
Author(s):  
Simona Duranti ◽  
Antonella Pietragalla ◽  
Gennaro Daniele ◽  
Camilla Nero ◽  
Francesca Ciccarone ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Hpv Infection ◽  
Phase Iii ◽  
Screening Programs ◽  
Cervical Cancers ◽  
Relapsed Disease

Human papillomavirus (HPV) infection is the recognized cause of almost all cervical cancers. Despite the reduction in incidence due to a wide use of screening programs and a specific vaccine, the prognosis of cervical cancer remains poor, especially for late-stage and relapsed disease. Considering the elevated rates of PD-L1 expression in up to 80% of cervical cancers, a strong rationale supports the use of immunotherapy to restore the immune response against tumor. The aim of this review is to analyze the possible role of immune checkpoint inhibitors in cervical cancer treatment, with a particular focus on the rationale and on the results of phase I and II clinical trials. An overview of ongoing phase III studies with possible future areas of development is also provided.

Human Papillomavirus (HPV)

2021 ◽  
Author(s):  
Anne Schuind
Keyword(s):  
Cervical Cancer ◽  
Neutralizing Antibodies ◽  
Invasive Cervical Cancer ◽  
Cancer Control ◽  
Middle Income ◽  
Middle Income Countries ◽  
Common Cancer ◽  
Associated Lesions ◽  
Hpv Types ◽  
E6 And E7

HPV is extremely common worldwide and mainly transmitted through sexual contact; most people are infected with HPV shortly after onset of sexual activity. There are >200 types of HPV, of which at least 12 are cancer-causing (oncogenic or high-risk types). HPV is a causal factor for several anogenital and a subset of oropharyngeal cancers with 2 HPV types (16 and 18) causing 72% of all HPV-associated cancers. Cervical cancer is the fourth most common cancer among women globally with nearly 90% of the deaths occurring in low- and middle-income countries. Comprehensive cervical cancer control includes primary prevention (vaccination against HPV), secondary prevention (screening and treatment of pre-cancerous lesions) as well as treatment of invasive cervical cancer. The currently licensed vaccines are L1 VLP-based and prophylactic; they have been shown to be safe and highly effective in preventing HPV infections and HPV-associated lesions, precancer and cancer. Neutralizing antibodies are the mechanism of protection for prophylactic HPV VLP-based vaccines. Therapeutic HPV vaccines targeting the oncoproteins E6 and E7 are in clinical development.

Deregulation of miR-21 and miR-29a in Cervical Cancer Related to HPV Infection

MicroRNA ◽  
2019 ◽  
Vol 8 (2) ◽  
pp. 110-115 ◽  
Author(s):  
Sara Zamani ◽  
Amir Sohrabi ◽  
Seyed Masoud Hosseini ◽  
Marjan Rahnamaye-Farzami ◽  
Abolfazl Akbari
Keyword(s):  
Cervical Cancer ◽  
Cancer Progression ◽  
Expression Patterns ◽  
Invasive Cervical Cancer ◽  
Hpv Infection ◽  
Micro Rna ◽  
Internal Reference ◽  
Specific Primers ◽  
Papilloma Virus

Background:Early diagnosis is an important factor to improve the survival of Invasive Cervical Cancer (ICC) patients. Molecular biomarkers such as micro RNA (miRNA) can be used in the early detection of ICC. The expression of miR-21 and miR-29a are deregulated in many types of human cancers.Objective:The aim of this study was to investigate the differences in miR-21 and miR-29a expression patterns in the Human Papilloma Virus (HPV) infection and various grades of cervical cancer among Iranian women.Methods:Small RNAs were extracted from positive for HPV, cervical cancer and healthy samples from 43, 50 and 46 individuals, respectively. Expression levels of miR-21 and miR-29a were analyzed by SYBR Green real-time RT-PCR using specific primers, and 5s rRNA as the internal reference gene.Results:Results have shown a significant increase in miR-21 and decrease in miR-29 in cancerous samples in comparison with the control groups (P < 0.0001).Conclusion:This study illustrated that miR-21 and miR-29a could be operated as an oncogene and tumor-suppressor in cervical cancer progression. More studies are needed to demonstrate the role of miR-21 and miR-29a as potential biomarkers for the diagnosis of cervical cancer in future investigations.

scholarly journals Microbiome and Cervical Cancer

Pathobiology ◽  
2020 ◽  
pp. 1-11
Author(s):  
Cristina Paula Castanheira ◽  
Mayara Luciana Sallas ◽  
Rafaella Almeida Lima Nunes ◽  
Noely Paula Cristina Lorenzi ◽  
Lara Termini
Keyword(s):  
Cervical Cancer ◽  
Genital Tract ◽  
Current Knowledge ◽  
Disease Onset ◽  
Female Genital Tract ◽  
Hpv Infection ◽  
Vaginal Microbiome ◽  
Associated Lesions ◽  
Cervical Disease ◽  
Female Genital

Persistent infection with some types of mucosal human papillomavirus (HPV) is the etiological factor for the development of cervical cancer and its precursor lesions. Besides, several cofactors are known to play a role in cervical disease onset and progression either by favoring or by preventing HPV infection and persistence. The microbiome of a healthy female genital tract is characterized by the presence of 1 or few varieties of lactobacilli. However, high-throughput studies addressing the bacterial diversity and abundance in the female genital tract have shown that several factors, including hormonal levels, hygiene habits, and sexually transmitted diseases may disrupt the natural balance, favoring the outgrowth of some groups of bacteria, which in turn may favor some pathological states. Recently, the vaginal microbiome has emerged as a new variable that could greatly influence the natural history of HPV infections and their clinical impact. In this context, changes in the vaginal microbiome have been detected in women infected with HPV and women with HPV-associated lesions and cancer. However, the role of specific bacteria groups in the development/progression or prevention/regression of HPV-associated pathologies is not well understood. In this review we summarize the current knowledge concerning changes in vaginal microbiome and cervical disease. We discuss the potential functional interplay between specific bacterial groups and HPV infection outcomes.

scholarly journals DNA Methylation Changes in Human Papillomavirus-Driven Head and Neck Cancers

Cells ◽  
2020 ◽  
Vol 9 (6) ◽  
pp. 1359 ◽  
Author(s):  
Chameera Ekanayake Weeramange ◽  
Kai Dun Tang ◽  
Sarju Vasani ◽  
Julian Langton-Lockton ◽  
Liz Kenny ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Human Papillomavirus ◽  
Head And Neck ◽  
Dna Methyltransferase ◽  
Long Control Region ◽  
Cancer Types ◽  
E6 And E7 ◽  
Hpv Oncoproteins ◽  
Cellular Dna ◽  
Methylation Patterns

Disruption of DNA methylation patterns is one of the hallmarks of cancer. Similar to other cancer types, human papillomavirus (HPV)-driven head and neck cancer (HNC) also reveals alterations in its methylation profile. The intrinsic ability of HPV oncoproteins E6 and E7 to interfere with DNA methyltransferase activity contributes to these methylation changes. There are many genes that have been reported to be differentially methylated in HPV-driven HNC. Some of these genes are involved in major cellular pathways, indicating that DNA methylation, at least in certain instances, may contribute to the development and progression of HPV-driven HNC. Furthermore, the HPV genome itself becomes a target of the cellular DNA methylation machinery. Some of these methylation changes appearing in the viral long control region (LCR) may contribute to uncontrolled oncoprotein expression, leading to carcinogenesis. Consistent with these observations, demethylation therapy appears to have significant effects on HPV-driven HNC. This review article comprehensively summarizes DNA methylation changes and their diagnostic and therapeutic indications in HPV-driven HNC.

scholarly journals Clinical comparison of two human papillomavirus detection assays: GenoFlow and reverse line blot

2020 ◽  
Vol 14 (01) ◽  
pp. 97-103
Author(s):  
Fatimah S Alhamlan ◽  
Hadeel H Khayat ◽  
Dalia A Obeid ◽  
Asma M Tulba ◽  
Teejan S Baduwais ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Developing Countries ◽  
Human Papillomavirus ◽  
Hpv Infection ◽  
Reverse Line Blot ◽  
Outpatient Clinics ◽  
Test Results ◽  
Screening Programs ◽  
Hpv Genotypes ◽  
Hpv Types

Introduction: Human papillomavirus (HPV) infection is typically critical in the oncogenesis of cervical cancer. However, available HPV detection kits differ in their ability and sensitivity to detect various types of HPV, and this variability has led to inconsistencies in the reporting of the geographic prevalence of HPV types, especially in developing countries. Here, we compared results of the recently developed GenoFlow HPV array test, which detects 33 HPV genotypes, to those of the well-established reverse line blot (RLB) assay, which detects 23 HPV types. Methodology: In total, 608 cervical specimens with cytology results ranging from normal to cancer were collected using an endocervical brush from women attending outpatient clinics in Riyadh, Saudi Arabia. Results: Sixty-nine specimens (11%) were positive for HPV. HPV genotype detection using the GenoFlow test had a sensitivity of 62% and a specificity of 100%. Overall agreement between the two HPV genotyping methods was 97%, with a concordance rate of 95%. Among the GenoFlow test results, 2% indicated additional HPV types that were not detected in the RLB assay, whereas the GenoFlow test missed 0.3% of the HPV types that were detected by the RLB; however, both tests were in agreement in detecting all major HPV types. Conclusion: The GenoFlow test was reliable, with results comparable to the RLB test. However, because the GenoFlow test is less labor-intensive and takes less total time (3 hours), it is a promising, affordable alternative to the RLB for HPV diagnosis and screening programs.

scholarly journals Positivity and prevalence of human papillomavirus among a large population of women in southeastern China

2019 ◽  
Vol 47 (12) ◽  
pp. 6171-6181 ◽  
Author(s):  
Sudong Liu ◽  
Xiaodong Gu ◽  
Ruiqiang Weng ◽  
Jing Liu ◽  
Zhixiong Zhong
Keyword(s):  
Cervical Cancer ◽  
Human Papillomavirus ◽  
Hpv Vaccine ◽  
Large Population ◽  
Hpv Infection ◽  
Southeastern China ◽  
Screening Programs ◽  
Specific Distribution ◽  
Luminex Technology ◽  
Hpv Genotypes

Objective To formulate strategies for prevention of cervical cancer, we investigated the prevalence of human papillomavirus (HPV) infection and the age-specific distribution among female participants in southeastern China. Methods From January 2016 to July 2018, 36,871 women from Meizhou People’s Hospital (Huangtang Hospital), Meizhou Hospital Affiliated to Sun Yat-sen University were enrolled in this prospective study. HPV genotypes were detected using Luminex technology. Results HPV infection was observed in 18.34% of the participants, and 79.98% were infected with high-risk HPVs. The five most prevalent genotypes were HPV52 (18.18%), HPV16 (16.06%), HPV58 (11.37%), HPV53 (8.82%), and HPV39 (6.42%). The 9-valent HPV vaccine efficiently reduced the HPV infection rate by more than 10%, which is twofold the rate of other vaccines. Most HPV infections were observed in women age 40 to 49 years, and those age 30 to 59 years accounted for 79.62% of positive patients. Conclusion Our findings regarding HPV genotypes and the age-specific distribution of HPV infection in the study area will contribute to the development of cervical cancer screening programs and vaccine strategies.

A Comprehensive Review on Crosstalk of Human Papilloma Virus oncoproteins and developmental/self-renewal pathways during the pathogenesis of uterine cervical cancer

2020 ◽  
Vol 20 ◽  
Author(s):  
Afza Ahmad ◽  
Irfan Ahmad Ansari
Keyword(s):  
Cervical Cancer ◽  
Human Papilloma Virus ◽  
Epithelial Mesenchymal Transition ◽  
Wnt Signaling Pathway ◽  
Hpv Infection ◽  
Uterine Cervical Cancer ◽  
Self Renewal ◽  
Papilloma Virus ◽  
Mesenchymal Transition ◽  
E6 And E7

: Cervical cancer, a cancer arising from the uterine cervix has been regarded as the fourth most frequent gynecological malignancy among females worldwide. Epidemiological reports have shown that uterine cervical cancer is a global health issue among womens of specially developing countries and consequently creates an economic and medical burden in the society. The main causative agent of cervical carcinoma is high risk human papilloma virus (HPV 16 and HPV 18). Molecular studies have revealed the expression two viral genes E6 and E7 after HPV infection in the epithelial cells of cervix. These gene products are known to inactivate the major tumor suppressors, p53 and retinoblastoma protein (pRB), respectively. Moreover, the role of self-renewal pathways such as Hedgehog, Notch and Wnt has also been linked with drug resistance in cancer cells and epithelial mesenchymal transition during metastasis in pathogenesis of cervical cancer. Although, the mechanism of interaction of HPV E6 and E7 with each and every component of above described developmental pathways is not elucidated yet, but preliminary reports of their crosstalk have begun to emerge. Understanding the interplay between these oncoproteins and developmental/self-renewal pathways is highly important in terms of designing new and targeted therapeutic approach against cervical cancer. Hence, this review cynosure the carcinogenesis of HPV with the brief description of its virology and also establishes the crosstalk between oncoproteins E6 & E7 and Hedgehog, Notch and Wnt signaling pathway.

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