Antibody reactivity to HPV E6 and E7 oncoproteins and early diagnosis of invasive cervical cancer

2003 ◽  
Vol 188 (1) ◽  
pp. 3-4 ◽  
Author(s):  
Margaret Stanley
Keyword(s):  
Cervical Cancer ◽  
Early Diagnosis ◽  
Invasive Cervical Cancer ◽  
Hpv E6 ◽  
Antibody Reactivity ◽  
E6 And E7 Oncoproteins ◽  
E6 And E7

scholarly journals The Efficacy of Therapeutic DNA Vaccines Expressing the Human Papillomavirus E6 and E7 Oncoproteins for Treatment of Cervical Cancer: Systematic Review

Vaccines ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 53
Author(s):  
Ayazhan Akhatova ◽  
Chee Kai Chan ◽  
Azliyati Azizan ◽  
Gulzhanat Aimagambetova
Keyword(s):  
Cervical Cancer ◽  
Human Papillomavirus ◽  
Public Health Problem ◽  
Clinical Implementation ◽  
Therapeutic Vaccines ◽  
Term Survival ◽  
Hpv E6 ◽  
E6 And E7 Oncoproteins ◽  
E6 And E7 ◽  
Lesion Regression

Cervical cancer is recognized as a serious public health problem since it remains one of the most common cancers with a high mortality rate among women despite existing preventative, screening, and treatment approaches. Since Human Papillomavirus (HPV) was recognized as the causative agent, the preventative HPV vaccines have made great progress over the last few years. However, people already infected with the virus require an effective treatment that would ensure long-term survival and a cure. Currently, clinical trials investigating HPV therapeutic vaccines show a promising vaccine-induced T-cell mediated immune response, resulting in cervical lesion regression and viral eradication. Among existing vaccine types (live vector, protein-based, nucleic acid-based, etc.), deoxyribonucleic acid (DNA) therapeutic vaccines are the focus of the study, since they are safe, cost-efficient, thermostable, easily produced in high purity and distributed. The aim of this study is to assess and compare existing DNA therapeutic vaccines in phase I and II trials, expressing HPV E6 and E7 oncoproteins for the prospective treatment of cervical cancer based on clinical efficacy, immunogenicity, viral clearance, and side effects. Five different DNA therapeutic vaccines (GX-188E, VGX-3100, pNGVL4a-CRT/E7(detox), pNGVL4a-Sig/E7(detox)/HSP70, MEDI0457) were well-tolerated and clinically effective. Clinical implementation of DNA therapeutic vaccines into treatment regimen as a sole approach or in combination with conservative treatment holds great potential for effective cancer treatment.

E6 and E7 oncoproteins: Potential targets of cervical cancer

2020 ◽  
Vol 27 ◽  
Author(s):  
Ramarao Malla ◽  
Mohammad Amjad Kamal
Keyword(s):  
Cervical Cancer ◽  
Drug Resistance ◽  
Host Cell ◽  
Molecular Mechanisms ◽  
Immune Therapy ◽  
Cervical Lesions ◽  
Diagnostic Strategies ◽  
E6 And E7 Oncoproteins ◽  
E6 And E7

: Cervical cancer (CC) is the fourth leading cancer in women in the age group 15-44 globally. Experimental as well as epidemiological studies identified that type16 and 18 HPV cause 70% of precancerous cervical lesions as well as cervical cancer worldwide by bringing about genetic as well as epigenetic changes in the host genome. The insertion of the HPV genome triggers various defense mechanisms including the silencing of tumor suppressor genes as well as activation of oncogenes associated with cancer metastatic pathway. E6 and E7 are small oncoproteins consisting of 150 and 100 amino acids respectively. These oncoproteins affect the regulation of the host cell cycle by interfering with p53 and pRb. Further these oncoproteins adversely affect the normal functions of the host cell by binding to their signaling proteins. Recent studies demonstrated that E6 and E7 oncoproteins are potential targets for CC. Therefore, this review discusses the role of E6 and E7 oncoproteins in metastasis and drug resistance as well as their regulation, early oncogene mediated signaling pathways. This review also uncovers the recent updates on molecular mechanisms of E6 and E7 mediated phytotherapy, gene therapy, immune therapy, and vaccine strategies as well as diagnosis through precision testing. Therefore, understanding the potential role of E6/E7 in metastasis and drug resistance along with targeted treatment, vaccine, and precision diagnostic strategies could be useful for the prevention and treatment of cervical cancer.

scholarly journals Antibodies against Early Proteins of Human Papillomaviruses as Diagnostic Markers for Invasive Cervical Cancer

1998 ◽  
Vol 36 (2) ◽  
pp. 475-480 ◽  
Author(s):  
Wolfgang Meschede ◽  
Klaus Zumbach ◽  
Joris Braspenning ◽  
Martin Scheffner ◽  
Luis Benitez-Bribiesca ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Invasive Cervical Cancer ◽  
Human Papillomaviruses ◽  
Antibody Detection ◽  
Diagnostic Tools ◽  
Immunological Monitoring ◽  
Hpv Dna ◽  
Native Proteins ◽  
Human Sera ◽  
E6 And E7

Cervical cancer is the most prevalent tumor in developing countries and the second most frequent cancer among females worldwide. Specific human papillomaviruses (HPVs) and, most notably, HPV types 16 and 18 are recognized as being causally associated with this malignancy. Antibodies against early HPV proteins E6 and E7 have been found more often in patients with tumors than in controls. Existing peptide enzyme-linked immunosorbent assays (ELISAs) for the detection of anti-E6 and anti-E7 antibodies in human sera have low levels of sensitivity and specificity and thus are not suitable for use as diagnostic tools. Based on highly purified recombinant native proteins, we developed four sandwich ELISAs for the detection of antibodies against HPV type 16 and 18 E6 and E7 proteins. We demonstrate their sensitivities and high degrees of specificity for cervical cancer. Among a total of 501 serum specimens from unselected patients with invasive cervical cancer, 52.9% reacted positively in at least one of the four assays. In contrast, among 244 serum specimens from control subjects without cervical cancer, only 2 reactive serum specimens (0.8%) were found. For 19 of 19 antibody-positive patients, the HPV type indicated by seroreactivity was identical to the HPV DNA type found in the tumor, which also indicates a high degree of specificity for antibody detection with respect to HPV type. In a direct comparison of 72 serum specimens from patients with cervical cancer, 56% of the specimens reacted in at least one of the four protein ELISAs, whereas 40% reacted in at least one of seven peptide ELISAs covering the four antigens. These assays could be of value for the detection of invasive cervical cancer in settings in which cytology-based early tumor screening is not available, for the clinical management of patients diagnosed with cervical cancer, and for the immunological monitoring of E6 and E7 vaccination trials.

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.

scholarly journals Complementary Targeting of Rb Phosphorylation and Growth in Cervical Cancer Cell Cultures and a Xenograft Mouse Model by SHetA2 and Palbociclib

Cancers ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 1269 ◽  
Author(s):  
Amy L. Kennedy ◽  
Rajani Rai ◽  
Zitha Redempta Isingizwe ◽  
Yan Daniel Zhao ◽  
Stanley A. Lightfoot ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Cyclin D1 ◽  
Cell Lines ◽  
Cancer Cell ◽  
Xenograft Model ◽  
Cervical Cancer Cell ◽  
Chi Square ◽  
Western Blots ◽  
Hpv E6 ◽  
E6 And E7

Cervical cancer is caused by high-risk human papillomavirus (HPV) types and treated with conventional chemotherapy with surgery and/or radiation. HPV E6 and E7 proteins increase phosphorylation of retinoblastoma (Rb) by cyclin D1/cyclin dependent kinase (CDK)4/6 complexes. We hypothesized that cyclin D1 degradation by the SHetA2 drug in combination with palbociclib inhibition of CDK4/6 activity synergistically reduces phosphorylated Rb (phospho-Rb) and inhibits cervical cancer growth. The effects of these drugs, alone, and in combination, were evaluated in SiHa and CaSki HPV-positive and C33A HPV-negative cervical cancer cell lines using cell culture, western blots and ELISA, and in a SiHa xenograft model. Endpoints were compared by isobolograms, ANOVA, and Chi-Square. In all cell lines, combination indexes documented synergistic interaction of SHetA2 and palbociclib in association SHetA2 reduction of cyclin D1 and phospho-Rb, palbociclib reduction of phospho-Rb, and enhanced phospho-Rb reduction upon drug combination. Both drugs significantly reduced phospho-Rb and growth of SiHa xenograft tumors as single agents and acted additively when combined, with no evidence of toxicity. Dilated CD31-negative blood vessels adjacent to, or within, areas of necrosis and apoptosis were observed in all drug-treated tumors. These results justify development of the SHetA2 and palbociclib combination for targeting phospho-Rb in cervical cancer treatment.

Factors Contributing to the Low Survival Among Women With a Diagnosis of Invasive Cervical Cancer in Ghana

2017 ◽  
Vol 27 (9) ◽  
pp. 1926-1934 ◽  
Author(s):  
Yvonne Nartey ◽  
Philip C. Hill ◽  
Kwabena Amo-Antwi ◽  
Kofi M. Nyarko ◽  
Joel Yarney ◽  
...  
Keyword(s):  
Health Care ◽  
Cervical Cancer ◽  
Early Diagnosis ◽  
Health Care Delivery ◽  
Cancer Survival ◽  
Care Delivery ◽  
Invasive Cervical Cancer ◽  
Financial Barriers

ConclusionsIn conclusion, cervical cancer survival is low in Ghana and is likely to be improved if a greater proportion of the disease is detected early. Improving knowledge of the disease for early diagnosis, reducing financial barriers, and greater organization of health care delivery are likely to improve survival from cervical cancer in Ghana.

scholarly journals Upregulation of PIR gene expression induced by human papillomavirus E6 and E7 in epithelial oral and cervical cells

Open Biology ◽  
2017 ◽  
Vol 7 (11) ◽  
pp. 170111 ◽  
Author(s):  
Diego Carrillo ◽  
Juan P. Muñoz ◽  
Hernán Huerta ◽  
Gabriel Leal ◽  
Alejandro Corvalán ◽  
...  
Keyword(s):  
Gene Expression ◽  
Human Papillomavirus ◽  
Dna Microarrays ◽  
Epithelial Mesenchymal Transition ◽  
Dependent Manner ◽  
Mesenchymal Transition ◽  
Hpv E6 ◽  
E6 And E7 Oncoproteins ◽  
E6 And E7 ◽  
Oral Cells

The hallmark of high-risk human papillomavirus (HR-HPV)-related carcinogenesis is E6 and E7 oncogene overexpression. The aim of this work was to characterize epithelial oral and cervical cancer cells that express HR-HPV E6 and E7 oncoproteins. Transcriptomic assay using DNA microarrays revealed that PIR gene expression was detected in oral cells in an HR-HPV E6/E7-dependent manner. In addition, PIR was overexpressed in HPV-positive SiHa and Ca Ski cells, whereas it was undetectable in HPV-negative C33A cells. The PIR expression was dependent on functional HR-HPV E6 and E7 oncoproteins even though the E7 oncoprotein had higher activity to induce PIR overexpression in comparison with E6. In addition, using an siRNA for PIR silencing in oral cells ectopically expressing HR-HPV E6/E7, there was a significant increase in E-cadherin transcripts and a decrease in Vimentin, Slug, Zeb and Snail transcripts, suggesting that HR-HPV-induced PIR overexpression is involved in epithelial–mesenchymal transition. Furthermore, migration of PIR-silenced cells was significantly decreased. Finally, using inhibitors of some specific pathways, it was found that EGFR/ERK and PI3 K/AKT signalling pathways are important for E7-mediated PIR overexpression. It can be concluded that PIR gene expression is highly dependent on the expression of HR-HPV oncoproteins and is important for EMT regulation.

scholarly journals E6-mediated activation of JNK drives EGFR signalling to promote proliferation and viral oncoprotein expression in cervical cancer

2020 ◽  
Author(s):  
Ethan L. Morgan ◽  
James A. Scarth ◽  
Molly R. Patterson ◽  
Christopher W. Wasson ◽  
Georgia C. Hemingway ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Human Papillomaviruses ◽  
Signalling Pathway ◽  
Viral Oncoprotein ◽  
Hpv E6 ◽  
Cervical Cancer Cells ◽  
E6 And E7 ◽  
Novel Therapeutic

AbstractHuman papillomaviruses (HPV) are a major cause of malignancy worldwide, contributing to ~5% of all human cancers including almost all cases of cervical cancer and a growing number of ano-genital and oral cancers. HPV-induced malignancy is primarily driven by the viral oncogenes, E6 and E7, which manipulate host cellular pathways to increase cell proliferation and enhance cell survival, ultimately predisposing infected cells to malignant transformation. Consequently, a more detailed understanding of viral-host interactions in HPV-associated disease offers the potential to identify novel therapeutic targets. Here, we identify that the c-Jun N-terminal kinase (JNK) signalling pathway is activated in cervical disease and in cervical cancer. The HPV E6 oncogene induces JNK1/2 phosphorylation in a manner that requires the E6 PDZ binding motif. We show that blockade of JNK1/2 signalling using small molecule inhibitors, or knockdown of the canonical JNK substrate c-Jun, reduces cell proliferation and induces apoptosis in cervical cancer cells. We further demonstrate that this phenotype is at least partially driven by JNK-dependent activation of EGFR signalling via increased expression of EGFR and the EGFR ligands EGF and HB-EGF. JNK/c-Jun signalling promoted the invasive potential of cervical cancer cells and was required for the expression of the epithelial to mesenchymal transition (EMT)-associated transcription factor Slug and the mesenchymal marker Vimentin. Furthermore, JNK/c-Jun signalling is required for the constitutive expression of HPV E6 and E7, which are essential for cervical cancer cell growth and survival. Together, these data demonstrate a positive feedback loop between the EGFR signalling pathway and HPV E6/E7 expression, identifying a regulatory mechanism in which HPV drives EGFR signalling to promote proliferation, survival and EMT. Thus, our study has identified a novel therapeutic target that may be beneficial for the treatment of cervical cancer.

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