scholarly journals Prevalence of antibodies against a cyclic peptide mimicking the FG loop of the human papillomavirus type 16 capsid among Tunisian women

2020 ◽  
Author(s):  
Elham Hassen ◽  
Devendra Bansal ◽  
Randa Ghdira ◽  
Anouar Chaieb ◽  
Hedi Khairi ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Human Papillomavirus ◽  
Capsid Protein ◽  
Sex Workers ◽  
Synthetic Peptide ◽  
Enzyme Linked Immunosorbent Assay ◽  
Squamous Intraepithelial Lesions ◽  
Hpv 16 ◽  
Intraepithelial Lesions ◽  
Legal Sex

Abstract Background In the past decades, several studies have identified cervical cancer is the second most common cancer in women worldwide and leading causes of death in developing countries. High-risk types of human papillomavirus (HR-HPV), mainly type 16, are the sexually transmitted agents etiologically linked to cervical cancer. The present epidemiological study aimed to investigate the efficacy of enzyme linked immunosorbent assay (ELISA) and assessed host humoral immune response against the oncogenic HPV-16 infection using the cyclic synthetic peptide mimicking the FG loop of the major L1 capsid protein of the HPV-16 among Tunisian women. Methods The antibody responses against synthetic peptides mimicking the FG loop of the HPV l6 major capsid protein L1 in sera and cervical secretions among 179 Tunisian women were assessed by ELISA. HPV infection was examined by a polymerase chain reaction-based method. Results The frequency of systemic antibodies, in contrast to HPV-16 DNA prevalence, was higher in women with low-grade squamous intraepithelial lesions (LGSIL) than in women with high-grade squamous intraepithelial lesions (HGSIL) (43.7% versus 14.8%; P=0.04). Compared to women from the general population, systemic IgG response frequency was significantly higher among legal sex workers (25.5%; P=0.002) and women with LGSIL (43.7%; P=0.001). In addition, systemic IgA and local IgG responses were higher, only among legal sex workers (P=0.002 and P=0.001 respectively). Conclusions Overall, the frequency of HPV DNA detection was significantly higher among women with HGSIL. We did not observe a positive IgG response in women with a positive HPV-16 infection, suggesting that the anti-peptide antibodies are protective and confirm that the FG loop contains neutralizing epitopes. This could have implications for future monitoring of women to predict clinical outcome and for the design of synthetic peptide-based vaccine.

scholarly journals Prevalence of antibodies against a cyclic peptide mimicking the FG loop of the human papillomavirus type 16 capsid among Tunisian women

2020 ◽  
Author(s):  
Elham Hassen ◽  
Devendra Bansal ◽  
Randa Ghdira ◽  
Anouar Chaieb ◽  
Hedi Khairi ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Monoclonal Antibodies ◽  
Human Papillomavirus ◽  
Sex Workers ◽  
Synthetic Peptide ◽  
Cyclic Peptides ◽  
Cyclic Peptide ◽  
Squamous Intraepithelial Lesions ◽  
Intraepithelial Lesions ◽  
Peptide Antibodies

Abstract Background In the past decade, the cervical cancer rank went down from the second to the fourth most common cancer in women worldwide but remains ranked second in developing countries. High-risk types of human papillomavirus, mainly type 16, are the sexually transmitted agents etiologically linked to cervical cancer. The present study aimed to investigate the usefulness of a cyclic synthetic peptide designed from the major L1 capsid protein of the HPV16 for detecting anti-HPV16 antibodies. Methods We designed and synthetized a peptide that corresponds to the full sequence of the surface-exposed FG loop. We tested against HPV16 L1 monoclonal antibodies the antigenicity of the linear and the cyclic peptides. Detection of anti-peptide antibodies was assessed by ELISA in sera and cervical secretions of 179 Tunisian women. For HPV DNA detection and genotyping, polymerase chain reaction and direct sequencing methods were applied. Results Both the linear and the cyclic peptides were recognized by the same neutralizing monoclonal antibodies but the cyclic peptide was more reactive with human sera. In contrast to HPV16 DNA prevalence, the prevalence of the anti-peptide antibodies in sera was higher in women with low-grade squamous intraepithelial lesions (LGSIL) than in women with high-grade squamous intraepithelial lesions (HGSIL) (44% and 15%, respectively). Compared to women from the general population, systemic IgG prevalence was significantly higher among sex workers (25%; P=0.002) and women with LGSIL (44%; P=0.001). In addition, systemic IgA and cervical IgG prevalence was higher, only among sex workers (p=0.002 and P=0.001 respectively). We did not observe anti-peptide IgG antibodies in women with a current HPV16 infection.Conclusion Anti-peptide IgG in sera or in cervical secretions could be markers of an effective natural immunization against the HPV16. This may open novel perspective for monitoring vaccinated women and for the design of synthetic peptide-based vaccine.

PECULIARITIES OF PAPILLOMAVIRUS GENOTYPING IN PATIENTS WITH CERVICAL INTRAEPITHELIAL NEOPLASIA

2020 ◽  
pp. 104-111
Author(s):  
N.A. Shmakova ◽  
G.N. Chistyakova ◽  
I.N. Kononova ◽  
I.I. Remizova
Keyword(s):  
Cervical Cancer ◽  
Human Papillomavirus ◽  
Viral Load ◽  
Cervical Intraepithelial Neoplasia ◽  
Intraepithelial Neoplasia ◽  
Squamous Intraepithelial Lesions ◽  
Hpv 16 ◽  
The World ◽  
Intraepithelial Lesions ◽  
Hpv 18

Recently, there has been a steady growth of cervical cancer all over the world, especially in Russia. Patients with cervical cancer have become much younger. At the same time, the human papillomavirus is not only the main factor in the neoplastic process, but it is also one of the most common sexually transmitted infections in the world. The aim of the paper is to assess the prevalence and characteristics of human papillomavirus genotypes in patients with cervical intraepithelial neoplasia. Materials and Methods. During the periodic screening we examined 213 women of a reproductive age with HPV infection. All patients underwent liquid-based cytology and human papillomavirus genotyping by polymerase chain reaction. Results. We revealed that the prevalence of cervical intraepithelial neoplasia among women with papillomavirus infection was 80.3 % (n=171). According to human papillomavirus genotyping, HPV 16 (38 %) and HPV 33 (32 %) prevailed. We also observed positive high correlation between high-grade squamous intraepithelial lesions (HSIL) and HPV 18 (r=+0.759, p=0.001), a negative mean correlation between HPV 45 and low-grade squamous intraepithelial lesions (LSIL) (r=-0.643, p=0.002). A cohort of patients with severe intraepithelial cervical lesions demonstrated high viral load rates. Conclusion. According to the results obtained, we established the dominance of HPV 16 and HPV 33 genotypes in cervical intraepithelial neoplasia. There were significant differences between HSIL and LSIL patients with HPV 18 and HPV 45. There was also a correlation between an increase in the viral load with the severity of the pathological process. Keywords: human papillomavirus, intraepithelial cervical neoplasms, cervical cancer. В последние годы в мире, особенно в России, наблюдается неуклонный рост и «омолаживание» рака шейки матки. При этом вирус папилломы человека является не только основным фактором прогрессирования неопластического процесса, но и одной из наиболее распространенных инфекций, предаваемых половым путем, в мире. Цель. Оценить распространенность и характеристику генотипов папилломавирусной инфекции у пациенток с цервикальными интраэпителиальными неоплазиями. Материалы и методы. Проведено обследование 213 пациенток репродуктивного возраста с ВПЧ-инфекцией, пришедших на профилактический осмотр. Всем женщинам было выполнено цитологическое исследование жидкостным методом и генотипирование вируса папилломы человека методом полимеразной цепной реакции. Результаты. Распространенность цервикальных интраэпителиальных неоплазий среди женщин с папилломавирусной инфекцией составила 80,3 % (171 пациентка). Согласно данным генотипирования вируса папилломы человека превалировал 16-й (38 %) и 33-й типы (32 %). Выявлена положительная высокая корреляционная связь между цервикальными неоплазиями высокой степени онкогенного риска (HSIL) и 18-м типом ВПЧ-инфекции (r=+0,759 при р=0,001), отрицательная средняя корреляционная связь 45-го типа ВПЧ с низкой степенью онкогенного риска (LSIL) (r=-0,643 при р=0,002). Продемонстрированы высокие показатели вирусной нагрузки в когорте пациенток с тяжелыми внутриэпителиальными цервикальными поражениями. Выводы. По результатам полученных данных установлено доминирование 16-го и 33-го генотипов ВПЧ при цервикальных интраэпителиальных неоплазиях с наличием значимых различий между пациентами с HSIL и LSIL в отношении 18-го и 45-го типов, а также связь роста уровня вирусной нагрузки с увеличением степени тяжести патологического процесса. Ключевые слова: вирус папилломы человека, интраэпителиальные новообразования шейки матки, рак шейки матки.

scholarly journals Prevalence of antibodies against a cyclic peptide mimicking the FG loop of the human papillomavirus type 16 capsid among Tunisian women

2020 ◽  
Author(s):  
Elham Hassen ◽  
Devendra Bansal ◽  
Randa Ghdira ◽  
Anouar Chaieb ◽  
Hedi Khairi ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Human Papillomavirus ◽  
Sex Workers ◽  
Synthetic Peptide ◽  
Cyclic Peptides ◽  
Cyclic Peptide ◽  
Low Grade ◽  
Squamous Intraepithelial Lesions ◽  
Intraepithelial Lesions ◽  
Peptide Antibodies

Abstract Background In the past decade, cervical cancer has gone from being the second to the fourth most common cancer in women worldwide, but remains the second most common in developing countries. This cancer is most commonly caused by high-risk types of human papillomavirus (HPV), mainly type 16 (HPV16), which are sexually transmitted. This study aimed to investigate the usefulness of a cyclic synthetic peptide designed from the major L1 capsid protein of HPV16 for detecting anti-HPV16 antibodies. Methods We designed and synthetized a peptide that corresponds to the full sequence of the surface-exposed FG loop. We tested the antigenicity of the linear and the cyclic peptides against HPV16 L1 monoclonal antibodies. We used ELISA to detect anti-peptide antibodies in sera and cervical secretions of 179 Tunisian women, and we applied polymerase chain reaction and direct sequencing methods to detect and genotype HPV DNA. Results Both the linear and the cyclic peptides were recognized by the same neutralizing monoclonal antibodies, but the cyclic peptide was more reactive with human sera. The prevalence of the anti-peptide antibodies in sera was higher in women with low-grade squamous intraepithelial lesions (LGSIL) than in women with high-grade squamous intraepithelial lesions (HGSIL) (44% and 15%, respectively). This contrasts with HPV16 DNA prevalence. Compared to women from the general population, systemic IgG prevalence was significantly higher among sex workers (25%; P=0.002) and women with LGSIL (44%; P=0.001). In addition, systemic IgA and cervical IgG prevalence was higher among sex workers only (p=0.002 and P=0.001 respectively). We did not observe anti-peptide IgG antibodies in women with a current HPV16 infection.Conclusion Anti-peptide IgG in sera or in cervical secretions could be markers of an effective natural immunization against HPV16. This may open novel perspectives for monitoring vaccinated women and for the design of synthetic peptide-based vaccines.

scholarly journals Genotype-specific human papillomavirus detection in cervical smears.

2008 ◽  
Vol 55 (4) ◽  
pp. 687-692 ◽  
Author(s):  
Slawa Szostek ◽  
Malgorzata Klimek ◽  
Barbara Zawilinska ◽  
Magdalena Kosz-Vnenchak
Keyword(s):  
Cervical Cancer ◽  
Human Papillomavirus ◽  
Cervical Carcinoma ◽  
Control Group ◽  
Squamous Intraepithelial Lesions ◽  
Hpv 16 ◽  
Hpv Dna ◽  
Cervical Smears ◽  
Hpv Types ◽  
Intraepithelial Lesions

Human papillomavirus (HPV) is widely accepted as a causative agent of cervical cancer. The distribution and prevalence of HPV types depend on geographic region and demographic factors. The aim of this study was to investigate the relationship between the presence of various HPV types and the outcome of cytological examination. Cervical smears were obtained from 125 women from southern Poland: low grade squamous intraepithelial lesions (LSIL) - 44, high grade squamous intraepithelial lesions (HSIL) - 12, cervical carcinoma - 27 and 42 women without abnormality in cytology as a control group. DNA was extracted from the smears and broad-spectrum HPV DNA amplification and genotyping was performed with the SPF 10 primer set and reverse hybridisation line probe assay (INNO-LiPA HPV Genotyping, Innogenetics). HPV DNA was detected in approximately 72% cases, more frequently in women with squamous intraepithelial lesions and cervical carcinoma than in the control group (P < 0.0005). The most frequent type found was HPV 16 (37%), followed by HPV 51 (28%) and HPV 52 (17%). A single HPV type was detected in 51% positive cases, more frequently in cervical cancer specimens. Multiple HPV infection was dominant in women with LSIL and normal cytology. Prevalence of HPV 16 increased with the severity of cervical smear abnormality. For women HPV 16 positive, the relative risk (odds ratio) of the occurrence of HSIL and cervical cancer versus LSIL was 14.4 (95% CI, 3.0-69.2; P=0.001) and 49.4 (95% CI, 6.5-372.8; P < 0.001), respectively. Genotyping of HPV will allow better classification of women with cervical abnormalities into different risk groups and could be useful in therapy.

scholarly journals Prevalence of antibodies against a cyclic peptide mimicking the FG loop of the human papillomavirus type 16 capsid among Tunisian women

2020 ◽  
Author(s):  
Elham Hassen ◽  
Devendra Bansal ◽  
Randa Ghdira ◽  
Anouar Chaieb ◽  
Hedi Khairi ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Human Papillomavirus ◽  
Sex Workers ◽  
Synthetic Peptide ◽  
Cyclic Peptides ◽  
Cyclic Peptide ◽  
Low Grade ◽  
Squamous Intraepithelial Lesions ◽  
Intraepithelial Lesions ◽  
Peptide Antibodies

Abstract Background In the past decade, cervical cancer has gone from being the second to the fourth most common cancer in women worldwide, but remains the second most common in developing countries. This cancer is most commonly caused by high-risk types of human papillomavirus (HPV), mainly type 16 (HPV16), which are sexually transmitted. This study aimed to investigate the usefulness of a cyclic synthetic peptide designed from the major L1 capsid protein of HPV16 for detecting anti-HPV16 antibodies. Methods We designed and synthetized a peptide that corresponds to the full sequence of the surface-exposed FG loop. We tested the antigenicity of the linear and the cyclic peptides against HPV16 L1 monoclonal antibodies. We used ELISA to detect anti-peptide antibodies in sera and cervical secretions of 179 Tunisian women, and we applied polymerase chain reaction and direct sequencing methods to detect and genotype HPV DNA. Results Both the linear and the cyclic peptides were recognized by the same neutralizing monoclonal antibodies, but the cyclic peptide was more reactive with human sera. The prevalence of the anti-peptide antibodies in sera was higher in women with low-grade squamous intraepithelial lesions (LGSIL) than in women with high-grade squamous intraepithelial lesions (HGSIL) (44% and 15%, respectively). This contrasts with HPV16 DNA prevalence. Compared to women from the general population, systemic IgG prevalence was significantly higher among sex workers (25%; P=0.002) and women with LGSIL (44%; P=0.001). In addition, systemic IgA and cervical IgG prevalence was higher among sex workers only (p=0.002 and P=0.001 respectively). We did not observe anti-peptide IgG antibodies in women with a current HPV16 infection.Conclusion Anti-peptide IgG in sera or in cervical secretions could be markers of an effective natural immunization against HPV16. This may open novel perspectives for monitoring vaccinated women and for the design of synthetic peptide-based vaccines.

scholarly journals Cloning and expression of Human Papilloma virus type 16 L1 capsid protein in bacteria

2019 ◽  
Vol 10 (2) ◽  
pp. 82-89
Author(s):  
Silvia Tri Widyaningtyas ◽  
Sofy Meilany ◽  
Budiman Bela
Keyword(s):  
Escherichia Coli ◽  
Cervical Cancer ◽  
Human Papillomavirus ◽  
Recombinant Protein ◽  
Capsid Protein ◽  
Recombinant Plasmid ◽  
Health Science ◽  
Science Journal ◽  
Hpv 16 ◽  
L1 Protein

Latar belakang: Secara alamiah protein kapsid L1 Human Papillomavirus (HPV) tipe 16 dapat mengalami auto assembly untuk membentuk Viral like particle (VLP). Terkait dengan penelitian vaksin HPV, VLP dapat digunakan untuk berbagai keperluan seperti vaksin, pseudovirion atau SpyTag-Spycatcher. Penelitian ini ditujukan untuk mendapatkan plasmid rekombinan yang digunakan untuk produksi protein L1 HPV 16. Metode: Gen penyandi protein L1 HPV 16 diklona ke dalam vector pQE80L, suatu plasmid yang mengandung sistem ekspresi untuk prokariota. DNA penyandi HPV 16 L1 disisipkan pada situs restriksi BamHI dan Hind III plasmid pQE80L. Plasmid rekombinan yang mengandung gen L1 HPV 16dikonfirmasi menggunakan PCR dan analisis enzim restriksi. Lebih lanjut untuk memastikan bahwa gen rekombinan L1 HPV 16 dapat diekspresikan dalam prokariota, plasmid rekombinan ditransformasikan ke bakteri Escherichia coli BL21 (DE3). Bakteri diinduksi dengan Isopropyl β-D-1-thiogalactopyranoside (IPTG) dengan berbagai konsentrasi dan berbagai waktu inkubasi. Hasil: protein rekombinan L1, berat 56 kDa, telah berhasil diekspresikan dalam sistem prokariota. Protein rekombinan L1 dapat dimurnikan menggunakan TalonR dalam kondisi denaturasi. Kesimpulan: gen L1 HPV 16 telah dikloning ke dalam pQE80L dan berhasil diekspresikan dalam sistem prokariota. (Health Science Journal of Indonesia 2019;10(2):82-9) Kata kunci: L1, HPV 16, cervical cancer   Abstract Background: Naturally Human Papillomavirus (HPV) type 16 L1 capsid protein can auto assemble to form Viral like particles (VLP). Concerning to vaccine development for HPV, VLP can be used for a variety of needs such as a vaccine, pseudovirion or SpyTag-Spycatcher. In this study, to obtain a vector expression that can be used in the production of HPV L1 protein, we cloned gene coding HPV 16 L1 protein into pQE80L a plasmid contains an expression system for prokaryote. Methods: The DNA coding HPV 16 L1 was inserted at BamHI and Hind III restriction sites of pQE80L plasmid. The recombinant plasmid containing the HPV L1 gene was confirmed using PCR colony and enzyme restriction. Further to ensure the recombinant HPV 16 L1 gene could be expressed in a prokaryote, the recombinant plasmid was transformed into bacteria Escherichia coli BL21 (DE3). The bacteria were induced with IPTG with various concentrations and various incubation time. Result: L1 recombinant protein, 56 kDa in weight, has successfully been expressed in prokaryote system. L1 recombinant protein can be purified using TalonR under denaturing conditions. Conclusion: L1 HPV 16 gene has been cloned into pQE80L and successfully expressed in prokaryote system. (Health Science Journal of Indonesia 2019;10(2):82-9) Keywords: L1, HPV 16, cervical cancer

scholarly journals Characteristics of Human Papillomavirus Infection Among Women With Cervical Cytological Abnormalities in the Zhoupu District, Shanghai City, China, 2014–2019

2020 ◽  
Author(s):  
Ping Li ◽  
Qing Liu ◽  
Wei Li ◽  
Zhou Liu ◽  
Baoling Xing ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Human Papillomavirus ◽  
Precancerous Lesions ◽  
Hpv Infection ◽  
Single Type ◽  
Squamous Intraepithelial Lesions ◽  
Shanghai City ◽  
Intraepithelial Lesions ◽  
Type Infection ◽  
Multiple Type

Abstract Background: Human papillomavirus (HPV) infection is the main cause of precancerous lesions and cervical cancer in women. To determine the epidemiological characteristics as well as the relationship between the HPV genotype and cytology test results among women, we retrospectively collected and analyzed the data from Zhoupu District hospital in Shanghai, China.Methods: We made a retrospective analysis of human papillomavirus prevalence rate of 23,724 women between 2014 and 2019 in the District Zhoupu of Shanghai City in China. Their cervical exfoliations were collected. HPV genotype testing was performed using a commercial kit designed to detect 21 HPV subtypes including 15 high-risk HPV subtypes(16, 18, 31, 33, 35, 39, 45, 51, 52, 53, 56, 58, 59, 66 ,68) and 6 low-risk HPV subtypes(6, 11, 42, 43, 44 and 81). And the thinPrep cytological test (TCT) was also performed at the same time.Results: Among all 23,724 cases, 3,816 (16.08%) women were infected with HPV. HPV52 (3.19%), HPV58 (2.47%) and HPV16 (2.34%) had higher prevalence. 3,480(91.20%) single-type infections were more common than 336(8.8%) multiple-type infections. Single-type infection was more frequently seen in women aged 50–60 years (16.63%) and <30 years (15.37%), and multiple-type infection was more common in those aged >= 60 (2.67%). Significant differences in secular trends from 2014 to 2019 were observed for subtypes HPV52, 58 and 16.HPV positive rates of women changed significantly along with the time period from 2014 to 2019.Among 4,502 TCT positive women, 15 (4.04%), 125 (2.64%) ,159 (1.54%), 4,202(17.71%) and 1(0.004%) had atypical squamous cells (ASC), high-grade squamous intraepithelial lesions (HSIL), low-grade squamous intraepithelial lesions (LSIL), atypical glandular cells (AGC) and cervical adenocarcinoma respectively. The HPV infection rates were 66.08%, 63.99%, 115.20%, 119.50%, and 31.72% for NILM, AGCs, HSILs LSILs and ASCs, respectively.Conclusions: HPV and TCT screening were a key step in the secondary prevention of cervical cancer. Further tracking the results of HPV and TCT was an important clinical strategy for the treatment of cervical precancerous lesions. The widespread use of preventive HPV vaccines can significantly reduce the incidence of pre-neoplastic and neoplastic cervical lesions.

scholarly journals Cervical Microbiome and Response to a Human Papillomavirus Therapeutic Vaccine for Treating High-Grade Cervical Squamous Intraepithelial Lesion

2019 ◽  
Vol 18 ◽  
pp. 153473541989306 ◽  
Author(s):  
Rahul Ravilla ◽  
Hannah N. Coleman ◽  
Cheryl-Emiliane Chow ◽  
Luisa Chan ◽  
Barbara J. Fuhrman ◽  
...  
Keyword(s):  
Human Papillomavirus ◽  
Phase I ◽  
Therapeutic Vaccine ◽  
High Grade ◽  
T Helper ◽  
Squamous Intraepithelial Lesions ◽  
Hpv 16 ◽  
Intraepithelial Lesions ◽  
Helper Type

Human papillomavirus (HPV) infection is associated with the vast majority of cervical cancer cases as well as with other anogenital cancers. PepCan is an investigational HPV therapeutic vaccine for treating cervical high-grade squamous intraepithelial lesions. The present study was performed to test whether the cervical microbiome influences vaccine responses and to explore host factors as determinants of the cervical microbiome composition in women with biopsy-proven high-grade squamous intraepithelial lesions. In a recently completed Phase I clinical trial of PepCan, histological response rate of 45% (14 of 31 patients), a significant increase in circulating T-helper type 1 cells, and a significant decrease in HPV 16 viral load were reported. DNA, extracted from liquid cytology specimens collected before and after vaccinations, were amplified and then hybridized to a G4 PhyloChip assay to characterize the microbiome. We describe trends that certain bacterial taxa in the cervix may be enriched in non-responders in comparison to responders ( Padj = .052 for phylum Caldithrix and Padj = .059 for phylum Nitrospirae). There was no difference in bacterial diversity between the 2 groups. A permutational analysis of variance performed for various demographic and immune parameters showed significant clustering with microbiome beta diversity for race, HPV 16 status, peripheral T-helper type 1 cells, and HLA-B40 ( P = .001, .014, .037, and .024, respectively). Further analyses showed significant differences at the empirical Operational Taxonomic Unit level for race and HPV 16 status. As these results are from a small Phase I study, further studies are needed to examine the role of cervical microbiome in response to HPV therapeutic vaccines.

scholarly journals Regulation of cell cycles is of key importance in human papillomavirus (HPV)-associated cervical carcinogenesis

2003 ◽  
Vol 121 (3) ◽  
pp. 128-132 ◽  
Author(s):  
Sylvia Michelina Fernandes Brenna ◽  
Kari Juhani Syrjänen
Keyword(s):  
Cell Cycle ◽  
Cervical Cancer ◽  
Human Papillomavirus ◽  
High Risk ◽  
Cell Cycle Checkpoints ◽  
Low Grade ◽  
Clinical Progression ◽  
Squamous Intraepithelial Lesions ◽  
High Risk Hpv ◽  
Intraepithelial Lesions

The rapid progress in molecular biology has allowed the identification of the genes involved in different functions of normal cells and has also improved our understanding of the mechanisms of human carcinogenesis. The human papillomavirus (HPV) is a small double-stranded DNA tumor virus and its genes can manipulate cell cycle control to promote viral persistence and replication. The E6 and E7 proteins of high-risk HPV bind to cell cycle regulatory proteins and interfere with both G1/S and G2/M cell cycle checkpoints much more effectively than the low-risk HPV. The difference between the ability of low and high-risk HPV types to induce immortalization and transformation may well lie in their abilities to interact with the various cell cycle components, resulting in the loss of multiple cell cycle checkpoints, which are important in host genome fidelity, thus potentially resulting in accumulation of genetic abnormalities. Cervical cancer is one of the leading malignancies in women worldwide, with substantial morbidity and mortality. According to current concepts, HPV is recognized as the single most important causal agent in the pathogenesis of this cancer. HPV infection clearly precedes the development of malignancy, while being regularly associated with cervical cancer precursor lesions (all grades of squamous intraepithelial lesions). HPV-infected low-grade squamous intraepithelial lesion (SIL) has three possible outcomes: a) it may regress; b) it can persist; or c) it can make a clinical progression to in situ or invasive carcinoma. It has been well established by prospective cohort studies that the spontaneous regression rate increases in parallel with follow-up duration. In contrast, the clinical progression of lesions usually takes place quite rapidly, i.e. during the first two years from diagnosis. The mechanisms responsible for this divergent clinical behavior of HPV-associated squamous intraepithelial lesions are largely unknown, but currently under intense study in different laboratories worldwide.

Sign in / Sign up

Export Citation Format

Share Document