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 ◽  
...  

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.

2020 ◽  
Author(s):  
Elham Hassen ◽  
Devendra Bansal ◽  
Randa Ghdira ◽  
Anouar Chaieb ◽  
Hedi Khairi ◽  
...  

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.


2020 ◽  
Author(s):  
Elham Hassen ◽  
Devendra Bansal ◽  
Randa Ghdira ◽  
Anouar Chaieb ◽  
Hedi Khairi ◽  
...  

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.


2020 ◽  
Author(s):  
Elham Hassen ◽  
Devendra Bansal ◽  
Randa Ghdira ◽  
Anouar Chaieb ◽  
Hedi Khairi ◽  
...  

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.


Author(s):  
N.A. Shmakova ◽  
G.N. Chistyakova ◽  
I.N. Kononova ◽  
I.I. Remizova

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.


2020 ◽  
Author(s):  
Ping Li ◽  
Qing Liu ◽  
Wei Li ◽  
Zhou Liu ◽  
Baoling Xing ◽  
...  

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.


2003 ◽  
Vol 121 (3) ◽  
pp. 128-132 ◽  
Author(s):  
Sylvia Michelina Fernandes Brenna ◽  
Kari Juhani Syrjänen

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.


2008 ◽  
Vol 55 (4) ◽  
pp. 687-692 ◽  
Author(s):  
Slawa Szostek ◽  
Malgorzata Klimek ◽  
Barbara Zawilinska ◽  
Magdalena Kosz-Vnenchak

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.


2021 ◽  
Author(s):  
Ping Li ◽  
Qing Liu ◽  
Wei Li ◽  
Zhou Liu ◽  
Baoling Xing ◽  
...  

Abstract Background: Human papillomavirus (HPV) infection is currently the main cause of cervical cancer and precancerous lesions in female patients. By analyzing 6-year patient data from Shanghai Zhoupu Hospital in China, we retrospectively analyzed the epidemiological characteristics of women to determine the relationship between HPV genotype and cytological test results.Methods: From 2014 to 2019, 23,724 cases of cervical shedding were collected from Zhoupu Hospital in Shanghai, China. By comparing the results of HPV and ThinPrep cytology test (TCT), the HPV infection rate of patients was retrospectively analyzed. HPV genotyping using commercial kits can detect 21 HPV subtypes (15 high-risk and 6 low-risk). According to the definition of the Bethesda system, seven types of cervical cytology results were involved.Results: 3,816 among 23,724 women, nearly 16.08%, were infected with HPV. The top three highest HPV prevalence rates were high-risk type infection, including HPV52 (3.19%), 58 (2.47%) and 16 (2.34%). The number of single-type HPV infections (3,480 (91.20%)) was much larger than the number of multi-type ones (336 (8.8%)). Single-type infections were mainly in women aged 50-60 (16.63%) and women under 30 (15.37%), while multi-type infections were more common in women over 60 (2.67%). By analyzing the long-term trends, between 2014 and 2019, HPV52, 58, and 16 subtypes changed significantly, and the HPV positive rate also changed significantly during this period.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 glandular cells (AGC), high-grade squamous intraepithelial lesions (HSIL), low-grade squamous intraepithelial lesions (LSIL), atypical squamous cells (ASC)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 very important steps in the secondary prevention of cervical cancer. Through the tracking and analysis of HPV and TCT results in this study, it can provide valuable information for Shanghai's HPV screening and prevention strategies, and provide references for clinical decision-making in the treatment of cervical cancer and precancerous lesions.


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