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

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.

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

10.21203/rs.3.rs-23621/v4 ◽

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

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

10.21203/rs.3.rs-23621/v2 ◽

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.

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

10.21203/rs.3.rs-23621/v1 ◽

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.

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Colposcopy, cervical cytology and human papillomavirus detection as screening tools for cervical cancer

Eastern Mediterranean Health Journal ◽

10.26719/2001.7.1-2.100 ◽

2001 ◽

Vol 7 (1-2) ◽

pp. 100-105

Author(s):

Al Alwan Al Alwan

Keyword(s):

Human Papillomavirus ◽

High Risk ◽

Pap Test ◽

Screening Tools ◽

Low Grade ◽

Squamous Intraepithelial Lesions ◽

Sampling Device ◽

Squamous Cells ◽

The Bethesda System ◽

Intraepithelial Lesions

A cohort of 77 women referred for routine screening or investigation of Pap test abnormality underwent colposcopic examination. Pap-stained liquid-based preparations were diagnosed and categorized according to the Bethesda system. Residual material on the sampling device was used to detect high-risk oncogenic human papillomavirus DNA. Although the colposcopic failure rate was higher than that of cytology, no lesion was missed when both methods were used together. High-risk types were recorded in 24% of patients with atypical squamous cells of undetermined significance, 45% with low-grade squamous intraepithelial lesions and 79% with high-grade squamous intraepithelial lesions-indicating that the efficacy of cytological screening can be improved by papillomavirus detection.

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Multiple types of human papillomavirus infection and anal precancerous lesions in HIV-infected men in Taiwan: a cross-sectional study

BMJ Open ◽

10.1136/bmjopen-2017-019894 ◽

2018 ◽

Vol 8 (1) ◽

pp. e019894 ◽

Cited By ~ 6

Author(s):

Shu-Hsing Cheng ◽

Kuo-Sheng Liao ◽

Chi-Chao Wang ◽

Chien-Yu Cheng ◽

Fang-Yeh Chu

Keyword(s):

Human Papillomavirus ◽

Cross Sectional Study ◽

Low Grade ◽

Sectional Study ◽

Squamous Intraepithelial Lesions ◽

Cross Sectional ◽

Anal Cytology ◽

Hpv Types ◽

The Relationship ◽

Intraepithelial Lesions

ObjectivesThis study aimed to assess the relationship between infection with multiple human papillomavirus (HPV) types and abnormal anal cytology in HIV-infected men.DesignAn observational, cross-sectional study.SettingA regional referral hospital in Taiwan.ParticipantsIn total, 714 HIV-infected men were enrolled between March 2011 and June 2016. Thin preparation anal Pap smears were interpreted according to the 2001 Bethesda System. Thirty-seven types of HPV were detected by reverse line blotting, including 13 oncogenic types and 24 non-oncogenic types.Outcome measuresThe relationship between anal HPV infection and abnormal anal cytology in people of Asian ethnicity and the coverage efficacy in HPV-vaccinated HIV-infected men.ResultsOn anal cytology, 175 (24.5%) subjects had atypical squamous cells of undetermined significance (ASCUS) or higher grades of dysplasia, including 87 (49.7%) with ASCUS, 73 (41.7%) with low-grade squamous intraepithelial lesions (LSILs) and 15 (8.6%) with high-grade squamous intraepithelial lesions (HSILs). A higher proportion of subjects with those without LSIL/HSIL (93.1% vs 67.3%, P<0.0001) had multiple HPV types. The odds of having LSIL/HSIL increased with an increasing number of HPV types: the ORs ranged from 1 for no HPV types to 6.96 (95% CI 2.38 to 20.37) for more than five types (Ptrend<0.0001). Multivariate logistic regression analysis showed a significant association between LSIL/HSIL and the number of HPV genotypes present (OR 1.20; 95% CI 1.02 to 1.42, P<0.05). HPV types covered by the nonavalent HPV vaccine (types 6/11/16/18/31/33/45/52/58) were detected in 70.1% of the patients in this study.ConclusionsThe odds of having anal LSIL/HSIL are approximately seventimes greater in HIV-infected men with than withoutsix or more types of HPV. Multiple HPV types in HIV-infected patients deserves aggressive follow-up, and HPV vaccination programme require scaling up.

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

Sao Paulo Medical Journal ◽

10.1590/s1516-31802003000300009 ◽

2003 ◽

Vol 121 (3) ◽

pp. 128-132 ◽

Cited By ~ 17

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.

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