scholarly journals Crystal Structures of Two Immune Complexes Identify Determinants for Viral Infectivity and Type-Specific Neutralization of Human Papillomavirus

mBio ◽  
2017 ◽  
Vol 8 (5) ◽  
Author(s):  
Zhihai Li ◽  
Daning Wang ◽  
Ying Gu ◽  
Shuo Song ◽  
Maozhou He ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
High Risk ◽  
High Resolution ◽  
Virus Infection ◽  
Crystal Structures ◽  
Major Capsid Protein ◽  
Structural Information ◽  
Hpv Infection ◽  
Human Papillomaviruses ◽  
Different Types

ABSTRACT Persistent, high-risk human papillomavirus (HPV) infection is the primary cause of cervical cancer. Neutralizing antibodies elicited by L1-only virus-like particles (VLPs) can block HPV infection; however, the lack of high-resolution structures has limited our understanding of the mode of virus infection and the requirement for type specificity at the molecular level. Here, we describe two antibodies, A12A3 and 28F10, that specifically bind to and neutralize HPV58 and HPV59, respectively, through two distinct binding stoichiometries. We show that the epitopes of A12A3 are clustered in the DE loops of two adjacent HPV58 L1 monomers, whereas 28F10 recognizes the HPV59 FG loop of a single monomer. Via structure-based mutagenesis and analysis of antibody binding, we further identified the residues HPV58 D154, S168, and N170 and HPV59 M267, Q270, E273, Y276, K278, and R283, which play critical roles in virus infection. By substituting these strategic epitope residues into other HPV genotypes, we could then redirect the type-specific binding of the antibodies to these genotypes, thus highlighting the importance of these specific residues, HPV58 R161, S168, and N308 and HPV59 Q270, E273, and D281. Overall, our findings provide molecular insights into potential structural determinants of HPV required for infectivity and type specificity. IMPORTANCE High-risk human papillomaviruses (HPVs) are considered the major causative pathogens of cancers that affect epithelial mucosa, such as cervical cancer. However, because of the lack of high-resolution structural information on the sites of neutralization, we have yet to determine the precise mode of HPV infection and how different types of HPV cause infection. Our crystal structures in this study have uncovered discrete binding stoichiometries for two different antibodies. We show that one A12A3 Fab binds to the center of one HPV58 pentamer, whereas five 28F10 Fabs bind along the top fringe of one HPV59 pentamer. Furthermore, through targeted epitope analysis, we show that 6 to 7 discontinuous residues of the L1 major capsid protein of HPV are determinants, at least in part, for virus infection and type specificity. This knowledge will help us to unravel the process of HPV infection and can potentially be used to drive the development of therapeutics that target neutralization-sensitive sites. IMPORTANCE High-risk human papillomaviruses (HPVs) are considered the major causative pathogens of cancers that affect epithelial mucosa, such as cervical cancer. However, because of the lack of high-resolution structural information on the sites of neutralization, we have yet to determine the precise mode of HPV infection and how different types of HPV cause infection. Our crystal structures in this study have uncovered discrete binding stoichiometries for two different antibodies. We show that one A12A3 Fab binds to the center of one HPV58 pentamer, whereas five 28F10 Fabs bind along the top fringe of one HPV59 pentamer. Furthermore, through targeted epitope analysis, we show that 6 to 7 discontinuous residues of the L1 major capsid protein of HPV are determinants, at least in part, for virus infection and type specificity. This knowledge will help us to unravel the process of HPV infection and can potentially be used to drive the development of therapeutics that target neutralization-sensitive sites.

scholarly journals HPV and Other Microbiota; Who’s Good and Who’s Bad: Effects of the Microbial Environment on the Development of Cervical Cancer—A Non-Systematic Review

Cells ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 714
Author(s):  
Matthias Läsche ◽  
Horst Urban ◽  
Julia Gallwas ◽  
Carsten Gründker
Keyword(s):  
Systematic Review ◽  
Cervical Cancer ◽  
High Risk ◽  
Cervical Carcinoma ◽  
Hpv Infection ◽  
Human Papillomaviruses ◽  
Inflammatory Reactions ◽  
Metabolic Signalling ◽  
Microbial Environment ◽  
High Risk Hpv

Cervical cancer is responsible for around 5% of all human cancers worldwide. It develops almost exclusively from an unsolved, persistent infection of the squamocolumnar transformation zone between the endo- and ecto-cervix with various high-risk (HR) human papillomaviruses (HPVs). The decisive turning point on the way to persistent HPV infection and malignant transformation is an immune system weakened by pathobionts and oxidative stress and an injury to the cervical mucosa, often caused by sexual activities. Through these injury and healing processes, HPV viruses, hijacking activated keratinocytes, move into the basal layers of the cervical epithelium and then continue their development towards the distal prickle cell layer (Stratum spinosum). The microbial microenvironment of the cervical tissue determines the tissue homeostasis and the integrity of the protective mucous layer through the maintenance of a healthy immune and metabolic signalling. Pathological microorganisms and the resulting dysbiosis disturb this signalling. Thus, pathological inflammatory reactions occur, which manifest the HPV infection. About 90% of all women contract an HPV infection in the course of their lives. In about 10% of cases, the virus persists and cervical intra-epithelial neoplasia (CIN) develops. Approximately 1% of women with a high-risk HPV infection incur a cervical carcinoma after 10 to 20 years. In this non-systematic review article, we summarise how the sexually and microbial mediated pathogenesis of the cervix proceeds through aberrant immune and metabolism signalling via CIN to cervical carcinoma. We show how both the virus and the cancer benefit from the same changes in the immune and metabolic environment.

scholarly journals Detection Rates of Human Papillomavirus Associated with Cervical Cancer in Women of Nizhny Novgorod

2020 ◽  
pp. 44-47
Author(s):  
NF Brusnigina ◽  
MA Makhova ◽  
OM Chernevskaya ◽  
KA Orlova ◽  
EA Kolesnikova ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Human Papillomavirus ◽  
High Risk ◽  
Hpv Infection ◽  
Human Papillomaviruses ◽  
Hpv 16 ◽  
Detection Rates ◽  
High Risk Hpv ◽  
Incident Cases ◽  
Oncogenic Hpv

The purpose of the study was to assess detection rates of human papillomavirus in cervical cancer cases of Nizhny Novgorod. Materials and methods. We used the real-time polymerase chain reaction (PCR) to test samples of mucosa lining of the cervical canal and/or transformation zone taken from 630 women with cervical dysplasia of different degrees and 107 incident cases of cervical cancer that did not undergo treatment. The detection and differentiation of 14 genotypes of high-risk human papillomaviruses (HPV) was carried out using the AmpliSens® HPV HCR-genotype-FRT PRC kit. Results. The overall infection rate of women with oncogenic human papillomaviruses was 41.8%. Among the genotypes, HPV 16 (39.2%), 18 (15.5%), 33 (16.6%), and 56 (11.9%) predominated. A high prevalence of oncogenic HPV was detected in the women with cervical intraepithelial neoplasia (58.1%) and cervical cancer (90%). The spectrum of genotypes in women with neoplasia of various degrees differed. In women with CIN II and CIN III, vaccine-preventable HPV genotypes (HPV 16 and 18) playing the leading role in the development of cervical cancer were the most frequent. The same genotypes dominated in the women with invasive cervical cancer. One oncogenic HPV genotype was usually found in the infected women (69%). The high-risk HPV infection was often combined with Ureaplasma ssp (49.3%), Mycoplasma hominis (20.1%), Cytomegalovirus (21.1%), and Herpes simplex I/II (18.2%) infections. Combinations of high-risk HPV with Chlamydia trachomatis and Herpes 6 were found in 8.3% and 5% of the cases, respectively. Conclusions. Our findings proved a wide prevalence of high carcinogenic risk HPV 16 and 18 genotypes, thus indicating the expediency of using Cervarix and Gardasil vaccines registered in the Russian Federation and containing antigens to these types of virus for specific prevention of the HPV infection.

scholarly journals The Laboratory Diagnosis of Genital Human Papillomavirus Infections

2005 ◽  
Vol 16 (2) ◽  
pp. 83-91 ◽  
Author(s):  
François Coutlee ◽  
Danielle Rouleau ◽  
Alex Ferenczy ◽  
Eduardo Franco
Keyword(s):  
Cervical Cancer ◽  
High Risk ◽  
Hpv Infection ◽  
Human Papillomaviruses ◽  
High Grade ◽  
Hpv Testing ◽  
Screening Programs ◽  
Detection Techniques ◽  
Hpv Types ◽  
High Risk Hpv

Human papillomaviruses (HPVs) are the etiological agents of several genital cancers, including cancer of the uterine cervix. The detection of HPV infection in genital samples may increase the sensitivity of primary and secondary screenings of cervical cancer. HPV testing may also improve the specificity of screening programs, resulting in the avoidance of overtreatment and cost savings for confirmatory procedures. The major determinants of clinical progression of HPV infection include persistence of HPV infection, involvement of high-risk HPV types, high HPV viral load, integration of viral DNA and presence of several potential cofactors. Signal amplification HPV-DNA detection techniques (Hybrid Capture II, Digene Corporation, USA) are standardized, commercially available, and capable of detecting several high-risk HPV types. They also increase the sensitivity of screening for high-grade lesions in combination with cytology. The sensitivity of these techniques to detect high-grade lesions is higher than that of cytology, but the referral rate for colposcopy is greater. These techniques are approved for the triage to colposcopy of women with cervical smears interpreted as atypical squamous cells of undetermined significance. Triage and screening for cervical cancer using HPV will probably be restricted to women aged 30 years or older because of the high prevalence of infection in younger women. Amplification techniques are ideal for epidemiological studies because they minimize the misclassification of HPV infection status. These techniques can detect low HPV burden infections. Consensus primers amplify most genital types in one reaction, and the reverse hybridization of amplicons with type-specific probes allows for the typing of HPV-positive samples. Consensus PCR assays are currently under evaluation for diagnostic purposes. HPV testing is currently implemented for the clinical management of women.

scholarly journals Prevalence of High Risk HPV in HIV-Infected Women From Belém, Pará, Amazon Region of Brazil: A Cross-Sectional Study

2021 ◽  
Vol 9 ◽  
Author(s):  
Jacqueline Cortinhas Monteiro ◽  
Ricardo Roberto de Souza Fonseca ◽  
Tuane Carolina de Sousa Ferreira ◽  
Luana Lorena Silva Rodrigues ◽  
Andreza Reis Brasil da Silva ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
High Risk ◽  
Hpv Infection ◽  
Cross Sectional Study ◽  
Reproductive Age ◽  
Transmitted Infection ◽  
Cross Sectional ◽  
Multiple Sexual Partners ◽  
Sexually Transmitted ◽  
High Risk Hpv

Human papillomavirus (HPV) is the most common sexually transmitted infection in the world. Several studies have shown a higher prevalence of HPV infection in HIV-infected women. The aim of this study was to determine the prevalence and the genotype diversity of HPV infection in HIV-infected women. From April 2010 to December 2012 cervical specimens were collected from 169 HIV-infected women who screening for cervical cancer at Reference Unit in Belém. The detection of HPV infection was performed by nested PCR and HPV type was performed using a commercial system. The prevalence of HPV infection was 63.3%. Of the 47 genotyped samples, 40.4% was found positive for high risk-HPV 16 and 12.8% for high risk-HPV 52. HPV infection was predominant in the group of women with no incidence of cytological abnormalities and more prevalent in women of reproductive age, unmarried, low education level, and who reported use condoms during sexual intercourse. It was observed an association between HPV infection and independent variables, such as condom use, multiple sexual partners, and history of sexually transmitted diseases. High-risk types of HPV infection were prevalent in our study. Infection with multiple high-risk HPV genotypes may potentiate the development of cervical cancer in HIV-infected women.

scholarly journals Acceptability and feasibility of human papillomavirus vaccination for adolescents in school environments in Libreville

2020 ◽  
Vol 9 (9) ◽  
pp. 3541
Author(s):  
Nathalie L. Ambounda ◽  
Sylvain H. Woromogo ◽  
Olive M. Kenmogne ◽  
Felicite E. Yagata Moussa ◽  
Vicky N. Simo Tekem ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Human Papillomavirus ◽  
High Risk ◽  
Precancerous Lesions ◽  
Hpv Vaccination ◽  
Immunization Coverage ◽  
Human Papillomaviruses ◽  
Professional Status ◽  
Human Papillomavirus Vaccination ◽  
Cross Sectional

Background: High-risk oncogenic human papillomaviruses (HPV) are the cause of sexually transmitted viral infection. Its persistence is a risk factor for precancerous lesions of the cervix, which will constitute the base of cervical cancer. In the world, the prevalence of high-risk oncogenic HPV is 66.7%, which is higher among women starting their sexual activity.Methods: An analytical cross-sectional study was conducted in high schools in Gabon regarding parents. The variables selected were the socio-cultural and demographic characteristics of the parents, their knowledge of human papillomavirus vaccination and their acceptability of HPV vaccination and finally the feasibility of HPV vaccination. The statistical test used was Pearson's Chi-square, and a difference was considered significant for p<0.05.Results: The majority of parents, 89%, were informed of the existence of cervical cancer. However, 73.4% of them were unaware of the existence of vaccination against cervical cancer. Only 2.4% of parents had vaccinated their daughters against cervical cancer at the time of the study. These parents only 53.4% expressed an interest in vaccinating their daughters in 53.4% of cases. The ability to vaccinate children is associated with the socio-professional status of parents (p˂0.000).Conclusions: The majority of parents approved school-based vaccination against human papillomavirus infections despite its reported cost and lack of information. The integration of anti-HPV vaccination into the expanded programme on immunization in Gabon will improve immunization coverage.

scholarly journals Human papillomavirus infection rate, distribution characteristics, and risk of age in pre- and postmenopausal women

2020 ◽  
Author(s):  
Yan Shen ◽  
Jing Xia ◽  
Hui hui Li ◽  
Yang Xu ◽  
San ping Xu
Keyword(s):  
Cervical Cancer ◽  
High Risk ◽  
Postmenopausal Women ◽  
Infection Rate ◽  
Genital Tract ◽  
Hpv Infection ◽  
Distribution Characteristics ◽  
Lower Genital Tract ◽  
Significant Difference ◽  
High Risk Hpv

Abstract BackgroundThe incidence rate of cervical cancer is increasing yearly. The persistent infection of high-risk Human Papillomavirus (HPV) is the main factor leading to cervical cancer. HPV infection is double peak type. This study aimed at analyzing the HPV distribution characteristics, infection rate, and risk of age in pre- and postmenopausal women. So as to provide reference for the prevention of HPV infection and cervical cancer screening strategy.MethodsA retrospective analysis of 4614 women who underwent cervical cytology, and HPV examination from January 2018 to October 2019 at the healthcare department of Wuhan Union Hospital was done. We explored the characteristics and distribution of HPV infections around the menopause, then comparing the infection rate of HPV in postmenopause and over 65 years old, in order to analyze the influence of different ages on HPV infection.ResultsGenerally, the HPV infection rate was 13.10% (539 / 4115), whereby the high-risk subtype constituted 73.84% (398 / 539) of all positive cases. On the other hand, the HPV39 infection was more common in postmenopausal women; however, there was no significant difference in the distribution of the other types in the pre- and postmenopausal women (Insert p value). The first four subtypes were 52 / 53 / 58 / 16, respectively. The infection rate of HPV in patients with lower genital tract inflammation was significantly higher, P = 0.000, 95% CI: 1.911 (1.416, 2.580) compared with those without lower genital tract inflammation. The results further showed that there was no significant difference between pre- and postmenopausal women in terms of HPV infection rate, but more susceptible to high-risk HPV infection after the age of 65 (P = 0.041). Except for 40 years old to menopause, the infection rate of high-risk HPV in this age group was different from that in postmenopause(P = 0.023,0.729(0.555,0.957)), other age groups had no significant effect on high-risk HPV infection.ConclusionsIt was concluded that whether menopause has nothing to do with HPV infection. Moreover, the infection rate of high-risk HPV increases after 65 years of age; hence the cutoff screening age should be appropriately prolonged.Trial registration: Retrospectively registered.

Characteristics of high-risk human papillomavirus infection in women with abnormal cervical cytology: a population-based study in Shanxi Province, China

2019 ◽  
Author(s):  
Li Song ◽  
Yuanjing Lyu ◽  
Ling Ding ◽  
Xiaoxue Li ◽  
Wen Gao ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Human Papillomavirus ◽  
High Risk ◽  
Hpv Infection ◽  
Cervical Cytology ◽  
Shanxi Province ◽  
Low Grade ◽  
Squamous Intraepithelial Lesion ◽  
Abnormal Cervical Cytology ◽  
Intraepithelial Lesion

Abstract Background: High-risk human papillomavirus (HR-HPV) infection is widely known as the major cause of cervical intraepithelial neoplasia (CIN) and cervical cancer and it’s characteristics vary greatly in different population. Women with abnormal cervical cytology could increase the risk of cervical cancer, however, HR-HPV infection characteristics in women with abnormal cervical cytology remains unclear. Methods: This study was based on baseline survey of the CIN Cohort established in Shanxi Province, China. A total number of 2300 women with cervical abnormalities were enrolled in this study. All participants gave informed consent and agreed to HPV and thinprepcytologic test (TCT). Each individual completed a questionnaire about characteristics related to HPV infection. Results: The overall prevalence of HR-HPV in 2300 women was 32.0%, and the proportion of single and multiple HR-HPV infections were 70.2% and 29.8% in HR-HPV infection women, respectively. The top five HR-HPV genotypes were ranked as HPV16, HPV58, HPV52, HPV53 and HPV51. The prevalence of HR-HPV in atypical squamous cells of undetermined significance (ASC-US), low-grade squamous intraepithelial lesion (LSIL) and high-grade squamous intraepithelial lesion and above(HSIL+) were 30.8%, 36.5% and 54.9%, respectively, showing an increasing trend with the severity of cervical cytology ( χ 2 trend =13.952; p <0.001). The women aged 35~45 years, with lower education level, less frequency of bathing, multiple gravidity, multiple parity, history of gynecological diseases and premenopausal women were prone to HR-HPV infection. Conclusions: We defined the characteristics related to HR-HPV infection in abnormal cervical cytology women, and provided an insight for the development and deeply research of HPV vaccine.

scholarly journals Prevalence and Subtype Distribution of High-Risk Human Papillomavirus Among Women Presenting for Cervical Cancer Screening at Karanda Mission Hospital

2020 ◽  
pp. 1276-1281 ◽  
Author(s):  
Paul Thistle ◽  
Rabea Parpia ◽  
Debanjan Pain ◽  
Hang Lee ◽  
Justen Manasa ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Human Papillomavirus ◽  
Cancer Screening ◽  
High Risk ◽  
Cervical Cancer Screening ◽  
Screening Program ◽  
Large Fraction ◽  
Human Papillomaviruses ◽  
Mission Hospital ◽  
Dna Types

PURPOSE High-risk human papillomaviruses (hrHPV) are the primary cause of cervical cancer. Human papillomavirus (HPV) vaccination is expected to prevent cervical cancers caused by the HPV types included in vaccines and possibly by cross-protection from other types. This study sought to determine the hrHPV type distribution in women at a rural Zimbabwe hospital. METHODS We implemented a cross-sectional study at the Karanda Mission Hospital. Using the Visual Inspection with Acetic Acid Cervicography technique, clinicians collected cervical swabs from 400 women presenting for screening for cervical cancer. Samples were initially analyzed by Cepheid GeneXpert; candidate hrHPV genotypes were further characterized using the Anyplex II HPV28 Detection Kit. RESULTS Twenty-one percent of the 400 women were positive for a high-risk genotype when using the GeneXpert analyzer; 17% were positive when using the multiplex analysis. Almost two thirds of the hrHPV women had a single DNA type identified, whereas one third had multiple genotypes, ranging from 2 to 5. hrHPV was observed more frequently in HIV-positive than in HIV-negative women (27% v 15%). Of the 113 isolates obtained, 77% were hrHPV genotypes not included in the bivalent or quadrivalent vaccines, and 47% represented DNA types not covered in the nonavalent vaccine. Forty-seven percent of the women with hrHPV harbored a single genotype that was not covered by the nonavalent vaccine. CONCLUSION A large fraction of hrHPV isolates from women participating in a cervical cancer screening program in northern Zimbabwe are DNA types not covered by the bivalent, quadrivalent, or nonavalent vaccines. These findings suggest the importance of characterizing the hrHPV DNA types isolated from cervical neoplasia in this population and determining whether cross-immunization against these genotypes develops after administration of the vaccines in current use.

scholarly journals Persistent High-Risk HPV Infection and Molecular Changes Related to the Development of Cervical Cancer

2020 ◽  
Vol 2020 ◽  
pp. 1-6
Author(s):  
Pablo Moreno-Acosta ◽  
Alfredo Romero-Rojas ◽  
Nicolas Vial ◽  
Antonio Huertas ◽  
Jinneth Acosta ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
High Risk ◽  
Invasive Cervical Cancer ◽  
Transition Process ◽  
Hpv Infection ◽  
Low Grade ◽  
Preneoplastic Lesions ◽  
Hpv 16 ◽  
Molecular Changes ◽  
High Risk Hpv

This article is a preliminary investigational study that is aimed at giving hints about the interesting biomarkers involved in the transition process from low-grade cervix lesion to invasive cervical cancer. Our study focuses on the risk factors and tumour molecular changes in one patient. First in 1986, she was diagnosed a preinvasive cervix lesion. Then, 16 years later, she was diagnosed an invasive cervical cancer. The 2002 diagnosis was a squamous cell carcinoma of the cervix, stage IIIB (FIGO), whereas in 1986, she had been diagnosed a high-grade squamous intraepithelial cervical lesion. Retrospectively, the analysis of samples of preneoplastic lesions and invasive cervical cancer confirmed the histopathological diagnoses and detected the presence of HPV type and HPV-16 variants, as well as the overexpression of proteins such as hTERT, IGF1Rα, IGF1Rβ, CAIX, and GLUT1. Finally, the Arg72Pro polymorphism was detected in TP53. The role of high-risk HPV and HPV-16 variants and of hTERT, IGF1Rα, IGF1Rβ, CAIX, and GLUT1 variations seemed confirmed in the development and progression of cervical cancer. As a result, analyzing the molecular changes in one and same tumour that progresses from a low-grade cervix lesion to invasive cervical cancer could provide valuable information in order to improve detection, diagnosis, and treatment in the future.

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