scholarly journals Phylogeny and polymorphism in the E6 and E7 of human papillomavirus: alpha-9 (HPV16, 31, 33, 52, 58), alpha-5 (HPV51), alpha-6 (HPV53, 66), alpha-7 (HPV18, 39, 59, 68) and alpha-10 (HPV6, 44) in women from Shanghai

2019 ◽  
Vol 14 (1) ◽  
Author(s):  
Junwei Zhao ◽  
Qin Zhan ◽  
Junhan Guo ◽  
Min Liu ◽  
Yetian Ruan ◽  
...  
Keyword(s):  
Phylogenetic Trees ◽  
Intraepithelial Neoplasia ◽  
Human Papillomaviruses ◽  
Therapeutic Interventions ◽  
Cervical Lesions ◽  
Intraepithelial Lesion ◽  
Species Groups ◽  
Hpv Types ◽  
E6 And E7 ◽  
Alpha 7

Abstract Background Persistent infection with human papillomaviruses (HPVs) has been associated with cervical intraepithelial neoplasia (CIN) and cervical cancer. However, why only a fraction of HPV cases progress to cancer is still unclear. Methods We focused on the heterogeneity, classification, evolution and dispersal of variants for 14 common HPV types in 262 HPV-positive patients with cervical lesions. The E6 and E7 genes of HPV were sequenced and compared with the HPV reference for sequence analysis. Phylogenetic trees were constructed using the neighbour-joining tree method with MEGA 7.0. Results In this study, 233 E6 and 212 E7 sequences were successfully amplified by PCR, and these sequences were divided into 5 species groups: alpha-9 (HPV16, 31, 33, 52, 58), alpha-5 (HPV51), alpha-6 (HPV53, 66), alpha-7 (HPV18, 39, 59, 68) and alpha-10 (HPV6, 44). The incidence of high-grade squamous intraepithelial lesion (HSIL) in patients infected with alpha-9 HPV was significantly increased compared with other groups (P < 0.0001), especially HPV16 (P < 0.0001). Strikingly, E7 had significantly fewer nonsynonymous variants in the HSIL compared to <HSIL groups (P = 3.17× 10− 4). The A388C (K93 N) variation in HPV58 E6 can significantly reduce the risk of HSIL (P = 0.015). However, T7220G (D32E) variation in HPV16 E6 and A7689G (N29S) in HPV16 E7 increased the incidence of HSIL compared to the <HSIL group (P = 0.036 and 0.022). Conclusions Strict conservation of E7 is important for HPV carcinogenicity, especially N29 of HPV16. The findings in this work provide preventative/therapeutic interventions for HPV infections and CIN.

scholarly journals Detection of Human Papillomaviruses DNA in paired peripheral blood and cervix samples patients with cervical lesions and healthy individuals

2021 ◽  
Author(s):  
Kamylla Conceicao Gomes Nascimento ◽  
Elyda Goncalves Lima ◽  
Barbara Simas Chagas ◽  
Zhilbelly Mota Nunes ◽  
Marconi Rego Barros Junior ◽  
...  
Keyword(s):  
Peripheral Blood ◽  
Intraepithelial Neoplasia ◽  
Human Papillomaviruses ◽  
Healthy Individuals ◽  
Cervical Lesions ◽  
Hpv16 E6 ◽  
Hpv Dna ◽  
Sexually Transmitted ◽  
Standard Procedures ◽  
Hpv Types

This study evaluated the presence of HPV DNA in the cervix and peripheral blood of women with cervical intraepithelial neoplasia (CIN I, II, and III) and healthy individuals. Overall, 139 paired peripheral blood and cervix samples of healthy women and women with CIN I, II, and III (n= 68) were tested for HPV DNA by using standard procedures. PCR-sequencing determined HPV types. Quantification of HPV16 E6 and E2 genes was performed to determine viral load and physical state. HPV DNA was detected in the cervix (21.1% in healthy individuals; 48.8-55.5% in CIN patients), blood (46.4% in healthy individuals; 44.1-77.7% in CIN patients), and paired peripheral blood and cervix samples (24% in healthy individuals; 32.5-44.4% in CIN patients). The most frequent types found in the cervix were HPV16, 18, 31, 33, 58, and 70, while HPV16, 18, 33, 58, and 66 were the most frequent types found in the blood. HPV DNA in the cervix was associated with previous sexually transmitted infections (STIs) (P=0.023; OR: 2.978; CI:1.34-7.821), HPV DNA in the blood (P=0.000; OR: 3.369; CI:3.700-18.540), and cervical lesions (CIN I/II or III) (P=0.001; OR: 3.369; CI:1.634-6.945). Binomial Logistic regression showed that HPV DNA in the blood (P=0.000; OR: 9.324; CI:3.612-24.072) and cervical lesions (P=0.011; OR: 3.622; CI:1.338-9.806) were associated with HPV DNA in the cervix. However, we did not find an association between HPV DNA in blood and cervical lesions (P=0.385). Our results showed that, although there is an association between HPV DNA in the cervix with HPV DNA in blood, only HPV DNA found in the cervix was associated with cervical lesions.

scholarly journals Abnormal colposcopic images in patients with preinvasive cervical lesions

2013 ◽  
Vol 3 (2) ◽  
pp. 98-102
Author(s):  
Adnan Babović ◽  
Dženita Ljuca ◽  
Gordana Bogdanović ◽  
Lejla Muminhodžić
Keyword(s):  
Intraepithelial Neoplasia ◽  
Control Group ◽  
Low Grade ◽  
High Grade ◽  
Cervical Lesions ◽  
Cytological Examination ◽  
Chi Square ◽  
Chi Square Test ◽  
Intraepithelial Lesion ◽  
Experimental Group

Introduction: The objective of the study was to determine frequency and to compare frequency of the abnormal colposcopic images in patients with low and high grade pre-invasive lesions of cervix.Methods: Study includes 259 patients, whom colposcopic and cytological examination of cervix was done. The experimental group of patients consisted of patents with pre-invasive low grade squamousintraepithelial lesion (LSIL) and high grade squamous intraepithelial lesion (HSIL), and the control group consisted of patients without cervical intraepithelial neoplasia (CIN).Results: In comparison to the total number of satisfactory fi ndings (N=259), pathological findings were registered in N=113 (43.6 %) and abnormal colposcopic fi ndings in N=128 (49.4%). The study did notinclude patients with unsatisfactory fi nding N=22 (8.5%). Abnormal colposcopic image is present most frequently in older patients but there are no statistically important difference between age categories(Pearson Chi-Square 0.47, df -3, p=0.923). Frequency of abnormal colposcopic fi ndings (N=128) is the biggest in pathological cytological (N=113) and HSIL 58 (45.3%), LSIL 36 (28.1%). There is statisticallysignifi cant difference in frequency of abnormal colposcopic images in patients with low-grade in comparison to patients with high-grade pre-invasive cervix lesions (Chi-Square test, Pearson Chi-Square 117.14,df-12 p<0.0001).Conclusion: Thanks to characteristic colposcopic images, abnormal epithelium is successfully recognized, but the severity grade of intraepithelial lesion cannot be determined.

scholarly journals Phylogenetic Incongruence among Oncogenic Genital Alpha Human Papillomaviruses

2005 ◽  
Vol 79 (24) ◽  
pp. 15503-15510 ◽  
Author(s):  
Apurva Narechania ◽  
Zigui Chen ◽  
Rob DeSalle ◽  
Robert D. Burk
Keyword(s):  
Phylogenetic Analyses ◽  
Similarity Measures ◽  
Human Papillomaviruses ◽  
Open Reading Frames ◽  
Total Evidence ◽  
Early Gene ◽  
Tree Length ◽  
Species Groups ◽  
E6 And E7 ◽  
Evolutionary Paths

ABSTRACT The human papillomaviruses (HPVs) have long been thought to follow a monophyletic pattern of evolution with little if any evidence for recombination between genomes. On the basis of this model, both oncogenicity and tissue tropism appear to have evolved once. Still, no systematic statistical analyses have shown whether monophyly is the rule across all HPV open reading frames (ORFs). We conducted a taxonomic analysis of 59 mucosal/genital HPVs using whole-genome and sliding-window similarity measures; maximum-parsimony, neighbor-joining, and Bayesian phylogenetic analyses; and localized incongruence length difference (LILD) analyses. The algorithm for the LILD analyses localized incongruence by calculating the tree length differences between constrained and unconstrained nodes in a total-evidence tree across all HPV ORFs. The process allows statistical evaluation of every ORF/node pair in the total-evidence tree. The most significant incongruence was observed at the putative high-risk (i.e., cancer-associated) node, the common oncogenic ancestor for alpha HPV species 9 (e.g., HPV type 16 [HPV16]), 11, 7 (e.g., HPV18), 5, and 6. Although these groups share early-gene homology, including high degrees of similarity among E6 and E7, groups 9 and 11 diverge from groups 7, 5, and 6 with respect to L2 and L1. The HPV species groups primarily associated with cervical and anogenital cancers appear to follow two distinct evolutionary paths, one conferred by the early genes and another by the late genes. The incongruence in the genital HPV phylogeny could have occurred from an early recombination event, an ecological niche change, and/or asymmetric genome convergence driven by intense selection. These data indicate that the phylogeny of the oncogenic HPVs is complex and that their evolution may not be monophyletic across all genes.

scholarly journals Clinical Significance of the Interaction between Human Papillomavirus (HPV) Type 16 and Other High-Risk Human Papillomaviruses in Women with Cervical Intraepithelial Neoplasia (CIN) and Invasive Cervical Cancer

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Arsenio A. Spinillo ◽  
Mattia M. Dominoni ◽  
Anna A. C. Boschi ◽  
Cecilia C. Sosso ◽  
Giacomo G. Fiandrino ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
High Risk ◽  
Residual Disease ◽  
Invasive Cervical Cancer ◽  
Intraepithelial Neoplasia ◽  
Human Papillomaviruses ◽  
Multiple Infections ◽  
Cervical Lesions ◽  
Hpv 16 ◽  
The Impact

The aim is to evaluate the clinical consequences of coinfection between HPV 16 and other high-risk HPVs among women with a histological diagnosis of CIN or invasive cervical cancer. A total of 2985 women, with a diagnosis of either CIN or cancer (<IB) on cervical or cone biopsy, were included. HPV genotypes were identified using the INNO-LiPA HPV genotyping assay, version EXTRA, on cervical scraping, before the colposcopic evaluation and the colposcopic biopsies or conization. In the overall population, HPV16 interacted positively with HPV18 (RR = 2, 95% CI 1.5–2.6) and negatively with HPV33, 51, 52, and 66, in log-linear analysis. There was an excess of CIN3 diagnoses among subjects coinfected with HPV16 and HPV18 or HPV52, although the absolute number of cases was relatively small. In a logistic model, the odds ratio of CIN3+ associated with coinfection of HPV16 and HPV18 (OR = 3.8, 95% CI 2.5–5.7, p = 0.004 compared to single HPV16) or HPV52 (OR = 3.6, 95% CI 2.6–5.1, p = 0.009 compared to single HPV) was higher than that associated with single HPV 16 infections. Finally, multiple infections had no effect on residual disease and did not influence the recurrence of high-grade CIN during a median follow-up of 25 months (IR 17–41). HPV16 interacted positively with HPV18 and negatively with HPV33, 51, 52, and 66 supporting the notion that HPV16 interacts mostly negatively with other HR-HPVs in CIN lesions. Among specimens coinfected with HPV16 and 18 or 52, there was an excess of CIN3+ although the impact on the prevalence of severe cervical lesions was limited.

scholarly journals Human papillomavirus type 38 E6 and E7 act as tumour promoters during chemically induced skin carcinogenesis

2013 ◽  
Vol 94 (4) ◽  
pp. 749-752 ◽  
Author(s):  
Daniele Viarisio ◽  
Karin Müller Decker ◽  
Birgit Aengeneyndt ◽  
Christa Flechtenmacher ◽  
Lutz Gissmann ◽  
...  
Keyword(s):  
Skin Lesions ◽  
Human Papillomaviruses ◽  
Skin Carcinogenesis ◽  
Non Melanoma Skin Cancer ◽  
Multi Stage ◽  
Chemically Induced ◽  
Contrast Exposure ◽  
Tumour Promoters ◽  
Hpv Types ◽  
E6 And E7

Many findings support a possible involvement of a subgroup of human papillomaviruses (HPVs), called cutaneous beta HPV types, in the development of non-melanoma skin cancer. The skin of transgenic (Tg) mice expressing viral oncoproteins E6 and E7 from different cutaneous beta HPV types, including HPV38, showed an increased susceptibility to UV-induced and/or chemically induced skin carcinogenesis compared with wild-type animals. In this study, we show that beta HPV38 E6 and E7 oncoproteins act as promoter and progression factors in multi-stage skin carcinogenesis, strongly cooperating with the initiator and DNA damage agent 7,12-dimethylbenz[a]anthracene. In contrast, exposure of HPV38 E6/E7 Tg mice to the promoter 12-O-tetradecanoylphorbol-13-acetate did not significantly result in the development of skin lesions. These findings further support the role of beta HPV types in skin carcinogenesis, providing additional insight into their precise contribution to the multi-step process.

scholarly journals Prevalence and Genetic Variability in Capsid L1 Gene of Rare Human Papillomaviruses (HPV) Found in Cervical Lesions of Women from North-East Brazil

2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
Ana Pavla Almeida Diniz Gurgel ◽  
Bárbara Simas Chagas ◽  
Carolina Maria Medeiros do Amaral ◽  
Eugênia Maria Bezerra Albuquerque ◽  
Ivi Gonçalves Soares Santos Serra ◽  
...  
Keyword(s):  
T Cell ◽  
Genetic Variability ◽  
B Cell ◽  
Cell Epitope ◽  
Human Papillomaviruses ◽  
T Cell Epitopes ◽  
Cervical Lesions ◽  
North East ◽  
Hpv Genotypes ◽  
Hpv Types

The aim of this study was to examine the prevalence and genetic variability of the capsid L1 gene of rare HPV genotypes that were found in the cervical lesions of women from North-East Brazil. A total number of 263 patients were included in this study. HPV detection was performed using PCR followed by direct sequencing of MY09/11, as well as type-specific PCR to detect the Alpha-9 species. Epitope prediction was performed to determine whether or not the genetic variants are inserted in B-cell and T-cell epitopes. The prevalence of rare HPV types in cervical lesions was found to be 9.47%. The rare HPV genotypes that were detected were HPV-53, 54, 56, 61, 62, 66, 70, and 81. The genetic variability in the L1 gene of rare HPV types involved thirty nucleotide changes, eight of which were detected for the first time in this study. Moreover, some of these variants are embedded in B-cell or T-cell epitope regions. The results of this research suggest that rare HPV types might be involved in cervical lesions and some of these variants can be found in B-cell and T-cell epitopes. Data on the prevalence and variability of rare HPV types will assist in clarifying the role of these viruses in carcinogenesis.

The Positive Predictive Value of High-Grade Squamous Intraepithelial Lesion on Cytology for the Histological Diagnosis of Cervical Intraepithelial Neoplasia 2 or Higher: A Systematic Review

2019 ◽  
Vol 63 (3) ◽  
pp. 206-214 ◽  
Author(s):  
Nina Karia ◽  
Alison Van Loon ◽  
Cindy Simoens ◽  
Ina Benoy ◽  
Johannes Bogers
Keyword(s):  
Systematic Review ◽  
Cervical Cancer ◽  
Positive Predictive Value ◽  
Cervical Intraepithelial Neoplasia ◽  
Predictive Value ◽  
Intraepithelial Neoplasia ◽  
Histological Diagnosis ◽  
High Grade ◽  
Cervical Lesions ◽  
Intraepithelial Lesion

Cervical cancer is a major worldwide health problem. Therefore, regular cervical screening in order to make an early diagnosis can help to prevent cervical cancer, through identifying and treating preinvasive cervical lesions. The aim of this review is to evaluate the correlation between the cytological screening result and the final gold standard histological outcome in the diagnosis of cervical lesions. More specifically, the correlation between high-grade intraepithelial lesion (HSIL) on cytology and histological cervical intraepithelial neoplasia grade 2 or higher (CIN2+) was intended, by calculating the positive predictive value (PPV). PPV is an important value from a clinical point of view. An electronic search was carried out in the electronic databases MEDLINE (through PubMed) and the Cochrane Library (last searched beginning of December 2017), supplemented with the related article feature in PubMed and snowballing. Article selection (predefined inclusion and exclusion criteria) and data extraction were evaluated by two independent reviewers (N.K. and A.V.L.). After identifying 1,146 articles, 27 articles were finally included in this systematic review, representing 28,783 cytological HSIL diagnoses in total. The PPV of HSIL was 77.5% (range: 45.4–95.2%) for the histological diagnosis of CIN2+ and 55.4% (range: 36.4–67.6%) for the diagnosis of CIN3+. In this systematic review, 77.5% of the HSIL-positive women eventually had a CIN2+ diagnosis. The diagnostic value of a cytological HSIL result (conventional or liquid-based cytology) in the diagnosis of CIN2+ lesions is good, but a combination of tests could raise this value.

scholarly journals Transforming Properties of Beta-3 Human Papillomavirus E6 and E7 Proteins

mSphere ◽  
2020 ◽  
Vol 5 (4) ◽  
Author(s):  
Lucia Minoni ◽  
Maria Carmen Romero-Medina ◽  
Assunta Venuti ◽  
Cécilia Sirand ◽  
Alexis Robitaille ◽  
...  
Keyword(s):  
High Risk ◽  
Expression Profiles ◽  
Expression Patterns ◽  
Biological Properties ◽  
Human Papillomaviruses ◽  
Hpv E6 ◽  
Hpv Types ◽  
Beta 2 ◽  
E6 And E7

ABSTRACT The beta human papillomaviruses (HPVs) are subdivided into 5 species (beta-1 to beta-5), and they were first identified in the skin. However, the beta-3 species appears to be more highly represented in the mucosal epithelia than in the skin. Functional studies have also highlighted that beta-3 HPV49 shares some functional similarities with mucosal high-risk (HR) HPV16. Here, we describe the characterization of the in vitro transforming properties of the entire beta-3 species, which includes three additional HPV types: HPV75, HPV76, and HPV115. HPV49, HPV75, and HPV76 E6 and E7 (E6/E7), but not HPV115 E6 and E7, efficiently inactivate the p53 and pRb pathways and immortalize or extend the life span of human foreskin keratinocytes (HFKs). As observed for HR HPV16, cell cycle deregulation mediated by beta-3 HPV E6/E7 expression leads to p16INK4a accumulation, whereas no p16INK4a was detected in beta-2 HPV38 E6/E7 HFKs. As shown for HPV49 E6, HPV75 and HPV76 E6s degrade p53 by an E6AP/proteasome-mediated mechanism. Comparative analysis of cellular gene expression patterns of HFKs containing E6 and E7 from HR HPV16, beta-3 HPV types, and beta-2 HPV38 further highlights the functional similarities of HR HPV16 and beta-3 HPV49, HPV75, and HPV76. The expression profiles of these four HPV HFKs show some similarities and diverge substantially from those of beta-3 HPV115 E6/E7 and beta-2 HPV38 E6/E7 HFKs. In summary, our data show that beta-3 HPV types share some mechanisms with HR HPV types and pave the way for additional studies aiming to evaluate their potential role in human pathologies. IMPORTANCE Human papillomaviruses are currently classified in different genera. Mucosal HPVs belonging to the alpha genus have been clearly associated with carcinogenesis of the mucosal epithelium at different sites. Beta HPV types have been classified as cutaneous. Although findings indicate that some beta HPVs from species 1 and 2 play a role, together with UV irradiation, in skin cancer, very little is known about the transforming properties of most of the beta HPVs. This report shows the transforming activity of E6 and E7 from beta-3 HPV types. Moreover, it highlights that beta-3 HPVs share some biological properties more extensively with mucosal high-risk HPV16 than with beta-2 HPV38. This report provides new paradigms for a better understanding of the biology of the different HPV types and their possible association with lesions at mucosal and/or cutaneous epithelia.

scholarly journals Human papillomavirus testing as an optional screening tool in low-resource settings of Latin America: experience from the Latin American Screening study

2006 ◽  
Vol 16 (3) ◽  
pp. 955-962 ◽  
Author(s):  
A. Longatto-Filho ◽  
M. Eržen ◽  
M. Branca ◽  
C. Roteli-Martins ◽  
P. Naud ◽  
...  
Keyword(s):  
Latin American ◽  
Screening Tool ◽  
Intraepithelial Neoplasia ◽  
Sexual Partners ◽  
Human Papillomaviruses ◽  
Hpv Test ◽  
High Prevalence ◽  
Cervical Disease ◽  
Screening Study ◽  
Intraepithelial Lesion

Hybrid capture II (HC II) test for oncogenic human papillomaviruses (HPV) was carried out in a cohort of 4284 women at their first clinical visit. Overall prevalence of HPV was 17.1%, decreasing with age from 33.9% among women below 20 years to only 11.0% among those older than 41 years. HPV prevalence was significantly higher among current smokers (odds ratio [OR] = 1.31; 95% CI 1.1–1.6), in women with two or more lifetime sexual partners (OR = 1.9; 95% CI 1.6–2.4), and those women with two or more sexual partners during the past 12 months prior to examination (OR = 1.6; 95% CI 1.2–2.2). HPV detection increased in parallel with increasing cytologic abnormality, being highest in women with high-grade squamous intraepithelial lesion (P = 0.001). Specificity of the HPV test in detecting histologically confirmed cervical disease was 85% (95% CI 83.9–86.1). Sensitivity of the HPV test in detecting histologic abnormalities increased in parallel with disease severity, ranging from 51.5% for cervical intraepithelial neoplasia (CIN) 1 to 96.5% for CIN 3 and 100.0% for cancer, with respective decline of positive predictive value. These data suggest that HPV testing with HC II assay might be a viable screening tool among this population with relatively high prevalence of cervical disease.

scholarly journals Quantification of HPV16 E6/E7 mRNA Spliced Isoforms Viral Load as a Novel Diagnostic Tool for Improving Cervical Cancer Screening

2018 ◽  
Vol 7 (12) ◽  
pp. 530 ◽  
Author(s):  
Claire Camus ◽  
Sébastien Vitale ◽  
Céline Loubatier ◽  
Guillaume Pénaranda ◽  
Hacène Khiri ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Cancer Screening ◽  
Cervical Intraepithelial Neoplasia ◽  
Cervical Cancer Screening ◽  
Diagnostic Performance ◽  
Pap Test ◽  
Intraepithelial Neoplasia ◽  
Human Papillomaviruses ◽  
Cervical Lesions ◽  
Hpv16 E6

High-risk human papillomaviruses (HPVs) have been identified as the main contributors to cervical cancer. Despite various diagnostic tools available, including the predominant Papanicolaou test (Pap test), technical limitations affect the efficiency of cervical cancer screening. The aim of this study was to evaluate the diagnostic performance of spliced HPV16 E6/E7 mRNA viral loads (VL) for grade 2 or higher cervical intraepithelial neoplasia diagnosis. A new dedicated (quantitative reverse transcription polymerase chain reaction) qRT-PCR assay was developed, allowing selective quantification of several HPV16 E6/E7 mRNA: Full length (FL) with or without all or selected spliced forms (total E6/E7 mRNA corresponding to SP + E6^E7 mRNA (T), + spliced E6/E7 mRNA containing intact E7 ORF (SP), and E6/E7 mRNA containing disrupted E6 and E7 ORFs calculated by the following subtraction T-SP (E6^E7)). Twenty HPV16 DNA and mRNA positive uterine cervical smears representative of all cytological and histological stages of severity were tested. We have shown that all E6/E7 mRNA isoforms expression levels were significantly increased in high grade cervical lesions. Statistical analysis demonstrated that the SP-E6/E7 VL assay exhibited: (i) The best diagnostic performance for identification of both cervical intraepithelial neoplasia (CIN)2+ (90% (56–100) sensitivity and specificity) and CIN3+ (100% (72–100) sensitivity and 79% (49–95) specificity) lesions; (ii) a greater sensitivity compared to the Pap test for CIN2+ lesions detection (80% (44–97)); (iii) a predictive value of the histological grade of cervical lesions in 67% of atypical squamous cells of unknown significance (ASC-US) and 100% of low-grade (LSIL) patients. Overall, these results highlight the value of SP-E6/E7 mRNA VL as an innovative tool for improving cervical cancer screening.

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