scholarly journals Human Papillomavirus (HPV) DNA Copy Number Is Dependent on Grade of Cervical Disease and HPV Type

1999 ◽  
Vol 37 (4) ◽  
pp. 1030-1034 ◽  
Author(s):  
David C. Swan ◽  
Ruth Ann Tucker ◽  
Guillermo Tortolero-Luna ◽  
Michele Follen Mitchell ◽  
Louise Wideroff ◽  
...  
Keyword(s):  
Human Papillomavirus ◽  
Copy Number ◽  
Dna Copy Number ◽  
Viral Dna ◽  
Normal Cytology ◽  
Hpv Dna ◽  
Copy Numbers ◽  
Cervical Disease ◽  
Hpv Types ◽  
Cellular Dna

The association between human papillomavirus (HPV) DNA copy number and cervical disease was investigated. Viral DNA copy number for the most common high-risk HPV types in cervical cancer (types 16, 18, 31, and 45) was determined in cervical cytobrush specimens from 149 women with high-grade cervical intraepithelial neoplasias (CIN II-CIN III), 176 with low-grade CIN (CIN I), and 270 with normal cytology. Quantitative, PCR-based fluorescent assays for each of the HPV genotypes and for the β-globin gene were used. The amount of cellular DNA increased significantly with increasing disease; thus, HPV was expressed as copies per microgram of cellular DNA. The assay had a dynamic range of >107, allowing documentation for the first time of the wide range of HPV copy numbers seen in clinical specimens. Median HPV DNA copy number varied by more than 104 among the viral types. HPV16 was present in the highest copy number; over 55% of HPV16-positive samples contained more than 108 copies/μg. Median copy number for HPV16 showed dramatic increases with increasing epithelial abnormality, an effect not seen with the other HPV types. HPV16 increased from a median of 2.2 × 107 in patients with normal cytology, to 4.1 × 107 in CIN I patients, to 1.3 × 109 copies/μg in CIN II-III patients. Even when stratified by cervical disease and viral type, the range of viral DNA copies per microgram of cellular DNA was quite large, precluding setting a clinically significant cutoff value for “high” copy numbers predictive of disease. This study suggests that the clinical usefulness of HPV quantitation requires reassessment and is assay dependent.

scholarly journals Association of serum and mucosal neutralizing antibodies to human papillomavirus type 16 (HPV-16) with HPV-16 infection and cervical disease

2008 ◽  
Vol 89 (4) ◽  
pp. 910-914 ◽  
Author(s):  
Zizipho Z. A. Mbulawa ◽  
Anna-Lise Williamson ◽  
Debbie Stewart ◽  
Jo-Ann S. Passmore ◽  
Lynette Denny ◽  
...  
Keyword(s):  
Human Papillomavirus ◽  
Neutralizing Antibodies ◽  
Antibody Responses ◽  
Normal Cytology ◽  
Hpv 16 ◽  
Human Papillomavirus Type 16 ◽  
Immunodeficiency Virus ◽  
Cervical Disease ◽  
Hpv Types

We investigated neutralizing antibodies to human papillomavirus type 16 (HPV-16) in serum and cervical washes from 84 women with normal cytology or cervical disease. Serum neutralizing antibodies were detected in 78 % of women infected at the cervix with HPV-16, compared with 35 % (P=0.002) of women infected with HPV-16-related types (α9 HPV types), 14 % (P<0.0001) of women infected with HPV-16 non-related types and none of HPV-uninfected women. A significant correlation between HPV-16 infection and serum HPV-16-neutralizing antibodies was observed (r s=0.97; P=0.032). Cervical neutralizing antibodies were detected in 38 % of women with HPV-16 infection and in 17 % of women infected with the HPV-16-related type HPV-31. Cervical neutralizing antibodies correlated with HPV-16 infection (r s=0.95; P=0.08), but not with cervical disease. Serum and cervical HPV-16 antibody responses were not affected significantly by human immunodeficiency virus type 1 infection. In conclusion, serum and cervical HPV-16-neutralizing antibodies were found to correlate with HPV-16 infection, but not with cervical disease.

scholarly journals Artificial Recruitment of UAF1-USP Complexes by a PHLPP1-E1 Chimeric Helicase Enhances Human Papillomavirus DNA Replication

2015 ◽  
Vol 89 (12) ◽  
pp. 6227-6239 ◽  
Author(s):  
David Gagnon ◽  
Michaël Lehoux ◽  
Jacques Archambault
Keyword(s):  
Human Papillomavirus ◽  
Dna Replication ◽  
Binding Site ◽  
Protein Interaction ◽  
Pleckstrin Homology Domain ◽  
Viral Dna ◽  
Viral Dna Replication ◽  
Hpv Dna ◽  
Hpv Types ◽  
Wd Repeat

ABSTRACTThe E1 helicase from anogenital human papillomavirus (HPV) types interacts with the cellular WD repeat-containing protein UAF1 in complex with the deubiquitinating enzyme USP1, USP12, or USP46. This interaction stimulates viral DNA replication and is required for maintenance of the viral episome in keratinocytes. E1 associates with UAF1 through a short UAF1-binding site (UBS) located within the N-terminal 40 residues of the protein. Here, we investigated if the E1 UBS could be replaced by the analogous domain from an unrelated protein, the pleckstrin homology domain and leucine-rich repeat protein phosphatase 1 (PHLPP1). We found that PHLPP1 and E1 interact with UAF1 in a mutually exclusive manner and mapped the minimal PHLPP1 UBS (PUBS) to a 100-amino-acid region sufficient for assembly into UAF1-USP complexes. Similarly to the E1 UBS, overexpression of PUBS intransinhibited HPV DNA replication, albeit less efficiently. Characterization of a PHLPP1-E1 chimeric helicase revealed that PUBS could partially substitute for the E1 UBS in enhancing viral DNA replication and that the stimulatory effect of PUBS likely involves recruitment of UAF1-USP complexes, as it was abolished by mutations that weaken UAF1-binding and by overexpression of catalytically inactive USPs. Although functionally similar to the E1 UBS, PUBS is larger in size and requires both the WD repeat region and C-terminal ubiquitin-like domain of UAF1 for interaction, in contrast to E1, which does not contact the latter. Overall, this comparison of two heterologous UBSs indicates that these domains function as transferable protein interaction modules and provide further evidence that the association of E1 with UAF1-containing deubiquitinating complexes stimulates HPV DNA replication.IMPORTANCEThe E1 protein from anogenital HPV types interacts with the UAF1-associated deubiquitinating enzymes USP1, USP12, and USP46 to stimulate replication of the viral genome. Little is known about the molecular nature of the E1-UAF1 interaction and, more generally, how UAF1-USP complexes recognize their substrate proteins. To address this question, we characterized the UAF1-binding site (UBS) of PHLPP1, a protein unrelated to E1. Using a PHLPP1-E1 chimeric helicase, we show that the PHLPP1 UBS (PUBS) can partially substitute for the E1 UBS in stimulating HPV DNA replication. This stimulation required conserved sequences in PUBS that meditate its interaction with UAF1, including a motif common to the E1 UBS. These results indicate that UAF1-binding sequences function as transferable protein interaction modules and provide further evidence that UAF1-USP complexes stimulate HPV DNA replication.

scholarly journals Distribution and Prevalence of High-Risk Human Papillomavirus Genotypes in Cervical Specimens

2020 ◽  
Vol 25 (3) ◽  
pp. 325-331
Author(s):  
Erkan Özmen ◽  
Ülkü Altoparlak ◽  
Muhammet Hamidullah Uyanık ◽  
Abdulkadir Gülen
Keyword(s):  
Cervical Cancer ◽  
Human Papillomavirus ◽  
Age Groups ◽  
Hpv Infection ◽  
High Rate ◽  
Genotype Distribution ◽  
Hpv Dna ◽  
Hpv Test ◽  
Significant Difference ◽  
Hpv Types

Introduction: Human papillomavirus (HPV) is frequently a sexually transmitted virus and can cause cervical cancer in women. Cervical cancer is the second most common type of cancer among the developing countries. In this study, cervical HPV DNA positivity and genotype distributions were investigated in female patients living in our region and the results were compared with different studies. Materials and Methods: Between 1 July, 2017 and 1 March, 2019, 433 cervical swabs were sent to Ataturk University, Medical Faculty Hospital, Medical Microbiology Laboratory due to suspicion of HPV. Swab samples were evaluated for HPV virus using molecular (Polymerase Chain Reaction-PCR) methods. For this purpose, Xpert HPV Test (Cepheid, Inc, Sunnyvale, CA) was used to identify HPV types 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and 68 t in a single sample. Results: Mean age of the patients ranged from 20 to 69 years, with a mean of 39.8 years (± 10.0). Positivity was detected in 62 of the 433 patients. Mean age of the positive patients was 40.2 years (± 11.3). When the positive patients were examined in terms of HPV types, the presence of HPV 16 was observed with a rate of 25.6%, while the HPV 18/45 types were found to be 9.0% in total. When patients were evaluated according to age groups, HPV DNA positivity was highest in the 25-34 age group with 38.7%. In our statistical study, there was no significant difference in HPV DNA positivity rate between the ages of 35 and under 35 years. Conclusion: This study demonstrates the prevalence and viral genotype distribution of HPV infection in women in Erzurum region. HPV type 16 is seen with a high rate in our region.

scholarly journals Human Papillomavirus and Coronary Artery Disease in Climacteric Women: Is There an Association?

2019 ◽  
Vol 2019 ◽  
pp. 1-6 ◽  
Author(s):  
Luciane Maria Oliveira Brito ◽  
Haissa Oliveira Brito ◽  
Rita da Graça Carvalhal Frazão Corrêa ◽  
Clariano Pires de Oliveira Neto ◽  
Joyce Pinheiro Leal Costa ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Human Papillomavirus ◽  
Coronary Artery ◽  
Sexual Behaviors ◽  
Hpv Infection ◽  
Demographic Variables ◽  
Hpv Dna ◽  
Hpv Types ◽  
Artery Disease ◽  
High Risk Hpv

Background. Cardiovascular diseases are leading causes of death worldwide. Recent studies suggest that infection by some viruses, including the human papillomavirus (HPV), may increase the risk of developing atheromatous lesions on coronary arteries. However, there is a lack of data regarding the possible association between HPV infection and coronary artery disease (CAD) in women. Objective. To investigate whether HPV infection is associated with the occurrence of CAD among climacteric women. Methods. The presence of CAD and cervical HPV DNA was investigated in 52 climacteric women. Social and demographic variables and metabolic profiles were also investigated. Results. Among 27 women with CAD, 16 were positive for HPV, whereas 11 were negative. The presence of cervical HPV was strongly associated with CAD, after adjusting for demographic variables, health and sexual behaviors, comorbidities, and known cardiovascular risk factors. HPV-positive women showed a greater likelihood of having CAD (odds ratio [OR] = 3.74; 95% confidence interval [CI]: 1.16 to 11.96) as compared with HPV-negative women, particularly those infected with high-risk HPV types (OR = 4.90; 95% CI: 1.26 to 19.08). Conclusion. These results support the hypothesis that HPV infection might be associated with CAD among climacteric women, though further studies are needed to investigate the mechanisms involved.

Prevalence and Distribution of High-Risk Human Papillomavirus Genotypes in Invasive Carcinoma of the Uterine Cervix in Uruguay

2013 ◽  
Vol 23 (3) ◽  
pp. 527-532 ◽  
Author(s):  
Nora Berois ◽  
Patricia De Cremoux ◽  
Daniel Mazal ◽  
Adela Sica ◽  
Mabel Cedeira ◽  
...  
Keyword(s):  
Human Papillomavirus ◽  
High Risk ◽  
Dna Sequences ◽  
Invasive Cervical Cancer ◽  
Human Papillomaviruses ◽  
Geographical Differences ◽  
Hpv Dna ◽  
High Prevalence ◽  
Hpv Types ◽  
High Risk Hpv

ObjectivesPersistent infection with specific genotypes of human papillomaviruses (HPVs) is the main cause of invasive cervical cancer (ICC). Only a few of the various HPV types account for most of the cases worldwide, and geographical differences in their distribution are evident. Data from locally prevalent genotypes are essential in view of introduction of HPV type-specific prophylactic vaccines.MethodsIn this work, we have investigated HPV type distribution in samples of ICC cases that occurred in Uruguayan women. DNA extracted from ICC treated in Centro Hospitalario Pereira Rossell of Montevideo between 1999 and 2007 were analyzed. Search and typing were performed by polymerase chain reaction using generic GP5+/GP6+ primers and specific primers for HPV types 16, 18, 33, and 45. Positive GP5+/GP6+ samples, which were negative for all 4 high-risk HPV-specific types screened were further analyzed by sequencing.ResultsHuman papillomavirus DNA sequences were found in 163 (92.6%) of 176 cases. The most prevalent genotypes were HPV16 (67.6%) and HPV18 (8.5%) followed by HPV45 (6.8%) and HPV33 (3.4%), as single or mixed infection. Other less frequent genotypes were HPV31, HPV35, HPV39, HPV51, HPV52, HPV58, HPV66, and HPV73. The viral type could not be determined (HPV X) in 1 case (0.6%) of the HPV DNA–positive cervical cancers and double infections were found in 1.7% of the cases. The higher percentage of most aggressive HPV (16/18/45) genotypes was detected in cases diagnosed at younger than 60 years old, whereas these genotypes were less frequent in older patients.ConclusionWe conclude that HPV types 16, 18, and 45 have a very high prevalence in ICC of Uruguayan women. Results provide evidence that 16 of 18 infections are more aggressive, but most cancers could be vaccine preventable.

scholarly journals Detection of Human Papillomavirus DNA by AffiProbe HPV-DNA Test Kit in Cervical Scrapes or Biopsies-Histopathologic Correlates

1994 ◽  
Vol 2 (3) ◽  
pp. 126-129
Author(s):  
Pekka Nieminen ◽  
Tarja Jalava ◽  
Arja Kallio ◽  
Marjut Ranki ◽  
Jorma Paavonen
Keyword(s):  
Human Papillomavirus ◽  
Dna Test ◽  
Hpv Dna ◽  
Test Kit ◽  
Histopathologic Diagnosis ◽  
Hybridization Test ◽  
Hpv Types ◽  
Working Day ◽  
Intraepithelial Lesions ◽  
Papillomavirus Dna

Objective: The aim of this study was to evaluate and compare the efficacy of punch biopsies and cervical scrapes in the detection of human papillomavirus (HPV) DNA from the cervix and compare the results with the histopathologic diagnosis.Methods: The specimens were collected simultaneously, and HPV DNA was detected using a liquid hybridization test.Results: Biopsies and scrapes were equally efficient, but each detected only two-thirds of all HPV-DNA-positive patients. Thus, the positivity rate increased when both tests were used. Overall, 13% of patients with normal histopathology, 38% of patients with benign atypia, and 66% of patients with squamous intraepithelial lesions (SIL) were HPV-DNA positive. HPV-DNA 16 was found in 54% of HPV-DNA-positive patients with SIL, in 20% of HPV-DNA-positive patients with atypia, and in none of patients with normal histopathology.Conclusions: The liquid hybridization test used in this study detects HPV DNA equally efficiently from both biopsies and scrapes. The test can be performed in 1 working day. However, the sensitivity of the test is low, and it only detects a limited number of HPV types.

scholarly journals Mitochondrial DNA copy number in cervical exfoliated cells and risk of cervical cancer among HPV-positive women

2019 ◽  
Author(s):  
Wei Sun ◽  
Xueyun Qin ◽  
Jing Zhou ◽  
Mingjing Xu ◽  
Zhangyan Lyu ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Logistic Regression ◽  
Mitochondrial Dna ◽  
Copy Number ◽  
Wald Test ◽  
Hpv Infection ◽  
Dna Copy Number ◽  
Mitochondrial Dna Copy Number ◽  
Exfoliated Cells ◽  
Hpv Types

Abstract Background Although human papillomavirus (HPV) infection has been recognized as the major cause of cervical cancer, only a minority of HPV-infected women develop this malignancy. An increasing amount of evidence suggests that alterations of mitochondrial DNA copy number (mtCN) may c ontribute to carcinogenesis. However, the relationship between mtCN and cervical cancer remains unknown. Methods In this case-control study, we included 591 cervical cancer cases and 373 cancer-free controls, all of whom were infected with high-risk HPV. Relative mtCN in cervical cancer exfoliated cells was measured by qRT-PCR assay s , and logistic regression analysis was performed to calculate odds ratios (ORs) and 95% confidence intervals (CIs). Interaction between mtCN and HPV types was assessed by using the Wald test in logistic regression models. Results HPV16, 18, 52, and 58 were the most common types in both case and control groups. Median mtCN in cases was significantly higher than that in controls ( P = 0.03). After adjustment for age and HPV types , the highest quartile of mtCN was associated with increased odds of having cervical cancer (OR = 1.77, 95% CI = 1.19, 2.62; P < 0.01), as compared to the lowest quartile. A dose-response effect of mtCN on cervical cancer was also observed ( P trend < 0.001). The interaction between mtCN and HPV types was statistically nonsignificant. Conclusions Increased mtCN in cervical exfoliated cells is associated with cervical cancer after HPV infection, suggesting a potential role of mtCN in cervical carcinogenesis.

scholarly journals Detection of Human Papillomavirus Types 6 and 11 in Pubic and Perianal Hair from Patients with Genital Warts

1999 ◽  
Vol 37 (7) ◽  
pp. 2270-2273 ◽  
Author(s):  
Ingeborg L. A. Boxman ◽  
Arjan Hogewoning ◽  
Linda H. C. Mulder ◽  
Jan Nico Bouwes Bavinck ◽  
Jan ter Schegget
Keyword(s):  
Human Papillomavirus ◽  
Clinical Importance ◽  
Genital Warts ◽  
Pubic Hair ◽  
Anogenital Warts ◽  
Perianal Region ◽  
Hpv Dna ◽  
Hair Samples ◽  
History Of ◽  
Hpv Types

Genital human papillomavirus (HPV) types 6 and 11 are of clinical importance due to their role in the development of anogenital warts. A pilot study was performed to investigate whether DNAs from HPV types 6 and 11 are present in hairs plucked from the pubic and perianal regions and eyebrows of patients with genital warts at present and patients with a recent history of genital warts. Genital HPV DNA was detected in 9 of 25 (36%) pubic hair samples and in 11 of 22 (50%) perianal hair samples by the CPI/CPIIg PCR. After sequencing of 17 of 20 samples, HPV type 6 or 11 was detected in 6 of 25 (24%) hair samples from the pubis and 8 of 22 (36%) hair samples from the perianal region. These types were not detected in plucked eyebrow hairs. In contrast, the HPV types associated with epidermodysplasia verruciformis were detected in similar proportions (62%) in both samples of pubic and eyebrow hairs. Moreover, HPV type 6 and 11 DNAs were detected in pubic hairs plucked from two patients who had been successfully treated and who did not show any lesion at the time of hair collection; this finding is an argument that HPV DNA may persist in this region. The presence of genital HPV types in plucked pubic and perianal hair suggests that there is an endogenous reservoir for HPV which may play a role in the recurrences of genital warts.

Serologic response to human papillomavirus 16 among Australian women with high-grade cervical intraepithelial neoplasia

2006 ◽  
Vol 16 (3) ◽  
pp. 1032-1035
Author(s):  
S. N. Tabrizi ◽  
I. H. Frazer ◽  
S. M. Garland
Keyword(s):  
Human Papillomavirus ◽  
Cervical Intraepithelial Neoplasia ◽  
Intraepithelial Neoplasia ◽  
High Grade ◽  
Hpv 16 ◽  
Hpv Dna ◽  
Human Papillomavirus 16 ◽  
Serologic Response ◽  
Poor Predictor ◽  
Hpv Types

This study evaluated the detection of human papillomavirus (HPV) 16 antibody in HPV 16–associated cervical intraepithelial neoplasia (CIN) in Australian women. Seroreactivity to HPV 16 L1 virus–like particles was assessed in patients with CIN 2 (n = 169) and CIN 3 (n = 229) lesions previously tested for the presence of HPV DNA. Seropositivity was significantly commoner in women with HPV 16 DNA–positive lesions (98/184) than in women with no HPV DNA in the lesion (15/47) or with HPV of types other than 16 in the lesion (43/167) (P = 0.0004). In addition, seropositivity was observed in 33% (55/169) of women with CIN 2 and 46% (106/229) of women with CIN 3, in keeping with the lower fraction of CIN 2 (57/169) than CIN 3 (127/229) biopsies positive for HPV 16 DNA. HPV 16 seropositivity is most common in women with HPV 16–associated CIN, but many patients with HPV-associated CIN 3 are seronegative, and HPV 16 seropositivity is common in women with CIN associated with other HPV types. Overall, HPV 16 serology is a poor predictor of presence of HPV 16–associated CIN 3 in patient population studied.

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