scholarly journals Cellular Changes Induced by Low-Risk Human Papillomavirus Type 11 in Keratinocytes That Stably Maintain Viral Episomes

2001 ◽  
Vol 75 (16) ◽  
pp. 7564-7571 ◽  
Author(s):  
Jennifer T. Thomas ◽  
Stephen T. Oh ◽  
Scott S. Terhune ◽  
Laimonis A. Laimins

ABSTRACT Infections by low-risk papillomavirus types, such as human papillomavirus (HPV) type 6 (HPV-6) and HPV-11, induce benign genital warts that rarely progress to malignancy. In contrast, lesions induced by high-risk HPV types have the potential to progress to cancer. Considerable information is available concerning the pathogenesis of high-risk HPV types, but little is known about the life cycle of low-risk HPV types. Although functionally distinct, both high- and low-risk virus types infect keratinocytes and induce virion production upon differentiation. This information suggests that they may share common mechanisms for regulating their productive life cycles. Using tissue culture methods developed to study high-risk HPV types, we examined the ability of HPV-11 to be stably maintained as episomes following transfection of normal human keratinocytes with cloned viral DNA. HPV-11 genomes were found to be maintained in keratinocytes for extended passages in cultures in 14 independent experiments involving transfection of cloned HPV-11 DNA. Interestingly, the HPV-11-positive cells exhibited an extended life span that averaged approximately twofold longer than that of control neomycin-transfected cells. In organotypic cultures, HPV-11-positive cells exhibited altered differentiation patterns, but the extent of disruption was less severe than that seen with high-risk HPV types. In addition, the amplification of HPV-11 DNA, as well as the induction of several viral messages, was observed following differentiation of transfected cells in semisolid media. To determine whether global changes in cellular gene expression induced by HPV-11 were similar to those observed with high-risk HPV-31 (Y. E. Chang and L. A. Laimins, J. Virol. 74:4174–4182, 2000), microarray analysis of 7,075 expressed sequences was performed. A spectrum of cellular genes different from that previously reported for HPV-31 was found to be activated or repressed by HPV-11. The expression of only a small set of genes was similarly altered by both high- and low-risk HPV types. This result suggests that different classes of HPVs have distinct effects on global cellular transcription patterns during infection. The methods described allow for a genetic analysis of HPV-11 in the context of its differentiation-dependent life cycle.

2000 ◽  
Vol 38 (1) ◽  
pp. 408-411
Author(s):  
József Kónya ◽  
György Veress ◽  
Attila Juhász ◽  
Krisztina Szarka ◽  
Tamás Sápy ◽  
...  

ABSTRACT The type specificity of the human papillomavirus (HPV) Hybrid Capture Tube (HCT) test was evaluated by using typing with PCR (MY09-MY11)-restriction fragment length polymorphism (RFLP) and sequencing. All samples HCT test positive for only low-risk HPV ( n = 15) or only high-risk HPV ( n = 102) were confirmed, whereas 9 of 12 HCT test double-positive samples contained only high-risk HPV types as determined by PCR-RFLP. Several high-risk HPV types (HPV-53, -58, -62, -66, -CP8304, and -MM4) not included in the HCT test were indeed detected, indicating a broader detection range with retained distinction between low-risk and high-risk HPV types.


1970 ◽  
Vol 25 (1) ◽  
pp. 65-68 ◽  
Author(s):  
Tahmina Sultana ◽  
Mohsina Huq ◽  
Anadil Alam ◽  
Dipak Kumar Mitra ◽  
Donald James Gomes

In developing countries, cervical cancer is the most common cause of cancer related to mortality in women. But the epidemiology of human papillomavirus (HPV) in different areas of Bangladesh is largely unknown both in risk groups and in the general population. The objective of the present study was to determine the risk factors associated with having HPV and the prevalence of high-risk HPV types among women with highrisk behaviour and to assess its potential impact on preventive strategies as the sex workers are at increased risk for sexually transmitted infections (STI), HPV and hence cervical cancer. Cervical swab from 293 sex workers in Dhaka City between August and September 2003 and between February 2005 and May 2006 were screened for HPV DNA using an HPV short fragment (E6) polymerase chain reaction (PCR) based assay. HPV positive samples were genotyped with nested multiplex polymerase chain reaction (NMPCR) for the highrisk types. The overall HPV prevalence in sex workers was 75.8%, whereas for the high risk type it was 49.8%. Prevalence of single genotype and multiple types of HPV was 33.1 and 16.7% respectively. The most prevalent high-risk HPV types, in order of prevalence rate, were HPV16, HPV18, HPV58, HPV45, HPV31 and HPV33. Both HPV 16 and HPV 18 were present in 21% of the cases. Targeting HPV 16 and 18 with prophylactic vaccines could possibly have an important impact on the incidence of invasive cervical carcinoma in this group of women. Primary prevention and cervical cancer screening programmes should be optimized more and run yearly among the general population. It is proposed to screen sex workers when they enter prostitution regardless of their age. Keywords: Human papillomavirus (HPV); High-risk HPV types; Cervical cancer; Sex workersDOI: http://dx.doi.org/10.3329/bjm.v25i1.4861 Bangladesh J Microbiol, Volume 25, Number 1, June 2008, pp 65-68


2003 ◽  
Vol 127 (11) ◽  
pp. 1471-1474 ◽  
Author(s):  
Alexandr Švec ◽  
Iva Mikyšková ◽  
Ondřej Hes ◽  
Ruth Tachezy

Abstract Context.—Human papillomaviruses (HPVs) play an important role in the etiology of squamous cell carcinoma of the uterine cervix. The possible role of the male urogenital tract as a reservoir of HPV infection is not fully understood. We inferred from our previous observation of HPV-31 in epididymal tissue in a case of chronic epididymitis that HPV might be commonly present in cases of epididymitis caused by sexually transmitted pathogens. Objective.—To assess the presence of HPV in the epididymis and ductus deferens in nontuberculous epididymitis. Design.—Epididymal samples obtained from 17 patients and epididymal and ductus deferens samples from 5 patients surgically treated for nontuberculous epididymitis were analyzed by nested polymerase chain reaction for the presence of HPV DNA. In positive samples, the HPV type was determined by DNA sequencing. Setting.—Tertiary-care academic hospital and national reference laboratory for papillomaviruses. Results.—Low-risk HPV type 6 and high-risk HPV types 16, 33, 35, 55, and 73 were detected in 7 patients (31%). Neither koilocytes nor dysplastic changes were found in the epididymis and ductus deferens. Conclusion.—Low-risk and high-risk HPV types were detected in the epididymis and ductus deferens of patients with nontuberculous epididymitis. The infection was not accompanied by koilocytic atypia or dysplasia. Our findings support the hypothesis that the male urogenital tract serves as a reservoir of HPV infection.


BMJ Open ◽  
2019 ◽  
Vol 9 (5) ◽  
pp. e023897 ◽  
Author(s):  
Cansheng Zhu ◽  
Yaofei Wang ◽  
Weihua Mao ◽  
Hongshan Zhang ◽  
Jiaju Ma

ObjectivesTo characterise the prevalence and distribution of human papillomavirus (HPV) types in genital warts in Xi’an, China.MethodsThis prospective study was conducted in Shaanxi Provincial Institute for Skin Disease and STD Control (SPISSC) between September 2014 and April 2017. Genital wart samples were obtained from 879 patients, including 512 men and 367 women. HPV genotyping was performed by using an automatic nucleic acid hybridisation system.ResultsOf the 879 patients with genital warts, the detectable rates of low-risk, high-risk and total HPV types were 45.4%, 34.5% and 57.8%, respectively. The detectable rate of low-risk HPV types (45.4%) was significantly higher than that of high-risk HPV types (34.5%) (χ2=21.85, p<0.01). The detectable rate of low-risk HPV types of men (52.3%) was significantly higher than that of women (35.7%) (χ2=23.90, p<0.01). The detectable rates of one HPV type infection and two and three or more HPV type coinfections were 26.1%, 17.5% and 14.2%, respectively. HPV6 (24.9%), HPV11 (17.9%), HPV52 (9.9%) and HPV16 (7.3%) were the four most common HPV types.ConclusionsThe results of this study suggest that low-risk HPV types are major pathogens of genital warts, but high-risk HPV type infections and multiple HPV type coinfections are also common in genital warts. HPV6, 11, 52 and 16 are the four most common HPV types in genital wart in Xi’an, China.


2012 ◽  
Vol 93 (2) ◽  
pp. 356-363 ◽  
Author(s):  
Maria Lidqvist ◽  
Olle Nilsson ◽  
Jan Holmgren ◽  
Sebastian Hölters ◽  
Eva Röijer ◽  
...  

The selection and characterization of a set of mouse mAbs against high-risk human papillomavirus (HPV) E7 oncoprotein and the development of protocols for immunocytochemistry (ICC) are described here. A large number of antibodies raised towards HPV16 and 18 E7 were tested for high-risk specificity by ELISA using a panel of HPV E7 proteins. Antibodies detecting low-risk E7 were discarded, resulting in 38 high-risk HPV E7-specific antibodies. The corresponding epitopes were mapped using overlapping HPV E7 fragments displayed on phage particles. Functionality in ICC against formalin-fixed cervical cancer cell lines was demonstrated for ten mAbs; their high-risk specificity was confirmed by Western blot analysis and ICC on transiently transformed cells expressing high- or low-risk HPV E7. These mAbs were specific for one or several of the high-risk strains HPV16, 18, 31, 35 and 45. Specific E7 staining of liquid-based cytology (LBC) samples was demonstrated for seven mAbs and optimized protocols were established. The E716-41 and E718-79 mAbs demonstrated particularly strong and specific staining of cells stored in LBC fluid for at least 6 months. It is proposed that the high-risk HPV E7 staining protocols established in this study may have the potential to be included in a complementary test for the detection and identification of malignantly transformed cells, in for example atypical squamous cells of undetermined significance samples.


2013 ◽  
Vol 23 (3) ◽  
pp. 527-532 ◽  
Author(s):  
Nora Berois ◽  
Patricia De Cremoux ◽  
Daniel Mazal ◽  
Adela Sica ◽  
Mabel Cedeira ◽  
...  

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.


2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Raúl Peralta ◽  
Cruz Vargas-De-León ◽  
Augusto Cabrera ◽  
Pedro Miramontes

Human papillomavirus (HPV) has been identified as the main etiological factor in the developing of cervical cancer (CC). This finding has propitiated the development of vaccines that help to prevent the HPVs 16 and 18 infection. Both genotypes are associated with 70% of CC worldwide. In the present study, we aimed to determine the emergence of high-risk nonvaccine HPV after actual vaccination scheme to estimate the impact of the current HPV vaccines. A SIR-type model was used to study the HPV dynamics after vaccination. According to the results, our model indicates that the application of the vaccine reduces infection by target or vaccine genotypes as expected. However, numerical simulations of the model suggest the presence of the phenomenon called vaccine—induced pathogen strain replacement. Here, we report the following replacement mechanism: if the effectiveness of cross-protective immunity is not larger than the effectiveness of the vaccine, then the high-risk nonvaccine genotypes emerge. In this scenario, further studies of infection dispersion by HPV are necessary to ascertain the real impact of the current vaccines, primarily because of the different high-risk HPV types that are found in CC.


2015 ◽  
Vol 22 (4) ◽  
pp. 413-420 ◽  
Author(s):  
Rachel A. Katzenellenbogen ◽  
Joseph J. Carter ◽  
Joshua E. Stern ◽  
Melinda S. Butsch Kovacic ◽  
Parinda A. Mehta ◽  
...  

ABSTRACTPersons with Fanconi anemia (FA) are at risk for human papillomavirus (HPV)-associated cancers; however, their natural HPV exposure and infection rates are unknown as is the adequacy with which they mount antibodies to HPV vaccination. This study aimed to determine, in 62 persons with FA, the seroprevalence of skin and mucosal HPV types, the seroprevalence in individuals self-reporting a history of HPV vaccination, and the factors associated with HPV seropositivity. A bead Luminex assay was used to determine seropositivity for HPV1, -2, and -4 (low-risk skin), -6 and -11 (low-risk mucosal, included in one HPV vaccine), -16 and -18 (high-risk mucosal, included in both HPV vaccines), and -52 and -58 (high-risk mucosal). Health- and behavior-related questionnaires were completed. Type-specific seroprevalence estimates and participant characteristics associated with seroprevalence were calculated; 48% reported HPV vaccination. Type-specific seropositivity in unvaccinated persons ranged from 7 to 21% for skin HPV types and 7 to 38% for mucosal HPV types. Among the unvaccinated participants, adults versus children demonstrated increased HPV1, -6, -16, and -58 seroprevalence of 45% versus 6%, 64% versus 22%, 64% versus 17%, and 36% versus 0%, respectively (allP< 0.05). The vaccinated participants versus the nonvaccinated participants demonstrated increased seroprevalence of HPV6, -11, -16, and -18 of 92% versus 38%, 92% versus 24%, 96% versus 34%, and 75% versus 7%, respectively (allP< 0.0001). Our data demonstrate that the unvaccinated participants had serologic evidence of prior skin and mucosal HPV infections and that seroprevalence increased among adults; in self-reported vaccinees, seroprevalence of HPV vaccine types was 75 to 96%.


Author(s):  
Deepti Bettampadi ◽  
Brittney Dickey ◽  
Martha Abrahamsen ◽  
Bradley Sirak ◽  
Maria Luiza Baggio ◽  
...  

Abstract Background Human papillomavirus (HPV) causes oral warts and oropharyngeal cancer (OPC). Human papillomavirus-attributable OPC incidence among men is significantly increasing worldwide, yet few studies have reported oral HPV across multiple countries or examined factors associated with low- and high-risk HPV separately. Methods Oral gargles from 3095 men in the multinational HPV Infection in Men (HIM) Study were HPV genotyped. Multivariable models assessed factors independently associated with high-risk and low-risk HPV prevalence. Results The prevalence of high-risk and low-risk HPV was 6.0% and 2.8%, respectively. Greater number of sexual partners was only associated with high-risk HPV (1.88; 95% confidence interval [CI], 1.22–2.90) prevalence. In multivariable models, residing in Mexico (1.66; 95% CI, 1.15–2.40) and smoking (1.66; 95% CI, 1.13–2.44) were significantly associated with high-risk HPV, and history of consistent gum bleeding (2.16; 95% CI, 1.35–3.45) was significantly associated with low-risk HPV. Gender of the sexual partner did not alter the results for either high- or low-risk HPV endpoints. Conclusions Different factors were independently associated with high- and low-risk oral HPV. Oral sexual behaviors were associated with high-risk HPV, and oral health was associated with low-risk HPV. High-risk HPV prevalence differed by country of residence, highlighting the need for additional studies in multiple countries.


2009 ◽  
Vol 2009 ◽  
pp. 1-4 ◽  
Author(s):  
Paola Menegazzi ◽  
Luisa Barzon ◽  
Giorgio Palù ◽  
Elisa Reho ◽  
Luigi Tagliaferro

Human papillomavirus (HPV) type-specific distribution was evaluated in genital samples collected from 654 women from the South of Italy undergoing voluntary screening and correlated with cyto-histological abnormalities. HPV DNA was detected in 45.9% of the samples, 41.7% of which had multiple infection and 89.0% had high-risk HPV infection. The prevalence of HPV infection and the rate of multiple infections decreased with age, suggesting natural selection of HPV types with better fitness. In line with other Italian studies, the most common HPV types were HPV-6 and HPV-16, followed by HPV-51, HPV-31, HPV-53, and HPV-66, in women with both normal and abnormal cytology. Cervical intraepithelial lesions grade 2 or 3 were associated with high-risk HPV-16, HPV-18, HPV-31, and HPV-51 infection. These data indicate that prophylactic HPV vaccination is expected to reduce the burden of HPV-related cervical lesions in this population, but also suggest the potential utility of new vaccines with larger type coverage.


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