scholarly journals Oestrogen and progesterone increase the levels of apoptosis induced by the human papillomavirus type 16 E2 and E7 proteins

2001 ◽  
Vol 82 (1) ◽  
pp. 201-213 ◽  
Author(s):  
Kenneth Webster ◽  
Anna Taylor ◽  
Kevin Gaston

Human papillomavirus (HPV) type 16 infects the genital tract and is generally acknowledged to be a causative agent of cervical cancer. HPV infection alone is not sufficient to induce cervical cancer and other factors such as steroid hormones are thought to play a role in the establishment and/or progression of this disease. The HPV-16 E2 protein is required for virus replication and modulates viral gene expression whereas the HPV-16 E7 protein is required for cell transformation. We and others have shown that both the E2 and E7 proteins can induce apoptotic cell death in HPV-transformed and non-HPV transformed cell lines. Here we show that the steroid hormones oestrogen and progesterone can both increase the levels of E2- and E7-induced apoptosis. The oestrogen metabolite 16α-hydroxyoestrone also increases E2- and E7-induced cell death and the dietary component indole-3-carbinol, which reduces the formation of 16α-hydroxyoestrone from oestrogen, blocks the effects of oestrogen. Thus the metabolism of oestrogen to 16α-hydroxyoestrone appears to be required for the effects of this hormone on E2- and E7-induced cell death. We also show that the oestrogen receptor antagonist 3-hydroxytamoxifen blocks the effects of oestrogen on E2- and E7-induced cell death, whereas the anti-progesterone RU486 blocks the effects of both progesterone and oestrogen. We discuss these results in terms of the origin and progression of cervical cancer.

2009 ◽  
Vol 30 (12) ◽  
pp. 2999-3005 ◽  
Author(s):  
Joo-Ho Kim ◽  
Il-Hoon Cho ◽  
Sung-Min Seo ◽  
Ji-Sook Kim ◽  
Kyu-Ha Oh ◽  
...  

2016 ◽  
Vol 19 (1) ◽  
pp. 160-166 ◽  
Author(s):  
Gustavo David García Muentes ◽  
Lindsay Karen García Rodríguez ◽  
Ramiro Israel Burgos Galarraga ◽  
Franklin Almeida Carpio ◽  
Juan Carlos Ruiz Cabezas

ABSTRACT: Introduction: Human papillomavirus (HPV) is considered a necessary causative agent for developing oropharyngeal, anal and cervical cancer. Among women in Ecuadorian population, cervical cancer ranks as the second most common gynecological cancer. Not many studies about HPV burden have been published in Ecuador, and genotypes distribution has not been established yet. The little data available suggest the presence of other genotypes different than 16 and 18. Objectives: In the present study, we attempt to estimate the prevalence of HPV 16, HPV 18 and other 35 genotypes among Ecuadorian women undergoing cervical cancer screening. The overall prevalence of HPV infection was also estimated. Methods: Routine cervical samples were analyzed using Linear Array(r) HPV Genotyping test (Roche). Results: A total of 1,581 cervical samples obtained from Ecuadorian women undergoing cervical cancer screening were included in this study. HPV DNA was detected in 689 cervical samples (43.58%). Of these samples, 604 (38.20%) were positive for a single HPV genotype, while another 85 (5.37%) samples were positive for multiple HPV types. Genotype 16 (5.50%) resulted in the most frequently detected type in both single and multiple infections. HPV 33 (4.55%) and HPV 11 (3.80%) occupied the second and the third place in frequency among all detected genotypes. Conclusions: Viral genotypes different from HPV 16 and HPV 18 are frequently detected among Ecuadorian women. The overall prevalence of HPV resulted higher than the one reported in other South American countries with a greater burden in the second and third decades of life.


2003 ◽  
Vol 13 (6) ◽  
pp. 834-842 ◽  
Author(s):  
M. Moodley ◽  
S. Sewart ◽  
C. S. Herrington ◽  
R. Chetty ◽  
R. Pegoraro ◽  
...  

Various risk factors have been implicated in the causation of cervical cancer including human papillomavirus (HPV), the early genes (E6 and E7) of which encode the main transforming proteins. Studies have suggested that steroid hormones may enhance the expression of these genes leading to loss of p53 gene-mediated cell apoptosis. A total of 120 cervical tissue samples were obtained from patients with proven cervical cancer. Patients who used depo-medroxyprogesterone acetate steroid contraception were recruited as part of the steroid arm. Only HPV DNA type 16 samples were used for the study. Controls included three cell lines (CaSki, SiHa, & C33A) and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) was used as an internal housekeeping gene. Of 120 patients, there were 111 patients with HPV type 16 identified. Of this number, RNA was present in 63 samples. There were 30 women (30/63) who used steroid contraception. In relation to patients who used contraception, HPV 16 E6 gene expression was present in 79% (n = 23) and 88% (n = 30) of steroid users compared to nonusers, respectively. In total there were 25 patients (40%) with expression of the HPV 16 E6*I gene and 30 patients with expression of the E6*II gene. There were 57% of steroid users (n = 17) who had expression of the E6*I/E6*II gene, compared to 52% (n = 17) of nonusers (P = 0.800). From a molecular level, this study does not confirm the role of injectable progesterones in cervical carcinogenesis.


2005 ◽  
Vol 20 (4) ◽  
pp. 257-263 ◽  
Author(s):  
I.N. Mammas ◽  
A. Zafiropoulos ◽  
S. Sifakis ◽  
G. Sourvinos ◽  
D.A. Spandidos

Objective Human papillomavirus (HPV) has been identified as the principal etiologic agent for cervical cancer and its precursors. Different HPV types have been associated with different oncogenic potential. The purpose of this study was to evaluate the relationship between specific HPV type infection and expression pattern of the ras family oncogenes in different grades of HPV-associated human cervical neoplasia. Methods HPV typing was performed using polymerase chain reaction (PCR) in 31 HPV-positive human cervical specimens from patients with squamous intraepithelial lesions (SIL) or squamous cervical carcinoma (SCC). The mRNA expression levels of H-, K- and N-ras oncogenes were examined using the reverse transcriptase polymerase chain reaction (RT-PCR) technique. Statistical analyses were performed using SPSS software. Results Among patients with SCC, H-, K- and N-ras expression levels were higher in HPV 16/18-associated cases compared to HPV 16/18-unassociated samples (p=0.003, p=0.004 and p=0.0001, respectively). The expression levels for H-, K-and N-ras were significantly higher in SCC patients with multiple HPV infection compared with SCC patients with single HPV infection (p=0.009, p=0.01 and p=0.021, respectively). Among patients with SIL, no statistically significant relationship was found between ras expression and HPV status. Conclusion Our findings indicate the possible role of ras signaling interaction with “high-risk” HPV 16/18 and multiple HPV infection in cervical cancer development.


2007 ◽  
Vol 81 (6) ◽  
pp. 2869-2879 ◽  
Author(s):  
Dai-Wei Liu ◽  
Yuh-Cheng Yang ◽  
Ho-Fan Lin ◽  
Mei-Fang Lin ◽  
Ya-Wen Cheng ◽  
...  

ABSTRACT Previously, we found that human papillomavirus type 16 (HPV-16) E5 protein is a tumor rejection antigen and can induce cytotoxic T-lymphocyte (CTL) activity. Therefore, in this study, human leukocyte antigen A*0201 (HLA-A*0201)-restricted human CTL epitopes of HPV-16 E5 protein were identified using a bioinformatics approach, and the abilities of these predicted peptides to induce an immune response in HLA-A*0201 transgenic mice were confirmed by assaying E5-specific CTLs and in vitro-generated CTLs from normal peripheral blood T lymphocytes of HLA-A2-positive human donors. Second, the CTL responses to HLA-A*0201 CTL epitopes (E5 63-71 and E7 11-20) were examined in HPV-16-infected patients with HLA-A2. Third, the effect of HLA-A-type alleles on CTL activities in response to the entire E5 and E7 proteins was examined in cervical cancer patients. E5 and E7 peptides (but not the whole proteins) stimulated E5- and E7-specific CTL recall responses in HPV-16- and HLA-A2-positive cervical cancer patients, and HPV-16 E5 and E7 proteins stimulated naïve T cells in HPV-16-negative cervical cancer patients with HLA-A11 and -A24 haplotypes. In summary, this is the first demonstration that E5 63-71 is an HLA-A*0201-restricted T-cell epitope of HPV-16 E5.


Author(s):  
Daniel Duarte ◽  
Rodrigo Vieira ◽  
Elza Brito ◽  
Maria Pinheiro ◽  
Jeniffer Monteiro ◽  
...  

Purpose The aim of this study was to evaluate the overall and type-specific prevalence of human papillomavirus (HPV) infection among females living in riverside communities in the state of Pará, in the Eastern Brazilian Amazon. These communities are inhabited by low-income people, and are accessible only by small boats. Cervical cytology and risk factors for HPV infection were also assessed. Methods Cervical samples from 353 women of selected communities were collected both for Papanicolau (Pap) test and HPV detection. Conventional polymerase chain reaction (PCR) and real-time PCR were used to assess the overall and type-specific prevalence of HPV-16 and HPV-18, the main oncogenic types worldwide. Epidemiological questionnaires were used for the assessment of the risk factors for HPV infection. Results The mean age of the participants was 37 years (standard deviation [SD] ± 13.7). Most were married or with a fixed sexual partner (79%), and had a low educational level (80%) and family monthly income (< U$ 250; 53%). Overall, HPV prevalence was 16.4% (n = 58), with 8 cases of HPV-16 (2.3%) and 5 of HPV-18 (1.4%). Almost 70% of the women surveyed had never undergone the Pap test. Abnormal cytology results were found in 27.5% (n = 97) of the samples, with higher rates of HPV infection according to the severity of the lesions (p = 0.026). Conclusions The infections by HPV-16 and HPV-18 were not predominant in our study, despite the high prevalence of overall HPV infection. Nevertheless, the oncogenic potential of these types and the low coverage of the Pap test among women from riverside communities demonstrate a potential risk for the development of cervical lesions and their progression to cervical cancer, since the access to these communities is difficult and, in most cases, these women do not have access to primary care and public health services.


Author(s):  
NF Brusnigina ◽  
MA Makhova ◽  
OM Chernevskaya ◽  
KA Orlova ◽  
EA Kolesnikova ◽  
...  

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.


2020 ◽  
Vol 42 ◽  
pp. e50005
Author(s):  
Alessandra Silva e Silva ◽  
Cláudia Giuliano Bica ◽  
Aniúsca Vieira ◽  
Cleiton Fantin

The natural history of cervical cancer is strongly related to the presence of human papillomavirus (HPV) infection, with its relationship with cervical cancer being a matter of concern. It is estimated that 70% of all cervical cancers worldwide are caused by HPV 16 and 18. Accordingly, the present study aimed to contribute to the identification of HPV subtypes circulating in a group of women of Manaus-Brazil.  Cervical samples were collected from 49 women, following the eligibility criteria of the study, and DNA was then extracted from the samples, which were analyzed for the presence of the virus in the genetic material through the polymerase chain reaction (PCR) using generic primers (GP05/06). Finally, identification of the viral subtypes was performed using specific primers for the detection of the main subtypes already examined (16 and 18). Positive HPV DNA was detected in 100% of the samples included in the study. Human papillomavirus 16 was the most prevalent subtype in the majority of lesions, accounting for 29 (59.2%) of the positive cases, and HPV 18 was detected in four (8.2%) women. In these 4 cases there was co-infection, with the presence of both HPV 18 and HPV 16. Therefore, 40.8% (20 cases) in which HPV DNA was detected presented infection with other subtypes of HPV not included in the study. This data has clinical implications related to cervical cancer prevention, as the current prophylactic HPV vaccines are only effective against high-risk HPV 16 and 18 subtypes.


2010 ◽  
Vol 4 (11) ◽  
pp. 732-739 ◽  
Author(s):  
Zaitouna Alhamany ◽  
Mohammed El Mzibri ◽  
Aicha Kharbach ◽  
Abderrahman Malihy ◽  
Redouane Abouqal ◽  
...  

Introduction: Many studies have indicated a causal relationship between genital human papillomavirus (HPV) infections and cervical cancer. This study aimed to determine the prevalence and genotypes of six high-risk oncogenic human papillomaviruses in cervical lesions from Moroccan women with normal and abnormal cytology. Methodology: The study included 938 women from the Children's and Mothers' Pathology Department of Ibn Sina Hospital, Rabat. Cytopathology examination was done by routine PAP smear testing. HPV DNA testing was conducted using DNA amplification by Polymerase Chain Reaction with subsequent typing by hybridization with specific probes for HPV types 16, 18, 31, 33, 35 and 45. Results: Cytopathology testing showed that only 16.3 % had an abnormal cytology, with a predominance of atypical squamous cell of undetermined significance (ASCUS) cases. The overall HPV prevalence was 15.7%. According to the cytology results, HPV infection was detected in 15.8% of normal and 14.38% of abnormal cases. Specific HPV genotyping showed a predominance of HPV 16 and 18. Double infection (HPV 16 + 18) was found in two cases whereas multiple infections (HPV 16+18+31) were detected in only one case. Evaluation of the relationship between HPV status and some environmental risk factors, including individual, socio-economic, and hygiene status, showed a significant association between HPV infection and oral contraceptive use. Conclusion: Based on these data, a combination of cytology and HPV DNA testing allows for identification of patients with a high risk of developing high-grade cervical lesions and improves cervical cancer prevention.


2003 ◽  
Vol 14 (4) ◽  
pp. 258-265 ◽  
Author(s):  
B Nonnenmacher ◽  
J Pintos ◽  
M C Bozzetti ◽  
I Mielzinska-Lohnas ◽  
A T Lorincz ◽  
...  

A population at low risk for developing cervical cancer in Southern Brazil was studied to identify the main determinants of serological response to human papillomavirus (HPV). Enzyme-linked immunosorbent assay tests were performed in 976 women to detect serum IgG antibodies against HPV 16 L1 virus-like particles (VLPs) and HPVs 16, 18, 6 and 11 L1 VLPs as a mixture of antigens. Women with four or more sexual partners were more likely to be seropositive than women with one partner (HPV 16 serology odds ratio [OR]=3.06, 95% confidence interval [CI]: 2.0-4.8; HPV 6/11/16/18 serology OR=4.64, 95% CI: 3.0-7.2). HPV DNA and both serological responses were associated. Those positives to HPV 16 serology were twice as likely to have a cytological diagnosis of squamous intraepithelial lesions (SILs) than seronegatives (OR=2.07; 95% CI: 1.0-4.5, and OR=1.73; 95% CI: 0.8-3.8). Seropositivity to HPV 16 and HPV 6/11/16/18 antigens seem to be better markers of past sexual activity than current HPV infection, and humoral response to HPV 16 or HPV 6/11/16/18 may not be a strong indicator of cervical lesions in populations at low risk for cervical lesions.


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