scholarly journals Human Papillomavirus 16 Oncoprotein Expression Is Controlled by the Cellular Splicing Factor SRSF2 (SC35)

2015 ◽  
Vol 89 (10) ◽  
pp. 5276-5287 ◽  
Author(s):  
Melanie McFarlane ◽  
Alasdair I. MacDonald ◽  
Andrew Stevenson ◽  
Sheila V. Graham
Keyword(s):  
Cervical Cancer ◽  
Human Papillomavirus ◽  
Tumor Progression ◽  
Colony Formation ◽  
Human Papillomaviruses ◽  
Splicing Factors ◽  
Cervical Tumor ◽  
Mrna Isoforms ◽  
Viral Oncoprotein ◽  
Human Papillomavirus 16

ABSTRACTHigh-risk human papillomaviruses (HR-HPV) cause anogenital cancers, including cervical cancer, and head and neck cancers. Human papillomavirus 16 (HPV16) is the most prevalent HR-HPV. HPV oncogenesis is driven by two viral oncoproteins, E6 and E7, which are expressed through alternative splicing of a polycistronic RNA to yield four major splice isoforms (E6 full length, E6*I, E6*II, E6*X). The production of multiple mRNA isoforms from a single gene is controlled by serine/arginine-rich splicing factors (SRSFs), and HPV16 infection induces overexpression of a subset of these, SRSFs 1, 2, and 3. In this study, we examined whether these proteins could control HPV16 oncoprotein expression. Small interfering RNA (siRNA) depletion experiments revealed that SRSF1 did not affect oncoprotein RNA levels. While SRSF3 knockdown caused some reduction in E6E7 expression, depletion of SRSF2 resulted in a significant loss of E6E7 RNAs, resulting in reduced levels of the E6-regulated p53 proteins and E7 oncoprotein itself. SRSF2 contributed to the tumor phenotype of HPV16-positive cervical cancer cells, as its depletion resulted in decreased cell proliferation, reduced colony formation, and increased apoptosis. SRSF2 did not affect transcription from the P97promoter that controls viral oncoprotein expression. Rather, RNA decay experiments showed that SRSF2 is required to maintain stability of E6E7 mRNAs. These data show that SRSF2 is a key regulator of HPV16 oncoprotein expression and cervical tumor maintenance.IMPORTANCEExpression of the HPV16 oncoproteins E7 and E6 drives HPV-associated tumor formation. Although increased transcription may yield increased levels of E6E7 mRNAs, it is known that the RNAs can have increased stability upon integration into the host genome. SR splicing factors (SRSFs) control splicing but can also control other events in the RNA life cycle, including RNA stability. Previously, we demonstrated increased levels of SRSFs 1, 2, and 3 during cervical tumor progression. Now we show that SRSF2 is required for expression of E6E7 mRNAs in cervical tumor but not nontumor cells and may act by inhibiting their decay. SRSF2 depletion in W12 tumor cells resulted in increased apoptosis, decreased proliferation, and decreased colony formation, suggesting that SRSF2 has oncogenic functions in cervical tumor progression. SRSF function can be targeted by known drugs that inhibit SRSF phosphorylation, suggesting a possible new avenue in abrogating HPV oncoprotein activity.

scholarly journals Prognostic significance of serum antibodies to human papillomavirus-16 E4 and E7 peptides in cervical cancer

Cancer ◽  
1994 ◽  
Vol 74 (8) ◽  
pp. 2307-2313 ◽  
Author(s):  
Katja N. Gaarenstroom ◽  
Gemma G. Kenter ◽  
J. Baptist Trimbos ◽  
Johannes M. G. Bonfrer ◽  
Catharina M. Korse ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Human Papillomavirus ◽  
Prognostic Significance ◽  
Serum Antibodies ◽  
Human Papillomavirus 16

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.

Cervical cancer: monitoring of the main indicators characterizing this pathology in Khabarovsk Krai (2009–2019)

GYNECOLOGY ◽  
2021 ◽  
Vol 23 (2) ◽  
pp. 155-160
Author(s):  
Tatyana Yu. Pestrikova ◽  
Ainur F. Ismaylova ◽  
Sergey N. Kiselev
Keyword(s):  
Cervical Cancer ◽  
Human Papillomavirus ◽  
Graphical Analysis ◽  
Reproductive Age ◽  
Annual Growth Rate ◽  
Khabarovsk Krai ◽  
Female Population ◽  
Human Papillomavirus 16 ◽  
Cervical Cancer Mortality ◽  
Advanced Stages

Aim. Conduct a comparative assessment of the main indicators of the incidence of cervical cancer in Khabarovsk Krai (20092019) аnd the prevalence of types of human papillomavirus among the female population. Materials and methods. A comparative analysis of the data of the official statistics of the Ministry of Health of Khabarovsk Krai, using the Rosstat database for the period 20092019, taking into account the incidence, mortality, prevalence of types of human papillomavirus, was carried out. The dynamics trend was determined in the process of graphical analysis of the diagram and by modeling trends. The results of the studies were subjected to the methods of statistical information processing. Results. The results revealed in our study indicate that the increase in the incidence of cervical cancer in Khabarovsk Krai from 2009 to 2019 was 44.4% (with an average annual growth rate of 4.5%). Most often, cervical cancer in Khabarovsk Krai is detected in urban residents. The share of urban women with this pathology in 2019 reached 77.2%. The proportion of stage III cancer detected exceeds the proportion of stage IIIIV cancer by 2.5 times. Mortality in patients with cervical cancer in Khabarovsk Krai exceeds that in the Russian Federation. Of the 1617 residents of the city of Khabarovsk of reproductive age, 883 (54%) women had the presence of human papillomavirus. For our region, most often, women had highly oncogenic types of human papillomavirus 16, 56, 51. Conclusion. Statistical analysis based on the results of diagnosing early and advanced stages of cervical cancer, mortality from this nosological form, and the spread of the human papillomavirus remain among the most important criteria. The data obtained make it possible to assess the effectiveness of the chosen tactics in the regions and take timely corrective measures aimed at both early detection of cervical cancer and a decrease in the persistence of the human papillomavirus in women with background cervical pathology.

scholarly journals SAMHD1 Regulates Human Papillomavirus 16-Induced Cell Proliferation and Viral Replication during Differentiation of Keratinocytes

mSphere ◽  
2019 ◽  
Vol 4 (4) ◽  
Author(s):  
Claire D. James ◽  
Apurva T. Prabhakar ◽  
Raymonde Otoa ◽  
Michael R. Evans ◽  
Xu Wang ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Human Papillomavirus ◽  
Life Cycle ◽  
Viral Replication ◽  
Cellular Proliferation ◽  
Specific Interaction ◽  
Viral Life Cycle ◽  
Human Papillomaviruses ◽  
Cellular Growth ◽  
Human Papillomavirus 16

ABSTRACT Human papillomaviruses induce a host of anogenital cancers, as well as oropharyngeal cancer (HPV+OPC); human papillomavirus 16 (HPV16) is causative in around 90% of HPV+OPC cases. Using telomerase reverse transcriptase (TERT) immortalized foreskin keratinocytes (N/Tert-1), we have identified significant host gene reprogramming by HPV16 (N/Tert-1+HPV16) and demonstrated that N/Tert-1+HPV16 support late stages of the viral life cycle. Expression of the cellular dNTPase and homologous recombination factor sterile alpha motif and histidine-aspartic domain HD-containing protein 1 (SAMHD1) is transcriptionally regulated by HPV16 in N/Tert-1. CRISPR/Cas9 removal of SAMHD1 from N/Tert-1 and N/Tert-1+HPV16 demonstrates that SAMHD1 controls cell proliferation of N/Tert-1 only in the presence of HPV16; the deletion of SAMHD1 promotes hyperproliferation of N/Tert-1+HPV16 cells in organotypic raft cultures but has no effect on N/Tert-1. Viral replication is also elevated in the absence of SAMHD1. This new system has allowed us to identify a specific interaction between SAMHD1 and HPV16 that regulates host cell proliferation and viral replication; such studies are problematic in nonimmortalized primary keratinocytes due to their limited life span. To confirm the relevance of our results, we repeated the analysis with human tonsil keratinocytes (HTK) immortalized by HPV16 (HTK+HPV16) and observed the same hyperproliferative phenotype following CRISPR/Cas9 editing of SAMHD1. Identical results were obtained with three independent CRISPR/Cas9 guide RNAs. The isogenic pairing of N/Tert-1 with N/Tert-1+HPV16, combined with HTK+HPV16, presents a unique system to identify host genes whose products functionally interact with HPV16 to regulate host cellular growth in keratinocytes. IMPORTANCE HPVs are causative agents in human cancers and are responsible for around of 5% of all cancers. A better understanding of the viral life cycle in keratinocytes will facilitate the development of novel therapeutics to combat HPV-positive cancers. Here, we present a unique keratinocyte model to identify host proteins that specifically interact with HPV16. Using this system, we report that a cellular gene, SAMHD1, is regulated by HPV16 at the RNA and protein levels in keratinocytes. Elimination of SAMHD1 from these cells using CRISPR/Cas9 editing promotes enhanced cellular proliferation by HPV16 in keratinocytes and elevated viral replication but not in keratinocytes that do not have HPV16. Our study demonstrates a specific intricate interplay between HPV16 and SAMHD1 during the viral life cycle and establishes a unique model system to assist exploring host factors critical for HPV pathogenesis.

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.

Long noncoding RNA SNHG12 modulated by human papillomavirus 16 E6/E7 promotes cervical cancer progression via ERK/Slug pathway

2020 ◽  
Vol 235 (11) ◽  
pp. 7911-7922 ◽  
Author(s):  
Shu‐Yu Lai ◽  
Hong‐Mei Guan ◽  
Jie Liu ◽  
Li‐Jun Huang ◽  
Xiao‐Lin Hu ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Human Papillomavirus ◽  
Cancer Progression ◽  
Long Noncoding Rna ◽  
Noncoding Rna ◽  
Human Papillomavirus 16
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