scholarly journals Μηχανισμοί απορρύθμισης των μορίων p16/cyclinD1/p53/MDM2 στο κολποτραχηλικό επιθήλιο κατά την HPV προσβολή του

2021 ◽  
Author(s):  
Γεώργιος Μεταξάς

Η πλειονότητα των προσβολών του κολποτραχηλικού επιθηλίου από τον ιο του ανθρώπινου θηλώματος (Human Papilloma Virus-HPV) χαρακτηρίζονται ασυμπτωματικές με τάση υποστροφής, ενώ η δημιουργία εμφανών κυτταρομορφολογικών αλλοιώσεων (κοιλοκύτταρα) στο τεστ ΠΑΠ εκτείνεται σε ένα διάστημα από 3 εβδομάδες εώς 9 μήνες μετά την ενσφήνωση του ιού στο κολποτραχηλικό επιθήλιο. Η ενσωμάτωση –σε αντίθεση με την απλή επισωματική προσβολή- των υψηλής επικινδυνότητας υπότυπων του ιού HPV στο DNA των κυττάρων του ξενιστή τροποποιεί τα επιθηλιακά κύτταρα με την απενεργοποίηση των ογκοκατασταλτικών πρωτεϊνών p53 και Rb (5,9,22). Κατά την HPV προσβολή του τραχηλικού συστήματος, η υπερέκφραση της πρωτείνης p16 πραγματοποιείται μέσω της ενεργοποίησης του Ε7 γονιδίου που οδηγεί σε αποσυγχρονισμό του Rb και του Ε2F μεταγραφικού παράγοντα. (11) Ο αποσυγχρονισμός του κυτταρικού κύκλου κατά την εμμένουσα High Risk HPV προσβολή του κολποτραχηλικού επιθηλίου εμπλέκει εκτός των προαναφερθέντων και τα μόρια cyclinD1 και MDM2, καθώς παρατηρείται διαταραχή στην έκφραση τους στα εν λόγω επιθήλια και αποτελεί νέο πεδίο έρευνας ειδικά για τα δίπολα p16/cyclinD1 και p53/MDM2. (23,26,56,58,59,82,85,103) Το εν λόγω ερευνητικό πρωτόκολλο σχεδιάστηκε με γνώμονα τη διερεύνηση του ρόλου της απορρύθμισης των πρωτεινών p16/cyclinD1/p53/MDM2 στο κολποτραχηλικό επιθήλιο κατά την προσβολή του από τον ιο των ανθρωπίνων θηλωμάτων (HPV) με βάση τα επίπεδα της έκφρασής τους σε παθολογικά κολποτραχηλικά επιχρίσματα. Όλοι οι εξεταζόμενοι πρωτεινικοί δείκτες εμφάνισαν διαφορετική έκφραση επί των εξεταζόμενων ανοσοχρωσμένων πλακιδίων (υπερέκφραση ως υψηλή και μέτρια ένταση χρώσης καθώς και χαμηλή). Υπερέκφραση της p53 παρατηρήθηκε σε 13/80 (16.25%), της MDM2 σε 27/80 (33.75%) της cyclin D1 σε 8/80 (10%) και της p16INK4 σε 9/80 (11.25%).

Author(s):  
Rahul Kumar ◽  
Vinita Trivedi ◽  
Richa Chauhan ◽  
Akhtar Parwez ◽  
Biplab Pal ◽  
...  

There is high incidence of cervical cancer in Bihar, India. Vaccination for cervical cancer in developed countries has played a crucial role in limiting the incidence rate of cervical cancer worldwide. In consideration of debate on clinical efficacy of Human Papilloma Virus (HPV) vaccine in India, study on the prevalence of high risk HPV 16/18 strains in different regions of the nation becomes very crucial. Few individual states have started vaccination but centralised vaccination program does not exist due to lack of sufficient genotypic study of Human Papilloma Virus in different parts of India. Bihar is the third most populous state of India and HPV 16/18 distribution has not been reported yet. The nationwide data of HPV 16/18will help to develop a unified centralised vaccination program. We carried out a distribution study of high risk HPV type 16 and 18 in cervical cancer patients attending a tertiary care hospital of Bihar, India.HPV 16/18 types were analysed in cervical cancer tissues (n = 96) of patients attending the regional cancer hospital of Bihar. Tissue samples were analysed for HPV 16 and HPV 18 using a Real Time PCR technique. The results suggest very high prevalence of HPV 16/18. HPV was identified in all the samples (96/96). About, 74 (77.08%) samples presented with HPV 16 whereas, 16 (16.67%) of the samples presented with HPV 18. 6 Co-infection was presented in 6 (6.25%) of the samples of cervical cancer tissues. HPV 16/18 prevalence is more in the women aged between 41 to 61 years.We report 100% prevalence of HPV16/18 in the cervical cancer tissue samples. A way to minimise this gynaecological concern would be to introduce prophylactic vaccines and early screening in the state of Bihar. The data generated would be crucial in drafting for community screening of HPV. We strongly emphasize the prophylactic HPV Vaccination against HPV 16 to control the alarming rate of cervical cancer in one of the most populous state of India, Bihar.


2020 ◽  
Author(s):  
Zhan Zhang ◽  
Ting Li ◽  
Dai Zhang ◽  
Xiaonan Zong ◽  
Huihui Bai ◽  
...  

Abstract Background: High-risk human papilloma virus (hrHPV) is regarded as the main causal factor of cervical precancer and cancer when persistent infection is left untreated. Previous studies have declared that HPV is associated with microecological environment of lower genital tract but haven’t discriminate vaginal microbiota from that of cervix. Objective: To analyze the distinction between vaginal and cervical microbiota in high-risk HPV(+) Chinese women. Methods: One hundred participants were recruited including 20 healthy women with HPV (-), 32 with other hrHPV (+), 38 subjects with HPV16/18 (+) and 10 with cervical carcinoma, demographics of whom were collected and analyzed. Vaginal and cervical microbiota were separately tested through next-generation sequencing technology (NGS) targeting the variable region (V3-V4) of bacterial ribosome 16S rRNA gene. Results: 1. Analysis of demographics demonstrated that hrHPV infected women tend to be accustomed to vaginal douching (p =0.001), show more frequent usage of sanitary pads (p =0.007), have more sex partners (p =0.047), be more sexually active (p =0.025), have more diverse ways of contraception (p =0.001) and history of vaginitis (p =0.002). 2. NGS identified microbial diversity of cervical microbiota was much higher than that of vagina with significantly increased Proteobacteria and decreased Lactobacillus. Variation of cervical microbiota of hrHPV(+) subjects partly similar to vaginal microbiota but had its unique features. Sphingomonas of α-Proteobacteria, almost invisible in the vagina, was more frequent at normal cervix whereas decreased remarkably at hrHPV(+) cervix. Reversely, γ-Proteobacteria showed a significant positive correlation with HPV16/18 and cervical cancer. BV related anaerobes like Gardnerella, Prevotella, Atopobium and Sneathia showed similar changes in both vaginal and cervical microbiota of hrHPV(+) women and did not exhibit cervical specificity. Conclusions: Cervical microbiota has its uniqueness from that of vagina in bacterial communities presenting a higher proportion of Proteobacteria, of which Sphingomonas is potentially predictive of a health guardian of hrHPV while Pseudomonas the opposite.


2011 ◽  
Vol 152 (45) ◽  
pp. 1804-1807
Author(s):  
Ádám Galamb ◽  
Attila Pajor ◽  
Zoltán Langmár ◽  
Gábor Sobel

Human papilloma virus (HPV) is the most common sexually transmitted infection in the 21st century. It has been established that infections with specific HPV types are contributing factors to cervical cancer. Approximately 99.7% of cervical cancers are associated with high risk HPV types. HPV testing plays an important role in the prevention, by decreasing the prevalence and the mortality of cervical cancer. There are 16 HPV-centers operating in Hungary, in which patients undergo HPV screening, cervical exams, and treatment based on standardized guidelines. Patients and methods: The first HPV-center was founded in 2007 in Budapest, at the 2nd Department of Obstetrics and Gynecology, Semmelweis University. This study aimed to define the presence and prevalence of HPV-DNA in the cervical swab samples obtained from patients in our center. Authors conducted to assess the age-specific-prevalence, and HPV type distribution, the associated cervical abnormalities, comparing our results with international data. Results: Overall 1155 woman underwent HPV-testing and genotyping, using polymerase chain reaction. Overall, 55.5% of patients had positive test for HPV DNA types, in which 38.5% for high-risk HPV DNA. Overall prevalence was the highest among females aged 15 to 25years (62.9%). The most common HPV type found was the high risk type 16 (19.5% among the patients with positive HPV testing). Presence of high risk HPV with concurrent cervical cytological abnormality was in 32%. More than two-thirds of woman with cytological atypia (70.6%) were infected with two or more high risk HPV types. HPV 16 was detected in 32% of patients with cytological abnormalities. Conclusions: The results suggest that the prevalence of HPV in this study population exceeds the international data. The results attracts the attention the peak prevalence of the high risk types in the youngest age-group, and the higher risk of cervical abnormality in case of presence of two or more HPV types. The dominance of type 16 and 18 was predictable, but the strong attendance of type 51 and 31 among patients who had cytological atypia, was slightly surprising. Orv. Hetil., 2011, 152, 1804–1807.


2012 ◽  
Vol 2012 ◽  
pp. 1-5 ◽  
Author(s):  
Francisco Romero-Pastrana

The primary underlying cause of cervical cancer is infection with one or more high-risk (HR) types of the human papilloma virus (HPV). Detection and typing of HPV have been commonly carried out by PCR-based assays, where HPV detection and typing are two separate procedures. Here, we present a multiplex PCR-based HPV typing assay that detects 20 HPV types (15 HR, 3 probably HR and 2 low risk) using type-specific primers and agarose gel electrophoresis. 46 cervical, urethral, and biopsy samples were analyzed by both Multiplex PCR and PGMY09/11 consensus PCR, and results were compared. 611 samples were further analyzed by Multiplex PCR, 282 were positive for HR HPV, and 101 showed multiple HR HPV infections. The relatively ease and economic accessibility of the method and its improved ability to detect high-risk HPV types in multiple HPV-infected samples make it an attractive option for HPV testing.


Biologicals ◽  
2016 ◽  
Vol 44 (5) ◽  
pp. 412-416 ◽  
Author(s):  
Miodrag Stamenković ◽  
Aleksandra Knežević ◽  
Ivana Knežević ◽  
Igor Kuzmanović ◽  
Danijela Karalić ◽  
...  

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