Human Papillomavirus Genotyping and E6/E7 mRNA Expression in Greek Women with Intraepithelial Neoplasia and Squamous Cell Carcinoma of the Vagina and Vulva

A large proportion of vaginal and vulvar squamous cell carcinomas (SCCs) and intraepithelial neoplasias (VAIN and VIN) are associated with HPV infection, mainly type 16. The purpose of this study was to identify HPV genotypes, as well as E6/E7 mRNA expression of high-risk HPVs (16, 18, 31, 33, and 45) in 56 histology samples of VAIN, VIN, vaginal, and vulvar SCCs. HPV was identified in 56% of VAIN and 50% of vaginal SCCs, 71.4% of VIN and 50% of vulvar SCCs. E6/E7 mRNA expression was found in one-third of VAIN and in all vaginal SCCs, 42.9% of VIN and 83.3% of vulvar SCCs. Our data indicated that HPV 16 was the commonest genotype identified in VAIN and VIN and the only genotype found in SCCs of the vagina and vulva. These findings may suggest, in accordance with other studies, that mRNA assay might be useful in triaging lesions with increased risk of progression to cancer

Immunocytochemical Expression of BAX and BAK Proteins in Cervical Smears of Women Positive for HPV Types: A Study of 120 Cases

Objective: Human Papillomavirus (HPV) infection is clearly associated with cervical cancer development. However, only a very small percentage of HPV-infected women will eventually develop cancer and the factors determining that progression have not yet been sufficiently clarified. It is known that HPV oncoproteins E6 and E7 interact with various squamous cell molecules towards promoting cell immortalization and carcinogenesis. Among these molecules are the proapoptotic proteins Bax and Bak, two key regulators of the intrinsic apoptotic pathway. The aim of this study is to test for possible statistically significant differences in the Bax and Bak expression in the Pap smears of HPV-positive and HPV-negative women and thus examine their potential value as prognostic markers.Methods: One hundred and twenty women were subtyped for HPV using microarrays hybridization and then Bax and Bak expression was assessed using immunocytochemistry staining on cytocentrifuged ThinPrep samples.Results: Statistical analysis determined that there was no statistically significant difference between the expression of Bax and Bak in the HPV-positive and HPV-negative women as this expression was detected by immunocytochemical assessment of ThinPrep samples.Conclusion: Although in several published studies there is evidence of HPV oncoproteins affecting the expression of Bax and Bak on squamous cells, our study indicates that this effect is not apparent by immunocytochemical protein staining

Prevalence of Human Papillomavirus in 45 Greek Patients with Oral Cancer

The relation between HPV and head and neck cancer has recently and extensively been investigated. The purpose of this study was to indentify HPV genotypes, as well as E6/E7 mRNA expression of high-risk HPVs (16, 18, 31, 33 and 45) in oral squamous cell carcinomas (OSCCs) from 45 Greek patients. The overall prevalence of HPV DNA positive OSCCs was 11.1% (5/45), while high-risk HPV DNA was found in 6.7% (3/45) of OSCCs. E6/E7 mRNA expression was detected in 8.9% (4/45) of the oral cavity samples. Our data indicated that HPV 16 was the commonest genotype identified in HPV-positive OSCCs by both DNA and RNA tests. This study confirms the prevalence of HPV infections among patients with OSCCs. Future analysis and followup of more OSCCs will enable us to correlate HPV detection and clinical outcome

HPV infection and cervical cancer

The aim of this study was to detect and identify HPV types that appear in a large sample of women from a wide age range, their incidence and mRNA from E6/E7 oncogenes of high-risk HPV types (HPV-16,18,31,33,45) correlating this data with cytology, smoking and oral contraceptives. The study group consisted of a consecutive sample of 1145 women 14-70 years old. 44.7% of all women were positive for HPV. HPV16 and HPV42 were the most frequent genotypes in total samples followed by HPV53 and HPV51. HPV frequency increased as the severity of cytological lesions was escalating. The higher prevalence of HPV infection was observed in the 14-25 years old age group. Perhaps the most important figure is the 3.6% of women who do not seem to harbour any of the five high risk types, but the mRNA assay is positive for at least one type. Finally, a quite significant relationship was found between tobacco use and the detection of at least one HPV type. E6/E7 mRNA detection in women with normal cytology or low grade lesions reflect the oncogenic activity of the above hrHPV types, therefore it could be used as screening marker for better surveillance in this subset of women.Σκοπός της μελέτης ήταν ο προσδιορισμός των τύπων HPV που εμφανίζονται σε ένα μεγάλο δείγμα γυναικών, η συχνότητα εμφάνισής τους καθώς και του mRNA των ογκογονιδίων Ε6/Ε7 των τύπων HPV υψηλού κινδύνου (HPV-16,18,31,33,45) συσχετίζοντας την εμφάνισή τους με την κυτταρολογία, το κάπνισμα και τη λήψη αντισυλληπτικών. Η ομάδα μελέτης αποτελούνταν από 1145 γυναίκες 14 έως 70 ετών. Επί του συνόλου των δειγμάτων θετικές ήταν το 44,7% των γυναικών. Ο HPV16 και ο HPV42 ήταν οι πιο συχνοί γονότυποι στα συνολικά δείγματα και ακολουθούν οι HPV53 και HPV51. Η συχνότητα του HPV αυξάνεται καθώς κλιμακώνεται η σοβαρότητα των κυτταρολογικών αλλοιώσεων. Το μεγαλύτερο ποσοστό HPV λοίμωξης παρατηρήθηκε στην ηλικιακή ομάδα 14-25 ετών. Το σημαντικότερο ίσως ποσοστό είναι το 3,6% των γυναικών οι οποίες δεν φαίνεται να έχουν κάποιον από τους πέντε τύπους υψηλού κινδύνου, αλλά στην εξέταση mRNA είναι θετικές. Τέλος βρέθηκε μία αρκετά σημαντική σχέση μεταξύ της χρήσης καπνού και ανίχνευσης κάποιου τύπου του ιού HPV. Η ανίχνευση των Ε6/Ε7 mRNA σε γυναίκες με φυσιολογική κυτταρολογία ή χαμηλού βαθμού αλλοιώσεις αντικατοπτρίζουν την ογκογόνο δραστικότητα τύπων HPV υψηλού κινδύνου, επομένως ο προσδιορισμός τους θα μπορούσε να χρησιμοποιηθεί ως δείκτης διαλογής για καλύτερη εποπτεία σε αυτές τις υποομάδες των γυναικώ

Bax and Bak expression in cervical smears of women with low-and high-risk HPV types: A study of 120 cases

Background: Human papillomavirus (HPV) is known to be involved in the carcinogenesis of squamous cells in uterine cervix cancer, mostly by binding and inactivating the p53 and pRb tumor suppressor genes. Lately, evidence has emerged suggesting that HPV oncoproteins may interact with proteins involved in cellular apoptosis as well. Aim: This study aimed to investigate the expression of proapoptotic proteins Bax and Bak in women with low-risk and high-risk HPV types as opposed to HPV-negative women, and in women with normal pap smear compared to women with abnormal Papanicolau test (Pap) smear. Materials and Methods: A total of 120 liquid-based cervical samples were subtyped for HPV types with microarray hybridization and then stained and evaluated immunocytochemically for Bax and Bak expression. Statistical analysis was performed on the Bax and Bak scores (percentage of positive cells × staining intensity), the overall percentage of positive cells, and the most prevalent staining intensity group found in each sample. Results: A weak association between negative Bax staining and cytologically normal Pap smears was discovered, whereas cytologically abnormal samples tended to stain weakly or moderately positive. No other statistically significant difference was found in the other analyzed parameters. Conclusion: Cytologically normal pap smears seem to have a slight tendency to stain negative for Bax as opposed to cytologically abnormal pap smears. Although the association is weak, it is an indication that there might be a connection between the expression of Bax and the development of cervical intraepithelial dysplasia, which warrants further investigation in larger-scale studies

A cross sectional study of HPV type prevalence according to age and cytology

<p>Abstract</p> <p>Background</p> <p>A cross sectional study to investigate HPV prevalence according to age and cytology.</p> <p>Methods</p> <p>Women presenting to a gynaecological outpatient clinic for a Pap smear test were included in the study (n=3177). All women had cervical cytology and HPV testing.</p> <p>Results</p> <p>Overall prevalence of any 24 HPV type analysed was 33.1% (95% CI 31.5% to 34.7%) and HPV 16 and HPV 42 were the most frequent (6.7% (95% CI 5.8% to 7.6%), 6.8% (95% CI 5.9% to 7.6%)), in total samples. Multiple HPV infection rate was 12.9% (95% CI 11.8% to 14.1%). High risk HPV (hrHPV) types were present in 27.4% (95% CI 25.8% to 28.9%) of the samples.</p> <p>HPV prevalence was highest among 14 to 19 y.o (46.6% (95% CI 40.7%-52.4%)) and second highest among 30–34 y.o. (39.7%, 95% CI 35.4%–44%). HPV 16 was highest among 20–24 (9.0% (95% CI 6.4%–11.6%)) and second highest among 50 to 54 y.o. (6.3% (95% CI 2.9% to 9.8%).</p> <p>In Low-grade Squamous Intraepithelial Lesions (LgSIL) cytology samples, the most frequently detected hrHPV types were: 16 (14.5% (95% CI 12.1% to 16.9%)), 51 (13.0% (95% CI 10.7% to 15.3%)) and 53 (9.1% (95% CI 7.2% to 11.1%)) and in High-grade Squamous Intraepithelial Lesions (HgSIL) were: HPV 16 (37.2% (95% CI 26.5% to 47.9%)), HPV 51 (17.9% (95% CI 9.4% to 26.5%)) and HPV 18 (12.8% (95% CI 5.4% to 20.2%)).</p> <p>Conclusions</p> <p>In the population studied, HPV 16 and 51 were the most frequent detected hrHPV types. HPV positivity, hrHPV and multiple HPV types infections were higher in young women, while HPV prevalence declined with increasing age and presented two peaks a higher (14–19 y.o.) and a lower one (30–34 y.o.) These results may contribute to the creation of a national screening programme.</p