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Aim: To describe the phenotypic and genotypic profiles of Klebsiella pneumoniae carbapenemase-producing K. pneumoniae (KPC-Kp) strains isolated from patients with invasive infections at an Italian university hospital in order to assess the epidemiological trend.Methods: An observational prospective study was undertaken at the University Hospital of Sassari, Italy to detect KPC-Kp strains in patients with invasive bacteraemia. Isolates were identified phenotypically; carbapenemase production was assessed using phenotypic and genotypic methods. Sequencing of blaKPC genes, pulsed-field gel electrophoresis and multi-locus sequence typing were performed.Results: During the period 2015-2017, 46 cases of invasive infection with K. pneumoniae were recorded. Two-thirds (67.4%) of the patients were male, and the mean age was 69.4 years. Most patients had at least one comorbidity (56.5%) and/or had been hospitalized previously (70.5%), 81.8% had current or recent medical device use, and 85.4% had recent antibiotic exposure. The mortality rate was 52.3%. A multi-drug-resistant pattern (including carbapenems, fluoroquinolones, third-/fourth-generation cephalosporins) was shown for all K. pneumoniae isolates. KPC-3 and -2 were produced by all strains. The most common sequence types were 512 (91.3%) and 101 (8.7%), grouped into three clusters (A, A1 and B).Conclusions: A high incidence of KPC-Kp in patients with invasive infections was recorded at an Italian university hospital compared with the incidence measured before 2015. This study confirmed the importance of the KPC-3 carbapenemase variant, as reported by other Italian studies. High mortality and comorbidity rates appear to be associated with KPC-Kp infection. [ABSTRACT FROM AUTHOR]

Introduction: DNA methylation-based biomarkers have been investigated as useful tools in the carcinogenesis process, including the triage of HPV-associated cancers. In this context, we conducted a systematic review and meta-analysis focused on evaluating the changes in the level of DNA methylation in cases of pre-cancerous (i.e., anal intraepithelial neoplasia, AIN-1, -2., -3) and cancerous (i.e., squamous cell carcinoma, SCC) anal lesions., Methods: A research in the PubMed, Scopus, and Web of Science databases was carried out, following the PRISMA 2020 protocol, using the following keywords: "anal cancer", "anal intraepithelial neoplasia", "methylation", and "epigenetic". All observational studies that reported the level of DNA methylation by grade of anal lesions and for different target genes were included. The QUADAS-2 tool was used to assess the studies' quality, whereas pooled prevalence, sensitivity, specificity, and diagnostic odds ratio (DOR) were employed to verify the accuracy of the test in the detection of high-grade lesions., Results: Eight studies met the inclusion criteria, involving a total of 1555 clinical samples. The prevalence of methylation-positive samples by histological grading was 27%, 45%, 54%, and 98% for AIN1, AIN2, AIN3, and SCC, respectively. Similar results were observed for the DOR, with higher ORs in more severe lesions. The pooled AUC (95%CI) for the diagnosis of ≥AIN2 was 0.68 (0.63-0.73)., Conclusions: The present review and meta-analysis support the introduction of DNA methylation-based biomarkers in the triage of subjects with low-grade anal lesions and in the monitoring of treatment outcomes. Standardized protocols and a prospective study design are needed to implement methylation tests in clinical practice.

Background: Epigenetic biomarkers in cancer have emerged as promising tools for early detection, prognosis, and treatment response prediction. In cervical cells, hypermethylation of the host and viral HPV-genome increases with the severity of lesions, providing a useful biomarker in the triage of hr-HPV-positive women and during treatment. The present study focuses on evaluating the clinical performance of the FAM19A4/miR124-2 methylation test in a population-based cervical screening program., Methods: Previously collected cervical samples, after bisulfite-converted DNA, were analyzed by PreCursor-M+ kit (distributed by Fujirebio Europe), for DNA methylation. The sensitivity, specificity, and negative/positive predictive values of DNA methylation were compared to histology, colposcopy, the HPV-DNA test, and cytology results., Results: Among the 61-sample set, the specificity of methylation vs. positive histology (≥CIN2) and colposcopy (≥G2) were 87% and 90%, whereas the sensitivity was 50% and 33.3%, respectively. The combination of methylation analysis with standard methods increases diagnostic accuracy., Conclusions: Overall, we found a good specificity of DNA methylation in comparison to currently used techniques. Further larger studies could support the use of FAM19A4/miR124-2 as reliable biomarkers in the prevention of cervical cancer as triage in the screening protocol.

Recurrent respiratory papillomatosis (RRP) is a non-malignant disease, characterized by the production of wart-like growths in the respiratory tract, affecting both young people and adults (juvenile-onset recurrent respiratory papillomatosis, JORRP, and adult-onset recurrent respiratory papillomatosis, AORRP, respectively). Infection caused by human papillomavirus (HPV) is known as the main factor involved in RRP development. Complications of RRP may rarely occur, including lung involvement and malignant transformation. The present systematic review aimed to evaluate the prevalence of severe complications, such as lung involvement and lung tumor in JORRP and AORRP patients, and assess the role of HPV genotypes in the progression of disease severity following the guideline for reporting systematic reviews and meta-analysis (PRISMA Statement). A total of 378 studies were found on PubMed and Scopus using the following MESH terms: "recurrent respiratory papillomatosis and lung tumor" and "pulmonary tumor and recurrent respiratory papillomatosis". Basing on inclusion and exclusion criteria, a total of 11 studies were included in the systematic review. We found a pooled prevalence of 8% (95% CI: 4-14%; I 2 : 87.5%) for lung involvement in RRP patients. In addition, we found a pooled risk difference of 5% in lung involvement between JORRP and AORRP (95% CI: -7-18%; I 2 : 85.6%, p -value: 0.41). Among patients with lung involvement, we observed a pooled prevalence of lung tumor of 4% (95% CI:1-7%; I 2 : 67.1%) and a pooled prevalence mortality for this group of 4% (95% CI:2-6%; I 2 : 0%). Overall, the positivity rate for HPV-6 and -11 in patients with RRP was 91%. Considering only cases with pulmonary involvement, the pooled prevalence for HPV-11 was 21% (95% CI: 5-45%; I 2 : 77.2%). Our results evidenced a low/middle risk of pulmonary involvement and lung tumor in JORRP and AORRP patients, with an increased risk for HPV-11-positive patients. Further studies should be performed to improve knowledge and adopt preventive measures to contrast the progression to severe diseases in RRP patients.

Background and Aim: Prompt administration of appropriate antibiotic therapy is crucial in improving outcomes, particularly in cases sustained by multi-drug resistant strains. Although phenotypic antimicrobial susceptibility testing (AST) represents the gold standard to address antibiotics treatment, the long time required to obtained affordable results could negatively affect the prognosis. In contrast, rapid genotypic AST provide essential information for treatment and surveillance program. In order to evaluate the potential adoption of rapid AST in clinical routine, we compared the genotypic and phenotypic antimicrobial profiles of different K.pneumoniae strains, characterized by different expression of carbapenemases-encoding genes., Methods: A set of 109 strains of Cr-Kp were tested for the antimicrobial drugs by the automatized Vitek II system and, in parallel, to the new combination of β-lactams/β-lactamases inhibitors (BL/BLI) by Etest. An antimicrobial resistance index (ARI) was calculated for each strain, assigning each 1 or 0 points based on observed resistance/susceptibility, and dividing the total by the number of antibiotics tested. Kruskal-Wallis test, followed by Dunn's post hoc test (Bonferroni correction), were used to compare quantitative variables among resistance gene subgroups., Results: We observed a higher ARI score in KPC/OXA-48 strains, similar profile in KPC alone and KPC/CTX-M groups and a significant lower resistance in no-carbapenemases-producing group. Same trend was observed in AST for BL/BLI., Conclusions: These preliminary results showed a close link between genotypic and phenotypic AST, supporting the adoption of rapid AST in cases of severe infections, ensuring to saving time and providing, the surveillance of MDR strains and improving stewardship programs.

Background: Whole-genome sequencing (WGS) provides important information for the characterization, surveillance, and monitoring of antimicrobial resistance (AMR) determinants, particularly in cases of multi- and extensively drug-resistant microorganisms. We reported the results of a WGS analysis carried out on carbapenemases-producing Klebsiella pneumoniae , which causes hospital-acquired infections (HAIs) and is characterized by a marked resistance profile., Methods: Clinical, phenotypic, and genotypic data were collected for the AMR surveillance screening program of the University Hospital of Sassari (Italy) during 2020-2021. Genomic DNA was sequenced using the Illumina Nova Seq 6000 platform. Final assemblies were manually curated and carefully verified for the detection of antimicrobial resistance genes, porin mutations, and virulence factors. A phylogenetic analysis was performed using the maximum likelihood method., Results: All 17 strains analyzed belonged to ST512, and most of them carried the bla KPC-31 variant bla OXA-48-like , an OmpK35 truncation, and an OmpK36 mutation. Phenotypic analysis showed a marked resistance profile to all antibiotic classes, including β-lactams, carbapenems, aminoglycosides, fluoroquinolone, sulphonamides, and novel β-lactam/β-lactamase inhibitors (BL/BLI)., Conclusion: WGS characterization revealed the presence of several antibiotic resistance determinants and porin mutations in highly resistant K. pneumoniae strains responsible for HAIs. The detection of bla KPC-31 in our hospital wards highlights the importance of genomic surveillance in hospital settings to monitor the emergence of new clones and the need to improve control and preventive strategies to efficiently contrast AMR.

Background: Given the diagnostic accuracy of HPV-DNA tests in terms of self-collected samples, in order to implement self-sampling in cervical screening programs, the standardization of the pre-analytical phase, including decisions concerning the choice of medium, the volume of elution, and storage conditions, are necessary, in addition to understanding the potential factors involved in acceptability by women. On this basis, we carried out a cross-sectional study to assess (i) the stability of dry vaginal self-collected samples stored at room temperature for up to 4 weeks after elution in 2 mL of eNat ® (Copan) medium, and (ii) the acceptability of self-collection in enrolled women., Methods: 185 women were enrolled in the LILT (Italian League Against Tumors) regional project. A self-sampling kit, including a dry FLOQSwab ® (Copan), instructions for use, and a satisfaction questionnaire, were supplied for each woman and sent by mail to the laboratory. The HPV-DNA test was carried out using the Anyplex™ II HPV HR (Seegene) kit. To evaluate the specimen's stability, 185 dry vaginal swabs were eluted in eNat ® , a lyses-based molecular medium and tested for HPV detection at two different time points (<6 days and 1 month after elution). The Cohen's Kappa coefficients and McNemar test were used to assess the agreement of HPV-DNA at different times., Results: We found high agreement in terms of HPV-DNA results among the samples tested at two different time points (Cohen K = 0.98; p < 0.0001). Moreover, most of the women found it easy to use self-collection devices and the pictorial instructions clear to understand. Approximately half of the enrolled women declared preferring self-sampling to clinician-collected methods., Conclusion: Our results display the high reliability and accuracy of HPV-DNA tests using dry vaginal self-collection FLOQSwabs ® devices eluted in 2 mL of molecular medium. The analysis of the questionnaire showed a high acceptability of self-collection among women, although a high percentage preferred standard collection devices. Overall, our preliminary results support the adoption of self-collection in screening programs, even though further analyses should be performed to optimize and standardize protocols for HPV tests on self-samples, and educational campaigns are needed to adequately inform and increase responsiveness in a target population.

The Innovation for Gender Equality in Academia (IGEA) project is focused on the analysis of the gender composition in academia, on the identification of the health needs of the academic population and on the assessment of their organizational wellbeing, in order to promote equal working conditions and opportunities. The study, focused on the identification of health needs, involved the construction of an ad hoc questionnaire in order to collect the socio-demographic characteristics and the perception of working environment of the participants. Differences between males and females were evaluated by the Mann-Whitney test, and Pearson Chi-Square or Fisher exact tests as appropriate, highlighting significant differences between genders regarding the occurrence of anxiety, panic, irritation and annoyance related to work activities. A multivariate logistic regression analysis was performed to identify factors associated with the perception of work-related anxiety/panic, showing a direct association with the difficulty in work performance and the work-related stress during the pandemic period, whereas, an indirect association was found with job satisfaction and the feeling of being appreciated by colleagues. Occupational stress can increase the risk of developing physical and mental conditions, also affecting work performance and absenteeism. It is therefore fundamental to plan targeted interventions, implement policies and specific actions, in order to avoid and reduce any differences related to gender., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Deiana, Dettori, Muresu, Puci, Saderi, Piga, Sias, Pisu, Foddai, Gazzolo, Fiorini, Milia, Mariotti, Sotgiu, Azara and Piana.)

Background: Carbapenem resistant Klebsiella pneumoniae (cr-Kp) causes serious infections associated with a high mortality rate. The clinical efficacy of ceftazidime/avibactam (CZA), meropenem/vaborbactam (M/V), and imipenem/relebactam (I/R) against cr-Kp is challenged by the emergence of resistant strains, making the investigation and monitoring of the main resistance mechanisms crucial. In this study, we reported the genome characterization of a Klebsiella pneumoniae strain isolated from a critically ill patient and characterized by a multidrug resistant (MDR) profile, including resistance to CZA, M/V, and I/R., Methods: An antimicrobial susceptibility test (AST) was performed by an automated system and E-test and results were interpreted following the EUCAST guidelines. Genomic DNA was extracted using a genomic DNA extraction kit and it was sequenced using the Illumina Nova Seq 6000 platform. Final assembly was manually curated and carefully verified for detection of antimicrobial resistance genes, porins modifications, and virulence factors., Results: The K. pneumoniae isolate belonged to sequence type ST512 and harbored 23 resistance genes, conferring resistance to all antibiotic classes, including bla KPC-31 and bla OXA-181, leading to carbapenems resistance. The truncation of OmpK35 and mutation OmpK36GD were also observed., Conclusions: The genomic characterization demonstrated the high resistant profile of new cr-Kp coharboring class A and D carbapenemases. The presence of KPC-31, as well as the detection of OXA-181 and porin modifications, further limit the therapeutic options, including the novel combinations of β-lactam/β-lactamase inhibitor antibiotics in patients with severe pneumonia caused by cr-Kp.

The accuracy of available HPV molecular assays on self-samples needs to be evaluated as compared to clinician-collected samples. This pilot study aimed to investigate the BD Onclarity™ HPV assay on vaginal and first-void urine samples. Sixty-four women referred to colposcopy for cervical dysplasia performed a vaginal self-collection and provided a first-void urine sample, after informed consent. A cervical specimen was collected during the clinician examination. All samples were tested using BD Onclarity™ HPV assay on the BD Viper™ LT System. Overall positive agreement (OPA) between cervical and self-sample results was evaluated using Cohen's kappa value (κ). Using a clinical cut-off of 38.3 Ct for HPV 16 and 34.2 Ct for other HR genotypes, compared to cervical sample, the self-collected vaginal sample OPA was 85.9%, and κ = 0.699. Without a clinical cut-off, the OPA was 95.3%, and the κ = 0.890. Data obtained comparing cervical and urine samples showed an OPA of 87.5% with a κ = 0.79 using a clinical cut-off, and an OPA of 90.6% with a κ = 0.776 without a clinical cut-off. Data showed a substantial agreement between both self-collected and clinician-collected samples. A specific clinical cut-off analysis should be considered based on type of sample analysed.

The aim of the present systematic review and meta-analysis was to compare native tissue repair (NTR) against transvaginal mesh augmentation for the repair of anterior vaginal prolapse. A total of 2289 articles were found but only 27 (24.8 %) were included in the review. Guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) were followed to guide the process of the systematic review and meta-analysis. The quality of the observational studies was evaluated according to the Scottish Intercollegiate Guidelines Network, whereas the quality of randomized control trials (RCT) was assessed by the Cochrane risk-of-bias scale. The mesh repair intervention was associated with a higher anatomical cure rate in comparison with NTR repair when the follow-up was ≤24 months [pooled risk difference (95 % CI): -0.18 % (-0.22 %; 0.13 %); p-value: <0.0001; I 2 : 36.0 %]. Studies reporting anatomical failure had similar findings [pooled risk difference (95 % CI): 0.17 % (0.01 %; 0.33 %); p-value: 0.03; I 2 : 88.6 %]. No differences in the risk of re-operation were observed between NTR repair and mesh augmentation. Pooled risk differences in the incidence of post-surgical and late complications were higher for the mesh repair intervention [-0.05 % (95 % CI: -0.10 %; 0.00 %) p-value: 0.05; I 2 : 68.3 %] [-0.05 % (95 % CI: -0.14 %; 0.03 %) p-value: 0.25; I 2 : 82.0 %]. Women who underwent mesh repair reported greater satisfaction than women who underwent NTR [pooled risk difference (95 % CI): -0.07 % (-0.16 %; 0.02 %); p-value: 0.15; I 2 : 65.3 %]. In conclusion, mesh repair surgery had higher anatomical cure and satisfaction rates, with no differences in re-operation rate, but had higher post-surgical and late complications in comparison with NTR., Competing Interests: Declaration of competing interest The authors declare that they have no competing interest., (Copyright © 2022 Elsevier B.V. All rights reserved.)

HPV infection is a clear etiopathogenetic factor in oropharyngeal carcinogenesis and is associated with a markedly better prognosis than in smoking- and alcohol-associated cases, as specified by AJCC classification. The aim of the present work is to evaluate the prevalence of HPV-induced OPSCC in an insular area in the Mediterranean and to assess the reliability of p16 IHC (immunohistochemistry) alone, as accepted by AJCC, in the diagnosis of HPV-driven carcinogenesis in such a setting. All patients with OPSCC consecutively managed by the referral center in North Sardinia of head and neck tumor board of AOU Sassari, were recruited. Diagnosis of HPV-related OPCSS was carried out combining p16 IHC and DNA testing on FFPE samples and compared with the results of p16 IHC alone. Roughly 14% (9/62) of cases were positive for HPV-DNA and p16 IHC. Three more cases showed overexpression of p16, which has a 100% sensitivity, but only 75% specificity as standalone method for diagnosing HPV-driven carcinogenesis. The Cohen's kappa coefficient of p16 IHC alone is 0.83 (excellent). However, if HPV-driven carcinogenesis diagnosed by p16 IHC alone was considered the criterion for treatment deintensification, 25% of p16 positive cases would have been wrongly submitted to deintensified treatment for tumors as aggressive as a p16 negative OPSCC. The currently accepted standard by AJCC (p16 IHC alone) harbors a high rate of false positive results, which appears risky for recommending treatment deintensification, and for this aim, in areas with a low prevalence of HPV-related OPSCC, it should be confirmed with HPV nucleic acid detection.

The etiology of bladder cancer is known to be associated with behavioral and environmental factors. Moreover, several studies suggested a potential role of HPV infection in the pathogenesis with controversial results. A systematic review was conducted to assess the role of HPV. A total of 46 articles that reported the prevalence of HPV infection in squamous (SCC), urothelial (UC), and transitional cell carcinomas (TCC) were selected. A pooled prevalence of 19% was found, with a significant difference in SCC that was mainly driven by HPV-16. Moreover, infection prevalence in case-control studies showed a higher risk of bladder cancer in HPV-positive cases (OR: 7.84; p-value < 0.00001). The results may suggest an etiologic role of HPV in bladder cancer. HPV vaccine administration in both sexes could be key to prevent the infection caused by high-risk genotypes.

Background: Cervical cancer is the fourth most common cancer in women, and it is well known that high-risk human papillomavirus (hrHPV) infections are the necessary carcinogenic factors for the development of cervical tumors. Moreover, the interaction between HPV and other sexually transmitted infections (STIs) may increase the risk of cancer progression. Self-sampling has been demonstrated to represent a valid and well-accepted alternative, favoring women's participation in screening programs. This study aimed to investigate the use of FLOQSwabs ® (FS) as compared to two other vaginal self-collection devices for the detection of hrHPV and other sexually transmitted infections., Methods: Cervical and vaginal self-samples were collected, using two different combinations of vaginal self-sampling devices, from 40 women referred to colposcopy for a documented abnormal Pap smear. All samples were tested for hrHPV and seven STI pathogens using two commercial molecular assays., Results: Data on hrHPV detection from the first group of women showed an almost perfect agreement (kappa: 0.89) between cervical vs. FS vaginal self-samples, and a substantial agreement (kappa: 0.79) between cervical and HerSwab™ (HS) samples. In the second group of women, an almost perfect agreement (kappa: 0.90) was demonstrated in the detection of hrHPV between cervical samples vs. FS, and a moderate agreement (kappa: 0.60) for cervical vs. Evalyn ® Brush (EB) self-collected samples. STI detections showed a very good agreement (kappa: 0.89 and kappa: 1.00) both among FS vs. HS and FS vs. EB, respectively. There was no statistically significant difference between the different devices used. The most frequently detected hrHPV genotypes in the studied population were HPV 16, 31, 35, 51, and 56; whilst the most frequently identified STI pathogens were Ureaplasma parvum and Mycoplasma hominis. Overall, investigated women did not report any discomfort in using the different vaginal self-collection devices., Conclusion: Evaluation of the three different vaginal self-collection devices confirmed their overall good acceptability by the studied population, as well as a similar agreement for hrHPV detection as compared to cervical samples. Our study indicated that the use of self-collected samples offers an alternative strategy to improve women's participation in cervical cancer screening programs, but also underlined the importance of evaluating the concordance in hrHPV detection of collection devices in combination with the molecular hrHPV assay.

Background: Carbapenem-resistant Klebsiella pneumoniae (CR-Kp) is endemic globally, causing severe infections in hospitalized patients. Surveillance programs help monitor and promptly identify the emergence of new clones. We reported the rapid spread of a novel clone of K. pneumoniae co-harbouring class A and D carbapenemases in colonized patients, and the potential risk factors involved in the development of infections. Methods: Rectal swabs were used for microbiological analyses and detection of the most common carbapenemase encoding genes by real-time PCR (i.e., blaKPC, blaOXA-48, blaNDM, blaVIM, and blaIMP). All strains co-harbouring KPC and OXA-48 genes were evaluated. For each patient, the following variables were collected: age, sex, length and ward of stay, device use, and outcome. Clonality of CR-Kp was assessed by preliminary pulsed field gel electrophoresis (PFGE), followed by multi-locus sequence typing (MLST) analyses. Results: A total of 127 isolates of K. pneumoniae co-harbouring KPC and OXA-48 were collected between September 2019 and December 2020. The median age (IQR) of patients was 70 (61-77). More than 40% of patients were admitted to intensive care unit (ICU). Around 25% of patients developed an invasive infection, the majority of which were respiratory tract infections (17/31; 54.8%). ICU stay and invasive infection increased the risk of mortality (OR: 5.39, 95% CI: 2.42-12.00; OR 6.12, 95% CI: 2.55-14.69, respectively; p -value ≤ 0.001). The antibiotic susceptibility test showed a resistance profile for almost all antibiotics considered. Monoclonal origin was confirmed by PFGE and MLST showing a similar restriction pattern and belonging to ST-512. Conclusions: We report the spread and the marked antibiotic resistance profiles of K. pneumoniae strains co-producing KPC and OXA-48. Further study could clarify the roles of clinical and microbiological variables in the development of invasive infection and increasing risk of mortality, in colonized patients.

The assessment of human papillomavirus (HPV) genotype dynamics could support the adoption of more tailored preventive actions against cervical cancer. The aim of the study was to describe the prevalence of HPV infection, HPV genotype distribution, and the epidemiological characteristics of women with ASC-US cytology since the introduction of HPV-DNA testing in Sardinia (Italy), (March 2016-December 2020). Specimens were tested by RT-PCR for 14 high-risk HPV genotypes. A total of 1186 patients were enrolled, with a median (IQR) age of 41 (38-48) years. Of these women, 48.1% were positive for at least one HPV genotype; 311 (26.2%) women were vaccinated with a median (IQR) age of 38 (30/47) years. The percentage of prevalence of HPV-16, -31, -66, -56, and -51 was 36.3%, 18.7%, 11.9%, 11.4% and 10.7%, respectively. The highest prevalence of infection was found in women aged <41 years, and single women. Moreover, women aged >41 years (OR: 0.51, 95% CI: 0.31-0.86; p -value: 0.01), having parity (OR: 0.57, 95% CI: 0.34-0.96, p -value: 0.04), and higher educational level (OR: 0.39, 95% CI: 0.18-0.87; p -value: 0.02) were associated with a lower CIN2+ risk. We did not find a significant difference in terms of prevalence of HPV-16 infection between vaccinated and non-vaccinated (18.3% vs. 17.1%; p -value < 0.001). Our results support the adoption of nonavalent HPV-vaccine to prevent the most prevalent infections caused by HPV-16 and -31 genotypes and underscore the need of surveillance to implement tailored vaccination programs and preventive strategies.

Background: Human Papillomavirus (HPV) infection is one of the most important causes of cancer. It can play a role in cervical and extra-cervical cancers. Penile cancer is rare, even if an increasing trend was recently reported. Aim of the present study was to assess the prevalence and distribution of HPV genotypes in cases of penile cancer diagnosed in Sardinia, Italy. Surrogate markers of HPV infection (i.e., E6 and p16 genes) were also evaluated in all cases., Methods: An observational, retrospective study which recruited all cases of penile cancer diagnosed between 2002 and 2019 at a tertiary care hospital in Sardinia, Italy, was carried out. HPV-DNA detection and genotyping were performed by Real-time PCR. Specimens were tested for oncogene E6 mRNA and for p16(INK4a) expression., Results: HPV prevalence was 28.1% (9/32); HPV-16 was the most prevalent genotype (7/9, 77.8%). p16INK4a positivity was found in 66.7% of the samples with a statistically significant difference between HPV-positive and -negative groups. E6-transcript was detected in 71% of the HPV-16 positive samples. The overall survival was not statistically different between HPV-positives and -negatives., Discussion: The present study confirms the etiologic role of HPV in penile cancer and supports the adoption of vaccination strategies in men and women. Further studies should clarify the diagnostic and prognostic role of E6 and p16 proteins., Conclusion: HPV infection can favor the occurrence of penile cancer, whose diagnosis and prognosis could be improved with the implementation of validated molecular techniques.

Objectives: Anal cancer is a rare disease. However, its incidence is increasing in some population groups. Infection caused by Human Papillomavirus (HPV) is strongly associated with the risk of anal cancer, whose variability depends on samples, histology, and HPV detection methods. The aim of the study was to assess prevalence and distribution of HPV genotypes in patients diagnosed with anal carcinoma. Methods : An observational, retrospective study was carried out in a tertiary care hospital in North Sardinia, Italy. Specimens of anal cancer diagnosed from 2002-2018 were selected. Demographic, epidemiological, and clinical variables were collected to assess their relationship with the occurrence of anal cancer. Results : The overall HPV positivity was 70.0% (21/30), with HPV-16 being the predominant genotype (~85%). The highest prevalence of anal cancer was in patients aged ≥55 years. HPV positivity was higher in women ( p -value > 0.05) and in moderately differentiated samples (G2) ( p -value < 0.05). p16 INK4a and E6-transcript positivity were found in 57% and 24% of the HPV positive samples, respectively. The OS (overall survival) showed a not statistically significant difference in prognosis between HPV positive sand negatives (10, 47.6%, vs. 4, 44.4%; p -value = 0.25). Conclusions : HPV-DNA and p16 INK4a positivity confirmed the role of HPV in anal carcinoma. Our findings could support the implementation and scale-up of HPV vaccination in males and females to decrease the incidence of HPV-associated cancers. Further studies are needed to better clarify the prognostic role of HPV/p16 status.

The aim of this study was to assess the role of a human papilloma virus (HPV) vaccine after loop electrosurgical excision procedure (LEEP) in reducing recurrent cervical dysplasia. A series of 503 women with cervical dysplasia received LEEP between January 2012 and October 2018. Of these patients, 379 were treated between January 2012 and June 2017, thus ensuring an adequate follow-up time. We made three attempts to establish telephone contact with each patient; 77 women did not respond and were excluded from the final study population, which consisted of 302 patients. One hundred eighty-two (60.7%) women were vaccinated with an HPV vaccine within 4 weeks of LEEP and 103 (34.3%) were followed up with but not vaccinated. Recurrence of cervical dysplasia requiring a further LEEP procedure occurred in 30 (10.5%) women, of whom 17 (16.5%) were not vaccinated and 13 (7.1%) were vaccinated ( p -value = 0.010). At univariate analysis, HPV vaccination after LEEP (odds ratio (OR) = 0.4, p -value = 0.020) emerged as an independent protective factor. Choosing as an outcome of the analysis only recurrence as severe cervical lesions, the protective role of HPV vaccination after LEEP was found to be much more relevant with an odds ratio of 0.2 (95% CI = 0.1-0.6, p -value = 0.02). Administration of an HPV vaccine after LEEP seems to reduce the risk of recurrence, thus suggesting that HPV vaccination has a role as an adjuvant treatment after LEEP.

Enteric fever is a foodborne infectious disease caused by Salmonella enterica serotypes Typhi and Paratyphi A, B and C. The high incidence in low income countries can increase the risk of disease in travelers coming from high income countries. Pre-travel health advice on hygiene and sanitation practices and vaccines can significantly reduce the risk of acquiring infections. Although the majority of the cases are self-limiting, life-threatening complications can occur. Delayed diagnosis and cases of infections caused by multi-drug resistant strains can complicate the clinical management and affect the prognosis. More international efforts are needed to reduce the burden of disease in low income countries, indirectly reducing the risk of travelers in endemic settings. Surveillance activities can help monitor the epidemiology of cases caused by drug-susceptible and resistant strains.

This study aims to evaluate HPV16 variants distribution in a population of Italian women living in two different regions (Lombardy and Sardinia) by sequence analyses of HPV16-positive cervical samples, in order to reconstruct the phylogenetic relationship among variants to identify the currently circulating lineages. Analyses were conducted starting from DNA isolated from 67 HPV16-positive cervical samples collected from two different Italian centres (31 from Lombardy and 36 from Sardinia) of women with normal and abnormal cervical cytology. The entire long control region (LCR) and 300 nt of the E6 gene was sequenced to identify intra-type variants. Sequence comparison and phylogenetic analysis were made using a distance-based neighbour joining method (NJ) and Kimura two-parameter model. Data obtained reported that Italian sequences mainly belonged to the European lineage, in particular sublineage A2. Only five sequences clustered in non-European branches: two in North American lineage (sublineage D1), two in African-1 (sublineage B1) and one in African-2. A new 27 nucleotide duplication in the central segment of the LCR region was found in a sequence obtained from a sample isolated in Sardinia. A predominance of European variants was detected, with some degree of variability among the studied HPV16 strains. This study contributes to the implementation of data regarding the molecular epidemiology of HPV16 variants., Competing Interests: The authors declare no conflict of interest.

Chlamydia trachomatis (Ct) and human papillomavirus (HPV) are the most prevalent sexually transmitted infections throughout the world. Despite the serious complications associated with chronic Ct infections in sexually active women, a screening program is not yet available in Italy. Moreover, HPV/Ct co-infections are also known to occur frequently, increasing the risk of HPV-induced carcinogenesis. The aim of this study was to evaluate the prevalence of Ct infections, the distribution of Ct serovars, and the incidences of Ct/HPV co-infections among women with a recent history of abnormal cervical cytology. Cervical samples were collected from 199 women referred for a gynecological visit following an abnormal Pap test results. All samples were tested for the presence of Ct and HPV DNA using real-time PCR assays; Ct typing of positive samples was performed by PCR-RFLP (restriction fragment length polymorphism) targeting the ompA gene. A high percentage of these women (12.8% and 21.7% with or without abnormal cytology on "retesting", respectively) were found to be Ct positive. Serovar F was the most prevalent type in Ct positive women, followed by E and K. Ct/HPV co-infections were detected in 7% (14/199) of enrolled women, with HPV-16, HPV-51, and HPV-52 being most frequently identified in co-infections. This study provides new epidemiological data on the prevalence of Ct and associated HPV infection in women with a recent history of abnormal cervical cytology in Italy, where notification of cases is not mandatory.