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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.

A multicenter, nonrandomized, prospective, controlled study was conducted to evaluate, as perioperative prophylactic treatment, the anti-infective effectiveness of 0.66% povidone-iodine eye drops (IODIM®) against the bacterial flora of the conjunctival surface of patients who undergo cataract surgery. Eye drops containing 0.66% povidone-iodine were applied to the eye undergoing cataract surgery, the untreated contralateral eye was used as control. One hundred and twenty patients set to receive unilateral cataract surgery were enrolled in 5 Italian Ophthalmology Centers and pretreated for three days with 0.66% povidone-iodine eye drops. The contralateral eye, used as control, was left untreated. Conjunctival swabs of both eyes were collected at the baseline visit and after three days of treatment, just before the cataract surgery. A qualitative and quantitative microbiological analysis of bacterial presence was evaluated by means of bacterial culture, followed by identification. Methicillin resistance determination was also performed on staphylococci isolates. Bacterial load before and after treatment of the eye candidate for cataract surgery was evaluated and compared to the untreated eye. A reduction or no regrowth on the culture media of the bacterial load was observed in 100% of the study subjects. A great heterogenicity of bacterial species was found. The 0.66% povidone-iodine eye drops, used for three days prior to cataract surgery, were effective in reducing the conjunctival bacterial load. The 0.66% povidone-iodine eye drops (IODIM®) might represent a valid perioperative prophylactic antiseptic adjuvant treatment to protect the ocular surface from microbial contamination in preparation of the surgical procedure.

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.

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&ndash, 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 &ge, 55 years. HPV positivity was higher in women (p-value &gt, 0.05) and in moderately differentiated samples (G2) (p-value &lt, 0.05). p16INK4a 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 p16INK4a 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.

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.

Background Naturally occurring variants of human papillomavirus (HPV) 58 have been defined as lineages and sublineages but little is known about the impact of this diversity on protein function. We investigated the impact of variation within the major (L1) and minor (L2) capsid proteins of HPV58 on susceptibility to neutralizing antibodies. Methods Pseudovirus (PsV) representing A1, A2, A3, B1, B2, C, D1, and D2 variants were evaluated for their susceptibility to antibodies elicited during natural infection, preclinical antisera generated against virus-like particles, and monoclonal antibodies (MAbs). Results Lineage C PsV demonstrated a decreased sensitivity to antibodies raised against lineage A antigens. Exchange of the DE, FG, and/or HI loops between sublineage A1 and lineage C demonstrated that residues within all 3 loops were essential for the differential sensitivity to natural infection antibodies, with slightly different requirements for the animal antisera and MAbs. Comparison between the HPV58 A1 L1 pentamer crystal structure and an HPV58 C homology model indicated that these differences in neutralization sensitivity were likely due to subtle epitope sequence changes rather that major structural alterations. Conclusions These data improve our understanding of the impact of natural variation on HPV58 capsid antigenicity and raise the possibility of lineage-specific serotypes.

Background: Accurate viral load (VL) determination is paramount to determine the efficacy of anti-HIV-1 therapy. The conventional method used, fit-point (FP), assumes an equal efficiency in the polymerase chain reaction (PCR) among samples that might not hold for low-input templates. An alternative approach, maxRatio, was introduced to compensate for inhibition in PCR. Methods: Herein, we assessed whether maxRatio could improve VL quantification using 2,544 QIAgen artus HI virus-1 RT-PCR reactions. The assay’s standard dilutions were used to build external standard curves with either FP or maxRatio that re-calculated the VLs. Results: FP and maxRatio were highly comparable (Pearson’s ρ=0.994, Cohen’s κ=0.885), and the combination of the two methods identified samples (n=41) with aberrant amplification profiles. Conclusions: The combination of maxRatio and FP could improve the predictive value of the assay.

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&ndash, 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 &ldquo, retesting&rdquo, 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.

The study purpose was to assess the efficacy of a preservative-free 0.6% povidone iodine eye drops as perioperative prophylactic treatment for reducing conjunctival bacterial load and the rate of needle contamination in patients undergoing intravitreal anti-vascular endothelial growth factor injection. Enrolled patients were randomized to either the study group (0.6% povidone iodine, three day-prophylactic treatment before the injection) or to the control group (placebo, three day-prophylactic treatment). Conjunctival swabs were obtained before and after the prophylactic treatment in both groups. Intravitreal injections were performed in a sterile fashion. The injection needle and a control needle were collected for microbiological culture. Data from 254 and 253 eyes in the study group and control group, respectively, were analyzed. Bacterial growth from conjunctival swab cultures was significantly lower after 0.6% povidone iodine prophylaxis compared to baseline and to placebo prophylaxis (p &lt, 0.001), showing an 82% eradication rate in the study group. No injection needle showed bacterial contamination in the study group, whereas six needles were culture-positive in the control group (p = 0.015). No serious ocular and non-ocular adverse events were recorded. The 0.6% povidone iodine solution proved an effective treatment in reducing conjunctival bacterial load and risk of needle contamination.

Purpose:To evaluate the bactericidal activity of a diluted povidone-iodine formulation (0.6%) in comparison with the most used 5% povidone-iodine solution ophthalmic preparation.Methods:In vitro bactericidal activity comparison between 0.6% povidone-iodine versus 5% povidone-iodine formulations, against these bacteria: Staphylococcus aureus ATCC 25923, Staphylococcus aureus ATCC 43300, Staphylococcus epidermidis ATCC 12228, linezolid-resistant Staphylococcus epidermidis α99 strain, a clinical isolate, Pseudomonas aeruginosa ATCC 27853, Escherichia coli ATCC 25922.Results:About 0.6% povidone-iodine formulation was demonstrated to be faster than 5% povidone-iodine preparation in killing Gram-positive as well as Gram-negative bacteria. Against a linezolid-resistant methicillin-resistant Staphylococcus epidermidis strain, 0.6% povidone-iodine formulation showed the best antiseptic efficacy requirement of 3-log10reduction in bacterial load, if compared with the 5% povidone-iodine formulation.Conclusion:Our investigation has demonstrated that the more diluted 0.6% preparation was more rapidly bactericidal than the 5% povidone-iodine formulation, most probably due to the fact that dilution from 5% to 0.6% increases the amount of free iodine. While our finding must be confirmed by in vivo clinical studies, this fact constitutes an intriguing news for what concerns the use of povidone-iodine eye drops in the ocular surface treatment before intravitreal injections as well as ophthalmic surgery.

Sexually transmitted infections (STIs) represent a major cause of morbidity in women and men worldwide. Human Papillomavirus (HPV) infections are among the most prevalent STIs and persistent infections with high-risk HPV (hrHPV) genotypes can cause cervical dysplasia and invasive cervical cancer. The association of other STIs with HPV cervical infection and/or dysplasia has however not yet been fully elucidated. The aim of this study was to assess the prevalence of HPV and other STIs among women presenting with an abnormal cervical cytology. Cervical infections with 28 HPV genotypes and seven other sexually transmitted pathogens were evaluated in 177 women referred for a colposcopy after an abnormal Pap smear. Positivity for at least one hrHPV genotype was shown in 87% of women, HPV 16 was the most prevalent (25.0%), followed by HPV 31 and HPV 51. The overall positivity for other STIs was 49.2%, with Ureaplasma parvum being the most prevalent microrganism (39.0%). Co-infections between hrHPV and other STIs were demonstrated in 17.5% of women, no significant association was demonstrated between multiple infections and the colposcopy findings. This study provides new epidemiological data on the prevalence of cervical infections associated with HPV and seven other common sexually transmitted pathogens in a population of women presenting with an abnormal cervical cytology.

Circulating HPV DNA has been previously described in women with advanced stages of cervical cancer and has been suggested to be a prognostic marker of disease recurrences and metastases. Only a few studies have reported the presence of HPV DNA in bloodstream of patients with low grade or precancerous cervical lesions. This study aimed to define if HPV DNA could be detected in plasma samples of 120 women referred for a recent history of cervical dysplasia who presented with lesions ranging from High Squamous Intraepithelial Lesion (H-SIL) to regressed normal cytology. HPV DNA detection was carried out in both plasma and cervical samples using type-specific real-time quantitative PCR assays identifying oncogenic HPV 16, 18, 31, 33, 45, 51 and 52. Overall, 34.2% (41/120) of plasma samples were shown to be positive for HPV DNA detection; HPV 45 (46.3%), HPV-51 (29.6%), and HPV 16 (18.5%) were the most frequently identified genotypes. The rate of HPV detection in paired cervical and plasma samples increased with advancing disease stage, ranging from 15.4% in women with regressed lesions to 38.9% in women with HSIL; HPV 16 resulted the most common genotype identified in women found to be HPV DNA positive in both cervical and plasma samples. Moreover, HPV 16 showed the highest median viral load value in both cervical and plasma samples, with 48,313 copies/104 cells and 1,099 copies/ml, respectively. Results obtained in this study confirm that HPV DNA can be detected and quantified in plasma samples of women with asymptomatic cervical infection. Further knowledge on HPV dissemination through the blood stream of women with cervical lesions would be very important in better understanding the natural history of HPV infection as well as its potential role in other distant tumors.

Antimicrobial resistance is one of the major and growing concerns in hospital- and community acquired infections, and new antimicrobial agents are therefore urgently required. It was reported that oxidative stress could contribute to the selection of resistant bacterial strains, since reactive oxygen species (ROS) revealed to be an essential driving force. In the present work 4-alkylidene-azetidinones, a new class of antibacterial agents, were functionalized with phytochemical polyphenolic acids such as protocatechuic, piperonyl, caffeic, ferulic, or sinapic acids and investigated as dual target antibacterial-antioxidant compounds. The best candidates showed good activities against multidrug resistant clinical isolates of MRSA (MICs 2–8 μg/mL). Among the new compounds, two revealed the best antioxidant capacity with TEAC-DPPH and TEAC-ABTS being significantly more active than Trolox®.

SUMMARYThe aim of this study was to investigate the epidemiological profile of HPV oropharyngeal infections in HIV-infected men who have sex with men. A total of 135 subjects were enrolled at the L. Sacco University Hospital (Milan, Italy) to evaluate their HPV oropharyngeal infection status at baseline and at a follow-up visit at least 12 months later. HPV DNA was detected from oropharyngeal swabs using an in-house nested PCR that amplifies a segment of the L1 gene. The PCR products were then sequenced and genotyped. A greater percentage of high-risk genotypes was identified compared to low-risk genotypes (13·7% vs. 6·9%, P < 0·05), and two uncommon alpha-HPV genotypes were detected, i.e. HPV-102 and HPV-114. HPV infection prevalence was 24·4% and the cumulative incidence was 24·1%. During the follow-up period, one case of HPV infection (HPV-33) persisted, while the overall rate of infection clearance was 58·3%. HPV oropharyngeal infection was widespread in the cohort examined, and most of the infections were transient and cleared within 12 months. These results may help to clarify the role of HPV in the oropharynx and may also improve our understanding of the need to implement preventive strategies in at-risk populations.

A major limitation when reconstructing the origin and evolution of HPV-16 is the lack of reliable substitution rate estimates for the viral genes. On the basis of the hypothesis of human HPV-16 co-divergence, we estimated a mean evolutionary rate of 1.47 × 10-7 (95% HPD = 0.64-2.47 × 10-7) subs/site/year for the viral LCR region. The results of a Bayesian phylogeographical analysis suggest that the currently circulating HPV-16 most probably originated in Africa about 110 thousand years ago (Kya), before giving rise to four known geographical lineages: the Asian/European lineage, which most probably originated in Asia a mean 38 Kya, and the Asian/American and two African lineages, which probably respectively originated about 33 and 27 Kya. These data closely reflect current hypotheses concerning modern human expansion based on studies of mitochondrial DNA phylogeny. The correlation between ancient human migration and the present HPV phylogeny may be explained by the co-existence of modes of transmission other than sexual transmission.

Background: Migrant women are one of the most vulnerable population to health problems and well-being. This study aimed at implementing a counseling and preventive strategy for sexually transmitted infections (STIs) in undocumented migrant women in Milan, Italy. Methods: Women (ages 18–65) were enrolled at the NAGA Centre (2012–2013) and asked for a urine sample in order to carry out molecular detection of Human papillomavirus (HPV), Chlamydia trachomatis (Ct), Trichomonas vaginalis (Tv), Neisseria gonorrhoeae (Ng)-DNA. Socio-demographic and sexual behavior information were collected. All HPV/Ct+ women were offered Pap tests and/or were prescribed antibiotic treatment. Results: 537/757 women participated in the study (acceptability rate: 70.9%). Most of the women were from Latin America (45.6%) and Eastern Europe (30.7%); >60% of them had stable partners, did not use contraception and had had at least one pregnancy. The prevalence rates of HPV, Ct, Tv and Ng infections were 24.2%, 7.8%, 4.8% and 0%, respectively. In all, 43.2% of the positive women agreed to undergo a gynecological examination and accepted suitable treatment. Conclusions: This study shows an overall high prevalence of STIs in undocumented migrant women in Milan. The screening strategy based on counseling and urine testing contributed to the successfully high acceptability rate. More appropriate health services that adequately address all aspects of women’s health are required.