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OBJECTIVE: The objective of this study was to assess safety, satisfaction, and anti- viral effect of a new carrageenan-based vaginal microbicide in a population of fertile female patients with genital human papillomavirus (HPV) infection. PATIENTS AND METHODS: Forty healthy and sexually active women aged 18-45 years with genital HPV infection were enrolled. Each subject was treated with a gel formulated with 0.02% carrageenan and Propionibacterium extract (CGP) (Carvir, Depofarma SpA, Mogliano Veneto, Treviso, Italy). The subjects were evaluated at baseline, after the I cycle of therapy and after the II cycle. At final status, treatment acceptability and satisfaction were evaluated using a 5-point Likert scale. Furthermore, the rate of HPV genital infection clearance at final follow-up was evaluated. These data were compared with the HPV genital infection clearance rate in a control group of patients not subjected to any therapy. RESULTS: Overall, 68 HPV infections were detected at baseline, among 40 subjects enrolled. The HPV 16 genotype was the most frequent (12%) followed by HPV 18 (10%), and HPV 53 (9%). At the end of the study, 22 (55%) patients were very satisfied, 14 (35%) were satisfied, 3 (7.5%) were uncertain, and only 1 (2.5%) was dissatisfied, with 0 very dissatisfied. Only 2 patients complained of a local adverse event. Analysing infection clearance at the end of the study, 60% of patients became HPV negative. Among these, 13 cases were high-risk HPV infection. There were 16 patients with persistent infection (“non-responders”). No patient developed a “de novo” genital lesion. After controlling for age, the intervention had an adjusted OR of 4.9 (95% CI 1.6-15.1) to clear HPV. CONCLUSIONS: The results of this work suggest that Carvir vulvovaginal microbicide gel is safe and well-tolerated. Furthermore, this experience supports the hypothesis that CG has a role in accelerating the normal clearance of genital HPV infection in women with a positive HPV-DNA test.

to investigate the reliability of laryngeal reflux finding score (RFS) and symptom index (RSI) in assessing gastroesophageal reflux (GER) in children and infants.patients with laryngeal or respiratory symptoms, who underwent laryngoscopy and esophageal pH-impedance (MII-pH) were recruited. RSI and RFS were correlated to MII-pH results. A RSI13, RFS7, acid exposure index7%, total reflux episodes100/24 h in infants or70/24 h in children, or a positive symptom index or association probability, were considered pathological. Analysis considering age (/12 months) was performed. Sensitivity, specificity, positive (PPV) and negative predictive values (NPV) of the laryngeal scores were calculated.197 children (median 53 months, 61 infants) were enrolled. MII-pH was pathological in 5/10 patients with RFS7, and in 17/31 with RSI13. RFS7 had 3.9% sensitivity, 93% specificity, a PPV of 50 and a NPV of 34 in predicting GER disease. RFS was inversely associated to weakly acidic and proximal GER. RSI13 had 13% sensitivity, 83% specificity, and a PPV and NPV similar to RFS. RSI was significantly associated with the number of acid reflux episodes, and, in infants, with bolus exposure index.RSI and RFS aren't accurate in predicting GER in infants and children. Acid reflux relates to laryngeal symptoms, but neither acid, nor proximal and weakly acidic GER relate to laryngeal alterations.

We aimed to evaluate if in oral squamous cell carcinoma (OSCC) there is a relationship between histological grading (HG), TNM clinical stage and HPV infection; and to study the performance of fuzzy logic compared to traditional statistics, in the analysis of HPV status and correlates of OSCC. In cross-sectional analysis, the study group comprised 63 patients (mean age 68.89 years (SD ± 11.78), range (32–93); males 28 (44.4%), females 35 (55.6%)) with OSCC histologically diagnosed. HPV-DNA was studied in exfoliated oral epithelial cells by nested PCR (MY09/MY11 and GP5+/GP6+ primers). Data were analysed in parallel by traditional statistics with multivariate analysis and a fuzzy logic (FL) technique (membership functions as input, the ANFIS methodology, and the Sugeno’s model of first order). HPV infection was detected in 24/63 (38.1%) of OSCC, as being HPV+ve 14/36 (38.9%) in G1, 7/18 (38.9%) in G2, and 3/9 (33.3%) in G3; HPV+ve 8/33 (24.2%) in Stage I, 9/12 (75.0%) in Stage II, 6/11(54.5%) in Stage III, and 1/7 (14.3%) in Stage IV. In both methods of analysis, no significantly increased risk of HPV infection was found for any HG score; whereas, TNM stage II was significantly associated to HPV infection (p = 0.004; OR = 9.375 (95% CI = 2.030:43.30); OR0 = 11.148 (95% CI = 1.951:43.30)), and, in particular, to primary tumour size T2 (p = 0.0036; OR = 7.812 (95% CI = 1.914:31.890); OR0 = 9.414 (95% CI = 1.846:48.013)); FL (% of prevision: 79.8; Root MeanSquare Error (RMSE): 0.29). No association was found between HPV infection and any demographical variable. Our findings show an association between HPV infection with TNM (stage II – T2), but not with histological grading of OSCC. Also, FL seems to be an additional effective tool in analysing the relationship of HPV infection with correlates of OSCC. c 2005 Elsevier Ltd. All rights reserved.

Sexually transmitted infections (STIs) are a serious global health problem. In Italy, data describing the vulnerability to STIs of specific sexual minorities and the influence of sociodemographic and behavioral determinants are limited, as most infections are not subject to mandatory notification. This retrospective study describes the sociodemographic profile and main sexual behaviors of patients attending a hospital in Palermo (Sicily, Italy) from January 2018 to March 2019 as predictors of STI risk. Patients were divided in subgroups: men-who-have-sex-with-men (MSM), men-who-have-sex-with-women (MSW), bisexual men and females. Data were obtained through an anonymous questionnaire. Patients were tested for chlamydia, syphilis, Mycoplasma genitalium infection, genital herpes and HPV infection. A total of 294 subjects with STIs (male/female ratio about 2:1) were screened. Of the total sample, 79.6% of patients were Italian. MSM accounted for 34.3%, MSW for 29.6%, bisexual men for 5.8% and females for 30.3%. A total of 44.5% of patients had a high education level, 42.5% reported irregular use of condoms, 20.7% reported having had 5–10 partners in the six months prior to the visit and 32.9% were HIV-positive. HPV infection and syphilis were the most prevalent STIs. Conclusions: The most common profile of patients attending our clinic was that of an adult, Italian man with a high level of education, poor use of condoms and a high number of partners. MSM had the highest sex-behavior-related risk for STIs. In addition, our results suggest that all STD teams need to implement counselling topics and recommendations to share with patients, as well as tips on how to approach sexual health education/counselling, thereby promoting patient-centered approaches and educational programs.

In August 2015, Dipodascus capitatus was isolated from two patients admitted to the neonatal intensive care unit. Nosocomial acquisition of the fungus was suspected and epidemiological studies were undertaken. The patients were simultaneously hospitalized, and the comparison of the two isolates by two independent molecular typing methods have confirmed clonal dissemination of a single strain of D. capitatus. Antimicrobial susceptibility testing was useful for identifying the appropriated antifungal therapy in micafungin. To our knowledge these are the first described cases of neonatal D. capitatus infection and also the first report of successful treatment by micafungin.

While bivalent and quadrivalent HPV vaccines have been used for about 10 years, a nonavalent vaccine against HPV types 6/11/16/18/31/33/45/52 and 58 has been recently approved by FDA and EMA and is now commercially available. The objective of our study was to evaluate the potential impact of the nonavalent vaccine on HPV infection and related low- and high-grade squamous intraepithelial lesions (LSIL, HSIL), compared to the impact of the quadrivalent vaccine, in a female population living in Sicily (Italy). Low estimates of HPV vaccine impact were calculated as prevalence of HPV 6/11/16/18/31/33/45/52 and 58 genotypes, alone or in association, but excluding presence of other HPV types; high estimates were calculated as prevalence of HPV 6/11/16/18/31/33/45/52 and 58 genotypes alone or in association, in the presence of other HPV types. The nonavalent HPV vaccine showed increased impact, compared to the quadrivalent vaccine. Estimates of potential impact varied from 30.9% (low estimate) to 53.3% (high estimate) for LSIL, and from 56.9% to 81,0% for HSIL. The proportion of additional cases potentially prevented by the nonavalent vaccine was 14.4%–23.8% for LSIL, and 19.0%–32.8% for HSIL. The benefit of the nonavalent vaccine compared to the quadrivalent vaccine was more than 80% for both low and high impact estimates for LSIL and more than 50% for both low and high impact estimates for HSIL. The present study confirms that the switch from a first generation HPV vaccines to a nonavalent vaccine would increase the prevention of cervical HSIL in up to 90% of cases.

Infection with High Risk (HR) Human Papillomaviruses (HPVs) is the main aetiological agent of Cervical Squamous Cell Carcinoma (CSCC) and also associated in a subgroup of other neoplasms, including Oropharyngeal Squamous cell Carcinoma (OPSCC). HPV infection, in genital as in oral mucosa, can also be subclinical or associated with benign proliferative lesions (common warts, condylomas, papillomas) caused mostly by infection with Low Risk (LR)-HPVs. In the last decades, extensive research has resulted in growing knowledge on HPV biology and specifically viral life cycle, biochemical properties of viral proteins and their interaction with the host proteins leading to potential new targets of prophylactic or therapeutic vaccines and therapies for HPV infection. In addition, notable progresses have been made in the field of diagnostics to detect HPV DNA or RNA. The recent epidemiological data suggest the significant changes in HPV endemic, due to the changes in sexual habits especially among young generations (i.e. early sexual debuts, multiple sexual partners, oral and anal sex); this scenario has urged on the need of adequate campaigns of primary (sexual education, vaccination programs) and secondary prevention (diagnostics of HPV-related diseases). Due to the growing interest on HPV infection and HPV related cancers, the authors made a narrative review of the literature on oral HPV infection and oral-genital transmission. After this, in view of the controversies about the strategies of therapy and prevention of HPV infection, the present review focuses on the current state of art about the available tools for the therapeutic and, if any, preventive management of oral HPV infection.

Human papillomavirus (HPV) infection is the commonest sexually transmitted infection, and high-risk HPV types are associated with cervical carcinogenesis. This study investigated: the HPV type-specific prevalence in 970 women with an abnormal cytological diagnosis; and the association of HPV infection and cervical disease in a subset of 626 women with a histological diagnosis. HPV-DNA was researched by nested PCR/sequencing and the INNOLiPA HPV Genotyping assay. The data were analysed by the chi-square test (p ? 0.05 significant). Overall, the HPV prevalence was 37.7%; high-risk genotypes were found in 88.5% of women and multiple-type infections in 30.9% of the HPV-positive women. The commonest types were HPV-16 (8.2%), HPV-6 (5.0%), HPV-51 (4.2%) and HPV-53 (3.6%). Among the women with histological diagnosis, HPV was evident in 19.9% of those without lesions, 65.8% of those with low-grade lesions and 100% (p = 0.002) of those with high-grade lesions. The commonest types were HPV-16 (in 14.7% low-grade and 42.8% high-grade lesions), HPV-31 (4.7% and 14.3%, respectively) and HPV-33 (2.0% and 14.3%, respectively). Two high-grade lesions contained exclusively one uncommon type, namely, HPV-83 and -85. This study confirmed the high prevalence of HPV infection and high-risk genotypes among women with cervical abnormalities living in Italy. These data may contribute to increasing the knowledge of HPV epidemiology and designing adequate vaccine strategies. © 2008 Elsevier B.V. All rights reserved.

Introduction: Adequate brushing of oral mucosa is important for accurate human papillomavirus (HPV) detection in potentially malignant (oral leukoplakia [OL], oral lichen planus [OLP]) and malignant (oral squamous cell carcinoma [OSCC]) lesions. Since various factors may limit the adequacy of oral brushing and, consequently, the accuracy of HPV detection, modified sampling procedures should be evaluated for their effect on HPV frequency and/or types detected. Aim: To compare the HPV frequency in samples obtained by brushing the lesion site with the frequency in samples obtained by brushing an apparently normal adjacent site. The correlation between HPV frequency and keratinization of the site affected by the lesion, as well as sociodemographic variables (age, sex, smoking and drinking habits), was also examined. Methods: HPV DNA was detected in brushing samples from 50 patients with OL, 49 with OLP, and 17 with OSCC. Polymerase chain reaction (PCR) amplification was performed by MY09/MY11 and GP05+/GP06+ primers; the HPV type was identified by DNA sequencing and a reverse hybridization (line probe) assay. Data were analyzed by the Z test, the Fisher’s exact test, the chi-square test, odds ratio (OR), and a logistic regression model. Results: HPV DNA was detected in 22% of samples from lesion sites and in 16% of samples from adjacent sites (p = 0.22) in patients with OL, in 24.5% and 22.4% of samples from lesion and adjacent sites, respectively, in patients with OLP (p = 0.40), and in 35.3% and 41.2% of samples from lesion and adjacent sites, respectively, in patients with OSCC (p = 0.36). Lesions adjacent to HPV-positive normal sites had an increased rate of HPV detection (OR = 30; 95% CI 9.57, 94.1). HPV-18 was the most frequent genotype, followed by HPV-6, -16, -33, and -53. HPV prevalence was reduced in lesions at keratinized sites (14.5%) compared with non-keratinized sites (34.4%; p = 0.007; OR = 0.32; 95% CI 0.13, 0.81). Discussion: In patients with OL, OLP, or OSCC, a high prevalence of HPV infection was shown in apparently normal sites adjacent to lesion sites infected by HPV. The lower HPV frequency in lesions at keratinized sites suggests that HPV detection by lesion brushing is affected by keratinization. The keratinized epithelium may be less susceptible to HPV infection or, alternatively, the highly proliferative activity in non-keratinized sites may predispose to HPV infection. Conclusion: Results from this study indicate that taking samples from normal sites adjacent to oral lesions may be of value in HPV detection, particularly when the lesions are located at keratinized sites. This sampling procedure may allow more accurate diagnosis of HPV infection compared with sampling only the lesion site, and may also represent a reliable method to investigate the biological characteristics of HPV infection and related oral carcinogenesis.

A retrospective analysis by molecular-sequence-based techniques was performed to correctly identify the etiological agent of 24 Mediterranean spotted fever cases occurring in Western Sicily, Italy, from 1987 to 2001. Restriction analysis of a 632-bp PCR-amplified portion of the ompA gene allowed presumptive identification of five clinical isolates as belonging to Rickettsia conorii subsp. israelensis , the etiological agent of Israeli spotted fever (ISF). The remaining 19 rickettsial isolates were Rickettsia conorii subsp. conorii , the only pathogenic rickettsia of the spotted fever group reported in Italy until the present. Sequence analysis of the ompA gene confirmed the identification of all the R. conorii subsp. israelensis isolates and demonstrated that rickettsiosis caused by R. conorii subsp. israelensis can be traced back to 1991 in Sicily. The recorded clinical data of the five ISF patients support the idea that these strains could correlate to more-severe forms of human disease. Three of five patients experienced severe disease, and one of them died.

Human papillomavirus (HPV) 58 accounts for a notable proportion of cervical cancers in East Asia and parts of Latin America, but it is uncommon elsewhere. The reason for such ethnogeographical predilection is unknown. In our study, nucleotide sequences of E6 and E7 genes of 401 HPV58 isolates collected from 15 countries/cities across four continents were examined. Phylogenetic relationship, geographical distribution and risk association of nucleotide sequence variations were analyzed. We found that the E6 genes of HPV58 variants were more conserved than E7. Thus, E6 is a more appropriate target for type-specific detection, whereas E7 is more appropriate for strain differentiation. The frequency of sequence variation varied geographically. Africa had significantly more isolates with E6-367A (D86E) but significantly less isolates with E6-203G, -245G, -367C (prototype-like) than other regions (p ≤ 0.003). E7-632T, -760A (T20I, G63S) was more frequently found in Asia, and E7-793G (T74A) was more frequent in Africa (p < 0.001). Variants with T20I and G63S substitutions at E7 conferred a significantly higher risk for cervical intraepithelial neoplasia grade III and invasive cervical cancer compared to other HPV58 variants (odds ratio = 4.44, p = 0.007). In conclusion, T20I and/or G63S substitution(s) at E7 of HPV58 is/are associated with a higher risk for cervical neoplasia. These substitutions are more commonly found in Asia and the Americas, which may account for the higher disease attribution of HPV58 in these areas.

Giant cell arteritis is an inflammatory vasculopathy that preferentially affects medium-sized and large arteries. A viral cause has been suspected but not confirmed in polymyalgia rheumatica and giant-cell arteritis. We report the case of a 81-year-old female who suffered from chronic active Epstein-Barr virus infection and developed giant cell temporal arteritis.

The concordance of human papillomavirus (HPV) groups and types was evaluated in 45 sexual couples with both partners HPV infected, by analyzing cervical samples from women and three genital sites (penile brushing, urethral brushing, and semen) from men. When grouping HPV types, no significant HPV group sharing was found between partners, either considering samples from any male site (concordance: 55.5%; P = 0.11) or from each site (concordance by penile brushing, 37.8%; urethral brushing, 24.5%; semen, 22.3%; P > 0.05). Examining individual HPV types, using samples from any male site, concordance was found in 29 (64.4%; P = 0.036) couples; significant concordance was evident for 16 HPV genotypes, the most frequent being HPV-6, -66, -31, -51, and -53. Using samples from specific male sites, concordance was found by penile brushing in 24 (53.3%) couples, urethral brushing in 16 (35.5%), and semen in 7 (15.5%; P = 0.014). Among the 16 HPV types shared by examining samples from any male site, 9 (56.3%) were in common by penile brushing, 11 (68.7%) by urethral brushing, and 6 (37.5%; P = 0.48) by semen. Combined penile brushing and urethral brushing sampling identified all the 29 couples concordant by the three male sites; combined penile brushing and semen detected 26 (89.6%) concordant couples. The most adequate approach to the assessment of HPV concordance in sexual couples could be based on the analysis of individual HPV types and the sampling of men by penile brushing combined with urethral brushing. The high and significant degree of HPV type-specific concordance confirms HPV transmission between sexual partners. J. Med. Virol. 79:1882–1888, 2007. © 2007 Wiley-Liss, Inc.

To evaluate in oral leukoplakia the relationship between HPV infection and markers of apoptosis (bcl-2, survivin) and proliferation (PCNA), also conditionally to age, gender, smoking and drinking habits of patients, by means of Fuzzy neural networks (FNN) system 21 cases of oral leukopakia, clinically and histologically diagnosed, were examined for HPV DNA presence, bcl-2, survivin and PCNA expression. HPV DNA was investigated in exfoliated oral mucosa cells by nested PCR (nPCR: MY09-MY11/GP5-GP6), and the HPV genotype determined by direct DNA sequencing. All markers were investigated by means of standardised immunohistochemistry procedure. Data were analysed by chi-square test, crude OR and the 95% Cl; in blindness, FNN was applied. HPV DNA was found in 8/21 OL (38.1%); survivin, PCNA, and tobacco smoking were associated in univariate analysis (p = 0.04) with HPV DNA status. HPV-18 was the most frequently detected genotype (6/8), followed by HPV-16 (2/8). FNN revealed that survivin and PCNA, both being expressed in all of OL HPV+ve, were associated with HPV infection. In conclusion, the FNN allowed to hypothesise a model of specific variables associated to HPV infection in OL. The relevance of survivin and PCNA suggest that they may be involved in HPV-mediated deregulation of epithelial maturation and, conversely, that HPV may have a role in the expression level of these two markers. FNN system seems to be an effective tool. in the analysis of correlates of OL and HPV infection. (c) 2005 Elsevier Ltd. All rights reserved.

Background and objectives: The current study compared the cervical cytological sub-category “atypical squamous cells of undetermined significance-favour reactive (AFR)”, recently recommended to be eliminated by the Bethesda system, to the sub-category “atypical squamous cells of undetermined significance-favour dysplasia (ASC-US)”, in terms of prevalence of coexistent squamous intraepithelial lesions of either low-grade (LSIL) or high-grade (HSIL) and rate of human papillomavirus (HPV) infection. Study design: One hundred women with AFR and 100 with ASC-US were consecutively included in the study. All patients underwent colposcopy, followed by biopsy when necessary, and were screened for HPV infection by the combined use of Hybrid Capture II (DIGENE) and PCR with MY09/11 primers, the latter followed by direct sequencing of the amplifications products for HPV genotyping. Results: LSIL were detected in 5.6% of AFR and 18.5% of ASC-US ( p = 0.00812), HSIL only in 4.3% of ASC-US. HPV infection was diagnosed in 11.2% of AFR and 38.0% of ASC-US ( p = 0.00003); high-risk HPV types (namely, HPV-16, -18, -31, -66, -67 and -70) were found in 6.7% of AFR and 22.8% of ASC-US ( p = 0.00239). Evidence of HPV infection in absence of SIL was proven in 7.1% of AFR and in 22.5% of ASC-US ( p = 0.00622). Conclusion: The association of AFR with SIL and high-risk HPV infection is low but not inexistent. Thus, to avoid the risk of leaving some high-risk AFR patients untreated or without follow-up, it could be proposed to keep AFR as a cytological category and to triage it by HPV testing, similarly to what has been already recommended for ASC-US.

Proliferative verrucous leukoplakia (PVL) is a very aggressive form of oral leukoplakia (OL) with high morbidity and mortality rates, hypothesised to be linked to HPV infection. This study aimed to determine the presence of HPV DNA in PVL in comparison with OL, and in relation to social-demographical variables (age, gender, smoking and drinking habits) in an Italian multi-centric hospital-based study. The study group consisted of 58 cases of PVL and 90 cases of OL as controls (47 homogeneous (H) and 43 non-homogeneous (non-H) form), both recruited from four Italian cohorts. HPV DNA was identified in exfoliated mucosal cells by nested PCR (nPCR) with MY09/MY11 and GP5+/GP6+ primer pairs and the HPV genotype determined by direct DNA sequencing. HPV DNA was found in 24.1% (14/58)of PVL and in 25.5% (23/90) of OL; there was thus no significant difference found between PVL and OL (both forms) for risk of HPV infection (OR=0.93; 95% IC:0.432-1.985). Similarly, in both groups of PVL and OL lesions, no statistic association was found between any demographical variable considered and HPV infection. HPV-18 was the most frequently detected genotype in all tissues, being found in 78.5% and 60.8% of HPV+ve PVL and OL, respectively. Other more rarely detected genotypes were HPV-16 (28.6% in PVL and 13% in OL), HPV-6 (17.4% in OL) and HPV-53 (8.8% in OL). PVL does not appear more likely to be associated to HPV infection than conventional OL lesions.

An antiserum against a hsp of the 70-kDa family was prepared, by means of a fusion protein, which was able to detect a constitutive 75-kDa hsc in the sea urchinP. lividus.This hsc was present both during oogenesis and at all developmental stages. A two-dimensional electrophoresis has revealed four isolectric forms of this 75-kDa hsc. The amino acid sequence of the fragment used to prepare the anti-hsp70 antibodies revealed a 43% identity with the corresponding part of sea urchin sperm receptor, and in mature eggs a brighter immunofluorescence was seen all around the cell cortex where the receptor for sea urchin sperm is localized. In oocytes the hsp75 was localized in the cytoplasms but not in the nuclei. In the embryos a higher hsp75 concentration was found in the portion facing the lumen of the cells which invaginate at gastrulation.