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Objective. Human Papillomavirus (HPV)-induced oropharyngeal squamous cell carcinoma (OPSCC) represents an increasing tumor entity with typical clinical and histopathological features, associated with a rising incidence and improved prognosis (1). Detection of HPV-DNA is the most widely used method to diagnose HPV infection in clinical samples. Commercially available diagnostic assays show variable sensitivity and specificity and no international standards have been proposed yet (2). The main purpose of this preliminary study was to evaluate the reliability of EasyPap Direct HPV DNA Test (Ulisse BioMed) on formalin-fixed paraffin-embedded samples (FFPE), despite this test has been designed to work in vaginal mucus, where preliminary data showed a sensitivity of 97%. The test is real-time PCR based, it does not require DNA extraction and it can perform high-risk HPV genotyping. Kit performances have been compared with a commercial kit which requires DNA extraction. Materials and Methods. This pilot study included 38 cases of OPSCC that were surgically treated in our institute. Tumor samples were fixed in buffered formalin, embedded in paraffin and stored at room temperature for 1-13 years (mean storage period 4 ± 4 years). In order to confirm histology and lesion grade, all samples were reviewed by hematoxylin-eosin staining. DNA extraction has been performed starting from FFPE samples through QIAamp® DNA FFPE Tissue Kit (Qiagen, Hilden, Germany) and HPV has been typed through Real Time PCR HPV sign® Pyro Mark System Q96 IDTM (CE-IVD Diatech Pharmacogentetics Iesi Italy). We found 16 cases positive for HPV16, 1 case positive for HPV35 and 21 HPV negative samples. In order to perform HPV detection through EasyPap Direct HPV DNA test, samples underwent deparaffinization with xylene and rehydration with ethanol. Genotyping data were compared to those obtained with Qiagen kit. Results. EasyPap Direct HPV DNA test identified 16 HPVpositive cases and 22 HPV negative cases. Genotyping data showed that 15 samples were HPV16 and 1 sample was HPV35 positive. Concordance analysis showed an agreement- coefficient Kappa Cohen K=0.95 IC95% [0.84-1.00] (excellent agreement, Fleiss classification). The sensibility and specificity of the EasyPap HPV DNA test was 94.1% (95%, confidence interval 80.1%-98.8%) and 100% (95%, confidence interval 88.6%-100%), respectively. The positive predictive value was 100% (95%, confidence interval 88.6%-100%) and the negative predictive value was 95.5% (95% confidence interval, 81.9%-99.3%). Conclusions. Hitherto it was well known that DNA extraction contributes to increase the sensitivity of PCR-based HPV test starting from FFPE tissue samples (3). Despite small sample size has been analyzed, preliminary data obtained through EasyPap Direct HPV DNA test successfully showed that high sensitivity and specificity can be achieved without DNA extraction, with a remarkable decrease of assay cost and time. These results lead us to perform large scale EasyPap testing.

OBJECTIVE. Human Papillomavirus (HPV)-related squamous cell carcinoma of the oropharynx (HPV-OPSCC) usually originates from the reticulated epithelium lining the crypts of Waldeyer’s ring. The increasing epidemiologic evidence of this type of tumors and the peculiar positive prognosis, suggested to introduce a dedicated staging system (1). The 8th edition of the American Joint Committe on Cancer (AJCC) staging manual presented a new classification to discriminate HPV-related cancers based on p16 over-expression, since it demonstrated to be an important biomarker (2). The detection of HPV-DNA could not be used as a defining factor due to its cost and lack of universal applicability. The main purpose of this preliminary study was to evaluate the concordance between the results of immunohistochemistry for p16 overexpression and the HPV-DNA detection performed with a commercial kit as control. MATERIALS AND METHODS. We retrospectively collected 32 cases of OPSCC diagnosed in 2016 at the Academic Hospital of Cattinara in Trieste, whose samples had been tested with Real Time PCR (Pyro Mark System Q96 IDTM - CE-IVD Diatech Pharmacogentetics Iesi Italy). The study was performed using tumor samples fixed in buffered formalin, embedded in paraffin and stored at room temperature for 6 to 18 months. All samples were selected by a pathologist based on sections stained with hematoxylin and eosin to confirm the adequacy of the tissue. The samples were tested for p16 by immunohistochemistry (CINtech® p16 Histology E6H4 ROCHE) and the positivity was assessed when nuclear expression was ≥+2/+3 intensity and ≥75% distribution according to the 8th edition of the AJCC staging manual. In the context of oropharyngeal cancer, the optimal cut-off for p16 overexpression is ≥+2/+3 intensity (+/- cytoplasmic staining) with ≥75% distribution. RESULTS. Seven cases were excluded because of lack of histological stored material for p16 immunohistochemical analysis (only cytological specimen). Among the remaining 25 cases, there were 5 HPV-positive and 20 HPV-negative tumors. The sensibility and specificity of the p16 immunostaining was equal to 100% (95%, confidence interval 83.4%-100%) and 100% (95%, confidence interval 83.4%-97.8%), respectively; the positive predictive value was 100% (95%, confidence interval 83.4%-100%) and the negative predictive value 100% (95% confidence interval, 83.4%-100%). CONCLUSIONS. In agreement with the literature, p16 overexpression demonstrated to be a reliable parameter to identify the cases of OPSCC in which performing an in-depth analysis by means the detection of HPV-DNA would be indicated. Indeed, it is widely known that the association of p16 immunostaining and HPV-DNA detection by quantitative PCR increases the prognostic discriminator (3). We intend to carry on this study adopting a prospective design increasing the sample size and the test accuracy.

l cancro di intervallo (CI) è un’entità patologica che viene descritta solo nell’ambito dei programmi di screening organizzato. Si intende per CI un carcinoma successivo ad un processo di screening negativo e comparso prima del passaggio di screening successivo. Qualsiasi sia la motivazione della loro genesi, i CI rappresentano un insuccesso del programma di screening che, in teoria, mira a diagnosticare tutti i carcinomi in fase di screening, e a non consentire la comparsa di CI. L’analisi dei CI (loro frequenza di comparsa nel tempo, caratteristiche morfologiche e cliniche, revisione della precedente mammografia di screening) è un momento fondamentale della valutazione di performance dello screening.Per questo motivo a 10 anni dall’attivazione del programma di Screening a Trieste, si è voluto confrontare i fattori prognostici dei carcinomi screening-detected (CSD) e dei (CI), alla luce dell’ampio dibattito in letteratura riguardo la maggior aggressività di questi ultimi.

Gli indicatori relativi ai tempi di attesa sono difficili da rispettare, come recentemente evidenziato al XIII Convegno ONS 2015 . Per questo motivo è fondamentale identificare in quale momento della gestione dei carcinomi screening-detected si concentrino i ritardi e stabilirne le cause (se attribuibili alla paziente o all’organizzazione del programma o intrinseci al tipo di lesione) così da proporre mirate modifiche migliorative. Metodi: L’analisi riguarda 146 carcinomi screening-detected consecutivi (biennio 2013-2014). Sono stati misurati i tempi tra le varie fasi diagnostiche (Mammografia di I° livello, Richiamo II° livello, I° approfondimento cito/microistologico, Comunicazione diagnosi) e i tempi chirurgici (Visita chirurgica, Intervento chirurgico, Referto istologico con marcatori biologici, Visita oncologica). Per ogni fase sono stati calcolati i tempi medi/mediani rappresentati tramite box plot e giustificati gli outliers.Risultati: La latenza nella presa in carico chirurgica è legato alla complessità degli esami preoperatori (3) (tempo mediano tra richiamo al II° livello ed intervento: 53 giorni (se unico esame pre-operatorio) vs 73 (se più di un esame pre-operatorio, p

Background: Spontaneous reporting of suspected adverse drug reactions (ADR) is considered the eornerstone of pharrnacovigilance as it allows to assess the risklbenefit ratio of alI marketed drugs. Regional health service has arranged numerous initiatives aimed at promoting the culture of pharrnacovigilance and the participation of ali health care professiona!s. Aim: To describe the evolution of spontaneous reporting in the EmiliaRomagna Region (ERR) in the period 2001-2010 through qualitative (e.g. proper compìlation of the report form) and quantitative indicators (number of annua! reports for Local Health Authority, source of the report, etc). Metbod: Data of regìonal spontaneous reporting 2001-2010 were extracted from the National Network of Pharrnacovigilance of the Italian Drug Agency (AIFA). Drugs were classified according to the ATC classification (Anatomical Therapeutic Chemica! Classification System). For the analysis of adverse drug reactions the dictionary of terminology of Regulatory Agencies MedDRA was used. Results: The contributìon of the Region in the decade was approximately lO % of the national amount (9,633 out of 99,321), with 8 reports per 100 physicians and 230 per million inhabitants. The number of national and regional reports progressively decreased from 200 1 onwards and then retumed to grow in recent years. Strong differences between the individuai Local Health Authorities were identified. The reports concerned more females than males (FIM ratio 1.3: l) and age classes 0-2 and 60-80 years. Hospital doctors were the main source of reports, followed by generai physicians while it is still negligible the contribution by nurses and pharmacists. 2,556 reports (26.5 %) were c1assified as serious and 125 cases were lethal (4.9 % of serious ADRs and 1.3 % of ali regional reports). Iomeprol, amoxicillinlclavulanic acid, lenalidomide and ticlopidine were the most reported suspected drngs. Several serious cases involved vaccines. Discussion: ERR contributes most to the national pharmacovigilance system. Several initiatives launched in recent years allowed to involve in the spontaneous reporting system nurses and pharmacists who in the past underestimated the importance of monitoring the safety of drngs, but there is considerable room for improvement. Generai practitioners lost their major role in spontaneous reporting, probably due to the loss of patenes of drugs and also for the marketing of new drugs made for hospital use only. Conclusion: The pharmacovigilance system of ERR participates in the periodic signal analysis, therefore the quality of the data and the number of reports are essenti al for the emergence of these signals that allow to reevaluate the safety profile of marketed drugs in the primary interest of public health.