Oral HPV Infection: Current Strategies for Prevention and Therapy

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

The use of IM in research: the IM-SA study

Dati di Modena della multicentrica europe

Shape memory nanocomposite of poly(L-lactic acid)/graphene nanoplatelets triggered by infrared light and thermal heating

In this study, the effect of graphene nanoplatelets (GNPs) on the shape memory properties of poly(L-lactic acid) (PLLA) was studied. In addition to thermal activation, the possibility of infrared actuating of thermo-responsive shape memory PLLA/GNPs nanocomposite was investigated. The incorporated GNPs were expected to absorb infrared wave’s energy and activate shape memory PLLA/GNPs. Different techniques such as differential scanning calorimetry (DSC), wide-angle X-ray diffraction (WAXD), field emission gun scanning electron microscope (FEG-SEM) and dynamic mechanical thermal analysis (DMTA) were used to characterize samples. DSC and WAXD results indicated that GNPs augmented crystallinity due to nucleating effect of graphene particles. GNPs improved both thermal and infrared activating shape memory properties along with faster response. Pure shape memory PLLA was slightly responsive to infrared light and its infrared actuated shape recovery ratio was 86% which increased to more than 95% with loading of GNPs. Drastic improvement in the crystallinity was obtained in nanocomposites with lower GNPs contents (0.5 and 1 wt%) due to finer dispersion of graphene which resulted in more prominent mechanical and shape memory properties enhancement. Infrared activated shape memory PLLA/GNPs nanocomposites can be developed for wireless remote shape control of smart medical and bio-systems

Medium-term culture of normal human oral mucosa: a novel three-dimensional model to study the effectiveness of drugs administration.

Tissue-engineered oral mucosal equivalents have been developed for in vitro studies for a few years now. However, the usefulness of currently available models is still limited by many factors, mainly the lack of a physiological extracellular matrix (ECM) and the use of cell populations that do not reflect the properly differentiated cytotypes of the mucosa of the oral cavity. For this reason, we have developed a novel three-dimensional culture model reflecting the normal architecture of the human oral mucosa, with the main aim of creating a better in vitro model where to test cellular responses to drugs administration. This novel 3D cell culture model (3D outgrowth) was set up using an artificial extracellular matrix (MatrigelTM), allowing the interactions required for proper differentiation of the various citotypes which form the mucosal layer. Biopsies of human oral mucosa, in fragments of about 0.5 mm3, were placed onto 6.5mm Transwells, covered with MatrigelTM and grown in a specific culture medium. A gradual formation of an architectural structure similar to that of the in vivo oral mucosa was observed. Transmission electron and confocal microscopy were employed to characterize the newly developed model: the cell components (keratinocytes and fibroblasts) differentiated properly within the outgrowth and reconstituted, in vitro, the physiological structure of the human oral mucosa, including a stratified non-keratinized squamous layer composed of four different layers, a proper basal membrane and a lamina propria where fibroblasts produce ECM. Moreover, keratinocytes expressed CK5, CK13, CK19 and E-cadherin, whereas fibroblasts expressed collagen type I and IV, laminin and fibronectin. 3D outgrowths could be considered a valid alternative to animal models, and provide useful information for researchers interested in studying the responses of the human oral mucosa to locally delivered drugs or other exogenous treatments

Repeatability and reproducibility of applanation resonance tonometry : a cross-sectional study

Background: To assess repeatability (intra-observer variability) and reproducibility (inter-operator variability) of intraocular pressure (IOP) measurements with servo-controlled Bioresonator Applanation Resonance Tonometry (ART) and to evaluate possible influential factors. Methods: The study included 178 patients (115 glaucoma and 63 controls; one eye per subject). IOP was measured once with a Goldmann applanation tonometer (GAT) and twice by ART (ART1, ART2), in randomized sequence, by a single operator to assess intra-operator variability. Each ART measurement consisted on 3 readings. To assess inter-operator variability 2 evaluators performed 2 measurements each (in random order) on the same patient. Repeatability and reproducibility were assessed by the coefficient of variation (CoV) and intraclass correlation coefficient (ICC). Results: In the entire cohort, ART1 was 0.4 \ub1 2.2 mmHg (-7.0 to 5.7 mmHg) higher than ART2 (p = 0.03) regardless of test order. Intra-operator CoV was 7.0% \ub1 6.3%, and ICC was 0.80-0.92. Inter-operator CoV ranged between 5.7% \ub1 6.1% and 8.2% \ub1 7.2%, and ICC between 0.86 and 0.97. ART1 and 2 were respectively 1.7 \ub1 3.1 and 1.3 \ub1 3.1 mmHg higher than GAT (p < 0.01). Test-retest difference with ART fell within \ub11 mmHg in 41% of cases, within \ub12 mmHg in 70%, within \ub13 mmHg in 85%. 15% had a test-retest difference higher than \ub1 3 mmHg; Bland-Altman 95% intervals of confidence were -3.9 and +4.6 mmHg. Results were unaffected by age, diagnosis, central corneal thickness, keratometry, operator, randomization sequence. Conclusions: In most cases ART repeatability and reproducibility were high, with no differences due to patients' characteristics. ART measurements overestimated GAT by a mean of 1.3-1.7 mmHg

A public early intervention approach to first-episode psychosis: Treated incidence over 7 years in the Emilia-Romagna region

AimTo estimate the treated incidence of individuals with first-episode psychosis (FEP) who contacted the Emilia-Romagna public mental healthcare system (Italy); to examine the variability of incidence and user characteristics across centres and years. MethodsWe computed the raw treated incidence in 2013-2019, based on FEP users aged 18-35, seen within or outside the regional program for FEP. We modelled FEP incidence across 10 catchment areas and 7 years using Bayesian Poisson and Negative Binomial Generalized Linear Models of varying complexity. We explored associations between user characteristics, study centre and year comparing variables and socioclinical clusters of subjects. ResultsThousand three hundred and eighteen individuals were treated for FEP (raw incidence: 25.3 / 100.000 inhabitant year, IQR: 15.3). A Negative Binomial location-scale model with area, population density and year as predictors found that incidence and its variability changed across centres (Bologna: 36.55; 95% CrI: 30.39-43.86; Imola: 3.07; 95% CrI: 1.61-4.99) but did not follow linear temporal trends or density. Centers were associated with different user age, gender, migrant status, occupation, living conditions and cluster distribution. Year was associated negatively with HoNOS score (R = -0.09, p &lt; .001), duration of untreated psychosis (R = -0.12, p &lt; .001) and referral type. ConclusionsThe Emilia-Romagna region presents a relatively high but variable incidence of FEP across areas, but not in time. More granular information on social, ethnic and cultural factors may increase the level of explanation and prediction of FEP incidence and characteristics, shedding light on social and healthcare factors influencing FEP

ITALIAN CANCER FIGURES - REPORT 2015: The burden of rare cancers in Italy = I TUMORI IN ITALIA - RAPPORTO 2015: I tumori rari in Italia

OBJECTIVES: This collaborative study, based on data collected by the network of Italian Cancer Registries (AIRTUM), describes the burden of rare cancers in Italy. Estimated number of new rare cancer cases yearly diagnosed (incidence), proportion of patients alive after diagnosis (survival), and estimated number of people still alive after a new cancer diagnosis (prevalence) are provided for about 200 different cancer entities. MATERIALS AND METHODS: Data herein presented were provided by AIRTUM population- based cancer registries (CRs), covering nowadays 52% of the Italian population. This monograph uses the AIRTUM database (January 2015), which includes all malignant cancer cases diagnosed between 1976 and 2010. All cases are coded according to the International Classification of Diseases for Oncology (ICD-O-3). Data underwent standard quality checks (described in the AIRTUM data management protocol) and were checked against rare-cancer specific quality indicators proposed and published by RARECARE and HAEMACARE (www.rarecarenet.eu; www.haemacare.eu). The definition and list of rare cancers proposed by the RARECAREnet "Information Network on Rare Cancers" project were adopted: rare cancers are entities (defined as a combination of topographical and morphological codes of the ICD-O-3) having an incidence rate of less than 6 per 100,000 per year in the European population. This monograph presents 198 rare cancers grouped in 14 major groups. Crude incidence rates were estimated as the number of all new cancers occurring in 2000-2010 divided by the overall population at risk, for males and females (also for gender-specific tumours).The proportion of rare cancers out of the total cancers (rare and common) by site was also calculated. Incidence rates by sex and age are reported. The expected number of new cases in 2015 in Italy was estimated assuming the incidence in Italy to be the same as in the AIRTUM area. One- and 5-year relative survival estimates of cases aged 0-99 years diagnosed between 2000 and 2008 in the AIRTUM database, and followed up to 31 December 2009, were calculated using complete cohort survival analysis. To estimate the observed prevalence in Italy, incidence and follow-up data from 11 CRs for the period 1992-2006 were used, with a prevalence index date of 1 January 2007. Observed prevalence in the general population was disentangled by time prior to the reference date (≤2 years, 2-5 years, ≤15 years). To calculate the complete prevalence proportion at 1 January 2007 in Italy, the 15-year observed prevalence was corrected by the completeness index, in order to account for those cancer survivors diagnosed before the cancer registry activity started. The completeness index by cancer and age was obtained by means of statistical regression models, using incidence and survival data available in the European RARECAREnet data. RESULTS: In total, 339,403 tumours were included in the incidence analysis. The annual incidence rate (IR) of all 198 rare cancers in the period 2000-2010 was 147 per 100,000 per year, corresponding to about 89,000 new diagnoses in Italy each year, accounting for 25% of all cancer. Five cancers, rare at European level, were not rare in Italy because their IR was higher than 6 per 100,000; these tumours were: diffuse large B-cell lymphoma and squamous cell carcinoma of larynx (whose IRs in Italy were 7 per 100,000), multiple myeloma (IR: 8 per 100,000), hepatocellular carcinoma (IR: 9 per 100,000) and carcinoma of thyroid gland (IR: 14 per 100,000). Among the remaining 193 rare cancers, more than two thirds (No. 139) had an annual IR &lt;0.5 per 100,000, accounting for about 7,100 new cancers cases; for 25 cancer types, the IR ranged between 0.5 and 1 per 100,000, accounting for about 10,000 new diagnoses; while for 29 cancer types the IR was between 1 and 6 per 100,000, accounting for about 41,000 new cancer cases. Among all rare cancers diagnosed in Italy, 7% were rare haematological diseases (IR: 41 per 100,000), 18% were solid rare cancers. Among the latter, the rare epithelial tumours of the digestive system were the most common (23%, IR: 26 per 100,000), followed by epithelial tumours of head and neck (17%, IR: 19) and rare cancers of the female genital system (17%, IR: 17), endocrine tumours (13% including thyroid carcinomas and less than 1% with an IR of 0.4 excluding thyroid carcinomas), sarcomas (8%, IR: 9 per 100,000), central nervous system tumours and rare epithelial tumours of the thoracic cavity (5%with an IR equal to 6 and 5 per 100,000, respectively). The remaining (rare male genital tumours, IR: 4 per 100,000; tumours of eye, IR: 0.7 per 100,000; neuroendocrine tumours, IR: 4 per 100,000; embryonal tumours, IR: 0.4 per 100,000; rare skin tumours and malignant melanoma of mucosae, IR: 0.8 per 100,000) each constituted &lt;4% of all solid rare cancers. Patients with rare cancers were on average younger than those with common cancers. Essentially, all childhood cancers were rare, while after age 40 years, the common cancers (breast, prostate, colon, rectum, and lung) became increasingly more frequent. For 254,821 rare cancers diagnosed in 2000-2008, 5-year RS was on average 55%, lower than the corresponding figures for patients with common cancers (68%). RS was lower for rare cancers than for common cancers at 1 year and continued to diverge up to 3 years, while the gap remained constant from 3 to 5 years after diagnosis. For rare and common cancers, survival decreased with increasing age. Five-year RS was similar and high for both rare and common cancers up to 54 years; it decreased with age, especially after 54 years, with the elderly (75+ years) having a 37% and 20% lower survival than those aged 55-64 years for rare and common cancers, respectively. We estimated that about 900,000 people were alive in Italy with a previous diagnosis of a rare cancer in 2010 (prevalence). The highest prevalence was observed for rare haematological diseases (278 per 100,000) and rare tumours of the female genital system (265 per 100,000). Very low prevalence (&lt;10 prt 100,000) was observed for rare epithelial skin cancers, for rare epithelial tumours of the digestive system and rare epithelial tumours of the thoracic cavity. COMMENTS: One in four cancers cases diagnosed in Italy is a rare cancer, in agreement with estimates of 24% calculated in Europe overall. In Italy, the group of all rare cancers combined, include 5 cancer types with an IR&gt;6 per 100,000 in Italy, in particular thyroid cancer (IR: 14 per 100,000).The exclusion of thyroid carcinoma from rare cancers reduces the proportion of them in Italy in 2010 to 22%. Differences in incidence across population can be due to the different distribution of risk factors (whether environmental, lifestyle, occupational, or genetic), heterogeneous diagnostic intensity activity, as well as different diagnostic capacity; moreover heterogeneity in accuracy of registration may determine some minor differences in the account of rare cancers. Rare cancers had worse prognosis than common cancers at 1, 3, and 5 years from diagnosis. Differences between rare and common cancers were small 1 year after diagnosis, but survival for rare cancers declined more markedly thereafter, consistent with the idea that treatments for rare cancers are less effective than those for common cancers. However, differences in stage at diagnosis could not be excluded, as 1- and 3-year RS for rare cancers was lower than the corresponding figures for common cancers. Moreover, rare cancers include many cancer entities with a bad prognosis (5-year RS &lt;50%): cancer of head and neck, oesophagus, small intestine, ovary, brain, biliary tract, liver, pleura, multiple myeloma, acute myeloid and lymphatic leukaemia; in contrast, most common cancer cases are breast, prostate, and colorectal cancers, which have a good prognosis. The high prevalence observed for rare haematological diseases and rare tumours of the female genital system is due to their high incidence (the majority of haematological diseases are rare and gynaecological cancers added up to fairly high incidence rates) and relatively good prognosis. The low prevalence of rare epithelial tumours of the digestive system was due to the low survival rates of the majority of tumours included in this group (oesophagus, stomach, small intestine, pancreas, and liver), regardless of the high incidence rate of rare epithelial cancers of these sites. This AIRTUM study confirms that rare cancers are a major public health problem in Italy and provides quantitative estimations, for the first time in Italy, to a problem long known to exist. This monograph provides detailed epidemiologic indicators for almost 200 rare cancers, the majority of which (72%) are very rare (IR&lt;0.5 per 100,000). These data are of major interest for different stakeholders. Health care planners can find useful information herein to properly plan and think of how to reorganise health care services. Researchers now have numbers to design clinical trials considering alternative study designs and statistical approaches. Population-based cancer registries with good quality data are the best source of information to describe the rare cancer burden in a population