Papillomavirus umano e carcinomi del tratto aerodigestivo: il punto sulle evidenze nella babele dei dati scientifici

I carcinomi squamosi dell'orofaringe associati all'infezione da papillomavirus umano (HPV) costituiscono ormai una entità ben caratterizzata, che interessa prevalentemente maschi, giovani adulti o di mezza età, non fumatori. Essi hanno generalmente una prognosi più favorevole rispetto alla controparte non associate ad infezione, e per questo è stato proposto di dedicare a questo gruppo di pazienti un approccio terapeutico meno aggressivo. L'incidenza dei carcinomi dell'orofaringe associati a HPV è in rapido aumento nella maggior parte dei paesi occidentali, ma per quanto riguarda la popolazione italiana non sono disponibili dati epidemiologici in merito. Per quanto riguarda le altre regioni del distretto testa-collo, una più modesta porzione di lesioni displastiche di alto grado e di neoplasie appare essere correlata all'infezione da HPV, mentre il ruolo del virus nei tumori della laringe è stato parzialmente ridimensionato. HPV determina la trasformazione neoplastica delle cellule infettate tramite l'espressione dei suoi due oncogeni, E6 ed E7, che interagiscono con i meccanismi di apoptosi e regolazione del ciclo cellulare della cellula ospite. L'unica metodica in grado di documentare con certezza l'espressione degli oncogeni virali è attualmente l'amplificazione dell'RNA messaggero trascritto dai due oncogeni. Il consenso riguardo la strategia per l'identificazione dei pazienti affetti da carcinoma dell'orofaringe associato a HPV dal punto di vista clinico e diagnostico è tuttora limitato. Le metodiche diagnostiche più utilizzate, singolarmente o in combinazione, comprendono l'immunocolorazione con anticorpi diretti contro p16, l'ibridazione in situ per genotipi virali ad alto rischio e l'amplificazione del DNA virale mediate PCR. La possibilità di ottenere una diagnosi precoce grazie all'identificazione dell'infezione virale nelle cellule epiteliali esfoliate dal cavo orale o dall'orofaringe non ha finora fornito risultati soddisfacenti, tuttavia la persistenza del virus nel cavo orale in pazienti trattati per carcinoma dell'orofaringe ha dimostrato una significativa associazione con il rischio di recidiva del tumore. Non sono ancora disponibili sufficienti dati che documentino in maniera dettagliata la storia naturale dell'infezione a la sua progressione verso lo sviluppo di una neoplasia, e che definiscano con chiarezza le modalità di trasmissione e i fattori di rischio, comunque è chiaro che i comportamenti sessuali hanno un peso rilevante nel determinare il rischio di sviluppo di neoplasia dell'orofaringe HPV-correlata. La progressive diffusione nelle giovani generazioni del vaccino contro HPV, e soprattutto la sua estensione agli adolescenti di entrambi i generi è sicuramente destinata a modificare in maniera rilevante anche l'epidemiologica dei tumori HPV-correlati nel distretto testa-collo nel prossimo futuro

Case Report: All That Glisters Is Not* Cancer

Properly performed staging in non-small-cell lung cancer (NSCLC) is necessary to avoid wrong therapeutic decisions. Here we present a case which manifested as advanced NSCLC but ultimately was composed of two different and rare pathologies. The first is a TTF-1 positive axillary lymph node that could be defined either as an unusual isolated differentiated cancer of unknown primary or as an even rarer case of ectopic lung epithelium which underwent malignant transformation. The second is sarcoidosis, a sarcoid-like alteration, in remission after oral steroids. The main implication of a correct diagnosis regards patient outcome and the avoidance of toxic inappropriate systemic chemotherapy

Adenocarcinoma classification: patterns and prognosis

Lung cancer is the most frequent human malignancy and the principal cause of cancer-related death worldwide. Adenocarcinoma is now the main histologic type, accounting for almost half of all the cases. The 2015 World Health Organization has adopted the classification recently developed by the International Association for the Study of Lung Cancer, American Thoracic Society, and European Respiratory Society. This new adenocarcinoma classification has incorporated up-to-date advances in radiological, molecular and oncological knowledge, providing univocal diagnostic criteria and terminology. For resection specimens, new entities have been defined such as adenocarcinoma in situ and minimally invasive adenocarcinoma to designate adenocarcinomas, mostly nonmucinous and ≤ 3 cm in size, with either pure lepidic growth or predominant lepidic growth with ≤ 5 mm invasion, respectively. For invasive adenocarcinoma, the new classification has introduced histological subtyping according to the predominant pattern of growth of the neoplastic cells: lepidic (formerly non mucinous brochioloalveolar adenocarcinoma), acinar, papillary, micropapillary, and solid. Of note, micropapillary pattern is a brand new histologic subtype. In addition, four variants of invasive adenocarcinoma are recognized, namely invasive mucinous (formerly mucinous brochioloalveolar adenocarcinoma), colloid, fetal, and enteric. Importantly, three variants that were considered in the previous classification have been eliminated, specifically mucinous cystadenocarcinoma, signet ring cell, and clear cell adenocarcinoma. This review presents the changes introduced by the current histological classification of lung adenocarcinoma and its prognostic implications

Neuropathological findings from COVID-19 patients with neurological symptoms argue against a direct brain invasion of SARS-CoV-2: A critical systematic review

Background and purpose: Neuropathological studies can elucidate the mechanisms of nervous system damage associated with SARS-CoV-2 infection. Despite literature on this topic is rapidly expanding, correlations between neurological symptoms and brain pathology findings in COVID-19 patients remain largely unknown. Methods: We performed a systematic literature review on neuropathological studies in COVID-19, including 438 patients from 45 articles published by April 22, 2021. We retrieved quantitative data regarding demographic, clinical, and neuropathological findings. We carried out a Wilcoxon rank sum test or χ2 test to compare patients' subgroups based on different clinical and brain pathology features. Results: Neuropathological findings in COVID-19 patients were microgliosis (52.5%), astrogliosis (45.6%), inflammatory infiltrates (44.0%), hypoxic-ischemic lesions (40.8%), edema (25.3%), and hemorrhagic lesions (20.5%). SARS-CoV-2 RNA and proteins were identified in brain specimens of 41.9% and 28.3% of subjects, respectively. Detailed clinical information was available from 245 patients (55.9%), and among them, 96 subjects (39.2%) had presented with neurological symptoms in association with typical COVID-19 manifestations. We found that: (i) the detection rate of SARS-CoV-2 RNA and proteins in brain specimens did not differ between patients with versus those without neurological symptoms; (ii) brain edema, hypoxic-ischemic lesions, and inflammatory infiltrates were more frequent in subjects with neurological impairment; (iii) neurological symptoms were more common among older individuals. Conclusions: Our systematic revision of clinical correlates in COVID-19 highlights the pathogenic relevance of brain inflammatory reaction and hypoxic-ischemic damage rather than neuronal viral load. This analysis indicates that a more focused study design is needed, especially in the perspective of potential therapeutic trials

New frontiers and emerging applications of 3D printing in ENT surgery: A systematic review of the literature

3D printing systems have revolutionised prototyping in the industrial field by lowering production time from days to hours and costs from thousands to just a few dollars. Today, 3D printers are no more confined to prototyping, but are increasingly employed in medical disci- plines with fascinating results, even in many aspects of otorhinolaryngology. All publications on ENT surgery, sourced through updated electronic databases (PubMed, MEDLINE, EMBASE) and published up to March 2017, were examined according to PRISMA guidelines. Overall, 121 studies fulfilled specific inclusion criteria and were included in our systematic review. Studies were classified according to the specific field of application (otologic, rhinologic, head and neck) and area of interest (surgical and preclinical education, customised surgical planning, tissue engineering and implantable prosthesis). Technological aspects, clinical implications and limits of 3D printing processes are discussed focusing on current benefits and future perspectives

Natural Language, Mixed-Initiative Personal Assistant Agents

The increasing popularity and use of personal voice assistant technologies, such as Siri and Google Now, is driving and expanding progress toward the long-term and lofty goal of using artificial intelligence to build human-computer dialog systems capable of understanding natural language. While dialog-based systems such as Siri support utterances communicated through natural language, they are limited in the flexibility they afford to the user in interacting with the system and, thus, support primarily action-requesting and information-seeking tasks. Mixed-initiative interaction, on the other hand, is a flexible interaction technique where the user and the system act as equal participants in an activity, and is often exhibited in human-human conversations. In this paper, we study user support for mixed-initiative interaction with dialog-based systems through natural language using a bag-of-words model and k-nearest-neighbor classifier. We study this problem in the context of a toolkit we developed for automated, mixed-initiative dialog system construction, involving a dialog authoring notation and management engine based on lambda calculus, for specifying and implementing task-based, mixed-initiative dialogs. We use ordering at Subway through natural language, human-computer dialogs as a case study. Our results demonstrate that the dialogs authored with our toolkit support the end user\u27s completion of a natural language, human-computer dialog in a mixed-initiative fashion. The use of natural language in the resulting mixed-initiative dialogs afford the user the ability to experience multiple self-directed paths through the dialog and makes the flexibility in communicating user utterances commensurate with that in dialog completion paths---an aspect missing from commercial assistants like Siri

Oral microbiota and vitamin D impact on oropharyngeal squamous cell carcinogenesis: a narrative literature review

An emerging body of research is revealing the microbiota pivotal involvement in determining the health or disease state of several human niches, and that of vitamin D also in extra-skeletal regions. Nevertheless, much of the oral microbiota and vitamin D reciprocal impact in oropharyngeal squamous cell carcinogenesis (OPSCC) is still mostly unknown. On this premise, starting from an in-depth scientific bibliographic analysis, this narrative literature review aims to show a detailed view of the state of the art on their contribution in the pathogenesis of this cancer type. Significant differences in the oral microbiota species quantity and quality have been detected in OPSCC affected patients; in particular, mainly high-risk human papillomaviruses (HR-HPVs), Fusobacterium nucleatum, Porphyromonas gingivalis, Pseudomonas aeruginosa and Candida spp. seem to be highly represented. Vitamin D prevents and fights infections promoted by the above identified pathogens, thus confirming its homeostatic function on the microbiota balance. However, its antimicrobial and antitumoral actions, well-described for the gut, have not been fully documented for the oropharynx yet. Deeper investigations of the mechanisms that link vitamin D levels, oral microbial diversity and inflammatory processes will lead to a better definition of OPSCC risk factors for the optimization of specific prevention and treatment strategies

PD-L1 in oral squamous cell carcinoma: A key biomarker from the laboratory to the bedside

Objectives and background: Oral squamous cell carcinoma (OSCC) is a highly malignant disease with an increasing incidence. The need to improve therapeutic strategies for patients affected by OSCC is an urgent challenge. Currently, the advent of immunotherapy represents an important step toward this aim. Programmed cell death-ligand 1 (PD-L1), a membrane protein that can be expressed on tumor and inflammatory cells is a key biomarker whose expression is determined by means of immunohistochemistry and is necessary for selecting patients for immunotherapy. Methods: In this study, we review the methods of PD-L1 assessment and outcomes achieved with immunotherapy in the treatment of OSCC patients. Results: Based on a meta-analysis we demonstrate a lack of prognostic significance of PD-L1 in OSCC. Conclusions: We also highlight unresolved issues including difficulties in standardizing PD-L1 evaluation and discuss future opportunities such as leveraging digital pathology