The aims of this investigation were to review the clinical behavior of deep neck infections (DNIs) treated in our institution in order to identify the predisposing factors of life-threatening complications and propose valuable recommendations for management and treatment. A total of 365 adult patients with DNIs were retrospectively identified. One-hundred and thirty-nine patients (38.1%) underwent surgical drainage. Overall, 226 patients (61.9%) responded effectively to intravenous antimicrobial therapy only. There were 67 patients (18.4%) developing life-threatening complications. Diabetes mellitus (odd ratio 5.43; P < 0.001) and multiple deep neck spaces involvement (odd ratio 4.92; P < 0.001) were the strongest independent predictors of complications. The mortality rate was 0.3%. Airway obstruction and descending mediastinitis are the most troublesome complications of DNIs. In selected patients, a trial of intravenous antibiotic therapy associated with an intensive computed tomography-based wait-and-watch policy may avoid an unnecessary surgical procedure. However, about one-fourth of patients present significant comorbidities, which may negatively affect the course of the infection. In these cases and in patients with large or multiple spaces infections, a more aggressive surgical strategy is mandatory.
ObjectivesTo investigate the frequency of Human papillomavirus (HPV)-driven head and neck squamous cell carcinoma (HNSCC) among patients living in North-East Italy, by assessing HPV-DNA positivity in all tumors and additional markers whenever possible.Material and methodsHPV types, viral load, viral RNA, HPV16/18 E6 protein and p16INK4a and pRb expression were determined in primary tumor tissues from 247 HNSCC patients. Tumor-specific HPV seropositivity was analyzed in 102 patients.ResultsTumor HPV-DNA prevalence was 8.5% overall (21/247) and 27% in oropharynx (17/63). HPV16 accounted for 95% of all HPV types found. Among HPV-DNA+ tumors, type-concordant HPV E6*I RNA prevalence was 79%. HPV DNA+ RNA+ tumors showed high viral load, up-regulated p16INK4a, down-regulated pRb and presence of HPV16 E6 protein. Eight cases showed tumor-specific HPV seropositivity, all type-concordant with the tumor. Tumors were defined as HPV-driven when positive for HPV-DNA plus 2 additional HPV transformation-related markers.ConclusionRelative prevalence of HPV-driven tumors (14 HPV16, 1 HPV58) was 6% overall and 20% among oropharyngeal cancers. In the oropharynx the HPV-driven group showed a trend for better survival versus the HPV-negative group.The relative prevalence of HPV-driven oropharyngeal cancer is low in North-East Italy as compared to Western and Northern Europe.
In the last years, the explosion of high throughput sequencing technologies has enabled epigenome-wide analyses, allowing a more comprehensive overview of the oropharyngeal squamous cell carcinoma (OPSCC) epigenetic landscape. In this setting, the cellular pathways contributing to the neoplastic phenotype, including cell cycle regulation, cell signaling, DNA repair, and apoptosis have been demonstrated to be potential targets of epigenetic alterations in OPSCC. Of note, it has becoming increasingly clear that HPV infection and OPSCC lifestyle risk factors differently drive the epigenetic machinery in cancer cells. Epigenetic changes, including DNA methylation, histone modifications, and non-coding RNA expression, can be used as powerful and reliable tools for early diagnosis of OPSCC patients and improve prognostication. Since epigenetic changes are dynamic and reversible, epigenetic enzymes may also represent suitable targets for the development of more effective OPSCC therapeutic strategies. Thus, this review will focus on the main known epigenetic modifications that can occur in OPSCC and their exploitation as potential biomarkers and therapeutic targets. Furthermore, we will address epigenetic alterations to OPSCC risk factors, with a particular focus on HPV infection, tobacco exposure, and heavy alcohol consumption.
Although the prevalence of human papillomavirus (HPV)-related oropharyngeal squamous cell carcinoma (OPSCC) is increasing in developed countries and becoming a relevant health issue, the natural history of oral HPV infection is still unclear. Estimating the infection’s prevalence in specific populations and identifying risk factors can widen our understanding of its natural history and help to delineate appropriate prevention strategies. This study sought to (i) determine oral HPV prevalence and genotype distribution in a large series of young Italian adults, (ii) validate an oral rinse sampling/storage protocol, and (iii) pinpoint factors associated with oral HPV infection. Five hundred students, nurses, and technicians (19–35 years-old) studying and working at/for the University of Padua were recruited. Each participant was provided with an oral rinse sampling kit and instructions for use. They were also asked to complete an anonymous questionnaire concerning their demographic characteristics and behaviors. The questionnaires and oral rinse containers were labeled with the same identification code number. The oral rinse samples were tested using a bead-based multiplex BSGP5+/6+-MPG genotyping assay which amplifies the L1 region of 51 mucosal HPV types. The prevalence of oral HPV infection was 4.0% (95% confidence interval (CI), 2.5%-6.1%); those of 14 high-risk HPV types and of HPV-type 16 (HPV16) infection were 2.2% (95% CI, 1.1%-3.9%) and 1.6% (95% CI, 0.6%-3.1%), respectively. HPV16 was the most frequent genotype (40.0% of oral HPV infections). No association was found between oral infection and the co-variables studied (gender, tobacco, alcohol and illegal drug use, number of sex and oral sex partners, HPV vaccination status, history of HPV and sexually transmitted infections, abnormal pap smears, recurrent tonsillitis and tonsillectomy). The oral rinse sampling protocol outlined here proved to be simple, efficient and well tolerated, and the prevalence rate can be considered reliable and thus useful to guide future research. Determinants of oral HPV infection are still unclear and further studies are certainly warranted.
Persistent infection with high-risk Human Papilloma Virus (HPV) leads to the development of several tumors, including cervical, oropharyngeal, and anogenital squamous cell carcinoma. In the last years, the use of high-throughput sequencing technologies has revealed a number of non-coding RNA (ncRNAs), distinct from micro RNAs (miRNAs), that are deregulated in HPV-driven cancers, thus suggesting that HPV infection may affect their expression. However, since the knowledge of ncRNAs is still limited, a better understanding of ncRNAs biology, biogenesis, and function may be challenging for improving the diagnosis of HPV infection or progression, and for monitoring the response to therapy of patients affected by HPV-driven tumors. In addition, to establish a ncRNAs expression profile may be instrumental for developing more effective therapeutic strategies for the treatment of HPV-associated lesions and cancers. Therefore, this review will address novel classes of ncRNAs that have recently started to draw increasing attention in HPV-driven tumors, with a particular focus on ncRNAs that have been identified as a direct target of HPV oncoproteins.
Interdigitating dendritic cell sarcoma (IDCS) is an exceedingly rare neoplasm originating from professional antigen presenting cells normally located in the T zone of the lymph node. The purpose of this report was to describe the first case of the IDCS of the submandibular gland and perform a review of the literature of head and neck IDCS. We present a case of an 81-year-old man with a 5 months history of slowly enlarging painless mass in right submandibular region. Fine needle aspiration cytology was suggestive of squamous cell carcinoma. The patient underwent surgical resection of the right submandibular gland and neck dissection. A malignant spindle cell proliferation involving the submandibular gland and colonizing one laterocervical lymph node was found. Morphology and immunophenotype prompted a differential diagnosis of a metastatic spindle cell melanoma versus an IDCS. Transmission electron microscopy was performed and supported a diagnosis of IDCS. The diagnosis of IDCS is a challenging task and may require a large array of techniques.
Aim To evaluate the role of baseline neutrophil‐to‐lymphocyte ratio (NLR) as prognostic marker in squamous cell carcinoma of the oropharynx (OPC) treated with definitive chemoradiotherapy (CRT) in the era of HPV status. Patients and methods A retrospective analysis of 125 patients (pts) affected with locally advanced OPC was performed. Inclusion criteria were age >18 years, stage III or IV (TNM 7th ed.) and definitive CRT. Haematological marker for their independent role as prognostic biomarkers for progression‐free survival (PFS) and overall survival (OS). Logistic models were used to assess the association with downstage in TNM 8th ed. Results Seventy‐seven (61.6%) pts had HPV/p16 + related OPC. Therapeutic choice consisted in sequential and concurrent CRT. Median follow‐up was 50 months. A value of NLR ≥3 was associated with poorer OS. Two‐year OS was 91% and 81% in pts with NLR <3 and ≥3, respectively. Conclusion A baseline NLR ≥ 3 at treatment initiation represented a negative prognostic marker for OPC treated with definitive CRT. These results are in line with literature data, and prognostic value of NLR has been confirmed restaging our cohort with new TNM staging (8th ed.). Therefore, NLR could be considered a valuable biomarker for risk stratification in pts with OPC.
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