Multidisciplinary Decision-Making-ITAlian Consensus After Two Years of Real Practice on the Management of Severe Uncontrolled CRSwNP by Biologics (ITACA Study).

PURPOSE OF REVIEW: We aimed to reach an Italian multidisciplinary consensus on some crucial aspects of treatment decision making in CRSwNP, following 2 years of clinical experience in order to support specialists in the management of CRSwNP in clinical practice. We addressed issues relating to therapeutic decision-making and shared criteria for the treatment choice, as well as appropriate timing and criteria for evaluating treatment response, and highlighted the need for repeated multidisciplinary assessments. RECENT FINDINGS: A national survey has been conducted recently to understand how rhinology practice has changed in Italy with the advent of biologics and how this affects patients with uncontrolled, severe CRSwNP. Despite the many published consensus documents, practical recommendations, and protocols on the use of biologics in CRSwNP, heterogenous behaviors in practice are still observed mainly conditioned by the novelty of the topic. The consensus procedure followed a modified Delphi approach. The scientific board included 18 otorhinolaryngologists and 8 allergists, who selected the 4 main topics to be addressed and developed overall 20 statements. Consensus on these statements was sought by a larger group of 48 additional experts, through two rounds of voting, the first web-based, the second in presence with discussion and possible refinement of the statements. The statements reaching an average score ≥ 7 at the second voting round were approved. Five statements were proposed for each of the following topics: baseline evaluation of patients eligible for biologic therapy; choice between different therapeutic options; assessment of the response to biologic treatment; multidisciplinary management. At the first voting round, 19 out of the 20 statements reached a mean score ≥ 7. Following the discussion and a few consequent amendments, at the second round of voting all the 20 statements were approved.

Dupilumab in the treatment of severe uncontrolled chronic rhinosinusitis with nasal polyps (CRSwNP): A multicentric observational Phase IV real-life study (DUPIREAL).

BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) is associated with significant morbidity and reduced health-related quality of life. Findings from clinical trials have demonstrated the effectiveness of dupilumab in CRSwNP, although real-world evidence is still limited. METHODS: This Phase IV real-life, observational, multicenter study assessed the effectiveness and safety of dupilumab in patients with severe uncontrolled CRSwNP (n = 648) over the first year of treatment. We collected data at baseline and after 1, 3, 6, 9, and 12 months of follow-up. We focused on nasal polyps score (NPS), symptoms, and olfactory function. We stratified outcomes by comorbidities, previous surgery, and adherence to intranasal corticosteroids, and examined the success rates based on current guidelines, as well as potential predictors of response at each timepoint. RESULTS: We observed a significant decrease in NPS from a median value of 6 (IQR 5-6) at baseline to 1.0 (IQR 0.0-2.0) at 12 months (p < .001), and a significant decrease in Sino-Nasal Outcomes Test-22 (SNOT-22) from a median score of 58 (IQR 49-70) at baseline to 11 (IQR 6-21; p < .001) at 12 months. Sniffin' Sticks scores showed a significant increase over 12 months (p < .001) compared to baseline. The results were unaffected by concomitant diseases, number of previous surgeries, and adherence to topical steroids, except for minor differences in rapidity of action. An excellent-moderate response was observed in 96.9% of patients at 12 months based on EPOS 2020 criteria. CONCLUSIONS: Our findings from this large-scale real-life study support the effectiveness of dupilumab as an add-on therapy in patients with severe uncontrolled CRSwNP in reducing polyp size and improving the quality of life, severity of symptoms, nasal congestion, and smell.

Inducible T-cell co-stimulator (ICOS) and ICOS ligand are novel players in the multiple-myeloma microenvironment.

The inducible T-cell co-stimulator (ICOS) is a T-cell receptor that, once bound to ICOS ligand (ICOSL) expressed on several cell types including the B-cell lineage, plays a decisive role in adaptive immunity by regulating the interplay between B and T cells. In addition to its immunomodulatory functions, we have shown that ICOS/ICOSL signalling can inhibit the activity of osteoclasts, unveiling a novel mechanism of lymphocyte-bone cells interactions. ICOS and ICOSL can also be found as soluble forms, namely sICOS and sICOSL. Here we show that: (i) levels of sICOS and sICOSL are increased in multiple myeloma (MM) compared to monoclonal gammopathy of undetermined significance and smouldering MM; (ii) levels of sICOS and sICOSL variably correlate with several markers of tumour burden; and (iii) sICOS levels tend to be higher in Durie-Salmon stage II/III versus stage I MM and correlate with overall survival as an independent variable. Moreover, surface ICOS and ICOSL are expressed in both myeloma cells and normal plasma cells, where they probably regulate different functional stages. Finally, ICOSL triggering inhibits the migration of myeloma cell lines in vitro and the growth of ICOSL+ MOPC-21 myeloma cells in vivo. These results suggest that ICOS and ICOSL represent novel markers and therapeutic targets for MM.

In Vitro Selection of Lactobacillus and Bifidobacterium Probiotic Strains for the Management of Oral Pathobiont Infections Associated to Systemic Diseases.

The human oral pathobionts Aggregatibacter actinomycetemcomitans, Streptococcus mitis and Streptococcus mutans, in dysbiosis-promoting conditions, lead to oral infections, which also represent a threat to human systemic health. This scenario may be worsened by antibiotic misuse, which favours multi-drug resistance, making the research on pathogen containment strategies more than crucial. Therefore, we aimed to in vitro select the most promising probiotic strains against oral pathogen growth, viability, biofilm formation, and co-aggregation capacity, employing both the viable probiotics and their cell-free supernatants (CFSs). Interestingly, we also assessed probiotic efficacy against the three-pathogen co-culture, mimicking an environment similar to that in vivo. Overall, the results showed that Lactobacillus CFSs performed better than the Bifidobacterium, highlighting Limosilactobacillus reuteri LRE11, Lacticaseibacillus rhamnosus LR04, Lacticaseibacillus casei LC04, and Limosilactobacillus fermentum LF26 as the most effective strains, opening the chance to deeper investigation of their action and CFS composition. Altogether, the methodologies presented in this study can be used for probiotic efficacy screenings, in order to better focus the research on a viable probiotic, or on its postbiotics, suitable in case of infections.

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.

Nasal Cytology in Radiofrequency Turbinate Volume Reduction.

INTRODUCTION: Radiofrequency turbinate volume reduction (RFTVR) is an effective treatment of inferior turbinate hypertrophy. RFTVR can reduce epithelial cell alterations in nasal mucosa. The aim of this observational study was to evaluate the effects of RFTVR on nasal obstruction and cytology, stratifying for different types of rhinitis. METHODS: Nasal cytology and subjective nasal obstruction were evaluated on 113 patients before RFTVR (T0) and after 3 months (T1). The patients were divided into groups on the basis of the underlying disease: allergic rhinitis, nonallergic rhinitis, rhinitis medicamentosa, and other diseases (e.g., hormonal-based turbinate hypertrophy). RESULTS: Nasal cytology at T0 identified 42 patients with allergic rhinitis, 40 with nonallergic rhinitis, 19 with rhinitis medicamentosa, and 12 with other diseases. An improvement of nasal cytology at T1 was observed in 29.2% of cases. They mainly consisted of patients with nonallergic rhinitis with neutrophils, whose neutrophil infiltrate decreased. Only 2 cases (1.7%) showed a worsening of nasal cytology at T1. A statistically significant decrease in subjective nasal obstruction was observed for every group (p < 0.05). Higher differences of nasal obstruction between T0 and T1 were found in patients with rhinitis medicamentosa or other diseases. CONCLUSION: RFTVR represents a safe and effective treatment for turbinate hypertrophy of various etiology. It is not responsible for a worsening of inflammatory infiltrate of the nasal mucosa.

Effects of glove finger- versus lidocaine-soaked nasal packing after endoscopic nasal surgery: a prospective randomized controlled trial.

PURPOSE: Nasal packing is a common but unpleasant procedure in patients who undergo endoscopic sinus surgery (ESS). The aim of this study was to assess whether a glove-finger pack strategy would reduce pain compared to lidocaine-soaked packs after ESS. METHODS: A prospective randomized controlled trial enrolling 120 consecutive patients affected by chronic rhinosinusitis, who underwent bilateral ESS. At the end of surgery 62 subjects received 10 cm non-absorbable pack soaked with 5 mL of 2%-lidocaine solution and 58 received a 10 cm non-absorbable pack coated with a latex free glove finger soaked with saline solution. Data concerning pain were collected using a 0 to 10 visual analogue scale at post-operative hours 1, 4, 8, and 16 and at pack removal (24 h ± 15 min). All post-operative analgesic rescue doses were registered. Also, bleeding was reported. RESULTS: The mean VAS score during pack-removal was significantly lower in glove-finger group than in the lidocaine group (3.22 ± 2.16 vs 4.89 ± 2.90, p = 0.0012). There was no statistically significant difference between re-soaking lidocaine-soaked-packs with saline solution or lidocaine at pack removal time (p = 0.42). CONCLUSION: Glove-finger nasal pack seems to provide better pain control after ESS, when compared with lidocaine-soaked pack, especially at pack removal time.

PYHIN genes as potential biomarkers for prognosis of human papillomavirus-positive or -negative head and neck squamous cell carcinomas.

The aim of the present study is to determine the expression levels of PYHIN (IFI16 and AIM2) and APOBEC3 (A3A, A3B, A3C, A3D, A3F, A3G, and A3H) gene family members in a cohort of patients with head and neck squamous cell carcinoma (HNSCC) and assess their potential correlation with human papillomavirus (HPV) infection status, clinical characteristics, and survival. For this purpose, 34 HNSCC tissue specimens along with healthy surrounding mucosa were collected from patients surgically treated for HNSCC. Nucleic acids were isolated to assess the presence of HPV and the expression levels of selected molecular markers. Survival analysis was carried out using the Kaplan-Meier method. In HPV-negative (HPV-) HNSCCs, we detected low mRNA expression levels of IFI16, A3A, and A3B, whereas these genes were upregulated of 2-100 folds in HPV-positive (HPV+) tumors (p < 0.05). Interestingly, AIM2 gene expression levels were predominantly unchanged in HPV+ HNSCCs compared to their HPV- counterparts, in which AIM2 was predominantly upregulated (10% vs. 50% of patients). In HPV- tumors, upregulation of TP53, NOTCH1, PD-L1, and IFI16 correlated with lower occurrence of nodal metastases. On the other hand, the expression of APOBEC family members did not correlate with clinical characteristics. Regarding survival, patients with upregulated A3F gene expression had a worse prognosis, while patients without changes in A3H expression had a lower survival rate. In conclusion, our findings indicate that the innate immune sensors IFI16 and AIM2 and some APOBEC family members could be potentially used as biomarkers for disease outcome in HNSCC patients regardless of HPV presence.

Endoscopic versus conventional septoplasty: objective/subjective data on 276 patients.

PURPOSE: Endoscopic approach represents a valid alternative to conventional septoplasty. The aim of this study is to analyze the objective and subjective data on 276 patients, who underwent traditional (147) or endoscopic (129) septoplasty. METHODS: This is a prospective observational study on 276 consecutive patients affected by deviated nasal septum (DNS), who underwent isolated septoplasty between 2011 and 2018. 147 of them were treated using an "open" approach, while 129 were treated with an endoscopic approach. The two groups were compared 3 months after surgery: the objective results (complications such as bleeding, hematoma, pain, synechiae, septal tears and incomplete correction), objective (rhinomanometric data) and subjective measurements (NOSE questionnaires). RESULTS: Both techniques are effective in decreasing nasal obstruction and discharge. Complications such as pain, synechiae, early postoperative bleeding, septal tears and incomplete correction are less frequent in the endoscopic group (p < 0.05). The rhinomanometric analysis reveal improvement in both groups without statistical differences. Subjective questionnaires show a good symptoms relief with an improved quality of life in all 276 patients without statistical difference between the two gropus. CONCLUSIONS: Both techniques are effective in reducing nasal obstruction and related symptoms with fewer overall complications in the endoscopic approach. The endoscope provides improved field of view, less mucosal damages and a more anatomic dissection. Finally, such approach can be a valuable teaching tool for assistants, residents and students.

Osteopontin at the Crossroads of Inflammation and Tumor Progression.

Complex interactions between tumor and host cells regulate systemic tumor dissemination, a process that begins early at the primary tumor site and goes on until tumor cells detach themselves from the tumor mass and start migrating into the blood or lymphatic vessels. Metastatic cells colonize the target organs and are capable of surviving and growing at distant sites. In this context, osteopontin (OPN) appears to be a key determinant of the crosstalk between cancer cells and the host microenvironment, which in turn modulates immune evasion. OPN is overexpressed in several human carcinomas and has been implicated in inflammation, tumor progression, and metastasis. Thus, it represents one of the most attracting targets for cancer therapy. Within the tumor mass, OPN is secreted in various forms either by the tumor itself or by stroma cells, and it can exert either pro- or antitumorigenic effects according to the cell type and tumor microenvironment. Thus, targeting OPN for therapeutic purposes needs to take into account the heterogeneous functions of the multiple OPN forms with regard to cancer formation and progression. In this review, we will describe the role of systemic, tumor-derived, and stroma-derived OPN, highlighting its pivotal role at the crossroads of inflammation and tumor progression.

Psychological distress and coping in nasopharyngeal cancer: an explorative study in Western Europe.

Nasopharyngeal carcinoma (NPC) is the head and neck cancer with the greatest impact on patients' quality of life. The aim of this explorative study is to investigate the psychological distress, coping strategies and quality of life of NPC patients in the post-treatment observation period. Twenty-one patients disease-free for at least two years were assessed with a medical and a psycho-oncological evaluation. Clinically relevant depressive symptoms (CRD) were present in 23.8% of patients and 33.3% reported clinically relevant anxiety symptoms (CRA). Patients with CRD and CRA showed a significantly higher score in the use of hopelessness/helplessness and anxious preoccupation coping strategies and a worse quality of life. Even in the post-treatment period, about a quarter of patients showed CRD and CRA. Results showed that patients with high anxiety or depressive symptoms seem to use dysfunctional coping strategies, such as hopelessness and anxious preoccupation, more than patients with lower levels of anxiety and depression. The use of these styles of coping thus seems to be associated to a higher presence of CRA or CRD symptomatology and to a worse quality of life.

3D HD Endoscopy in Skull Base Surgery: From Darkness to Light.

The introduction of modern endoscopy in neurosurgery brought light to one of the darkest areas: the skull base. In particular, the trans-nasal route allowed skull base surgeons to visualize and dominate the entire midline skull base. We analyzed our surgical series of 199 patients that were affected by several pathologies (pituitary adenomas, clivalchordomas, craniopharyngioma, Rathke's cleft cysts, tuberculum sellaemeningiomas, and craniovertebral junction pathologies with bulbar compression) and treated each by using a 3D-HD endoscope between December 2012 and December 2015 and reviewed the literature. We present our results in terms of tumor resections and decompression inpatients affected by craniovertebral junction pathologies. Analyzing our direct experience, as well as the literature, we can assert that the amount and accuracy of necessary movements in order to achieve a determined target are affected by the screen clarity and image resolution of the device. Additionally, the experience of the surgeon has an important role in the surgical outcome. Moreover, depth perception is critical in order to obtain precise and accurate movements. Our observations and the experts' opinion indicate that this modality provides improved surgical dexterity by affording the surgeon with depth perception while manipulating tissue and maneuvering the endoscope in the endonasal corridor, which is especially crucial in reducing the learning curve of young neurosurgeons.

Late sensorial alterations in different radiotherapy techniques for nasopharyngeal cancer.

Intensity-modulated radiation therapy (IMRT) for nasopharyngeal cancer (NPC) allowed a better distribution of the dose to the tumor volume, sparing surrounding structures. Aim of the study is the objective evaluation of olfactory and gustatory impairments in patients who underwent chemo-radiotherapy for NPC. Correlation between smell and taste alterations, xerostomy, and radiation technique was investigated. Thirty healthy subjects and 30 patients treated with chemo-radiation therapy for NPC, with at least a 2-years follow-up period, were evaluated. All subjects underwent symptoms evaluation, endoscopic fiber optic nasal examination, taste strips, Sniffin' sticks tests, Radiation Therapy Oncology Group/European Organisation for Research and Treatment of Cancer late radiation morbidity scoring system. Patients were divided in 2 groups: 2-dimensional radiotherapy/conformal 3-dimensional radiotherapy and IMRT. A higher percentage of rhinorrhea, nasal obstruction, xerostomy, hyposmia, hypogeusia, mucosal hyperemia, and presence of nasopharyngeal secretions was found in irradiated subjects (P < 0.05). Concerning olfactory and gustatory scores, we demonstrated a statistically significant difference between healthy subjects and irradiated patients (P < 0.05), with lower gustatory total score in IMRT group (P < 0.01). In conclusion, chemo-radiotherapy for NPC induces long-term smell and taste impairments, which can compromise quality of life. Although based on small samples, it is also important to consider that IMRT can induce higher taste dysfunction compared with traditional techniques.

Detection of herpesviruses 1-6 and community-acquired respiratory viruses in patients with chronic rhinosinusitis with nasal polyposis.

OBJECTIVE: To evaluate the prevalence of human herpesviruses (HHV) 1-6 and community-acquired respiratory viruses (CARVs) in specimens from patients with nasal polyposis undergoing functional endoscopic sinus surgery (FESS) and investigate the potential clinical role. METHODS: Viral occurrence was evaluated by molecular methods in polyp, turbinate mucosa, and pre- and postoperative scraping specimens from 35 consecutive patients at different time points in relation to FESS. RESULTS: Overall, 21 patients (60%) were positive to at least one virus in at least one specimen; in particular, 12.1% of all specimens for HHV-6 (3/35 polyps, 11/31 turbinates, 1 presurgical scraping) and 10.5% for Epstein-Barr virus (EBV) (8/35 polyps, 3/31 turbinates, 1/29 pre- and 1/29 postsurgical scraping), followed by CMV and HSV-1 (both 1.6%; 1/35 polyps, 1/29 postsurgical scraping and 2/35 polyps, respectively). EBV positivity tended to be higher in polyps, as well as HHV-6 in adjacent healthy turbinate mucosa, although no significant association was found. Only one preoperative cytological specimen was positive to parainfluenza virus-1. CONCLUSION: No association between the development of nasal polyps, herpesviruses and CARVs seems to exist. However, the higher EBV frequency in polyps could suggest a causative role or persistence in the inflammatory lymphoid tissue.

Ear, nose and throat foreign bodies: the experience of the Pediatric Hospital of Turin.

AIM: Ear, nose and throat (ENT) foreign body (FB) injuries represent an emerging problem in the paediatric population because of their human and social costs. The aim of the study is the site-specific evaluation of FB injuries in the paediatric population referred to the emergency department of the Pediatric Hospital of Turin. METHODS: This retrospective analysis was carried out sifting medical reports between 2002 and 2011. We collected information about 338 patients' FB characteristics, complications and hospitalisation. RESULTS: The mean age was 4.2 ± 2.9 years. Nose and ear are the most involved anatomical sites, followed by pharynx, oesophagus and trachea-bronchi. The most common FBs are balls, beads and toys parts (29.6%), followed by fishbones (13.6%). A lower mean age is observed in tracheo-bronchial and oesophageal FBs. The 9.2% of cases reported complications. CONCLUSIONS: A quick and proper diagnosis followed by an effective treatment of FB injuries and their complication is mandatory. Surveillance registries have a key role in prevention and management of FB injuries; useful information can be obtained also for nurse and ENT specialist training in order to create professionals ready to recognise and manage FB injuries in the most effective way.

Iatrogenic rhinopharyngeal isolated argyria induced by silver-containing nasal drug.

Localized nasal argyria has been reported in 3 published articles as secondary to occupational exposure and involving the anterior part of the nose. No previous cases of such pathology involving the rhinopharynx were described. Here we report the first case of localized argyria of the roof and of the posterior wall of the rhinopharynx secondary to prolonged use of nasal drops containing colloidal silver protein. The recognition of such pathology can be useful to increase the number of conditions that must be considered in the differential diagnosis of rhinopharyngeal mucosa alterations.

A technical note about flap fixation technique to prevent salivary fistulas in reconstructive oral cavity surgery.

Salivary fistulas are frequent complications in oral oncological reconstructive surgery by means of pedicled or free flaps. The most common risk factors are malnutrition, advanced disease, and healing alterations due to radiation therapy or infections. However, they can be observed also in healthy patients where the flap suture breakdown is the only cause. During the reconstructive phase, flaps are anchored to the remnant tongue, hyoid bone, and residual gingival mucosa; the last structure often does not offer suitable margins for a strong suture. The aim of this study was to propose a transmandibular fixation of the flap that allows, in a safe, efficient, and unexpensive way, the creation of a saliva-proof neofloor of the mouth, independently from the quality and thickness of residual gingival mucosa.

Oral and oropharyngeal malignant minor salivary gland tumors: A retrospective study.

INTRODUCTION: Tumors of minor salivary gland origin are uncommon lesions, representing 2-3 % of all malignant neoplasms of the upper aerodigestive tract and 9-23 % of all salivary gland tumors. The aim of this study is to report the demographic features, sites, histological types and the management and outcomes of oral and oropharyngeal minor salivary gland tumors diagnosed and treated in a University Hospital with a multidisciplinary head and neck team. MATERIALS AND METHODS: A single-center retrospective observational study was conducted in a cohort of patients who received diagnosis of minor salivary gland carcinoma of oropharynx and oral cavity between July 30th 2000 and 30th September 2021. The following data of the included patients were collected: age, gender, smoke history, alcohol consumption, past medical history, comorbidities, anatomic location of the tumor, histopathology, staging, management, and outcomes. RESULTS: A total of 30 cases (16 females, 14 males) of oral and oropharyngeal minor salivary gland tumors were reviewed. The most frequent histotype was polymorphous adenocarcinoma (12 patients). The majority of patients presented with low stage at diagnosis, with 66,66 % of the population classified as stage I or II at diagnosis. On the whole, 29 patients out of 30 benefitted from a surgical approach as first treatment. In 11 patients, adjuvant radiotherapy was performed and in 6 cases it was associated with chemotherapy. Brachytherapy with different timing was performed in 5 cases. The recurrence rate was 26.66 %. Overall disease specific survival at five and ten years was found to be approximately 81 % and 33 % respectively. CONCLUSIONS: Surgery is still considered to be the gold standard of the treatment of minor salivary gland tumors. Radiation therapy, in spite of not being considered as a curative primary treatment for salivary malignancies, is extensively used as an adjuvant treatment.

Influence of Prior Endoscopic Sinus Surgery Extent on Dupilumab Effectiveness in CRSwNP Patients.

BACKGROUND: Guidelines recommend that the vast majority of patients with severe uncontrolled chronic rhinosinusitis with nasal polyps (CRSwNP) should have at least one endoscopic sinus surgery (ESS) prior to starting biologics. Because ESS can be performed with a variable extension, the aim of this study would be to evaluate the association between surgical extensiveness, as measured by ACCESS score, and outcomes collected in patients treated with Dupilumab. MATERIALS AND METHODS: This is a multicentric retrospective study; patients affected by CRSwNP who were subjected to Dupilumab therapy and who underwent at least one ESS prior to Dupilumab initiation were included. ACCESS score was assigned to each patient's pre-Dupilumab CT scan. Subjective and objective parameters (SNOT-22, NPS, VAS scores, Sniffin' Sticks) were collected before and during the administration of therapy. Statistical correlations between ACCESS scores and clinical outcomes were investigated. RESULTS: A total of 145 patients were included; mean time from last previous ESS was 68.6 months, and on average, patients were subjected to 2.2 surgeries. Many correlations with ACCESS scores were demonstrated: better NPS at all timepoints and subjective scores (30-days SNOT-22, VAS nasal obstruction, and rhinorrhea) were achieved in patients with low ACCESS score (more extensive ESS). On the other hand, significantly worse VAS loss of smell values were demonstrated in patients with lower ACCESS scores. CONCLUSION: Dupilumab patients subjected to a prior extensive ESS may have reduced size of polyps and improved subjective indicators, together with a decreased chance to recover smell, when compared with patients who underwent a minimal excision. LEVEL OF EVIDENCE: 3 Laryngoscope, 134:1556-1563, 2024.

Human papillomavirus tumor-infiltrating T-regulatory lymphocytes and P53 codon 72 polymorphisms correlate with clinical staging and prognosis of oropharyngeal cancer.

The association between human papillomavirus (HPV) DNA positivity, p53 codon 72 polymorphisms, and the type of leukocyte infiltration in head and neck squamous cell carcinomas (HNSCC) and their combined impact upon patient survival is poorly investigated. For this reason, leukocyte infiltration profile and p53 codon 72 polymorphisms were assessed in freshly removed HNSCC specimens (N=71 patients). HPV detection was performed by nested-PCR followed by DNA sequencing. Viral loads were determined by quantitative RT-PCR. The choice to investigate fresh instead of archive paraffin-embedded specimens was privileged to avoid possible artifacts due to sample processing. HPV DNA was detected in 14% of cases. Oropharyngeal carcinomas were the most frequently associated with the presence of HPV16 DNA (41%) and were associated with p53 Pro/Pro or Pro/Arg polymorphisms. In HPV16-positive oropharyngeal carcinomas increased infiltrations of CD3+ and FoxP3+ T-cells correlated with higher HPV16 copy numbers. The presence of HPV may trigger a stronger immune response and may be considered a reliable marker for clinical staging and a more favorable prognosis of oropharyngeal carcinoma.