Antigen peptide transporters are upregulated in squamous cell carcinoma of the oral tongue and show sex-specific associations with survival.

Transporter associated with antigen processing 1 (TAP1) and TAP2 serve pivotal roles in adaptive immunity. Tumor cells often show reduced antigen presentation on their surface as one mechanism to escape immune recognition. Whether downregulation of TAPs is a common mechanism of tumor immune evasion in squamous cell carcinoma of the oral tongue (SCCOT) is unclear. In the present study, samples from 78 patients with SCCOT and 17 patients with benign hyperplastic tongue lesions were analyzed for TAP1 and TAP2 expression by immunohistochemistry. The percentage of positive cells and staining intensity were scored. Associations with clinicopathological variables and survival outcome were also investigated. The results demonstrated that TAP1 and TAP2 levels were highly associated with each other in individual samples and were upregulated in SCCOT compared with benign lesions (P<0.001). The proportion of TAP1- or TAP2-positive tumor cells was >80% in all but two of the tumors, whereas 25.6 and 23.0% of the tumors showed weak intensity of TAP1 and TAP2, respectively. There were no significant associations with clinicopathological variables or survival outcomes between TAP-intermediate/strong and TAP-weak tumors. However, in patients <70 years old and with early stage SCCOT, male patients had better outcomes than female patients (log-rank P<0.05), and the best outcome was observed in male patients with intermediate/strong TAP expression. In conclusion, loss of TAP was not a frequent event in SCCOT and stronger TAP expression in male patients was associated with improved survival, providing further evidence for sex-specific immune modulation in cancer.

Base of tongue squamous cell carcinomas, outcome depending on treatment strategy and p16 status. A population-based study from the Swedish Head and Neck Cancer Register.

BACKGROUND: The base of tongue squamous cell carcinoma (BOTSCC) is mainly an HPV-related tumor. Radiotherapy (EBRT) ± concomitant chemotherapy (CT) is the backbone of the curatively intended treatment, with brachytherapy (BT) boost as an option. With four different treatment strategies in Sweden, a retrospective study based on the population-based Swedish Head and Neck Cancer Register (SweHNCR) was initiated. MATERIAL AND METHODS: Data on tumors, treatment and outcomes in patients with BOTSCC treated between 2008 and 2014 were validated through medical records and updated as needed. Data on p16 status were updated or completed with immunohistochemical analysis of archived tumor material. Tumors were reclassified according to the UICC 8th edition. RESULTS: Treatment was EBRT, EBRT + CT, EBRT + BT or EBRT + CT + BT in 151, 145, 82 and 167 patients respectively (n = 545). A p16 analysis was available in 414 cases; 338 were p16+ and 76 p16-. 5-year overall survival (OS) was 68% (95% CI: 64-72%), with76% and 37% for p16+ patients and p16- patients, respectively. An increase in OS was found with the addition of CT to EBRT for patients with p16+ tumors, stages II-III, but for patients with tumor stage I, p16+ (UICC 8) none of the treatment strategies was superior to EBRT alone. CONCLUSION: In the present retrospective population-based study of BOTSCC brachytherapy was found to be of no beneficial value in curatively intended treatment. An increase in survival was found for EBRT + CT compared to EBRT alone in patients with advanced cases, stages II and III (UICC 8), but none of the regimes was significantly superior to EBRT as a single treatment modality for stage I (UICC 8), provided there was p16 positivity in the tumor. In the small group of patients with p16- tumors, a poorer prognosis was found, but the small sample size did not allow any comparisons between different treatment strategies.

Comparison Between the Video Head Impulse Test and Caloric Irrigation During Acute Vertigo.

Caloric irrigation (CI) is the gold standard to investigate peripheral vestibular dysfunction. The video head impulse test (vHIT) is faster and more accessible and may be useful during acute vertigo stroke risk differentiation. Comparative studies between the two methods are needed. The objective of this study was to compare vestibular function data derived from caloric irrigation with that from vHIT. This study included 80 patients with acute onset vertigo who underwent caloric irrigation and vHIT. CI derived sum of slow phase velocities (SPVs) and unilateral weakness (UW) were compared with vHIT vestibulo-ocular reflex (VOR) gain and gain asymmetry (GA) using correlation analyses. Optimal cut offs for vHIT VOR gain and GA were calculated using Youden indexes. There was a strong positive correlation between the asymmetry measures UW and GA whereas the correlation between the sum of SPVs and VOR gain was weaker. The optimal cut offs to diagnose unilateral vestibular weakness were 0.80 for VOR gain and 28% for GA; with specificities for predicting normal caloric irrigation results of 55% and 93%, respectively. In one third of cases the results from caloric irrigation and vHIT dissociated. The results from vHIT correlated with those from CI, still neither test seem to have the accuracy to replace the other. GA appears as an attractive measure in acute vertigo as the high specificity can be used to identify those with a substantial probability of normal vestibular function in need of more comprehensive work-up for central causes. To diagnose vestibular dysfunction, CI remains gold standard.

Variation in Plasma Levels of TRAF2 Protein During Development of Squamous Cell Carcinoma of the Oral Tongue.

As early detection is crucial for improvement of cancer prognosis, we searched for biomarkers in plasma from individuals who later developed squamous cell carcinoma of the oral tongue (SCCOT) as well as in patients with an already established SCCOT. Levels of 261 proteins related to inflammation and/or tumor processes were measured using the proximity extension assay (PEA) in 179 plasma samples (42 collected before diagnosis of SCCOT with 81 matched controls; 28 collected at diagnosis of SCCOT with 28 matched controls). Statistical modeling tools principal component analysis (PCA) and orthogonal partial least square - discriminant analysis (OPLS-DA) were applied to provide insights into separations between groups. PCA models failed to achieve group separation of SCCOT patients from controls based on protein levels in samples taken prior to diagnosis or at the time of diagnosis. For pre-diagnostic samples and their controls, no significant OPLS-DA model was identified. Potentials for separating pre-diagnostic samples collected up to five years before diagnosis (n = 15) from matched controls (n = 28) were seen in four proteins. For diagnostic samples and controls, the OPLS-DA model indicated that 21 proteins were important for group separation. TNF receptor associated factor 2 (TRAF2), decreased in pre-diagnostic plasma (< 5 years) but increased at diagnosis, was the only protein showing altered levels before and at diagnosis of SCCOT (p-value < 0.05). Taken together, changes in plasma protein profiles at diagnosis were evident, but not reliably detectable in pre-diagnostic samples taken before clinical signs of tumor development. Variation in protein levels during cancer development poses a challenge for the identification of biomarkers that could predict SCCOT development.

Downregulation of TAP1 in Tumor-Free Tongue Contralateral to Squamous Cell Carcinoma of the Oral Tongue, an Indicator of Better Survival.

Oral cancers are surrounded by epithelium that histologically might seem normal, but genetically has aberrations. In patients with squamous cell carcinoma of the oral tongue (SCCOT), it is therefore important to study not only the tumor but also the clinically tumor-free contralateral tongue tissue that remains in the patient after treatment to map changes of prognostic and/or diagnostic value. The transporter associated with antigen processing (TAP) dimer is a key factor in the process of activating cytotoxic T cells. By downregulating the expression of TAP, tumor cells can escape cytotoxic T cell recognition. Biopsies from tumor and clinically tumor-free contralateral tongue tissue in 21 patients with SCCOT were analyzed together with tongue biopsies from 14 healthy individuals, which served as the control group. Dividing patients into TAP1-high and TAP1-low groups according to the median TAP1 level in tumor-free samples showed that patients with lower TAP1 mRNA levels in tumor-free samples had better overall (p = 0.003) and disease-free survival (p = 0.002). The results showing that TAP1 levels in tumor-free tongue tissue contralateral to the SCCOT correlate with survival is an important contribution to early diagnosis and follow up of SCCOT.

High podoplanin and low E-cadherin levels correlate with better prognosis in adenoid cystic carcinoma.

Objectives: As tumour spread is a complicating event for malignant salivary gland tumours, we decided to study factors related to cell adhesion and lymph vessel formation in two of the three most common malignant salivary gland tumours, mucoepidermoid carcinoma (MEC) and adenoid cystic carcinoma (ACC), to clarify the clinical relevance and potential usefulness of these factors. We also included a group of polymorphous adenocarcinoma (PAC) as this tumour, in common with ACC often shows perineural growth, but in contrast to ACC has an overall good prognosis. Material and methods: Eighteen patients with ACC, 15 with MEC, and six with PAC were included. Protein expression of podoplanin and E-cadherin was evaluated as percentage of cells expressing the protein and intensity of expression. Ki-67 expression was included in the study as a marker of proliferative activity. Results: Looking at podoplanin, significantly more ACCs were high expressing compared with both MECs (P = .001) and PACs (P = .028). Also when looking at Ki-67 expression, significantly more ACCs were high expressing compared with MECs (P = .003). Significantly better survival was also seen for ACCs with high podoplanin (P = .022) and low E-cadherin expression (P = .021), respectively. Conclusions: Our findings show that ACCs express significantly higher levels of podoplanin compared with both MECs and PACs and that high levels are correlated to better survival. Even though the group of PACs analysed was small, these tumours, despite their tendency to perineural spread, which they have in common with ACC, differ from ACCs concerning expression of factors with a known connection to tumour spread.

Autoclaving of the middle ear ossicles in an animal experimental model.

CONCLUSION: Autoclaving the ossicles for 4 min at 134°C impacts superficial devitalization and elimination of the squamous epithelium on the surface of the ossicles. Bone maintains the integrity, firmness, and lamellar structure and ossicles are integrated into the middle ear without any adverse reactions. OBJECTIVE: Sixteen guinea pigs were used to explore the effect of autoclaving on middle ear ossicles. METHODS: Harvested incudomallear complex was autoclaved for 4 min at 134°C and implanted back into the middle ear cavity. Exploration of the middle ear was carried out 30 days after implantation. Results were compared with a control group of 16 non-autoclaved ossicles. RESULTS: Autoclaved ossicles maintained their integrity, firmness, shape, and lamellar structure with Haversian systems. Autoclaving substantially decreased the vitality of the ossicles. The middle ear mucosa overgrew on the ossicular surface. No adverse reactions of soft tissue against ossicles occurred. Although the autoclaved ossicles were implanted with tympanic membrane (squamous epithelium) the histological examination did not demonstrate any residuum of squamous epithelium. In the control group we proved the presence of squamous epithelium on the manubrium surface in all cases; all ossicles were vital without signs of ostitis.

Cytology of the nasal mucosa after total laryngectomy.

CONCLUSION: This study demonstrates morphological changes in the nasal mucosa as a consequence of functional changes of the nasal cavity after total laryngectomy (TLE). OBJECTIVE: Observation of the changes of the nasal mucosa in patients after TLE. PATIENTS AND METHODS: A cohort observational study contained 30 patients after TLE. These patients underwent nasal endoscopy and cytological and microbiological examination of the nasal mucosa. The control group comprised 30 patients. RESULTS: In patients who underwent TLE, morphological changes occurred in the nasal mucosa. The hyperplasia of the cells in the basal zone was the most remarkable change after TLE. The difference was statistically significant (p=0.0002) in comparison with the control group. No statistically significant difference was shown in the incidence of squamous cell metaplasia. The inflammatory changes in the nasal mucosa were found in only 10% of patients after TLE; in comparison with the control group the statistically significant decrease was proven (p=0.003). The presence of bacteria in the nasal mucosa without any signs of inflammation was demonstrated in 27% of the patients who underwent TLE. That finding was not seen in the control group. The statistically significant difference was demonstrated (p=0.0046).

Histomorphologic study of nasal turbinates after surgical treatment: a comparison of laser surgery and radiofrequency-induced thermotherapy effects in animals.

CONCLUSIONS: From the clinical point of view, the healing process following radiofrequency-induced thermotherapy (RFITT) is faster and less painful for the patient. This corresponds with the histopathological findings, as in a case of diode laser treatment, the damage to the tissue was greater, and the regenerative and reparative processes were less prominent. OBJECTIVE: Comparison of histopathologic changes and the healing process in the turbinate tissue regarding the kind of treatment and intensity of energy used for surgery. MATERIALS AND METHODS: Pigs were chosen as laboratory animals for this study. The animals were divided into two groups. Two different techniques were used: treatment with diode laser fiber applied submucosally in contact mode and RFITT. The first tissue samples were taken on the third postoperative day; further sampling was done on the eight postoperative day. RESULTS: Histological features of the specimens taken from turbinates 8 days after the surgery included necrosis and ulceration, fibrin deposition in the mucosa, necrotizing sialometaplasia, as well as proliferation of the granulation tissue. Generally, the changes found in the turbinates treated by diode laser were more severe, with more intensive tissue damage and less prominent regenerative and reparative changes.