Human papillomavirus (HPV) DNA methylation changes in HPV-associated head and neck cancer.

Despite the rising incidence, currently, there are no early detection methods for HPV-driven HNC (HPV-HNC). Cervical cancer studies suggest that HPV DNA methylation changes can be used as a biomarker to discriminate cancer patients from HPV-infected individuals. As such, this study was designed to establish a protocol to evaluate DNA methylation changes in HPV late genes and long control region (LCR) in saliva samples of HPV-HNC patients and HPV-positive controls. Higher methylation levels were detected in HPV late genes (L1 and L2) in both tumour and saliva samples of HPV-HNC patients compared with HPV-positive controls. Moreover, methylation patterns between tumours and corresponding saliva samples were observed to have a strong correlation (Passing-Bablok regression analysis; τ = 0.7483, P < 0.0001). Considering the differences between HNC and controls in methylation levels in late genes, and considering primer amplification efficiencies, 13 CpG sites located at L1 and L2 genes were selected for further evaluation. A total of 18 HNC saliva samples and 10 control saliva samples were assessed for the methylation levels in the selected sites. From the CpG sites evaluated statistically significant differences were identified for CpG sites at L2-CpG 6 (P = 0.0004), L1-CpG 3 (P = 0.0144), L1-CpG 2 (P = 0.0395) and L2-CpG 19 (P = 0.0455). Our pilot data indicate that higher levels of DNA methylation in HPV late genes are indicative of HPV-HNC risk, and it is a potential supplementary biomarker for salivary HPV detection-based HPV-HNC screening.

Outcomes of a first point of contact speech language therapy clinic for patients requiring vocal cord check pre and post thyroid/parathyroid surgery.

INTRODUCTION: Speech Language Therapy First Point of Contact Clinic (SLT-FPOCC) models can assist assessment of low-risk patient populations referred to ear, nose and throat (ENT) services. To further improve ENT waitlist management and compliance with best-practice care, consideration of other low-risk populations that could be safely managed through this service model is needed. The aims of this paper are to evaluate the clinical and service outcomes of completing vocal cord check (VCC) assessments for patients' pre and post thyroid/parathyroid surgery within an SLT-FPOCC model and examine consumer perceptions. METHODS & PROCEDURES: The service followed existing SLT-FPOCC procedures, with ENT triaging referrals, then SLT completing pre- and postoperative VCC assessment (interview, perceptual assessment, flexible nasendoscopy), with assessment data later reviewed by ENT to diagnose laryngeal pathology. Clinical and service outcomes were collected prospectively. Patients completed an anonymous post-service satisfaction survey. RESULTS: Of the first 100 patients referred for preoperative VCCs, SLT assessment identified 42 with dysphonia and 30 reporting dysphagia, while ENT confirmed 9 with significant preoperative anatomical findings. Eighty-three underwent surgery, with 63 (95 nerves at surgical risk) returning for a postoperative VCC. Postoperative VCC identified three temporary neuropraxias (3.2%) and three unilateral vocal fold paresis (3.2%). Patients were highly satisfied with the service. All 163 pre-/postoperative VCCs were completed with no adverse events. CONCLUSION & IMPLICATIONS: The current data support SLT-FPOCC service expansion to include pre and post thyroid/parathyroid surgery VCC checks, with positive consumer perception. The model supports delivery of best practice management (i.e., pre- and postoperative VCC) for patients receiving surgery for thyroid/parathyroid dysfunction, and associated efficiencies for ENT services. WHAT THIS PAPER ADDS: What is already known Assessment of laryngeal function via flexible nasoendoscopy is recommended best practice for patients pre and postthyroid/parathyroid surgery, as recurrent laryngeal nerve injury is a low incidence (<10%), yet well-recognised risk of these surgeries. Traditionally, general surgeons refer presurgical patients to ear, nose and throat (ENT) for vocal cord check (VCC) assessment. However, with access to specialist outpatient services under increasing pressure, there is growing support for utilisation of other health professionals, such as speech-language therapists working in first point of contact (FPOCC) models, to assist with the administration of pre- and postsurgical assessments of such low-risk populations. What this study adds This work expands on the emerging body of evidence for speech language therapy (SLT) led FPOCC models within ENT outpatient services, providing clinical and service outcomes to support the safety of a new model designed to administer VCCs for patients pre and post thyroid/parathyroid surgery. Adopting a similar model to a prior published SLT-led FPOCC model, the trained SLT completes the pre- and postsurgical VCC including flexible nasoendoscopy and videostroboscopy, with images and clinical information then presented to ENT for diagnosis and management planning. This study also provides the first data on consumer perceptions of this type of service model. Clinical implications of this study Data on 100 consecutive presurgical patients revealed positive service findings, supporting the safety of this model. Nature and incidence of clinical findings pre and post surgery were consistent with previously published studies using traditional models of care (i.e., ENT completing the flexible nasendoscopy). Consumer perception was positive. This model enables delivery of pre-and postsurgical assessments for patients receiving thyroid/parathyroid surgery, consistent with best practice care, and reduces burden on ENT services. In total 163 ENT appointments were avoided with this model, with positive implications for ENT waitlist management.

Evaluation of health service outcomes for an audiology first point of contact retrocochlear clinic: a 6-year retrospective cohort study.

OBJECTIVE: Although existing studies of audiology first point of contact clinics which screen for retrocochlear pathology have demonstrated positive clinical outcomes, they have provided limited information regarding service impacts. Thus, this study aimed to evaluate both the clinical and health service outcomes of an audiology first point of contact (FPOC) clinic for adults referred to ENT services with suspected retrocochlear pathology. DESIGN: Retrospective cohort study. STUDY SAMPLE: All 1123 patients referred to the clinic over a 6-year period (2013-2019). RESULTS: Most (73.7%) of the 1123 patients referred to the Retrocochlear Clinic were managed and discharged by the audiologist and did not require ENT appointment. Almost half (43.1%) were directly referred for MRI imaging, of which 4 (1.1%) were diagnosed with Vestibular Schwannoma. Waiting times for first appointments significantly (p < 0.001) reduced from a median of 748 days to 63.5 days over the 6-year period. Attendance rates also significantly (p < 0.001) improved over this time (from 52.2% to 90%). There were no adverse events reported. Of those discharged without attending an ENT appointment, 1.8% were rereferred to ENT within 12 months of discharge. CONCLUSIONS: This audiology FPOC Retrocochlear Clinic was shown to be a safe and effective alternative service model.

Oral HPV16 Prevalence in Oral Potentially Malignant Disorders and Oral Cavity Cancers.

The role of human papillomavirus type 16 (HPV16) in oral potentially malignant disorders (OPMD) and oral cavity carcinoma (OC) is still under debate. We investigated HPV16 prevalence in unstimulated saliva, oral rinse samples, oral swabs and tumour biopsies collected from OPMD (n = 83) and OC (n = 106) patients. HPV16 genotype, viral load, physical status (episomal vs. integrated) and tumour p16INK4a expression were determined. Oral HPV16 prevalence was higher in OC than in OPMD, but this difference was not statistically significant (7.5% (8/106) versus 3.6% (3/83), odds ratio (OR): 2.18, 95% confidence interval (CI): 0.56, 8.48, p = 0.26). There was a significant association (p < 0.05) between oral HPV16 infection and heavy tobacco consumption. Real-time PCR results indicated that no integration events occurred in either OPMD or OC cases based on the HPV16 E2/E6 ratio. HPV16 positive OPMD and OC patients had similar HPV16 E2 and E6 viral loads. The inter-rater agreement between tumour p16INK4a expression and oral HPV16 infection was considered as fair (k = 0.361) for OC. Our data suggest that the involvement of HPV16 in oral carcinogenesis is limited.

Effectiveness and Safety of Advanced Audiology-Led Triage in Pediatric Otolaryngology Services.

OBJECTIVES: Expansion of the scopes of practice of allied health practitioners has the potential to improve the efficiency and cost-effectiveness of healthcare, given the identified shortages in medical personnel. Despite numerous examples in other allied health disciplines, this has yet to be applied to pediatric Audiology. This study aimed to investigate the effectiveness and safety of using audiologists with advanced training to independently triage children referred to otolaryngology (ORL) services, and compare the subsequent use of specialist resources, and postoperative grommet care to a standard medical ORL service. DESIGN: One hundred twenty children consecutively referred to a large ORL outpatient service in Queensland, Australia, for middle ear and hearing concerns were prospectively allocated to either the ORL service or Advanced Audiology-led service. Demographic and clinical data were extracted from electronic medical records and compared between the two services. Clinical incidents and adverse events were recorded for the Advanced Audiology-led service. RESULTS: Approximately half of all children referred to ORL for middle ear or hearing concerns were discharged without requiring any treatment, with the remaining half offered surgical treatment. The Advanced Audiology-led model increased the proportion of children assessed by ORL that proceeded to surgery from 57% to 82% compared with the standard medical ORL model. Children followed up by the audiologists after grommet insertion were more likely to be discharged independently and at the first postoperative review appointment compared with the standard medical ORL service. There were no reports of adverse events or long-term bilateral hearing loss after discharge by the Advanced Audiology-led service. CONCLUSIONS: These findings indicate that an Advanced Audiology-led service provides a safe and effective triaging model for the independent management of children not requiring treatment, and children requiring routine postoperative grommet review, and improves the effective use of specialist resource compared with the standard medical ORL service.

A Collective Route to Head and Neck Cancer Metastasis.

Distant metastasis (DM) from head and neck cancers (HNC) portends a poor patient prognosis. Despite its important biological role, little is known about the cells which seed these DM. Circulating tumour cells (CTCs) represent a transient cancer cell population, which circulate in HNC patients' peripheral blood and seed at distant sites. Capture and analysis of CTCs offers insights into tumour metastasis and can facilitate treatment strategies. Whilst the data on singular CTCs have shown clinical significance, the role of CTC clusters in metastasis remains limited. In this pilot study, we assessed 60 treatment naïve HNC patients for CTCs with disease ranging from early to advanced stages, for CTC clusters utilizing spiral CTC enrichment technology. Single CTCs were isolated in 18/60-30% (Ranging from Stage I-IV), CTC clusters in 15/60-25% (exclusively Stage IV) with 3/15-20% of CTC clusters also containing leukocytes. The presence of CTC clusters associated with the development of distant metastatic disease(P = 0.0313). This study demonstrates that CTC clusters are found in locally advanced patients, and this may be an important prognostic marker. In vivo and in vitro studies are warranted to determine the role of these CTC clusters, in particular, whether leukocyte involvement in CTC clusters has clinical relevance.

Surgical management of plunging ranulas: a 10-year case series in South East Queensland.

BACKGROUND: Plunging ranulas are rare mucous extravasation pseudocysts that arise in the floor of the mouth and pass into the submandibular space of the neck. The aim of this study was to investigate the diagnosis, surgical management and outcomes of patients with a plunging ranula at our institution in South East Queensland over a 10-year period. METHODS: A retrospective analysis of adult patients diagnosed with and treated for plunging ranula between 2006 and 2016 at Logan Hospital was conducted. Patient demographics, preoperative investigations, surgical management and post-operative outcomes were collected from medical records. RESULTS: A total of 18 adult patients were treated for plunging ranula. Of the 18 cases, 17 were treated via transoral excision of the sublingual gland. The mean age at presentation was 28.8 years with a 3:1 female to male predominance. Fifty-six percent of patients were of Polynesian descent. The success rate was 94% with only one patient experiencing recurrence and requiring re-excision of remnant sublingual gland tissue. Three patients (17%) developed complications related to post-operative bleeding. There was a slight predominance for right-sided disease (56%) compared with left and one case of bilateral plunging ranulas in this series. CONCLUSION: This study demonstrates that excision of the sublingual gland is an effective and safe treatment for plunging ranula. The majority of plunging ranulas occur in patients aged <30 years with a higher incidence in patients of Polynesian heritage, which is consistent with previous studies suggesting a possible underlying genetic predisposition for this condition.

Diagnosis and management of hearing loss in elderly patients.

BACKGROUND: Hearing loss is the most common sensory deficit in elderly patients, and is often under-recognised and poorly managed. It is essential for all clinicians to have awareness and knowledge in this field to enable the institution of early and appropriate care. OBJECTIVE: The goal of this article is to review the causes, diagnosis and management of hearing loss as it applies to elderly patients. The review describes a useful approach that clinicians can apply to daily practice. DISCUSSION: For elderly patients presenting with hearing loss, the basic assessment should include history, physical examination and pure tone audiometry. Management depends on the cause and type of hearing loss, and options include medical therapy, surgery and amplification. In the absence of a simple and correctable cause, consider referring patients to an otolaryngologist for further assessment.

Differential rate responses to nicotine in rat heart: evidence for two classes of nicotinic receptors.

Nicotinic acetylcholine receptors are pentameric, typically being composed of two or more different subunits. To investigate which receptor subtypes are active in the heart, we initiated a series of experiments using an isolated perfused rat heart (Langendorff) preparation. Nicotine administration (100 microM) caused a brief decrease (-7 +/- 2%) followed by a much larger increase (17 +/- 5%) in heart rate that slowly returned to baseline within 10 to 15 min. The nicotine-induced decrease in heart rate could be abolished by an alpha7-specific antagonist, alpha-bungarotoxin (100 nM). In contrast, the nicotine-induced increase in heart rate persisted in the presence of alpha-bungarotoxin. These results suggest that the nicotinic acetylcholine receptors (nAChRs) that mediate the initial decrease in heart rate probably contain alpha7 subunits, whereas those that mediate the increase in heart rate probably do not contain alpha7 subunits. To investigate which subunits may contribute to the nicotine-induced increase in heart rate, we repeated our experiments with cytisine, an agonist at nAChRs that contain beta4 subunits. The cytisine results were similar to those obtained with nicotine, thereby suggesting that the nAChRs on sympathetic nerve terminals in the heart probably contain beta4 subunits. Thus, the results of this study show that pharmacologically distinct nAChRs are responsible for the differential effects of nicotine on heart rate. More specifically, our results suggest that alpha7 subunits participate in the initial nicotine-induced heart rate decrease, whereas beta4 subunits help to mediate the subsequent nicotine-induced rise in heart rate.