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Oropharyngeal cancer is increasingly caused by human papillomavirus (HPV), and this increase is believed to be caused by changing sexual behaviour. It has been hypothesised that an immune response to HPV through sexual intercourse is much stronger than an immune response elicited from oral sex. Therefore, people who have their debut of oral sex before or at the same time as sexual intercourse would have a weaker immune response to HPV and hence be more likely to develop a persistent oral HPV infection and oropharyngeal cancer. Drake et al (Cancer. 2021;127[7]:1029-1038) found some evidence that supported this hypothesis. We have reanalysed two of our Australian cohorts with similar data in order to provide a perspective of Drake and colleagues' publication, as sexual behaviour varies depending on culture and geographical location. We found that engaging in oral sex (OR 4.46, 95% CI [1.88-10.62]) and being younger than 20 years at oral sex debut (OR 9.46, 95% CI [3.53-25.31]) were both very strong risk factors for oropharyngeal cancer. Participants in the general population cohort who had their sexual intercourse debut before the age of 18 were more likely to be oral HPV positive (OR 2.69, 95% CI [1.50-4.83]). Oral sex debut before sexual intercourse debut was quite uncommon in our two Australian cohorts. However, timing of or sexual debuts may further add to risks of oropharyngeal cancer, and future studies should be designed to investigate timing and order of sexual debuts to help clarify the roles of these potential causal factors.

Immune checkpoint inhibitors have shown promising antitumour activity. Application in head and neck cutaneous squamous cell carcinoma (cSCC) large nerve perineural spread (PNS) is limited.Retrospective review of 13 patients with PNS receiving anti-PD-1 therapy from September 2017 to May 2021 is presented. Primary endpoints were objective response (complete or partial response) and median time to progression, determined by Head and Neck Multi-Disciplinary Team (MDT) and independent radiology review of magnetic resonance imaging (MRI) and/or computed tomography/positron emission tomography (CT/PET).Objective response was observed in 9/13 patients (69%), with complete response in 6 (46%) and partial response in 3 patients (23%). Median time to response was 2.1 months (IQR 1.8-2.7 months). There were 3 (23%) patients with progressive disease, with median time to progression of 3.5 months. There were no grade 3-4 treatment related adverse events.This case series supports developing evidence for anti-PD-1 checkpoint inhibitor therapy for perineural spread, supporting future prospective clinical trials in this patient population.

Background: Smoking status at point of diagnosis is not used in defining risk groups for human papillomavirus (HPV)-associated oropharyngeal cancer (OPC) despite its prognostic value in head and neck cancer. Methods: Retrospective analysis of consecutive patients treated with chemoradiotherapy between January 2005 and July 2017 was performed with multivariable analysis to explore the impact of smoking status at diagnosis (current/former/never) on overall survival (OS), cancer-specific survival (CSS) and progression-free survival (PFS). Results: Median follow-up was 61 months. Four hundred and four patients were included. Current smokers had inferior OS versus never and former smokers [adjusted HR 2.37 (95% CI 1.26–4.45, p < 0.01) and 2.58 (95% CI 1.40–4.73, p < 0.01), respectively] and inferior PFS versus never smokers [adjusted HR 1.83 (95% CI 1.00–3.35, p = 0.04)]. Smoking status did not predict for CSS. Conclusion: Detailed smoking behavior should be considered in refining risk groups in HPV-associated OPC treated with radiotherapy and in future trial design eligibility and stratification.

Background: Head and neck squamous cell carcinoma, and in particular hypopharyngeal squamous cell carcinoma, has long been associated with disfiguring treatment options, significant morbidity and limited long-term survival outcomes. Total pharyngolaryngectomy (TPL) with free flap reconstruction followed by post-operative radiation therapy or chemoradiotherapy is a widely accepted treatment of choice for advanced disease of the hypopharynx. Methods: Our unit undertook a 11-year review of all primary TPL patients aiming to provide an update on survival outcomes, morbidity, post-operative complications and evolving management strategies. We report one of the largest single-centre series to date with 89 patients undergoing primary TPL between 2003 and 2013, and compare these outcomes to 180 patients undergoing TPL at the same facility in the previous 23 years. Results: Between study periods, we saw a shift in patient population towards higher stage disease (T-stage 3 or 4 97% 2003–2013; 68% 1979–2002) and increased nodal involvement (node positive 88% 2003–2013; 70% 1979–2002) without a subsequent reduction in 5-year disease-specific survival (52% 2003–2013; 52% 1979–2002) or 5-year overall survival (32% 2003–2013; 33% 1979–2002).

Now is an exciting era of development in immunotherapy checkpoint inhibitors and their effect on the treatment of NPC. While the general prognosis of R/M disease is poor, immunotherapy offers some promise in a malignancy associated with EBV and characterized by a peritumoural immune infiltrate. Our study aims to review past and on-going clinical trials of monoclonal antibody therapies against the checkpoint inhibitors (e.g. PD1 and CTLA-4), in R/M NPC. All randomized and nonrandomized controlled trials involving immune checkpoint inhibitor interventions for treatment of NPC were included in the study. We utilized a validated "risk of bias" tool to assess study quality. Four separate Phase I-II trials report the potential of PD1 inhibitor treatment for patients with NPC. Within the observed groups, camrelizumab combined with chemotherapy achieved an objective response in 91% of patients as first-line treatment for metastatic NPC (PFS 68% at 1-year) but this was associated with a high rate of grade >3 adverse events (87%; CTCAE version 4.03). The remaining three studies focused on recurrent NPC disease in patients who had received at least one line of prior chemotherapy. Within this group, camrelizumab monotherapy achieved an objective response in 34% of patients (PFS 27% at 1-year; range across all three studies 20.5-34%). No NPC trial has yet reported on specific outcomes for non-PD1 checkpoint inhibitors but 11 on-going studies include alternative targets (e.g. PD-L1/CTLA-4) as combination or monotherapy treatments. In considering checkpoint immunotherapies for NPC, initial results show promise for anti-PD1 interventions. Further phase I-III trials are in progress to clarify clinical outcomes, fully determine safety profiles, and optimize drug combinations and administration schedules.

The incidence of oropharyngeal squamous cell carcinomas (SCCs) is increasing and is believed to reflect changing sexual practices in recent decades. For this case-case comparative study, we collected medical and life-style information and data on sexual behavior from 478 patients treated at the head and neck clinic of a tertiary hospital in Brisbane, Australia. Patients were grouped as (i) oropharyngeal SCC (n 5 96), (ii) oral cavity, larynx and hypopharynx SCC ("other HNSCCs," n 5 96), (iii) other SCCs (n 5 141), and (iv) other diagnoses (n 5 145). We fitted multivariable logistic regression models to estimate odds ratios (ORs) and 95% confidence intervals (CIs) associated with lifestyle factors and sexual behaviors. Compared to the other three patient groups, the oropharyngeal SCC patients had overall more sexual lifetime partners (kissing, oral sex and sexual intercourse). Oropharyngeal SCC patients were significantly more likely to have ever given oral sex compared to the other three patient groups-93% of oropharyngeal SCC patients, 64% of other HNSCC patients, and 58% of patients with other SCC or other diagnoses. Oropharyngeal SCC patients were significantly more likely to have given oral sex to four or more partners when compared to patients with other HNSCC (odds ratio [OR] 11.9; 95% CI 3.5-40.1), other SCC (OR 16.6; 95% CI 5.3-52.0) or patients with other diagnoses (OR 25.2; 95% CI 7.8-81.7). The very strong associations reported here between oral sex practices and risks of oropharyngeal SCC support the hypothesis that sexually transmitted HPV infections cause some of these cancers.

Objectives/Hypothesis To investigate balance, community mobility, gaze instability, and dizziness handicap and assess falls risk in people who are conservatively managed with small vestibular schwannoma (VS). Study Design Cross-sectional study with controls. Methods The study involved 18 people (mean age 58.7 ± 12.2 years) diagnosed with VS (

BackgroundWhile human papillomavirus (HPV) is an accepted risk factor for oropharyngeal squamous cell carcinoma (SCC), its aetiological role in oral cavity SCC remains unclear. This study aimed to determine the HPV prevalence in an Australian population.

Objectives/Hypothesis: To determine the feasibility of using a mouse tumor model as a microsurgical training tool for otolaryngology-head and neck surgery (OHNS) trainees.

Background Queensland, Australia, has the highest rates of cutaneous squamous cell carcinoma (SCC). Perineural invasion (PNI) is associated with reduced local control and survival. Methods A retrospective review of a prospective database of patients with clinical PNI from cutaneous SCC of the head and neck (SCCHN) treated with surgery and postoperative radiotherapy (PORT) between 2000 and 2011 and a minimum of 24 months follow-up. Patients were excluded if immunosuppressed, had non-SCC histology, or were treated palliatively. Results Fifty patients (mean age, 60 years) with median follow-up of 50 months were included in this study. A total of 54.8% of known primary tumors had incidental PNI. Ten percent had nodal disease at presentation. MRI neurogram was positive in 95.8%. Recurrence-free survival (RFS) at 5-years was 62%. Five-year disease-specific survival (DSS) and overall survival (OS) were 75% and 64%, respectively. There were no perioperative deaths. Conclusion This report demonstrates that long-term survival is achievable in patients with clinical PNI from cutaneous SCCHN after surgery and PORT.

This article by the Perineural Invasion (PNI) Registry Group aims to clarify clinical and histopathological ambiguities surrounding PNI in non-melanoma skin cancer (NMSC). PNI is reportedly present in approximately 2–6% of cases of NMSC and is associated with greater rates of morbidity and mortality. The distinction between clinical PNI and incidental PNI is somewhat unclear, especially in regard to management and prognosis. One important objective of the PNI Registry is to develop a standardised method of classifying perineural invasion. Hence, in this article we propose a definition for PNI and for its sub-classification. This article also provides a critical analysis of the current literature on the treatment of incidental PNI by evaluating the key cohort studies that have investigated the use of surgery or radiotherapy in the management of incidental PNI. At present, there are no universal clinical guidelines that specify the acceptable treatment of NMSC exhibiting incidental PNI. Consequently, patients often receive surgery with varying wider margins, or radiotherapy despite the limited evidence substantiating such management options. It is evident from the existing literature that current opinion is divided over the benefit of adjuvant radiotherapy. Certain prognostic factors have been proposed, such as the size and depth of tumour invasion, nerve diameter, the presence of multifocal PNI and the type of tumour. The PNI Registry is a web-based registry that has been developed to assist in attaining further data pertaining to incidental PNI in NMSC. It is envisaged that this information will provide the foundation for identifying and defining best practice in managing incidental PNI.

BackgroundNonmelanoma skin cancer (NMSC) with perineural invasion (PNI) is most commonly seen in cutaneous squamous cell carcinoma of the head and neck (SCCHN). The cranial nerves are a conduit for skin cancer to reach the brainstem.

Background. The purpose of this study was to assess whether a positron emission tomography (PET)-directed policy remains appropriate for managing neck nodes (N3; >6 cm) in head and neck squamous cell carcinoma (HNSCC). Methods. All patients with N3 (>6 cm) HNSCC treated with definitive che- moradiotherapy (CRT) at our institution between 2005 and 2012 were included in the analysis. Patients underwent PET assessment before and 12 weeks after CRT. Neck dissections were performed for PET-avid resid- ual nodal abnormalities after complete response at the primary site. Rate of isolated nodal failure (INF) was the primary outcome.

Advances in the field of skull base surgery aim to maximize anatomical exposure while minimizing patient morbidity. The petroclival region of the skull base presents numerous challenges for surgical access due to the complex anatomy. The transcochlear approach to the region provides adequate access; however, the resection involved sacrifices hearing and results in at least a grade 3 facial palsy. An endoscopic endonasal approach could potentially avoid negative patient outcomes while providing a desirable surgical window in a select patient population.Cadaveric study.Endoscopic access to the petroclival region was achieved through an endonasal approach. For comparison, a transcochlear approach to the clivus was performed. Different facets of the dissections, such as bone removal volume and exposed surface area, were computed using computed tomography analysis.The endoscopic endonasal approach provided a sufficient corridor to the petroclival region with significantly less bone removal and nearly equivalent exposure of the surgical target, thus facilitating the identification of the relevant anatomy. The lateral approach allowed for better exposure from a posterolateral direction until the inferior petrosal sinus; however, the endonasal approach avoided labyrinthine/cochlear destruction and facial nerve manipulation while providing an anteromedial viewpoint. The endonasal approach also avoided external incisions and cosmetic deficits. The endonasal approach required significant sinonasal resection.Endoscopic access to the petroclival region is a feasible approach. It potentially avoids hearing loss, facial nerve manipulation, and cosmetic damage.

Perineural invasion (PNI) in cutaneous squamous cell carcinoma of the head and neck (CSCCHN) is associated with decreased survival. Large-nerve PNI presents with clinical signs and symptoms and/or magnetic resonance imaging evidence of cranial nerve involvement. We sought to determine which variables predict a worse outcome and to analyze patterns of failure.Case series with planned data collection.Tertiary care center.Patients with large-nerve PNI from CSCCHN between 1996 and 2006 were identified from a prospectively collected database. Clinical and demographic variables were recorded. Local control rates and survival analysis were performed using Kaplan-Meier curves.Thirty-six patients were identified (28 men and 8 women). The mean age was 61 years. Twenty-nine were treated with curative intent, and 7 received palliation. The mean follow-up was 35 months. Involvement of V3, disease zone, and the type of therapy were significantly associated with overall survival (P.05). The 5-year disease-free survival for patients by therapy was 50% for subcranial surgeries, 53.6% for skull base surgery, and 0% for radiation and palliative therapies (P.001). None of the patients treated with a skull base resection had a central recurrence, while all patients who received palliation had a central failure.Disease extent, type of therapy, and involvement of V3 are all significant predictors of survival in PNI from CSCCHN. We confirmed that the natural history of the disease is central progression and that this can be halted, if detected early enough, by a properly planned skull base resection.

Background. The purpose of this study was to present our prospectively evaluated positron emission tomog- raphy (PET)-directed policy for managing the neck in node- positive head and neck squamous cell carcinoma (NþHNSCC) after definitive radiotherapy (RT) with or without concurrent sys- temic therapy. Methods. One hundred twelve consecutive patients who achieved a complete response at the primary site underwent a 12-week posttherapy nodal response assessment with PET and diagnostic CT. Patients with an equivocal PET underwent a repeat PET 4 to 6 weeks later. Patients with residual CT nodal abnormalities deemed PET-negative were uniformly observed regardless of residual nodal size. Results. Median follow-up from commencement of RT was 28 months (range, 13-64 months). Residual CT nodal abnormal- ities were present in 50 patients (45%): 41 PET-negative and 9 PET-positive. All PET-negative residual CT nodal abnormalities were observed without subsequent isolated nodal failure. Conclusion. PET-directed management of the neck after definitive RT in node-positive HNSCC appropriately spares neck dissections in patients with PET-negative residual CT nodal abnormalities. V C 2011 Wiley Periodicals, Inc. Head Neck 00:000-000, 2011

Perineural invasion (PNI) in cutaneous squamous cell carcinoma of the head and neck (CSCCHN) is associated with decreased survival, particularly in patients with clinical signs of cranial nerve involvement. There is evidence to indicate that neural cell adhesion molecule (N-CAM) confers capability of PNI. We analyzed our own patient population to determine if N-CAM predicted clinical PNI in CSCCHN.Tissue from patients with CSCCHN and clinical PNI, who underwent surgery between 1998 and 2005, was immunostained for N-CAM. In addition, non-PNI CSCCHN and normal nerve sections were also stained. A section of neuroendocrine tumor was included in each slide as a positive control. In addition, most of the sections also had an "inbuilt control" in the CD56 positive natural killer T cells that formed part of the inflammatory reaction to the tumors.Tissue was available from 14 patients with CSCCHN and clinical PNI. The analysis was carried out in 14 patients without PNI and 4 normal nerves. N-CAM was not expressed in any of our PNI CSCCHN specimens or non-PNI controls. It was strongly expressed in the neuroendocrine tumors and positive in-built controls, as well as in normal nerve tissue.N-CAM expression did not predict neurotropism in our patient population. Additional studies are required to identify the cell surface markers expressed by CSCCHN which confer neurotropism capabilities.

Large nerve perineural spread represents a rare but potentially fatal form of metastasis for cutaneous malignancy most prevalent in the head and neck region. This often misunderstood and misdiagnosed condition is particularly prevalent in Queensland and is most commonly seen with squamous cell carcinomas. It is not known whether small nerve (incidental) and large nerve (clinical) represent a spectrum of the same disease processes but it is clear that the two have much different prognostic significance. An overview of large nerve disease will be discussed including which nerves are commonly affected and patterns of failure. Finally, current management regimes will be covered including staging of the disease and specific skull base techniques used for varying nerve involvement.

The aim of this study was to document the rate of pathologic neck disease in patients presenting with metastatic cutaneous squamous cell carcinoma (CSCC) to the parotid gland following parotidectomy and neck dissection in the clinically and radiologic negative neck.Case series with chart review.Tertiary referral center.The study involved a retrospective chart review from 1999 to 2008 of patients presenting with metastatic CSCC to the parotid at the Princess Alexandra Hospital, Brisbane, Australia.Eighty-one patients with metastatic parotid disease were identified. A total of 51 (63%) patients had no clinical or radiological evidence of cervical nodal disease. Forty-five patients (88%) were male, median age was 69 (range, 42-91) years, and the median follow-up was 16 (interquartile range, 9-44) months. Thirty-four of these patients underwent a parotidectomy and neck dissection with/without postoperative radiotherapy (RT). Occult pathological cervical nodal disease was found in 5 (14.7%) patients. Of those who received a neck dissection, 3 patients relapsed in the parotid, 1 in the neck alone, and 1 distantly.This series has shown that the rate of pathologically involved neck nodes in patients with metastatic CSCC to the parotid in the clinically node negative neck is low. Given many of these patients warrant postoperative RT to the parotid bed, an elective neck dissection may not be warranted as the parotid and neck may be treated in continuity with RT.

We describe a rare case of a surgically proven myxoma arising within the masticator space probably from a pterygoid muscle. The lesion showed characteristic hyperintensity on T2-weighted images and did not enhance following gadolinium.