We present a cohort review of TORS resection for HPV-associated oropharyngeal squamous cell carcinoma (OPSCC) and its associated oncological outcomes spanning a 10-year period. A retrospective case series review was performed of patients undergoing primary surgical treatment for HPV-associated OPSCC through the St. Vincent's Head and Neck Cancer service from 2011 to 2022. The primary outcomes were to investigate complete resection of the primary tumour, rates of recurrence, and survival analysis. Secondary outcomes included complications, rates of adjuvant therapy, sites of recurrence and rates of percutaneous endoscopic gastrostomy (PEG). 184 patients underwent TORS-based therapy with neck dissection, and guideline-directed adjuvant therapy for HPV-associated OPSCC. Our median follow-up was 46 months. The positive margin rate on final histopathology analysis was 10.9%. Adjuvant therapy was indicated in 85 patients (46%). The local recurrence rate was 10.9% with the majority (80%) of patients recurring in the first 3 years since treatment. The disease-specific survival at 3 years was 98.6% and at 5 years was 94.4%. The 3-year and 5-year OS for the cohort was 96.7% and 92.5%, respectively. The presence of extranodal extension and positive margins were associated with increased risk of recurrence, whereas adjuvant therapy was found to be a protective factor for both overall recurrence and survival. Major complications occurred in 12 patients (6.5%), resulting in one death. This study has demonstrated that primary surgical therapy for HPV-associated OPSCC is a safe and effective treatment modality with low local recurrence and complication rates, and overall survival benefits.

OBJECTIVE:To analyse the rate of contralateral nodal metastasis in human papillomavirus (HPV)-associated oropharyngeal carcinoma and identify the patient cohorts that would benefit from bilateral neck treatment. METHODS:A retrospective cohort review was performed on 110 HPV-positive oropharyngeal carcinoma patients who underwent transoral robotic surgery and bilateral neck dissections from 2012 to 2022. The primary outcome was to investigate the pathological incidence and location of contralateral neck node metastasis. RESULTS:The contralateral nodal disease rate was 12.7 per cent (n = 14), of which 2 patients (2 per cent) were occult findings, with comparable results between tongue base and tonsil sub-groups. The most commonly involved contralateral nodal station was level II (11 of 110 patients, 10 per cent). The presence of extra-nodal extension and multiple ipsilateral positive nodes was associated with increased risk of contralateral nodal disease. CONCLUSION:The incidence of contralateral nodal and occult disease in the studied cohort is low. The characteristics of patients who may benefit from bilateral neck treatment were demonstrated.

Head and neck cancers, representing the seventh most common malignancy globally, have seen a shift in causative factors from traditional smoking and alcohol use to human papillomavirus (HPV) infection, now accounting for up to 80% of oropharyngeal cancers. We identify the cellular and clonal mechanisms underlying immune avoidance and metastasis by analysing single-cell and spatial genomic data from primary and metastatic cancers. We first map the clonal evolution of malignant cells based on the accumulation of mutations. We identify metastasising clones based on mutational similarity scores between cells in the primary and lymph node metastasis. Genomic analysis of metastasising and non-metastasising clones identified virally mediated protein translation relief ( P =4.24x10-24) pathway underlying metastatic expansion. We show that in metastatic clones, this process is driven through upregulation of transition-initiating factors, EIF4E ( P =1.5x10-13) and EIFG1 ( P <2.22x10-16), and suppression of regulatory kinases EIF4EBP1 ( P =2.1x10), EIF2AK2 ( P <2.22x10-16), and EIF2S1 ( P <2.22x10-16). We subsequently identify that metastatic clones have a corresponding downregulation of the JAK/STAT pathway and immunoproteasome genes PSMB8 ( P <2.22x10- 16) and PSMB9 ( P <2.22x10-16), suggesting these clones escape immune surveillance through decreased INF inflammatory response and antigen presentation. We validate these results using spatial RNA-seq data, where metastatic cancer clones show decreased cell-to-cell interactions with CD4 T-effector memory cells (CD4TEM) ( P =0.0077), CD8 T-exhausted cells (CD8Ex) ( P =0.0191), and innate lymphoid cells (ILC) ( P =0.04). Finally, we demonstrate that the upregulation of cap-independent translational drives cell proliferation in metastatic clones through the expression of translation initiation factors ( EIF4G1: P <2.22x10-16). Our results provide evidence of the mechanisms by which virally induced cancer clones lead to advanced disease and poor prognosis in patients. ### Competing Interest Statement The authors have declared no competing interest.

BACKGROUND:Neoplasms showing perivascular epithelioid cell differentiation (PEComas) are uncommon tumors of the sinonasal tract. They are often misdiagnosed as angiomyolipoma or a simple benign tumor or polyp. We present a further case of a sinonasal PEComa and review the literature in an attempt to ascertain their malignant potential. METHODS:Published evidence on invasiveness and characteristics were defined on systematic review. MEDLINE and EMBASE were searched from 1966 and 1980, respectively, to week 3 of December 2010. Publications reporting PEComa or angiomyolipoma were sought. Only those describing a sinonasal origin were included. Demographics, anatomic site, local invasion, recurrence rates, and mortality were recorded. A case report of a locally invasive intranasal PEComa is described. RESULTS:In addition to the case we present, 12 case reports were located (n = 13). The mean age of patients was 59.6 (SD, 14.98 years) years. The location was within the right sinonasal tract in 54% of cases, the left sinonasal tract in 38% of cases, and not reported in 8% of cases. Treatment focused on local surgical excision and this was achieved endoscopically in 100% of cases. Recurrence rate was 8%. Mean follow-up was 17.4 (SD, 20.68 months) months. Invasion was noted in 23% of cases. There was a single death recorded. CONCLUSION:PEComas of the paranasal sinuses and skull base appear to have a biological behavior different from simple benign angiomyolipomas reported elsewhere in the body. PEComa may be more intermediate or malignant in clinical behavior.