Incidence, trends, and survival of oropharyngeal squamous cell cancer in Aotearoa New Zealand, 2006-2020.

BACKGROUND: An increasing trend of oropharyngeal cancer (OPC) has been reported in several countries with different demographic characteristics, and often attributed to increases in human papillomavirus (HPV) infection. The survival of patients with OPC has steadily improved, especially for those with positive HPV status. This study assessed the incidence, trends, and survival of OPC in Aotearoa New Zealand (NZ) by age at diagnosis, sex and ethnicity. METHODS: The study included all 2109 patients resident in NZ with a primary diagnosis of oropharyngeal squamous cell carcinoma from 2006 to 2020, identified from the National Cancer Registry. We assessed age-standardised incidence rate (ASR), annual percent change (APC) and overall and relative survival rates. RESULTS: The average annual incidence of OPC was 2.2 per 100,000 population. There was a steady increase of 4.9% per year over 15 years. Although the incidence rates were higher in males over the study period, the overall rate of increase was similar in males (4.9%) and in females (4.3%). The incidence was highest in the 50-69-year group (8.8/100,000 population). This age group had an incidence that increased by 7.5% per year to 2018, and then declined. The main increase in rates was seen between the birth cohort of 1946-50 and that of 1956-60. The increase in incidence was seen in Maori and Pakeha/European populations, but no increase was seen in Pacific or Asian populations. The 5-year overall relative survival rate improved from 69% in 2006-13 to 78% in 2014-20. Survival rates were lower in older patients, females, and Maori patients. CONCLUSION: This study confirmed a substantial increase in OPC incidence in NZ, with some evidence to suggest a recent slowing in this increase. Maori and Pakeha/European had the highest incidence, while Pacific and Asian populations showed the lowest rates and no increase over the study period. Survival rates have improved over time, but remained lower in some demographic groups.

Evaluation of a novel database for quality assurance at a head and neck service in New Zealand: an audit of free flap head and neck reconstruction.

BACKGROUND: Clinical audit is a critical quality improvement exercise, yet efficient audit tools are lacking. The main objective of this study was to evaluate a recently deployed database in facilitating the process of clinical audit, and the secondary objective was to evaluate the outcomes of free flap reconstruction of the head and neck at our centre. METHODS: A head and neck cancer-specific database was customized to suit the needs of our head and neck multidisciplinary team. Data has been entered prospectively into this database since March of 2018. An audit of free flap reconstruction of the head and neck over a 12-month period was performed using the database and analysed as a case study to examine its efficacy as a clinical audit tool. Additionally, the outcomes of free flap reconstruction at our centre were compared to those reported in the international literature. RESULTS: The database allows flexible and specific queries, analysis and export of data, and can provide immediate results. However, issues with data quality and completeness were identified. In this audit, the overall 30-day complication rate and 30-day mortality in patients undergoing free flap reconstruction of the head and neck were 58% and 3%, respectively. CONCLUSION: The database is fit for its intended purpose as an audit tool. Outcomes of free flap reconstruction of the head and neck at our centre are comparable to those of institutions overseas.

Impact of Tumour Hypoxia on Evofosfamide Sensitivity in Head and Neck Squamous Cell Carcinoma Patient-Derived Xenograft Models.

Tumour hypoxia is a marker of poor prognosis and failure of chemoradiotherapy in head and neck squamous cell carcinoma (HNSCC), providing a strategy for therapeutic intervention in this setting. To evaluate the utility of the hypoxia-activated prodrug evofosfamide (TH-302) in HNSCC, we established ten early passage patient-derived xenograft (PDX) models of HNSCC that were characterised by their histopathology, hypoxia status, gene expression, and sensitivity to evofosfamide. All PDX models closely resembled the histology of the patient tumours they were derived from. Pimonidazole-positive tumour hypoxic fractions ranged from 1.7-7.9% in line with reported HNSCC clinical values, while mRNA expression of the Toustrup hypoxia gene signature showed close correlations between PDX and matched patient tumours, together suggesting the PDX models may accurately model clinical tumour hypoxia. Evofosfamide as a single agent (50 mg/kg IP, qd × 5 for three weeks) demonstrated antitumour efficacy that was variable across the PDX models, ranging from complete regressions in one p16-positive PDX model to lack of significant activity in the three most resistant models. Despite all PDX models showing evidence of tumour hypoxia, and hypoxia being essential for activation of evofosfamide, the antitumour activity of evofosfamide only weakly correlated with tumour hypoxia status determined by pimonidazole immunohistochemistry. Other candidate evofosfamide sensitivity genes-MKI67, POR, and SLFN11-did not strongly influence evofosfamide sensitivity in univariate analyses, although a weak significant relationship with MKI67 was observed, while SLFN11 expression was lost in PDX tumours. Overall, these data confirm that evofosfamide has antitumour activity in clinically-relevant PDX tumour models of HNSCC and support further clinical evaluation of this drug in HNSCC patients. Further research is required to identify those factors that, alongside hypoxia, can influence sensitivity to evofosfamide and could act as predictive biomarkers to support its use in precision medicine therapy of HNSCC.

Human papillomavirus and oropharyngeal squamous cell carcinoma: a New Zealand cohort study.

BACKGROUND: Human papillomavirus (HPV)-related oropharyngeal squamous cell carcinomas (OPSCC) are clinically, epidemiologically and prognostically distinct from other OPSCCs. The incidence of HPV-related OPSCCs has increased significantly worldwide over the past few decades. However, no studies of OPSCC with direct molecular HPV testing has been conducted in New Zealand. AIMS: To estimate the proportion of OPSCCs attributable to HPV infections in a New Zealand population with a validated HPV testing algorithm. METHODS: HPV-status was determined by p16 immunohistochemistry and polymerase chain reaction (PCR) of both L1 and E6/7 genes on 55 OPSCCs diagnosed in 2010 and 2011 in Central and South Auckland. Baseline and survival analyses were performed according to HPV status. RESULTS: Forty-one (75%) of OPSCC tumours had HPV infections. There was 98% concordance between p16 immunohistochemistry and real-time E6/E7 PCR. After a median follow-up period of 2.6 years, patients with OPSCC of HPV aetiology had more favourable outcomes compared to patients with HPV-negative OPSCC (hazard ratio 0.14, P = 0.02) after adjustment for other variables. CONCLUSION: This study highlights the significant role that HPV plays in the aetiology of OPSCC in New Zealand, and confirms the high rate of accuracy of p16 immunostaining.

Salivary duct carcinoma arising in IgG4-related autoimmune disease of the parotid gland.

Hyper IgG4 disease or IgG4-related sclerosing/autoimmune disease is a multisystem condition characterized histologically by fibrosis, lymphoplasmacytic infiltration, and abundant IgG4 plasma cells associated with raised serum IgG4 levels. We present a case of salivary duct carcinoma of the parotid gland in a background of chronic sclerosing sialadenitis that also involved the submandibular gland with associated regional lymphadenopathy. The serology showed raised total IgG levels of 16.3 g/L (reference range, 6.0-15.0) and raised IgG4 levels of 3.41 g/L (reference range, 0.07-1.70). The salivary duct carcinoma contained areas of dense fibrosis and abundant IgG4-positive plasma cells (>100 per high-power field [hpf]). The adjacent noncarcinomatous areas, submandibular gland, and regional lymph nodes also contained plasma cells immunoreactive to IgG4 with densities higher than 100/hpf. To the best of our knowledge, this case is the first documentation of malignancy occurring in a background of IgG4-related autoimmune disease of the salivary gland.