Distribution and Clinical Significance of HPV16 Variants in Head and Neck Squamous Cell Carcinomas: Data from a Portuguese Cohort and Systematic Review.

INTRODUCTION: Genomic variants of the human papillomavirus type 16 (HPV16) are thought to play differential roles in the susceptibility to head and neck squamous cell carcinomas (HNSCC) and its biological behaviour. This study aimed to establish the prevalence of HPV16 variants in an HNSCC cohort and associate them with clinical pathological characteristics and patient survival. METHODS: We retrieved samples and clinical data from 68 HNSCC patients. DNA samples were available from tumour biopsy at the time of the primary diagnosis. Targeted next-generation sequencing was used to obtain whole-genome sequences, and variants were established based on phylogenetic classification. RESULTS: 74% of samples clustered in lineage A, 5.7% in lineage B, 2.9% in lineage C, and 17.1% in lineage D. Comparative genome analysis revealed 243 single nucleotide variations. Of these, one hundred were previously reported, according to our systematic review. No significant associations with clinical pathological variables or patient survival were observed. The E6 amino acid variations E31G, L83V, and D25E and E7 N29S, associated with cervical cancer, were not observed, except for N29S in a single patient. CONCLUSION: These results provide a comprehensive genomic map of HPV16 in HSNCC, highlighting tissue-specific characteristics which will help design tailored therapies for cancer patients.

PIK3CA Gene Mutations in HNSCC: Systematic Review and Correlations with HPV Status and Patient Survival.

PIK3CA mutations are believed to contribute to the pathogenesis of human papillomavirus (HPV)-associated head and neck squamous cell carcinomas (HNSCC). This study aims to establish the frequency of PIK3CA mutations in a Portuguese HNSCC cohort and to determine their association with the HPV status and patient survival. A meta-analysis of scientific literature also revealed widely different mutation rates in cohorts from different world regions and a trend towards improved prognosis among patients with PIK3CA mutations. DNA samples were available from 95 patients diagnosed with HNSCC at the Portuguese Institute of Oncology in Lisbon between 2010 and 2019. HPV status was established based on viral DNA detected using real-time PCR. The evaluation of PIK3CA gene mutations was performed by real-time PCR for four mutations (H1047L; E542K, E545K, and E545D). Thirty-seven cases were found to harbour PIK3CA mutations (39%), with the E545D mutation (73%) more frequently detected. There were no significant associations between the mutational status and HPV status (74% WT and 68% MUT were HPV (+); p = 0.489) or overall survival (OS) (3-year OS: WT 54% and MUT 65%; p = 0.090). HPV status was the only factor significantly associated with both OS and disease-free survival (DFS), with HPV (+) patients having consistently better outcomes (3-year OS: HPV (+) 65% and HPV (-) 36%; p = 0.007; DFS HPV (+) 83% and HPV (-) 43%; p = 0.001). There was a statistically significant interaction effect between HPV status and PIK3CA mutation regarding DFS (Interaction test: p = 0.026). In HPV (+) patients, PIK3CA wild-type is associated with a significant 4.64 times increase in the hazard of recurrence or death (HR = 4.64; 95% CI 1.02-20.99; p = 0.047). Overall, PIK3CA gene mutations are present in a large number of patients and may help define patient subsets who can benefit from therapies targeting the PI3K pathway. The systematic assessment of PIK3CA gene mutations in HNSCC patients will require further methodological standardisation.

Paragangliomas da Cabeça e Pescoço: A Experiência de um Centro Oncológico do Sul da Europa.

INTRODUCTION: Paragangliomas are usually benign slow-growing tumors, but they are locally invasive and can cause significant morbidity. The aim of this study was to characterize the presenting symptoms, secretory status, genetics, imaging features, treatment modalities, post-treatment complications and survival of patients with head and neck paragangliomas treated at a single institution. MATERIAL AND METHODS: We retrospectively reviewed the clinical records of patients managed at our center between 1997 and 2020. RESULTS: Seventy-three patients were included in the study, encompassing 89 head and neck paragangliomas. Forty-eight patients (65.8%) were female and 15 (20.5%) had multiple tumor sites (including 10 patients with multicentric benign paragangliomas and five with disseminated malignant disease). Regarding location, our series encompassed 40 temporal bone paragangliomas (44.9%), 24 carotid body paragangliomas (27%), 22 vagal paragangliomas (24.7%), two laryngeal paragangliomas (2.2%) and one sinonasal paraganglioma (1.1%). Excessive catecholamine secretion was detected in 11 patients (15.1%). Sixty-four patients (87.7%) underwent genetic testing. Of those, 24 (37.5%) exhibited pathogenic succinate dehydrogenase complex germline mutations. Regarding patients who presented with untreated disease, 45 patients (66.2%), encompassing 55 tumors, underwent surgery as primary treatment modality, 20 (29.4%; 23 tumors) were initially treated with radiotherapy and three patients (4.4%, encompassing three solitary tumors) were kept solely under watchful waiting. Five-year overall survival was 94.9% and disease-free survival was 31.9%. CONCLUSION: Head and neck paragangliomas are rare, slow-growing but locally aggressive tumors resulting in high morbidity but low mortality rates.

Introdução: Os paragangliomas apresentam frequentemente um comportamento benigno e um crescimento indolente. Apesar disso, são localmente invasivos, podendo causar morbilidade significativa. O objetivo deste trabalho foi descrever as manifestações clínicas, atividade secretora, estudos genéticos e imagiológicos, modalidades terapêuticas, complicações e sobrevivência dos doentes com paragangliomas da cabeça e pescoço. Material e Métodos: Estudo retrospetivo dos doentes com paragangliomas da cabeça e pescoço observados num centro hospitalar terciário entre 1997 e 2020. Resultados: Foram incluídos no estudo 73 doentes, englobando 89 paragangliomas. Quarenta e oito doentes (65,8%) eram do sexo feminino e 15 (20,5%) apresentavam múltiplos focos tumorais (10 por multicentricidade e cinco por doença maligna disseminada). Foram incluídos 40 paragangliomas do osso temporal (44,9%), 24 tumores do corpo carotídeo (27%), 22 vagais (24,7%), dois laríngeos (2,2%) e um nasossinusal (1,1%). A secreção excessiva de catecolaminas foi detetada em 11 doentes (15,1%). Sessenta e quatro doentes (87,7%) foram alvo de teste genético. Desses, 24 (37,5%) exibiram mutações patogénicas do complexo succinato desidrogenase. Dos doentes com doença primária, 45 (66,2%; 55 tumores) foram submetidos a tratamento cirúrgico, 20 (29,4%; 23 tumores) a radioterapia e três (4,4%) ficaram sob vigilância. Aos cinco anos, a sobrevida global foi de 94,9% e a sobrevida livre de doença foi de 31,9%. Conclusão: Os paragangliomas da cabeça e pescoço são tumores raros, de crescimento lento, mas localmente agressivos que resultam em elevadas taxas de morbilidade, mas baixas taxas de mortalidade.

Localised laryngotracheal amyloidosis: a differential diagnosis not to forget.

We present a case of multifocal laryngotracheal amyloidosis (LTA) in a 43-year-old man with persistent and progressive dysphonia and dyspnoea, and a first inconclusive histology. Although laryngeal amyloidosis accounts for fewer than 1% of all benign laryngeal tumours, it is in fact the most common site of amyloid deposition in the head, neck and respiratory tract. The clinical scenario is non-specific and diagnosis depends on a high degree of suspicion and on histology. Imaging is useful in mapping lesions, which are often more extensive than they appear during laryngoscopy. Despite being a benign entity, the prognosis is variable with a high-rate and long-latency recurrences, requiring long-term follow-up.

External auditory canal carcinoma: clinical characteristics and long-term treatment outcomes.

PURPOSE: Evidence-based treatment recommendations for external auditory canal (EAC) carcinoma are lacking in available literature. This study aims to evaluate the clinical characteristics and long-term outcomes of EAC carcinoma in a tertiary referral centre in a period of 15 years and identify independent prognostic factors. METHODS: Retrospective observational study enrolling all patients with primary EAC carcinoma who underwent primary surgical treatment at the Portuguese Institute of Oncology (Lisbon) between 2004 and 2018. Epidemiological, clinical, histopathological and surgical data were retrieved from clinical records and analysed. RESULTS: Twenty-seven patients were identified, with a median age of 77 years (range 29-92 years) and a slight female predominance (59.3%). Squamous cell carcinoma (55.6%) was the most common histological type, followed by basal cell carcinoma (40.7%) and ceruminous adenocarcinoma (3.7%). Pittsburgh tumour staging was distributed as early stage in 51.9% (I: 40.7%; II: 11.1%) and advanced stage in 48.1% (III: 29.6%; IV: 18.5%). Median follow-up period was 21 months (interquartile-range: 47). Four patients (14.8%) showed recurrence; recurrence rate was significantly higher in individuals aged < 60 years (p = 0.025) and with lymphovascular invasion (p = 0.049). Median overall survival was 88 months and estimated 2-year and 5-year overall survival rates were both 66%. Survival rates were higher in early stage patients (p = 0.021) and in those without facial palsy (p = 0.032). CONCLUSION: Based on the available evidence in this review, individuals aged < 60, facial nerve impairment, advanced stage lesions, presence of lymphovascular invasion and squamous cell carcinoma histology are all associated with poor outcome and may be considered when discussing optimal treatment strategies in patients with EAC carcinoma.

Diagnostic accuracy and utility of fine-needle aspiration cytology in therapeutic management of parotid gland tumours.

INTRODUCTION AND OBJECTIVES: The utility of fine-needle aspiration cytology (FNAC) in parotid tumours remains widely debated. This study aims to evaluate the accuracy of FNAC in diagnosing parotid tumours. MATERIALS AND METHODS: We performed a retrospective analysis of patients with tumour disease of the parotid gland treated at a Portuguese Oncology Institute, over a period of 25 years. The preoperative FNAC results were compared with the final histopathological diagnosis. We calculated the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of FNAC for malignancy. Association between malignancy on histopathology and FNAC results were evaluated with the Chi-square test. RESULTS: The study sample consisted of 155 patients (77 males and 78 females) with a mean age of 56.6±17.0 years. In 27 cases (17.4%), the FNAC result was indeterminate. In this group of patients there was a higher proportion of malignancy on histology (48.1%) (X2; p<0.001). In the group with a conclusive result on FNAC, the sensitivity and specificity of FNAC for malignancy was 66.7% and 99.0%, respectively. PPV was 94.1% and NPV was 92.8%. CONCLUSIONS: A benign result on FNAC should be used with caution, due to its low sensitivity for malignancy. An indeterminate result on FNAC should raise suspicion for a malignant tumour.

Nasopharyngeal carcinoma: our experience.

The objectives of our study were to characterize nasopharyngeal carcinoma patients in the Portuguese Institute of Oncology Hospital in Lisbon (IPOLFG) and identify the main factors that interfere with patients survival rate. We performed a retrospective study involving 157 patients (65% male and 35% female) between the years 2000 and 2005, and a histological classification according to Health World Organization. We constructed a Kaplan-Meier survival curve for the studied patients and evaluated the significance of the different studied factors with a Pearson correlation study. With an average age of 53 years, most of the carcinomas were type III (58%), followed by type II (30%) and at last type I (8%). Fifty-one of carcinomas were in stage IV at time of diagnosis. Ninety-five patients (60%) had remission. Five-year actuarial survival rate of all patients was 65.1%. There was a significant difference (P = 0.033) in the actuarial survival rate of staged IV patients treated with adjuvant chemotherapy. Undifferentiated nasopharyngeal carcinoma is the most frequent type in our geographic area. Chemotherapy improves survival rate, mainly in late stages.