An updated mortality risk analysis of the post-pubertal undescended testis.

INTRODUCTION: The undescended testicle (UDT) presents a problem in post-pubertal (PP) men, as it carries an increased risk of developing a germ cell tumour (GCT). Management of the PP patient with an UDT must weigh the relative risk (RR) of perioperative mortality (POM) from orchiectomy against the lifetime risk of death from a GCT. METHODS: The most recent data on GCT mortality were obtained from the National Centre for Health Statistics. Standard life tables were used to calculate the cumulative risk over a man's lifetime based on age. The increased RR of GCT in men with UDT was determined by weighing the observed and expected rates from literature review. Life table data was then multiplied by the RR to define the risk of GCT in men with UDT. Data from patients undergoing similar risk surgical procedures stratified by American Society of Anesthesiologists (ASA) class was used to determine POM. RESULTS: Lifetime risk of dying from GCT decreases with increasing age. POM exceeded risks of death from GCT for men after age 50.2 for ASA class 1 and age 35.4 for ASA class 2. Men with an ASA class higher than 2 have a higher risk of POM compared to GCT for all ages. CONCLUSIONS: We found different ages from previous reports at which observation is advised. We consider prophylactic orchiectomy only in men who are under 50.2 years if ASA class 1 and under 35.4 years if ASA class 2. Men with an ASA class 3 or higher should always undergo observation.

[HPV - A different view on Head and Neck Cancer]. / HPV ­ Das andere Kopf-Hals-Karzinom.

Head and neck cancer is the sixth most common cancer with over 500000 annually reported incident cases worldwide. Besides major risk factors tobacco and alcohol, oropharyngeal squamous cell carcinomas (OSCC) show increased association with human papillomavirus (HPV). HPV-associated and HPV-negative OSCC are 2 different entities regarding biological characteristics, therapeutic response, and patient prognosis. In HPV OSCC, viral oncoprotein activity, as well as genetic (mutations and chromosomal aberrations) and epigenetic alterations plays a key role during carcinogenesis. Based on improved treatment response, the introduction of therapy de-intensification and targeted therapy is discussed for patients with HPV OSCC. A promising targeted therapy concept is immunotherapy. The use of checkpoint inhibitors (e.g. anti-PD1) is currently investigated. By means of liquid biopsies, biomarkers such as viral DNA or tumor mutations in the will soon be available for disease monitoring, as well as detection of treatment failure. By now, primary prophylaxis of HPV OSCC can be achieved by vaccination of girls and boys.

Hypoxia-inducible factor-1α activation in HPV-positive head and neck squamous cell carcinoma cell lines.

PURPOSE: Human papillomavirus (HPV) is a causative agent for a rising number of head and neck squamous cell carcinomas (HNSCC), which are characterized by distinct tumor biology. Hypoxia inducible-factor (HIF) signaling influences initiation and progression of carcinogenesis and HPV oncoproteins have evolved to highjack cellular pathways for viral reproduction. Therefore, we investigated whether HPV activates HIF-1α expression in HNSCC. EXPERIMENTAL TECHNIQUE: HPV-positive and -negative HNSCC cells were examined for adaptive responses to hypoxia. Expression of HIF-1α, prolyl hydroxylase-domain protein 2 (PHD2) and E-cadherin was analyzed by Western blotting, immunofluorescence (IF) microscopy and migration/wound healing assays. RESULTS: HPV-positive HNSCC cells showed higher HIF-1α and PHD2 protein levels under normoxia and hypoxia. HIF-1α hydroxylation was reduced in HPV-positive HNSCC cell lines under PHD and proteasomal inhibition. In vitro wound healing assays showed impairment of migration and proliferation by HIF-1α pathway activation in HPV-negative cell lines only. In contrast, migration and proliferation in HPV-positive cell lines was impaired by HIF-1α specific siRNA. CONCLUSIONS: HPV-positive HNSCC cells show activation of the HIF pathway and adaptation to HIF-1α upregulation, representing potential therapeutic targets in this emerging tumor entity.

Intraindividual homogeneity of 18F-FDG PET/CT parameters in HPV-positive OPSCC.

OBJECTIVES: 18F-FDG PET/CT is widely used in clinical oncology. Human papillomavirus (HPV)-related oropharyngeal squamous cell carcinoma (OPSCC) represents an emerging disease that differs from HPV-negative OPSCC in clinical behavior and tumour biology. In these tumours, HPV-oncogenes might lead to distinct alterations in metabolic pathways. Therefore, we compared metabolic parameters using 18F-FDG PET/CT in HPV-positive and HPV-negative OPSCC in relation to histopathological findings. MATERIALS: Eighty-six patients with OPSCC received pre-therapeutic 18F-FDG PET/CT. Standardised uptake volume (SUV), total lesion glycolysis (TLG) and metabolic tumour volume (MTV) were analysed for the primary tumour. SUVmax was determined for neck lymph nodes. HPV-status was determined; overall survival rates (OS) were estimated. RESULTS: 32/86 patients (37.2%) had HPV-related OPSCC. Overall, PET-parameters in primary tumours of both groups did not differ significantly. Comparing early with locally advanced primary tumours, there was a significant increase in 18F-FDG uptake in HPV-negative patients (p<0.001). Positive nodes of HPV-related OPSCC showed significantly higher SUVmax values (p=0.039) compared to HPV-negative OPSCC. Strikingly, there was a higher intraindividual homogeneity of 18F-FDG uptake between primary and respective positive nodes in HPV-related primary OPSCC (p=0.001). SUV-max and -mean values did not correlate with OS in HPV-related OPSCC. CONCLUSION: The intraindividual homogeneity of 18F-FDG uptake in HPV-related OPSCC could reflect the more homogenously, HPV-triggered carcinogenesis compared to the mutation-driven carcinogenesis in the HPV-negative OPSCC with heterogenic 18F-FDG uptake.

Human Papillomavirus-Related Head and Neck Cancer.

Human papillomavirus(HPV)-related head and neck cancer is recognized as a distinct tumor entity with rising incidence reported for several countries. These tumors arise from squamous cells, typically in the oropharynx. In contrast to cancer associated with other risk factors, HPV-related cancer is driven by viral oncoprotein activity and has individual profiles regarding protein expression, and genetic and epigenetic alterations. Molecular characteristics are p16IN4A overexpression, absence of p53 inactivating mutations, and PI3K/AKT and Wnt pathway modulation. Patients with HPV-related head and neck cancer have improved survival compared to those with HPV-negative tumors, and p16INK4A staining has been introduced into tumor staging recently. However, no specific or toxicity-reduced treatment modalities have been established for this entity so far. Although the still incomplete and partially inconsistent data in this field needs further study, particular features of HPV-related cancers such as specific microRNA expression, immunology, or gene methylation patterns certainly have the potential to be implemented in future diagnostic and therapeutic concepts.