Treatment de-escalation in HPV-positive oropharyngeal carcinoma: ongoing trials, critical issues and perspectives.

Due to the generally poor prognosis of head and neck squamous cell carcinoma (HNSCC), treatment has been intensified, these last decades, leading to an increase of serious side effects. High-risk human papillomavirus (HR-HPV) infection has been recently etiologically linked to a subset of oropharyngeal squamous cell carcinoma (OPSCC), which is on the increase. These tumors are different, at the clinical and molecular level, when compared to tumors caused by traditional risk factors. Additionally, their prognosis is much more favorable which has led the medical community to consider new treatment strategies. Indeed, it is possible that less intensive treatment regimens could achieve similar efficacy with less toxicity and improved quality of life. Several clinical trials, investigating different ways to de-escalate treatment, are currently ongoing. In this article, we review these main approaches, discuss the rationale behind them and the issues raised by treatment de-escalation in HPV-positive OPSCC.

Do high-risk human papillomaviruses cause oral cavity squamous cell carcinoma?

High-risk human papillomaviruses (HR-HPV) are an established etiologic factor for a growing number of oropharyngeal cancers. However, their potential role in other upper aerodigestive tract locations is still a matter of debate, particularly in the oral cavity. This is of paramount importance as in the future diagnosis, treatment and follow up in head and neck squamous cell carcinoma may vary according to HPV status. This article reviews the recent published data and highlights some of the pitfalls that have hampered the accurate assessment of HR-HPV oncological role outside the oropharynx. We demonstrate that, in contrast to the oropharynx, only a small fraction of cancers located in the oral cavity seem to be HPV-related even in young non-smoking non-drinking patients. We emphasize several relevant factors to consider in assumed HPV-induced oral cavity cancers and discuss the current theories that explain why HPV-induced cancers arise preferentially in the oropharynx.

Oropharyngeal cancers: relationship between epidermal growth factor receptor alterations and human papillomavirus status.

High-risk human papillomavirus (HR-HPV), particularly type 16, is now recognised as a causative agent in a subset of oropharyngeal squamous cell carcinomas (OPSCCs). These tumours are on the increase and generally have a better prognosis than their HPV negative counterparts. This raises the question of de escalation therapy to reduce long term consequences in a younger cohort of patients with a long life expectancy. Several clinical trials with anti-epidermal growth factor receptor (EGFR) therapies, particularly cetuximab, are ongoing. Few data exist on the relationship between EGFR and HPV induced oropharyngeal cancers. We summarise the main studies in relation to EGFR alterations (gene copy number, protein expression and mutations) and the impact on prognosis of HPV positive tumours that express high levels of EGFR. We also discuss the opportunity of targeting this pathway in light of recent studies.

External auditory canal paraganglioma: an atypical presentation.

OBJECTIVE: We present the first published description of a painful paraganglioma of the external auditory canal. Atypical histopathology made the diagnosis difficult. We discuss the potential pitfalls of clinical diagnosis and treatment of such a case. CLINICAL PRESENTATION: A 49-year-old woman presented with left-sided otalgia, hearing loss and tinnitus. Physical examination revealed a firm swelling arising from the superior portion of the left external auditory canal. A clinical diagnosis of otitis externa was made. INTERVENTION: There was minimal response to medical treatment. The swelling was aspirated, leading to brisk bleeding. A tumour was suspected from the computed tomography scan, and confirmed by a biopsy. The patient underwent excision of the paraganglioma. The histopathology was atypical, making diagnosis difficult. CONCLUSION: Such unusual masses of the external ear should always be borne in mind, especially when dealing with atypical presentations of commonly encountered diseases. Clinicians should have a low threshold for early intervention with imaging and biopsy.

Technical tutorial: How to pack a nose with bismuth iodoform paraffin paste gauze safely and effectively.

The current primary treatment for epistaxis in accident and emergency departments is the insertion of Merocel packs. If these are properly inserted, but fail to control bleeding, it is necessary to insert a bismuth iodoform paraffin paste (BIPP) pack. A BIPP pack, when properly inserted, has the potential to stop most bleeds, but books and journals suggest a method of insertion that limits its effectiveness. A safer and more effective way of packing a nose with BIPP than the traditional method is described.

Absence of cyclin-D2 and Bcl-2 expression within the germinal centre type of diffuse large B-cell lymphoma identifies a very good prognostic subgroup of patients.

AIMS: To validate and improve the existing algorithm (proposed by Hans et al.) to classify diffuse large B-cell lymphoma (DLBCL). METHODS AND RESULTS: Tissue microarrays constructed from 81 patients with DLBCL were studied by immunohistochemistry for expression of CD10, Bcl-6, MUM1, Bcl-2, cyclin-D2, FOXP1 and PKC-gamma proteins. Cases were classified as either germinal centre B-like (GCB) or non-GC according to Hans et al. An alternative classification was also employed, in which cases positive for either CD10 or Bcl-6 were considered as a GC subgroup and cases negative for both CD10 and Bcl-6 were considered as a non-GC subgroup. GC was further subdivided into favourable GC (negative for both Bcl-2 and cyclin-D2) and unfavourable GC (positive for either Bcl-2 or cyclin-D2). The 5-year event-free survival (EFS) amongst patients classified as favourable GC versus 'others' was 49.5% and 7.3%, respectively (log rank P < 0.0001). Similarly, the 5-year overall survival (OS) amongst patients classified as favourable GC versus 'others' was 58.6% and 13.7%, respectively (log rank P = 0.0001). The difference in survival was independent of the international prognostic index. CONCLUSIONS: In this group of patients the risk stratification based on the new algorithm was better than that proposed by Hans et al.

Angiotensin-converting enzyme inhibitor related angioedema and the anaesthetist.

Angioedema of the face and neck is an uncommon but potentially life-threatening complication of angiotensin-converting enzyme (ACE) inhibitor therapy. This condition is of particular concern to the anaesthetist as it can rapidly progress to upper airway obstruction. We describe the presentation and management of five cases of ACE inhibitor related angioedema, all of which were associated with significant upper airway obstruction.