United Kingdom Multicentre Hpv Oropharynx Cancer Cross-sectional Study - An Evolution In The Understanding Of Disease Aetiology

Presentation: S303
Topic: Oropharynx
Type: Oral
Date: Tuesday, July 19, 2016
Session: 10:30 AM - 12:00 PM Best of Clinical II
Authors: Andrew G Schache, MD, PhD1, Ned Powell, PhD2, Kate Cuschieri, PhD3, Max Robinson, PhD4, Sam Leary, PhD5, Hisham Mehanna, MD, PhD6, Davy Rapozo7, Anna Long4, Heather Cubie3, Elizabeth Junor8, Hannah Monaghan9, Kevin Harrington, PhD10, Christopher M Nutting, PhD10, Ulrike Schick10, Andy S Lau1, Jon Sheard1, Catharine M West, PhD11, Ken Oguejiofor11, Steve Thomas, PhD5, Andy R Ness, PhD5, Miranda Pring5, Dennis J McCance, PhD12, Jacqueline A James, PhD13, Michael Moran, MD, PhD14, Emma V King, PhD15, Gareth Thomas, PhD16, Phil Sloan4, Richard J Shaw, MD1, Mererid Evans, MD, PhD17, Terry M Jones, MD1
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Institution(s): 1University of Liverpool, 2Cardiff University, 3Scottish Human Papillomavirus Reference Laboratory, 4Newcastle University, 5University of Bristol, 6University of Birmingham, 7Brazilian National Cancer Institute, 8Edinburgh Cancer Research Centre, 9Royal Infirmary of Edinburgh, 10The Royal Marsden Hospital, 11University of Manchester, 12University of New Mexico, 13Northern Ireland Molecular Pathology Laboratory, 14University College London Hospital NHS Trust, 15Poole Hospital NHS Foundation Trust, 16University of Southampton, 17Velindre Cancer Centre
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Background: Substantial increases in the incidence of oropharyngeal squamous cell carcinoma (OPSCC) have been observed throughout the developed world. This observation has frequently been attributed to Human Papillomavirus (HPV). This pan-United Kingdom (UK) multicentre, cross-sectional study aimed to determine the incidence of HPV positive and negative OPSCC within the population.

Methods: OPSCC cases diagnosed between 2002 and 2011 were collated from 11 geographically distributed centres across the UK. An overall target sample-size of 1710 was deemed sufficient to allow comparison of prevalence between years with 7.5% precision. To avoid selection bias, the first 17 cases (11 cases for two smaller centres) diagnosed in each calendar year, with available formalin-fixed paraffin embedded (FFPE) tumour blocks, were included, irrespective of the definitive treatment modality employed.

Of the 1602 archival tumour-tissue blocks returned, 1529 samples met inclusion criteria and were tested for HPV using three commercial tests performed in accredited laboratories (p16 immunohistochemistry, HPV DNA in-situ hybridisation, and multiplex HPV PCR). Valid HPV diagnostic data were obtained for 1474 cases.

UK Incidence data for OPSCC corresponding to the same decade (2002-2011) were obtained from the UK Cancer registries.

The study determined the overall proportion of OPSCC caused by HPV and assessed HPV prevalence by gender, age and anatomical subsite over time. Overall incidence rates for OPSCC in the UK were calculated, and the proportion of OPSCC attributable to HPV estimated.

Results: The overall proportion of OPSCC caused by HPV (2002-2011) was 51.8% (95% CI: 49.3, 54.4).
There was no change in the proportion of HPV-attributable cases over time (unadjusted risk ratio: 1.00 (95% CI: 0.99, 1.02)). This lack of change was irrespective of the HPV diagnostic test employed and the finding remained consistent after adjustment for gender, age at diagnosis, anatomical subsite and study centre (adjusted risk ratio: 1.00 (95% CI: 0.98, 1.03)).

Over the same period however, the incidence of OPSCC in the UK underwent a 2-fold increase (age standardised rate (ASR) 2002: 2.1(95% CI: 1.9, 2.2); 2011: 4.1 (95% CI: 4.0, 4.3)). 

Conclusions: Although the absolute numbers of OPSCC diagnosed within the UK between 2002 and 2011 almost doubled, the proportion of HPV-attributable cases remained static within the same period, at approximately 50%.
These results provide the first evidence that the rapidly increasing incidence of OPSCC cannot be solely attributable to the influence of HPV.
The reasons for the parallel increase in HPV-negative disease warrant further investigation so that future appropriate prevention strategies for both HPV-positive and negative disease can be implemented. 

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