Habbous Steven, Chu Karen P, Lau Harold, Schorr Melissa, Belayneh Mathieos, Ha Michael N, Murray Scott, O'Sullivan Brian, Huang Shao Hui, Snow Stephanie, Parliament Matthew, Hao Desiree, Cheung Winson Y, Xu Wei, Liu Geoffrey
Ontario Cancer Institute (Habbous, O'Sullivan, Huang, Liu) and Department of Biostatistics (Xu), Princess Margaret Cancer Centre, Toronto, Ont.; Radiation Oncology (Chu, Belayneh, Parliament), Cross Cancer Institute, Edmonton, Alta.; Department of Oncology (Lau, Hao), University of Calgary, Alberta Health Services, Calgary, Alta.; Department of Oncology (Schorr, Hao), Division of Medical Oncology, Tom Baker Cancer Centre, Calgary, Alta.; Division of Medical Oncology (Ha, Murray, Snow), Nova Scotia Cancer Centre, Dalhousie University, Halifax, NS; Department of Radiation Oncology (O'Sullivan, Huang), Department of Medicine (Liu) and Department of Epidemiology, Dalla Lana School of Public Health (Liu), University of Toronto, Toronto, Ont.; Medical Oncology (Cheung), BC Cancer Agency, Vancouver, BC
Ontario Cancer Institute (Habbous, O'Sullivan, Huang, Liu) and Department of Biostatistics (Xu), Princess Margaret Cancer Centre, Toronto, Ont.; Radiation Oncology (Chu, Belayneh, Parliament), Cross Cancer Institute, Edmonton, Alta.; Department of Oncology (Lau, Hao), University of Calgary, Alberta Health Services, Calgary, Alta.; Department of Oncology (Schorr, Hao), Division of Medical Oncology, Tom Baker Cancer Centre, Calgary, Alta.; Division of Medical Oncology (Ha, Murray, Snow), Nova Scotia Cancer Centre, Dalhousie University, Halifax, NS; Department of Radiation Oncology (O'Sullivan, Huang), Department of Medicine (Liu) and Department of Epidemiology, Dalla Lana School of Public Health (Liu), University of Toronto, Toronto, Ont.; Medical Oncology (Cheung), BC Cancer Agency, Vancouver, BC.
CMAJ. 2017 Aug 14;189(32):E1030-E1040. doi: 10.1503/cmaj.161379.
The incidence of oropharyngeal cancer has risen over the past 2 decades. This rise has been attributed to human papillomavirus (HPV), but information on temporal trends in incidence of HPV-associated cancers across Canada is limited.
We collected social, clinical and demographic characteristics and p16 protein status (p16-positive or p16-negative, using this immunohistochemistry variable as a surrogate marker of HPV status) for 3643 patients with oropharyngeal cancer diagnosed between 2000 and 2012 at comprehensive cancer centres in British Columbia (6 centres), Edmonton, Calgary, Toronto and Halifax. We used receiver operating characteristic curves and multiple imputation to estimate the p16 status for missing values. We chose a best-imputation probability cut point on the basis of accuracy in samples with known p16 status and through an independent relation between p16 status and overall survival. We used logistic and Cox proportional hazard regression.
We found no temporal changes in p16-positive status initially, but there was significant selection bias, with p16 testing significantly more likely to be performed in males, lifetime never-smokers, patients with tonsillar or base-of-tongue tumours and those with nodal involvement ( < 0.05 for each variable). We used the following variables associated with p16-positive status for multiple imputation: male sex, tonsillar or base-of-tongue tumours, smaller tumours, nodal involvement, less smoking and lower alcohol consumption ( < 0.05 for each variable). Using sensitivity analyses, we showed that different imputation probability cut points for p16-positive status each identified a rise from 2000 to 2012, with the best-probability cut point identifying an increase from 47.3% in 2000 to 73.7% in 2012 ( < 0.001).
Across multiple centres in Canada, there was a steady rise in the proportion of oropharyngeal cancers attributable to HPV from 2000 to 2012.
在过去20年中，口咽癌的发病率有所上升。这种上升归因于人乳头瘤病毒（HPV），但加拿大全国范围内HPV相关癌症发病率的时间趋势信息有限。
我们收集了2000年至2012年期间在不列颠哥伦比亚省（6个中心）、埃德蒙顿、卡尔加里、多伦多和哈利法克斯的综合癌症中心确诊的3643例口咽癌患者的社会、临床和人口统计学特征以及p16蛋白状态（p16阳性或p16阴性，使用该免疫组织化学变量作为HPV状态的替代标志物）。我们使用受试者工作特征曲线和多重填补法来估计缺失值的p16状态。我们根据已知p16状态样本的准确性以及p16状态与总生存期之间的独立关系选择了最佳填补概率切点。我们使用了逻辑回归和Cox比例风险回归。
我们最初发现p16阳性状态没有时间变化，但存在显著的选择偏倚，男性、终生不吸烟者、扁桃体或舌根肿瘤患者以及有淋巴结受累的患者进行p16检测的可能性显著更高（每个变量<0.05）。我们使用以下与p16阳性状态相关的变量进行多重填补：男性、扁桃体或舌根肿瘤、较小的肿瘤、淋巴结受累、吸烟较少和饮酒量较低（每个变量<0.05）。通过敏感性分析，我们表明p16阳性状态的不同填补概率切点均显示从2000年到2012年有所上升，最佳概率切点显示从2000年的47.3%增加到2012年的73.7%（<0.001）。
在加拿大的多个中心，2000年至2012年期间，HPV所致口咽癌的比例稳步上升。
