Garnaes Emilie, Kiss Katalin, Andersen Luise, Therkildsen Marianne H, Franzmann Maria B, Filtenborg-Barnkob Bettina, Hoegdall Estrid, Krenk Lene, Josiassen Michael, Lajer Christel B, Specht Lena, Frederiksen Kirsten, Friis-Hansen Lennart, Nielsen Finn C, Kjaer Susanne K, Norrild Bodil, von Buchwald Christian
Department of Otorhinolaryngology, Head and Neck Surgery and Audiology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
Int J Cancer. 2015 May 1;136(9):2196-203. doi: 10.1002/ijc.29254. Epub 2014 Oct 13.
The aim was to explore whether the incidence of tonsillar squamous cell carcinomas (TSCCs) increased in Eastern Denmark, 2000-2010, and whether human papillomavirus (HPV) could explain the increase, and to assess the association of HPV prevalence with gender, age, and origin (i.e., the certainty of tonsillar tumor origin). We applied HPV DNA PCR and p16 immunohistochemistry to all TSCCs registered in the Danish Head and Neck Cancer Group (DAHANCA) and in the Danish Pathology Data Bank (n = 632). Pathologists reviewed and subdivided the tumors into two groups: specified and nonspecified TSCCs. Approximately 10% of HPV-positive tumors was genotyped by amplicon next-generation sequencing. The overall crude incidence of TSCCs increased significantly (2.7% per year) and was explained by an increasing incidence of HPV-positive TSCCs (4.9% per year). The overall HPV prevalence was 58%, with HPV16 being the predominant HPV type. In multivariate analysis, the HPV prevalence was associated with age (<55 vs. >60 years) (OR, 1.72; 95% CI 1.13-2.63) and origin (nonspecified vs. specified TSCCs) (OR, 0.15; 95% CI 0.11-0.22). The association of HPV prevalence with origin increased over time in specified TSCCs (OR per year, 1.10; 95% CI 1.01-1.19), whereas no change over time was observed among nonspecified TSCCs (OR per year, 0.99; 95% CI 0.90-1.08). In conclusion, the observed increase in the number of HPV-positive TSCCs can explain the increasing number of TSCCs in Eastern Denmark, 2000-2010. HPV prevalence was associated with younger age (<55 years) and a high certainty of tonsillar tumor origin.
本研究旨在探讨2000 - 2010年丹麦东部扁桃体鳞状细胞癌（TSCC）的发病率是否上升，以及人乳头瘤病毒（HPV）能否解释这一上升趋势，并评估HPV感染率与性别、年龄及肿瘤起源（即扁桃体肿瘤起源的确定性）之间的关联。我们对丹麦头颈癌研究组（DAHANCA）和丹麦病理数据库中登记的所有TSCC病例（n = 632）进行了HPV DNA聚合酶链反应（PCR）和p16免疫组化检测。病理学家对肿瘤进行了复查并分为两组：明确型和非明确型TSCC。约10%的HPV阳性肿瘤通过扩增子二代测序进行基因分型。TSCC的总体粗发病率显著上升（每年2.7%），这是由HPV阳性TSCC发病率的上升（每年4.9%）所导致的。HPV总体感染率为58%，其中HPV16是主要的HPV类型。多因素分析显示，HPV感染率与年龄（<55岁与>60岁）（比值比[OR]，1.72；95%置信区间[CI] 1.13 - 2.63）及肿瘤起源（非明确型与明确型TSCC）（OR，0.15；95% CI 0.11 - 0.22）相关。在明确型TSCC中，HPV感染率与肿瘤起源的关联随时间增加（每年OR，1.10；95% CI 1.01 - 1.19），而非明确型TSCC中未观察到随时间的变化（每年OR，0.99；95% CI 0.90 - 1.08）。总之，2000 - 2010年丹麦东部观察到的HPV阳性TSCC数量的增加可以解释TSCC数量的增加。HPV感染率与较年轻年龄（<55岁）及扁桃体肿瘤起源的高确定性相关。
