Differences in the Prevalence of Human Papillomavirus (HPV) in Head and Neck Squamous Cell Cancers by Sex, Race, Anatomic Tumor Site, and HPV Detection Method.
Differences in the Prevalence of Human Papillomavirus (HPV) in Head and Neck Squamous Cell Cancers by Sex, Race, Anatomic Tumor Site, and HPV Detection Method.
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DOI：
10.1001/jamaoncol.2016.3067
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发表时间：
2017-02-01
期刊：
影响因子：
28.4
通讯作者：
Fakhry C
中科院分区：
文献类型：
--
作者：
D'Souza G;Westra WH;Wang SJ;van Zante A;Wentz A;Kluz N;Rettig E;Ryan WR;Ha PK;Kang H;Bishop J;Quon H;Kiess AP;Richmon JD;Eisele DW;Fakhry C
人乳头瘤病毒（HPV）引起口咽鳞状细胞癌（OPSCC）的比例增加，特别是在白色男性中。HPV在其他人口统计学人群和HNSCC其他解剖部位的患病率尚不清楚。探讨HPV肿瘤状态在女性和非白人OPSCC患者以及非口咽头颈部鳞状细胞癌（non-OP HNSCC）患者中的作用。在2个三级学术中心进行的回顾性队列研究，包括1995年至2012年诊断的病例，对少数民族和女性进行过采样。采用分层随机抽样的方法，对863例新诊断的口腔、口咽、喉或鼻咽鳞状细胞癌患者进行了研究。结果是通过p16免疫组化分析、HPV 16 DNA原位杂交（ISH）和高危型HPV E6/E7 mRNA ISH测量的HPV状态。在863例患者中，551例（63.9%）为男性，中位年龄为58岁（四分位距，51-68岁）。在240例OPSCC中，144例（60%）为p16阳性（p16+），115例（48%）为HPV 16 DNA ISH阳性（ISH 16+），134例（56%）为任何致癌HPV类型阳性（ISH+）。从1995年到2012年，女性中p16+ OPSCC的比例显著增加（从29%到77%;趋势P = 0.005）和男性（36%到72%;趋势P <0.001），以及白人（39%到86%;趋势P <0.001）和非白人（32%到62%;趋势P = 0.02）。ISH+ OPSCC观察到相似的结果（所有P ≤ .01）。在623例非OP HNSCC中，p16+的比例高于ISH阳性（62例[10%] vs 30例[5%]; P = 0.001）。这些p16+非OP HNSCC中的高比例（26/62 [42%]）发现于口咽附近部位。不同性别的p16+和ISH+非OP HNSCC的比例相似。随着时间的推移，p16+（或ISH+）的非OP HNSCC比例在白人中增加（趋势P = .04），但在非白人中没有增加（趋势P > .51）。在OPSCC中，p16对ISH阳性的敏感性（100%）、特异性（91%）、阳性预测值（93%）和阴性预测值（100%）均较高。在非OP HNSCC中，p16对ISH阳性的敏感性（83%）和阳性预测值（40%）较低，但特异性（94%）和阴性预测值（99%）较高。在1995年至2012年期间，由HPV引起的OPSCC的比例显着增加。这种增长并不局限于白色男性，而是女性和男性以及白色和非白色种族群体的一致趋势。少数非OP HNSCC与HPV相关。P16阳性是OPSCC中ISH+肿瘤状态的良好替代，但不是非OP HNSCC的良好替代。
Human papillomavirus (HPV) causes an increasing proportion of oropharyngeal squamous cell carcinomas (OPSCCs), particularly in white men. The prevalence of HPV among other demographic groups and other anatomic sites of HNSCC is unclear. To explore the role of HPV tumor status among women and nonwhites with OPSCC and patients with nonoropharyngeal head and neck squamous cell carcinoma (non-OP HNSCC). Retrospective cohort study at 2 tertiary academic centers including cases diagnosed 1995 through 2012, oversampled for minorities and females. A stratified random sample of 863 patients with newly diagnosed SCC of the oral cavity, oropharynx, larynx, or nasopharynx was used. Outcomes were HPV status as measured by p16 immunohistochemical analysis, HPV16 DNA in situ hybridization (ISH), and high-risk HPV E6/E7 mRNA ISH. Of 863 patients, 551 (63.9%) were male and median age was 58 years (interquartile range, 51-68 years). Among 240 OPSCCs, 144 (60%) were p16 positive (p16+), 115 (48%) were HPV16 DNA ISH positive (ISH16+), and 134 (56%) were positive for any oncogenic HPV type (ISH+). From 1995 to 2012, the proportion of p16+ OPSCC increased significantly among women (from 29% to 77%; P = .005 for trend) and men (36% to 72%; P < .001 for trend), as well as among whites (39% to 86%; P < .001 for trend) and nonwhites (32% to 62%; P = .02 for trend). Similar results were observed for ISH+ OPSCC (P ≤ .01 for all). Among 623 non-OP HNSCCs, a higher proportion were p16+ compared with ISH positive (62 [10%] vs 30 [5%]; P = .001). A high proportion (26 of 62 [42%]) of these p16+ non-OP HNSCCs were found in sites adjacent to the oropharynx. The proportion of p16+ and ISH+ non-OP HNSCCs were similar by sex. Overtime, the proportion of non-OP HNSCCs that were p16+ (or ISH+) increased among whites (P = .04 for trend) but not among nonwhites (each P > .51 for trend). Among OPSCCs, p16 had high sensitivity (100%), specificity (91%), and positive (93%) and negative predictive value (100%) for ISH positivity. In non-OP HNSCCs, p16 had lower sensitivity (83%) and positive predictive value (40%) but high specificity (94%) and negative predictive value (99%) for ISH positivity. During 1995 through 2012, the proportion of OPSCCs caused by HPV has increased significantly. This increase was not restricted to white men but was a consistent trend for women and men, as well as for white and nonwhite racial groups. Few non-OP HNSCCs were HPV related. P16 positivity was a good surrogate for ISH+ tumor status among OPSCC, but not a good surrogate for non-OP HNSCC.
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