了解高危型人乳头瘤病毒对台湾口咽鳞状细胞癌的影响：一项回顾性队列研究。
Understanding the impact of high-risk human papillomavirus on oropharyngeal squamous cell carcinomas in Taiwan: A retrospective cohort study.
机构信息
Division of Head and Neck Surgery, Department of Otolaryngology, University of Michigan Medical School, Ann Arbor, Michigan, United States of America.
University of Michigan Rogel Cancer Center, Ann Arbor, Michigan, United States of America.
出版信息
PLoS One. 2021 Apr 23;16(4):e0250530. doi: 10.1371/journal.pone.0250530. eCollection 2021.
BACKGROUND AND OBJECTIVES
Human papillomavirus (HPV)-driven oropharyngeal squamous cell carcinoma (OPSCC) is increasing globally. In Taiwan, HPV-positive OPSCC is obscured by tobacco, alcohol, and betel quid use. We investigated the role of high-risk HPV (hrHPV) in a large retrospective Taiwan OPSCC cohort.
METHODS AND RESULTS
The cohort of 541 OPSCCs treated at Chang Gung Memorial Hospital from 1998-2016 consisted of 507 men (94%) and 34 women (6%). Most used tobacco (81%), alcohol (51%), and betel quid (65%). Formalin-fixed, paraffin-embedded tissue was used for p16 staining (a surrogate marker for HPV) and testing for HPV DNA presence and type by Multiplex HPV PCR-MassArray. HPV DNA and/or p16 staining (HPV-positive) was found in 28.4% (150/528) tumors. p16 and HPV DNA were strongly correlated (F < 0.0001). HPV16 was present in 82.8%, and HPV58 in 7.5% of HPV-positive tumors. HPV was associated with higher age (55.5 vs. 52.7 years, p = 0.004), lower T-stage (p = 0.008) better overall survival (OS) (hazard ratio [HR] 0.58 [95% CI 0.42-0.81], p = 0.001), and disease-free survival (DFS) (HR 0.54 [95% CI 0.40-0.73], p < 0.0001). Alcohol was strongly associated with recurrence and death (OS: HR 2.06 [95% CI 1.54-2.74], p < 0.0001; DFS: HR 1.72 [95% CI 1.33-2.24], p < 0.0001). OS and DFS in HPV-positive cases decreased for alcohol users (p < 0.0001). Obscured by the strong alcohol effect, predictive associations were not found for tobacco or betel quid.
CONCLUSIONS
As with HPV-positive OPSCC globally, HPV is an increasingly important etiological factor in Taiwanese OPSCC. HPV-positive OPSCC has considerable survival benefit, but this is reduced by alcohol, tobacco, and betel quid use. hrHPV is a cancer risk factor in males and females. Vaccinating both sexes with a multivalent vaccine including HPV58, combined with alcohol and tobacco cessation policies will be effective cancer-prevention public health strategies in Taiwan.
背景与目的
人乳头瘤病毒（HPV）驱动的口咽鳞状细胞癌（OPSCC）在全球范围内呈上升趋势。在台湾，HPV 阳性 OPSCC 被烟草、酒精和槟榔的使用所掩盖。我们研究了高危型 HPV（hrHPV）在大型回顾性台湾 OPSCC 队列中的作用。
方法和结果
1998 年至 2016 年在长庚纪念医院治疗的 541 例 OPSCC 患者组成了该队列，其中 507 例为男性（94%），34 例为女性（6%）。大多数患者使用烟草（81%）、酒精（51%）和槟榔（65%）。使用福尔马林固定、石蜡包埋组织进行 p16 染色（HPV 的替代标志物），并通过多重 HPV PCR-MassArray 检测 HPV DNA 的存在和类型。在 528 例肿瘤中有 28.4%（150/528）发现 HPV DNA 和/或 p16 染色（HPV 阳性）。p16 和 HPV DNA 呈强相关性（F<0.0001）。HPV16 阳性率为 82.8%，HPV58 阳性率为 7.5%。HPV 与较高的年龄（55.5 岁 vs. 52.7 岁，p=0.004）、较低的 T 分期（p=0.008）、更好的总生存（OS）（风险比[HR]0.58[95%CI 0.42-0.81]，p=0.001）和无病生存（DFS）（HR 0.54[95%CI 0.40-0.73]，p<0.0001）相关。酒精与复发和死亡强烈相关（OS：HR 2.06[95%CI 1.54-2.74]，p<0.0001；DFS：HR 1.72[95%CI 1.33-2.24]，p<0.0001）。HPV 阳性病例中，酒精使用者的 OS 和 DFS 下降（p<0.0001）。由于酒精的强烈影响，未发现烟草或槟榔与生存相关的预测关联。
结论
与全球 HPV 阳性 OPSCC 一样，HPV 是台湾 OPSCC 越来越重要的病因因素。HPV 阳性 OPSCC 具有相当大的生存获益，但这一获益因酒精、烟草和槟榔的使用而降低。高危型 HPV 是男性和女性的癌症危险因素。在台湾，通过使用包含 HPV58 的多价疫苗对两性进行疫苗接种，并结合酒精和烟草戒断政策，将是有效的癌症预防公共卫生策略。
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