辅助性HPV疫苗接种与口咽鳞状细胞癌生存：一项真实世界数据库的探索性分析。

文献信息

中文摘要

目的： 儿童期HPV疫苗接种可降低口咽癌（OPC）发病率，但关于HPV暴露后或OPC诊断后接种疫苗的证据仍然有限。虽然已在宫颈发育不良、肛门生殖器癌症和喉乳头状瘤病中记录到获益，但对OPC结局的影响尚不清楚。
方法： 使用前瞻性TrinetX数据库，按HPV疫苗接种状态对OPC患者进行分层。接种疫苗的患者被分为三个队列：在OPC诊断前接种、诊断后1年内接种以及任何时间点接种。这些队列按年龄、种族、民族、性别和癌症分期与未接种疫苗的对照进行倾向性匹配。使用绝对风险降低和Kaplan-Meier分析评估诊断后2年、5年和>5年的生存结局。
结果： 倾向性匹配产生162例任何时间接种疫苗的患者、24例诊断后1年内接种疫苗的患者和79例诊断前接种疫苗的患者，匹配的对照组数量相等，且显示无人口学差异。在OPC诊断前接种疫苗者中以女性为主（73%），而诊断后接种疫苗者中男性占80%。与从未接种疫苗的患者相比，任何时间接种疫苗队列的HPV疫苗接种与2年总生存改善相关（97% vs. 91%，p = 0.29）、5年（97% vs. 89%，p = 0.019）和>5年（93% vs. 74%，p = 0.0003），相当于5年时绝对风险降低5.14%。在诊断前和诊断后接种疫苗亚组中，趋势持续但缺乏统计学显著性。
结论： HPV暴露后接种HPV疫苗与OPC患者生存改善相关。然而，HPV确定不完善、接种疫苗队列规模小以及潜在选择偏倚（包括健康接种者效应）妨碍了因果推断，这种关联不应被解释为治疗效果的证据。需要前瞻性和随机临床试验来确定辅助性HPV疫苗接种是否能为OPC带来真正的生存获益。鉴于治疗的发病率低且潜在生存影响高，开展临床试验是合理的。
证据等级： 3。

英文摘要

OBJECTIVE: Childhood HPV vaccination reduces oropharyngeal cancer (OPC) incidence, but evidence regarding vaccination after HPV exposure or OPC diagnosis remains limited. While benefits are documented in cervical dysplasia, anogenital cancers, and laryngeal papillomatosis, the impact on OPC outcomes is unknown.
METHODS: Using the prospective TrinetX database, OPC patients were stratified by HPV vaccination status. Vaccinated patients were divided into three cohorts: vaccinated before OPC diagnosis, within 1 year after diagnosis, and at any timepoint. Cohorts were propensity-matched with unvaccinated controls by age, race, ethnicity, sex, and cancer stage. Survival outcomes were assessed at 2, 5, and > 5 years post-diagnosis using absolute risk reduction and Kaplan-Meier analyses.
RESULTS: Propensity matching yielded 162 patients vaccinated at any time, 24 vaccinated within 1 year post-diagnosis, and 79 vaccinated pre-diagnosis, with equal matched controls showing no demographic differences. Women predominated among those vaccinated before OPC diagnosis (73%), while men comprised 80% of those vaccinated after diagnosis. HPV vaccination was associated with improved overall survival at 2 years (97% vs. 91%, p = 0.29), 5 years (97% vs. 89%, p = 0.019), and > 5 years (93% vs. 74%, p = 0.0003) for the vaccinated-anytime cohort versus never-vaccinated patients, translating to 5.14% absolute risk reduction at 5 years. Trends persisted but lacked statistical significance in pre- and post-diagnosis vaccination subgroups.
CONCLUSION: HPV vaccination after HPV exposure was associated with improved survival in OPC patients. However, imperfect HPV ascertainment, small vaccinated cohorts, and potential selection bias, including a healthy vaccinee effect, preclude causal inference, and this association should not be interpreted as evidence of a therapeutic effect. Prospective and randomized clinical trials are needed to determine whether adjuvant HPV vaccination confers a true survival benefit in OPC. Given the low morbidity of therapy and high potential survival impact, a clinical trial is warranted.
LEVEL OF EVIDENCE: 3.