与HPV相关的口咽癌相比，HPV无关的口咽癌发生同步性肝胆第二原发性恶性肿瘤的风险更高：一项基于监测、流行病学和最终结果（SEER）数据库的人群研究。

HPV-unrelated oropharyngeal cancer has elevated risk of synchronous hepatobiliary second primary malignancies compared to HPV-related oropharyngeal cancer: a population-based study from SEER.

作者信息

Cao Shaopan, Asad Ayoubi Mehran

机构信息

China-Japan Union Hospital of Jilin University, No. 2519 Jiefang Road, Chaoyang District, Changchun City, Jilin Province postal code: 130026, China.

Alumni Network, Lund University, Stora Algatan 4, Lund postal code: 223 50, Sweden.

出版信息

Cancer Epidemiol. 2025 Aug;97:102826. doi: 10.1016/j.canep.2025.102826. Epub 2025 Apr 18.

DOI:10.1016/j.canep.2025.102826

PMID:40250084

Abstract

BACKGROUND

Our aim was to compare risk of synchronous and metachronous hepatobiliary second primary malignancies (SPMs) in survivors of human papillomavirus (HPV)-related [i.e., p16(+)] and HPV-unrelated [i.e., p16(-)] oropharyngeal cancer (OPC).

METHODS

A retrospective study was conducted for cases with OPC diagnosis during years 2018-2021 who had known p16 status using data of USA from Surveillance, Epidemiology, and End Results (SEER) Program [Incidence - SEER Research Limited-Field Data, 22 Registries (excl IL and MA), Nov 2023 Sub (2000-2021)]. In the statistical analyses, death was considered as a competing event for the development of a hepatobiliary SPM. Bias due to unbalanced baseline characteristics was eliminated by adjustments using propensity score and inverse probability of treatment weighting (IPTW). Risk of development of a hepatobiliary SPM was assessed using propensity-score-adjusted time-varying Cox proportional hazard regression [adjusted hazard ratio (aHR) with 95 % confidence interval (95 % CI)].

RESULTS

Overall, 25759 cases with tumor status of p16(-) (6353) and p16(+) (19406) with median (interquartile range) follow-up times of 14 (6, 26) and 20 (9, 32) months, respectively, were included. From these, 48 had a hepatobiliary SPM. Compared to HPV-related OPC, HPV-unrelated OPC had significantly elevated risk of synchronous all hepatobiliary SPMs [aHR= 2.39 (95 % CI, 1.11-5.15); P = 0.026] and synchronous hepatocellular carcinoma (HCC) SPM [aHR= 2.86 (95 % CI, 1.18-6.92); P = 0.020], but not metachronous ones. Curves of cumulative incidence of a hepatobiliary (or HCC) SPM and cumulative survival probability for those with a hepatobiliary SPM, both stratified by p16 status and adjusted by IPTW, were generated. The median survival time among patients with a hepatobiliary SPM was shorter for HPV-unrelated OPC (0.8 years) compared to HPV-related OPC (2.6 years).

CONCLUSION

The observed elevated risk was likely due to heavy alcohol and tobacco use and the protective role of HPV infection against HCC development in carriers of hepatitis C virus.

摘要

背景

我们的目的是比较人乳头瘤病毒（HPV）相关[即p16(+)]和HPV不相关[即p16(-)]口咽癌（OPC）幸存者发生同时性和异时性肝胆第二原发性恶性肿瘤（SPM）的风险。

方法

利用美国监测、流行病学和最终结果（SEER）计划的数据[发病率-SEER研究有限区域数据，22个登记处（不包括伊利诺伊州和马萨诸塞州），2023年11月版本（2000 - 2021年）]，对2018 - 2021年期间诊断为OPC且已知p16状态的病例进行回顾性研究。在统计分析中，将死亡视为肝胆SPM发生的竞争事件。通过倾向评分和治疗逆概率加权（IPTW）调整消除基线特征不平衡导致的偏差。使用倾向评分调整的时变Cox比例风险回归[调整后风险比（aHR）及95%置信区间（95%CI）]评估发生肝胆SPM的风险。

结果

总体纳入25759例病例，其中p16(-)（6353例）和p16(+)（19406例），中位（四分位间距）随访时间分别为14（6，26）个月和20（9，32）个月。其中，48例发生了肝胆SPM。与HPV相关的OPC相比，HPV不相关的OPC发生同时性所有肝胆SPM的风险显著升高[aHR = 2.39（95%CI，1.11 - 5.15）；P = 0.026]以及同时性肝细胞癌（HCC）SPM的风险显著升高[aHR = 2.86（95%CI，1.18 - 6.92）；P = 0.020]，但异时性肝胆SPM的风险未升高。生成了按p16状态分层并经IPTW调整的肝胆（或HCC）SPM累积发病率曲线以及发生肝胆SPM者的累积生存概率曲线。与HPV相关的OPC（2.6年）相比，HPV不相关的OPC发生肝胆SPM患者的中位生存时间较短（0.8年）。