Mustasam Arfa, Parza Kevin, Ionescu Filip, Gullapalli Keerthi, Paravathaneni Mahati, Kim Youngchul, Sandstrom Reagan E, Al Assaad Majd, Grass G Daniel, Johnstone Peter, Eschrich Steven, Safa Houssein, Chadha Juskaran, Souza Gabriel Roman, David Jerel, Semaan Adele, Zacharias Niki M, Pettaway Curtis, Giuliano Anna R, Spiess Philippe E, Chahoud Jad
Department of Genitourinary Oncology, Moffitt Cancer Center, Tampa, FL.
Department of Hematology Oncology, University of Florida College of Medicine-Jacksonville, Jacksonville, FL.
J Natl Compr Canc Netw. 2025 Jan 3;23(2):e247078. doi: 10.6004/jnccn.2024.7078.
HPV infection is implicated in approximately half of global penile squamous cell carcinoma (PSCC) cases. Previous studies on HPV DNA and p16INK4a status in PSCC have yielded inconclusive prognostic findings. This meta-analysis aims to elucidate the prognostic role of HPV in PSCC by pooling data on disease-free survival (DFS), disease-specific survival (DSS), and overall survival (OS).
We systematically searched Medline and Embase up to January 2023 for relevant human studies. Data from eligible publications reporting HPV DNA or p16INK4a status, along with and DFS, DSS, or OS outcomes, were extracted. A random-effects meta-analysis model was used to synthesize data, with study weights based on size and significance. The study protocol was registered with PROSPERO (CRD42019131355).
Out of 544 studies screened, 34 publications were included, comprising a pooled sample size of 3,944 patients. p16INK4a-positive status was associated with improved OS (hazard ratio [HR], 0.54; 95% CI, 0.39-0.75; I2=31%), DFS (HR, 0.52; 95% CI, 0.29-0.94; I2=20%), and DSS (HR, 0.34; 95% CI, 0.23-0.50; I2=18%). HPV DNA positivity was significantly associated with improved DFS (HR, 0.63; 95% CI, 0.46-0.87; I2=13%) and DSS (HR, 0.46; 95% CI, 0.29-0.75; I2=47%) but not OS (HR, 0.92; 95% CI, 0.74-1.11; I2=0%).
This meta-analysis, comprising the largest number of patients with PSCC to date, shows a notable correlation between p16INK4a immunohistochemistry positivity and survival outcomes. These findings support the understanding that penile cancer cases not associated with HPV tend to behave more aggressively. We support p16INK4a immunohistochemistry testing as part of the initial diagnostic evaluation of patients with PSCC.
全球约一半的阴茎鳞状细胞癌（PSCC）病例与HPV感染有关。先前关于PSCC中HPV DNA和p16INK4a状态的研究所得出的预后结果尚无定论。本荟萃分析旨在通过汇总无病生存期（DFS）、疾病特异性生存期（DSS）和总生存期（OS）的数据，阐明HPV在PSCC中的预后作用。
我们系统检索了截至2023年1月的Medline和Embase数据库，以查找相关的人体研究。提取符合条件的出版物中报告HPV DNA或p16INK4a状态以及DFS、DSS或OS结果的数据。采用随机效应荟萃分析模型对数据进行综合分析，研究权重基于样本量和显著性。该研究方案已在PROSPERO（CRD42019131355）注册。
在筛选的544项研究中，纳入了34篇出版物，汇总样本量为3944例患者。p16INK4a阳性状态与改善的OS（风险比[HR]，0.54；95%置信区间，0.39 - 0.75；I2 = 31%）、DFS（HR，0.52；95%置信区间，0.29 - 0.94；I2 = 20%）和DSS（HR，0.34；95%置信区间，0.23 - 0.50；I2 = 18%）相关。HPV DNA阳性与改善的DFS（HR，0.63；95%置信区间，0.46 - 0.87；I2 = 13%）和DSS（HR，0.46；95%置信区间，0.29 - 0.75；I2 = 47%）显著相关，但与OS无关（HR，0.92；95%置信区间，0.74 - 1.11；I2 = 0%）。
这项荟萃分析纳入了迄今为止数量最多的PSCC患者，显示p16INK4a免疫组化阳性与生存结果之间存在显著相关性。这些发现支持了这样一种认识，即与HPV无关的阴茎癌病例往往行为更具侵袭性。我们支持将p16INK4a免疫组化检测作为PSCC患者初始诊断评估的一部分。
