Arfa Mustasam, Kevin Parza, Filip Ionescu, Keerthi Gullapalli, Mahati Paravathaneni, Youngchul Kim, Reagan E Sandstrom, Majd Al Assaad, G Daniel Grass, Peter Johnstone, Steven Eschrich, Houssein Safa, Juskaran Chadha, Gabriel Roman Souza, Jerel David, Adele Semaan, Niki M Zacharias, Curtis Pettaway, Anna R Giuliano, Philippe E Spiess, Jad Chahoud
{"title":"HPV或p16INK4a在阴茎鳞状细胞癌中的预后作用：一项荟萃分析","authors":"Arfa Mustasam, Kevin Parza, Filip Ionescu, Keerthi Gullapalli, Mahati Paravathaneni, Youngchul Kim, Reagan E Sandstrom, Majd Al Assaad, G Daniel Grass, Peter Johnstone, Steven Eschrich, Houssein Safa, Juskaran Chadha, Gabriel Roman Souza, Jerel David, Adele Semaan, Niki M Zacharias, Curtis Pettaway, Anna R Giuliano, Philippe E Spiess, Jad Chahoud","doi":"10.6004/jnccn.2024.7078","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>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).</p><p><strong>Methods: </strong>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).</p><p><strong>Results: </strong>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%).</p><p><strong>Conclusions: </strong>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.</p>","PeriodicalId":17483,"journal":{"name":"Journal of the National Comprehensive Cancer Network","volume":" ","pages":"1-9"},"PeriodicalIF":14.8000,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"The Prognostic Role of HPV or p16INK4a Status in Penile Squamous Cell Carcinoma: A Meta-Analysis.\",\"authors\":\"Arfa Mustasam, Kevin Parza, Filip Ionescu, Keerthi Gullapalli, Mahati Paravathaneni, Youngchul Kim, Reagan E Sandstrom, Majd Al Assaad, G Daniel Grass, Peter Johnstone, Steven Eschrich, Houssein Safa, Juskaran Chadha, Gabriel Roman Souza, Jerel David, Adele Semaan, Niki M Zacharias, Curtis Pettaway, Anna R Giuliano, Philippe E Spiess, Jad Chahoud\",\"doi\":\"10.6004/jnccn.2024.7078\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>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).</p><p><strong>Methods: </strong>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).</p><p><strong>Results: </strong>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%).</p><p><strong>Conclusions: </strong>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.</p>\",\"PeriodicalId\":17483,\"journal\":{\"name\":\"Journal of the National Comprehensive Cancer Network\",\"volume\":\" \",\"pages\":\"1-9\"},\"PeriodicalIF\":14.8000,\"publicationDate\":\"2025-01-03\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of the National Comprehensive Cancer Network\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.6004/jnccn.2024.7078\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"ONCOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of the National Comprehensive Cancer Network","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.6004/jnccn.2024.7078","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ONCOLOGY","Score":null,"Total":0}
The Prognostic Role of HPV or p16INK4a Status in Penile Squamous Cell Carcinoma: A Meta-Analysis.
Background: 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).
Methods: 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).
Results: 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%).
Conclusions: 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.
期刊介绍：
JNCCN—Journal of the National Comprehensive Cancer Network is a peer-reviewed medical journal read by over 25,000 oncologists and cancer care professionals nationwide. This indexed publication delivers the latest insights into best clinical practices, oncology health services research, and translational medicine. Notably, JNCCN provides updates on the NCCN Clinical Practice Guidelines in Oncology® (NCCN Guidelines®), review articles elaborating on guideline recommendations, health services research, and case reports that spotlight molecular insights in patient care.
Guided by its vision, JNCCN seeks to advance the mission of NCCN by serving as the primary resource for information on NCCN Guidelines®, innovation in translational medicine, and scientific studies related to oncology health services research. This encompasses quality care and value, bioethics, comparative and cost effectiveness, public policy, and interventional research on supportive care and survivorship.
JNCCN boasts indexing by prominent databases such as MEDLINE/PubMed, Chemical Abstracts, Embase, EmCare, and Scopus, reinforcing its standing as a reputable source for comprehensive information in the field of oncology.
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