Multiple Mutations—A Genetic Marker for Extracapsular Spread in Human Papillomavirus/p16-Positive Oropharyngeal Carcinoma

IF 1.6 4区医学 Q2 OTORHINOLARYNGOLOGY

Laryngoscope Investigative Otolaryngology Pub Date : 2025-02-04 DOI:10.1002/lio2.70094

Raphaela Graessle, Iris Piwonski, Cora Husemann, Karsten Kleo, Deema Sabtan, Achim Franzen, Heidi Olze, Ulrike Erben, Michael Hummel, Annekatrin Coordes

{"title":"Multiple Mutations—A Genetic Marker for Extracapsular Spread in Human Papillomavirus/p16-Positive Oropharyngeal Carcinoma","authors":"Raphaela Graessle, Iris Piwonski, Cora Husemann, Karsten Kleo, Deema Sabtan, Achim Franzen, Heidi Olze, Ulrike Erben, Michael Hummel, Annekatrin Coordes","doi":"10.1002/lio2.70094","DOIUrl":null,"url":null,"abstract":"<div>\n \n \n <section>\n \n <h3> Background</h3>\n \n <p>In the 8th edition of the TNM classification, extracapsular spread (ECS) became a factor in classifying the UICC stage of oropharyngeal carcinomas (OPSCC). We aimed to find genetic markers for ECS and to identify differences between HPV/p16-positive and HPV/p16-negative cases.</p>\n </section>\n \n <section>\n \n <h3> Methods</h3>\n \n <p>We performed targeted next-generation sequencing on 99 samples of operable OPSCC and a retrospective analysis of clinical data.</p>\n </section>\n \n <section>\n \n <h3> Results</h3>\n \n <p>We included 55 HPV/p16-positive and 44 HPV/p16-negative patients. We found a significant difference between both groups, particularly in TP53 mutation (<i>p</i> < 0.001). Among other things, a small primary tumor (<i>p</i> < 0.001), no ECS (<i>p</i> = 0.026) were identified as predictors for survival. Multiple mutations were associated with an increased incidence of ECS, especially in HPV+/p16+ cases (<i>p</i> = 0.017). A mutation in PIK3CA occurred more frequently in nonsmokers, especially in HPV−/p16− patients (<i>p</i> = 0.027). A PTEN mutation—which only occurred in HPV+/p16+ tissues—reduced disease-free survival (DFS, <i>p</i> = 0.026).</p>\n </section>\n \n <section>\n \n <h3> Conclusion</h3>\n \n <p>The presence of multiple mutations in HPV+/p16+ OPSCC was associated with a higher risk of ECS.</p>\n </section>\n \n <section>\n \n <h3> Level of Evidence</h3>\n \n <p>3</p>\n </section>\n </div>","PeriodicalId":48529,"journal":{"name":"Laryngoscope Investigative Otolaryngology","volume":"10 1","pages":""},"PeriodicalIF":1.6000,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/lio2.70094","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Laryngoscope Investigative Otolaryngology","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1002/lio2.70094","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"OTORHINOLARYNGOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Background

In the 8th edition of the TNM classification, extracapsular spread (ECS) became a factor in classifying the UICC stage of oropharyngeal carcinomas (OPSCC). We aimed to find genetic markers for ECS and to identify differences between HPV/p16-positive and HPV/p16-negative cases.

Methods

We performed targeted next-generation sequencing on 99 samples of operable OPSCC and a retrospective analysis of clinical data.

Results

We included 55 HPV/p16-positive and 44 HPV/p16-negative patients. We found a significant difference between both groups, particularly in TP53 mutation (p < 0.001). Among other things, a small primary tumor (p < 0.001), no ECS (p = 0.026) were identified as predictors for survival. Multiple mutations were associated with an increased incidence of ECS, especially in HPV+/p16+ cases (p = 0.017). A mutation in PIK3CA occurred more frequently in nonsmokers, especially in HPV−/p16− patients (p = 0.027). A PTEN mutation—which only occurred in HPV+/p16+ tissues—reduced disease-free survival (DFS, p = 0.026).