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Extracapsular extension of neck nodes and absence of human papillomavirus 16‐DNA are predictors of impaired survival in p16‐positive oropharyngeal squamous cell carcinoma
Background Human papillomavirus (HPV)‐driven oropharyngeal squamous cell carcinomas (OPSCCs) demonstrate superior outcome compared with HPV‐negative OPSCCs. The eighth edition of the American Joint Committee on Cancer/Union for International Cancer Control (AJCC/UICC) tumor, lymph node, metastasis (...
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| Published in: | Cancer 2020-05, Vol.126 (9), p.1856-1872 |
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| container_issue | 9 |
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| creator | Freitag, Josefine Wald, Theresa Kuhnt, Thomas Gradistanac, Tanja Kolb, Marlen Dietz, Andreas Wiegand, Susanne Wichmann, Gunnar |
| description | Background
Human papillomavirus (HPV)‐driven oropharyngeal squamous cell carcinomas (OPSCCs) demonstrate superior outcome compared with HPV‐negative OPSCCs. The eighth edition of the American Joint Committee on Cancer/Union for International Cancer Control (AJCC/UICC) tumor, lymph node, metastasis (TNM) classification (TNM 2017) modifies OPSCC staging based on p16 positivity as a surrogate for HPV‐driven disease. In p16‐negative OPSCCs, lymph node (N) categories include extracapsular/extranodal extension (ECE); and, in p16‐positive OPSCCs, N categories are based on the number of positive neck lymph nodes omitting ECE status. The objective of the current study was to assess the prognostic impact of positive ECE status and the detection of HPV16 DNA in patients with p16‐positive OPSCC.
Methods
In a cohort of 92 patients with p16‐positive, lymph node (N)‐positive (stage III‐IVB) OPSCC who underwent surgery and neck dissection, allowing for a pathologic examination of positive lymph nodes, 66 of 92 patients (71.4%) were p16‐positive/HPV16 DNA‐positive, 62 of 92 (67%) were ECE‐positive, and 45 of 62 (72.6%) were ECE‐positive, p16‐positive, and HPV16 DNA‐positive. Differences in outcome were assessed using Kaplan‐Meier plots and Cox proportional hazard regression (CoxR) for tumor‐specific survival and overall survival (OS).
Results
The mean numbers of positive lymph nodes in ECE‐positive patients (5.0 positive lymph nodes; 95% CI, 3.8‐6.4 positive lymph nodes) and ECE‐negative patients (2.4 positive lymph nodes; 95% CI, 1.8‐2.9 positive lymph nodes) were different (P = .0007). ECE affected OS and tumor‐specific survival in p16‐positive patients (P = .007 and P = .047, respectively) and in p16‐positive/HPV16 DNA‐positive patients (P = .013 and P = .026, respectively). Related to the unequal distributions of ECE‐positive/HPV16 DNA‐negative tumors, the TNM 2017 failed to discriminate OS in patients with UICC stage I, II, and III disease (mean OS, 54.5, 73.4, and 45 months, respectively; median OS, 64.7 months, not reached, and 41.1 months, respectively). According to a univariate CoxR, the presence of ECE predicted impaired OS in patients with p16‐positive OPSCC (hazard ratio, 3.40; 95% CI, 1.17‐9.89; P = .025) and even greater impaired OS in those with p16‐positive/HPV16 DNA‐positive OPSCC (HR, 8.64; 95% CI, 1.12‐66.40; P = .038). Multivariate CoxR confirmed ECE and HPV16 DNA detection as independent predictors.
Conclusions
ECE and HPV16 DNA status should be inclu |
| doi_str_mv | 10.1002/cncr.32667 |
| format | article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_journals_2389187452</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2389187452</sourcerecordid><originalsourceid>FETCH-LOGICAL-c3607-7b5853d5ec1888d4eca0bff41c08affd1ce5ade29b7647046f8402892019529e3</originalsourceid><addsrcrecordid>eNp9kU9u1TAQhy1ERV8LGw6ALLFDSut_SZxl9VpKpapICCR20cSZUJfEdu3k0e44AifhUJykfn2FJauRZ775RtaPkNecHXHGxLFxJh5JUVX1M7LirKkLxpV4TlaMMV2USn7dJwcp3eRnLUr5guxLwaRQSqzI77O7OYKBkJYRIsW7GV2y3lE_UIfmO3W-x0TB9RS6hM7gdnK9TOBogGDH0U-wsXFJlFd_fv46vTqhEJGGiL01s49py9spgM0dmpa4sRsYqc3rjwvBJzvbTdZGH64h3rtvmOfpdoHJZ6vBcaQGorEuX3pJ9gYYE756qofky_uzz-sPxeXH84v1yWVhZMXqou5KXcq-RMO11r1CA6wbBsUN0zAMPTdYQo-i6epK1UxVg1ZM6EYw3pSiQXlI3u68IfrbBdPc3vglunyyFVI3XNeqFJl6t6NM9ClFHNoQ7ZT_0HLWbqNpt9G0j9Fk-M2Tcukm7P-hf7PIAN8BP-yI9_9Rteur9aed9AGd_p7D</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2389187452</pqid></control><display><type>article</type><title>Extracapsular extension of neck nodes and absence of human papillomavirus 16‐DNA are predictors of impaired survival in p16‐positive oropharyngeal squamous cell carcinoma</title><source>Wiley</source><source>EZB Electronic Journals Library</source><creator>Freitag, Josefine ; Wald, Theresa ; Kuhnt, Thomas ; Gradistanac, Tanja ; Kolb, Marlen ; Dietz, Andreas ; Wiegand, Susanne ; Wichmann, Gunnar</creator><creatorcontrib>Freitag, Josefine ; Wald, Theresa ; Kuhnt, Thomas ; Gradistanac, Tanja ; Kolb, Marlen ; Dietz, Andreas ; Wiegand, Susanne ; Wichmann, Gunnar</creatorcontrib><description>Background
Human papillomavirus (HPV)‐driven oropharyngeal squamous cell carcinomas (OPSCCs) demonstrate superior outcome compared with HPV‐negative OPSCCs. The eighth edition of the American Joint Committee on Cancer/Union for International Cancer Control (AJCC/UICC) tumor, lymph node, metastasis (TNM) classification (TNM 2017) modifies OPSCC staging based on p16 positivity as a surrogate for HPV‐driven disease. In p16‐negative OPSCCs, lymph node (N) categories include extracapsular/extranodal extension (ECE); and, in p16‐positive OPSCCs, N categories are based on the number of positive neck lymph nodes omitting ECE status. The objective of the current study was to assess the prognostic impact of positive ECE status and the detection of HPV16 DNA in patients with p16‐positive OPSCC.
Methods
In a cohort of 92 patients with p16‐positive, lymph node (N)‐positive (stage III‐IVB) OPSCC who underwent surgery and neck dissection, allowing for a pathologic examination of positive lymph nodes, 66 of 92 patients (71.4%) were p16‐positive/HPV16 DNA‐positive, 62 of 92 (67%) were ECE‐positive, and 45 of 62 (72.6%) were ECE‐positive, p16‐positive, and HPV16 DNA‐positive. Differences in outcome were assessed using Kaplan‐Meier plots and Cox proportional hazard regression (CoxR) for tumor‐specific survival and overall survival (OS).
Results
The mean numbers of positive lymph nodes in ECE‐positive patients (5.0 positive lymph nodes; 95% CI, 3.8‐6.4 positive lymph nodes) and ECE‐negative patients (2.4 positive lymph nodes; 95% CI, 1.8‐2.9 positive lymph nodes) were different (P = .0007). ECE affected OS and tumor‐specific survival in p16‐positive patients (P = .007 and P = .047, respectively) and in p16‐positive/HPV16 DNA‐positive patients (P = .013 and P = .026, respectively). Related to the unequal distributions of ECE‐positive/HPV16 DNA‐negative tumors, the TNM 2017 failed to discriminate OS in patients with UICC stage I, II, and III disease (mean OS, 54.5, 73.4, and 45 months, respectively; median OS, 64.7 months, not reached, and 41.1 months, respectively). According to a univariate CoxR, the presence of ECE predicted impaired OS in patients with p16‐positive OPSCC (hazard ratio, 3.40; 95% CI, 1.17‐9.89; P = .025) and even greater impaired OS in those with p16‐positive/HPV16 DNA‐positive OPSCC (HR, 8.64; 95% CI, 1.12‐66.40; P = .038). Multivariate CoxR confirmed ECE and HPV16 DNA detection as independent predictors.
Conclusions
ECE and HPV16 DNA status should be included in the prognostic staging of patients with p16‐positive OPSCC because several lines of evidence demonstrate their impact on survival.
In a consecutive sample of 92 patients with p16‐positive oropharyngeal squamous cell carcinoma who underwent surgery with or without adjuvant radiotherapy/chemotherapy, extracapsular extension of neck lymph nodes and the absence of detectable human papillomavirus (HPV) subtype 16 DNA are linked to impaired outcomes. The staging of these patients should not omit but, rather, should include an assessment of HPV type 16 DNA and extracapsular extension because both are independent prognostic factors for overall survival and other outcome measures.</description><identifier>ISSN: 0008-543X</identifier><identifier>EISSN: 1097-0142</identifier><identifier>DOI: 10.1002/cncr.32667</identifier><identifier>PMID: 32032442</identifier><language>eng</language><publisher>United States: Wiley Subscription Services, Inc</publisher><subject>Adult ; Aged ; Cancer ; Cyclin-Dependent Kinase Inhibitor p16 - metabolism ; Deoxyribonucleic acid ; DNA ; DNA, Viral - genetics ; extracapsular extension (ECE) ; Extranodal Extension - pathology ; Female ; Head & neck cancer ; head and neck squamous cell carcinoma (HNSCC) ; Health hazards ; Human papillomavirus ; human papillomavirus (HPV) ; Human papillomavirus 16 - genetics ; Humans ; independent predictor ; lymph node ; Lymph nodes ; Lymphatic system ; Male ; Metastases ; metastasis (TNM) classification ; Middle Aged ; multivariate regression analysis ; Neck ; Neoplasm Staging ; Nodes ; Oncology ; Oropharyngeal Neoplasms - metabolism ; Oropharyngeal Neoplasms - pathology ; Oropharyngeal Neoplasms - virology ; oropharyngeal squamous cell carcinoma (OPSCC) ; Oropharyngolaryngeal carcinoma ; p16 expression ; Papillomavirus Infections - metabolism ; Papillomavirus Infections - pathology ; Prognosis ; Squamous cell carcinoma ; Squamous Cell Carcinoma of Head and Neck - metabolism ; Squamous Cell Carcinoma of Head and Neck - pathology ; Squamous Cell Carcinoma of Head and Neck - virology ; Surgery ; Survival ; Survival Analysis ; Throat cancer ; tumor ; tumor staging ; Tumors</subject><ispartof>Cancer, 2020-05, Vol.126 (9), p.1856-1872</ispartof><rights>2020 The Authors. published by Wiley Periodicals, Inc. on behalf of American Cancer Society</rights><rights>2020 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society.</rights><rights>2020 American Cancer Society</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3607-7b5853d5ec1888d4eca0bff41c08affd1ce5ade29b7647046f8402892019529e3</citedby><cites>FETCH-LOGICAL-c3607-7b5853d5ec1888d4eca0bff41c08affd1ce5ade29b7647046f8402892019529e3</cites><orcidid>0000-0001-6191-2095</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32032442$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Freitag, Josefine</creatorcontrib><creatorcontrib>Wald, Theresa</creatorcontrib><creatorcontrib>Kuhnt, Thomas</creatorcontrib><creatorcontrib>Gradistanac, Tanja</creatorcontrib><creatorcontrib>Kolb, Marlen</creatorcontrib><creatorcontrib>Dietz, Andreas</creatorcontrib><creatorcontrib>Wiegand, Susanne</creatorcontrib><creatorcontrib>Wichmann, Gunnar</creatorcontrib><title>Extracapsular extension of neck nodes and absence of human papillomavirus 16‐DNA are predictors of impaired survival in p16‐positive oropharyngeal squamous cell carcinoma</title><title>Cancer</title><addtitle>Cancer</addtitle><description>Background
Human papillomavirus (HPV)‐driven oropharyngeal squamous cell carcinomas (OPSCCs) demonstrate superior outcome compared with HPV‐negative OPSCCs. The eighth edition of the American Joint Committee on Cancer/Union for International Cancer Control (AJCC/UICC) tumor, lymph node, metastasis (TNM) classification (TNM 2017) modifies OPSCC staging based on p16 positivity as a surrogate for HPV‐driven disease. In p16‐negative OPSCCs, lymph node (N) categories include extracapsular/extranodal extension (ECE); and, in p16‐positive OPSCCs, N categories are based on the number of positive neck lymph nodes omitting ECE status. The objective of the current study was to assess the prognostic impact of positive ECE status and the detection of HPV16 DNA in patients with p16‐positive OPSCC.
Methods
In a cohort of 92 patients with p16‐positive, lymph node (N)‐positive (stage III‐IVB) OPSCC who underwent surgery and neck dissection, allowing for a pathologic examination of positive lymph nodes, 66 of 92 patients (71.4%) were p16‐positive/HPV16 DNA‐positive, 62 of 92 (67%) were ECE‐positive, and 45 of 62 (72.6%) were ECE‐positive, p16‐positive, and HPV16 DNA‐positive. Differences in outcome were assessed using Kaplan‐Meier plots and Cox proportional hazard regression (CoxR) for tumor‐specific survival and overall survival (OS).
Results
The mean numbers of positive lymph nodes in ECE‐positive patients (5.0 positive lymph nodes; 95% CI, 3.8‐6.4 positive lymph nodes) and ECE‐negative patients (2.4 positive lymph nodes; 95% CI, 1.8‐2.9 positive lymph nodes) were different (P = .0007). ECE affected OS and tumor‐specific survival in p16‐positive patients (P = .007 and P = .047, respectively) and in p16‐positive/HPV16 DNA‐positive patients (P = .013 and P = .026, respectively). Related to the unequal distributions of ECE‐positive/HPV16 DNA‐negative tumors, the TNM 2017 failed to discriminate OS in patients with UICC stage I, II, and III disease (mean OS, 54.5, 73.4, and 45 months, respectively; median OS, 64.7 months, not reached, and 41.1 months, respectively). According to a univariate CoxR, the presence of ECE predicted impaired OS in patients with p16‐positive OPSCC (hazard ratio, 3.40; 95% CI, 1.17‐9.89; P = .025) and even greater impaired OS in those with p16‐positive/HPV16 DNA‐positive OPSCC (HR, 8.64; 95% CI, 1.12‐66.40; P = .038). Multivariate CoxR confirmed ECE and HPV16 DNA detection as independent predictors.
Conclusions
ECE and HPV16 DNA status should be included in the prognostic staging of patients with p16‐positive OPSCC because several lines of evidence demonstrate their impact on survival.
In a consecutive sample of 92 patients with p16‐positive oropharyngeal squamous cell carcinoma who underwent surgery with or without adjuvant radiotherapy/chemotherapy, extracapsular extension of neck lymph nodes and the absence of detectable human papillomavirus (HPV) subtype 16 DNA are linked to impaired outcomes. The staging of these patients should not omit but, rather, should include an assessment of HPV type 16 DNA and extracapsular extension because both are independent prognostic factors for overall survival and other outcome measures.</description><subject>Adult</subject><subject>Aged</subject><subject>Cancer</subject><subject>Cyclin-Dependent Kinase Inhibitor p16 - metabolism</subject><subject>Deoxyribonucleic acid</subject><subject>DNA</subject><subject>DNA, Viral - genetics</subject><subject>extracapsular extension (ECE)</subject><subject>Extranodal Extension - pathology</subject><subject>Female</subject><subject>Head & neck cancer</subject><subject>head and neck squamous cell carcinoma (HNSCC)</subject><subject>Health hazards</subject><subject>Human papillomavirus</subject><subject>human papillomavirus (HPV)</subject><subject>Human papillomavirus 16 - genetics</subject><subject>Humans</subject><subject>independent predictor</subject><subject>lymph node</subject><subject>Lymph nodes</subject><subject>Lymphatic system</subject><subject>Male</subject><subject>Metastases</subject><subject>metastasis (TNM) classification</subject><subject>Middle Aged</subject><subject>multivariate regression analysis</subject><subject>Neck</subject><subject>Neoplasm Staging</subject><subject>Nodes</subject><subject>Oncology</subject><subject>Oropharyngeal Neoplasms - metabolism</subject><subject>Oropharyngeal Neoplasms - pathology</subject><subject>Oropharyngeal Neoplasms - virology</subject><subject>oropharyngeal squamous cell carcinoma (OPSCC)</subject><subject>Oropharyngolaryngeal carcinoma</subject><subject>p16 expression</subject><subject>Papillomavirus Infections - metabolism</subject><subject>Papillomavirus Infections - pathology</subject><subject>Prognosis</subject><subject>Squamous cell carcinoma</subject><subject>Squamous Cell Carcinoma of Head and Neck - metabolism</subject><subject>Squamous Cell Carcinoma of Head and Neck - pathology</subject><subject>Squamous Cell Carcinoma of Head and Neck - virology</subject><subject>Surgery</subject><subject>Survival</subject><subject>Survival Analysis</subject><subject>Throat cancer</subject><subject>tumor</subject><subject>tumor staging</subject><subject>Tumors</subject><issn>0008-543X</issn><issn>1097-0142</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>24P</sourceid><recordid>eNp9kU9u1TAQhy1ERV8LGw6ALLFDSut_SZxl9VpKpapICCR20cSZUJfEdu3k0e44AifhUJykfn2FJauRZ775RtaPkNecHXHGxLFxJh5JUVX1M7LirKkLxpV4TlaMMV2USn7dJwcp3eRnLUr5guxLwaRQSqzI77O7OYKBkJYRIsW7GV2y3lE_UIfmO3W-x0TB9RS6hM7gdnK9TOBogGDH0U-wsXFJlFd_fv46vTqhEJGGiL01s49py9spgM0dmpa4sRsYqc3rjwvBJzvbTdZGH64h3rtvmOfpdoHJZ6vBcaQGorEuX3pJ9gYYE756qofky_uzz-sPxeXH84v1yWVhZMXqou5KXcq-RMO11r1CA6wbBsUN0zAMPTdYQo-i6epK1UxVg1ZM6EYw3pSiQXlI3u68IfrbBdPc3vglunyyFVI3XNeqFJl6t6NM9ClFHNoQ7ZT_0HLWbqNpt9G0j9Fk-M2Tcukm7P-hf7PIAN8BP-yI9_9Rteur9aed9AGd_p7D</recordid><startdate>20200501</startdate><enddate>20200501</enddate><creator>Freitag, Josefine</creator><creator>Wald, Theresa</creator><creator>Kuhnt, Thomas</creator><creator>Gradistanac, Tanja</creator><creator>Kolb, Marlen</creator><creator>Dietz, Andreas</creator><creator>Wiegand, Susanne</creator><creator>Wichmann, Gunnar</creator><general>Wiley Subscription Services, Inc</general><scope>24P</scope><scope>WIN</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7TO</scope><scope>7U7</scope><scope>C1K</scope><scope>H94</scope><scope>K9.</scope><scope>NAPCQ</scope><orcidid>https://orcid.org/0000-0001-6191-2095</orcidid></search><sort><creationdate>20200501</creationdate><title>Extracapsular extension of neck nodes and absence of human papillomavirus 16‐DNA are predictors of impaired survival in p16‐positive oropharyngeal squamous cell carcinoma</title><author>Freitag, Josefine ; Wald, Theresa ; Kuhnt, Thomas ; Gradistanac, Tanja ; Kolb, Marlen ; Dietz, Andreas ; Wiegand, Susanne ; Wichmann, Gunnar</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3607-7b5853d5ec1888d4eca0bff41c08affd1ce5ade29b7647046f8402892019529e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Cancer</topic><topic>Cyclin-Dependent Kinase Inhibitor p16 - metabolism</topic><topic>Deoxyribonucleic acid</topic><topic>DNA</topic><topic>DNA, Viral - genetics</topic><topic>extracapsular extension (ECE)</topic><topic>Extranodal Extension - pathology</topic><topic>Female</topic><topic>Head & neck cancer</topic><topic>head and neck squamous cell carcinoma (HNSCC)</topic><topic>Health hazards</topic><topic>Human papillomavirus</topic><topic>human papillomavirus (HPV)</topic><topic>Human papillomavirus 16 - genetics</topic><topic>Humans</topic><topic>independent predictor</topic><topic>lymph node</topic><topic>Lymph nodes</topic><topic>Lymphatic system</topic><topic>Male</topic><topic>Metastases</topic><topic>metastasis (TNM) classification</topic><topic>Middle Aged</topic><topic>multivariate regression analysis</topic><topic>Neck</topic><topic>Neoplasm Staging</topic><topic>Nodes</topic><topic>Oncology</topic><topic>Oropharyngeal Neoplasms - metabolism</topic><topic>Oropharyngeal Neoplasms - pathology</topic><topic>Oropharyngeal Neoplasms - virology</topic><topic>oropharyngeal squamous cell carcinoma (OPSCC)</topic><topic>Oropharyngolaryngeal carcinoma</topic><topic>p16 expression</topic><topic>Papillomavirus Infections - metabolism</topic><topic>Papillomavirus Infections - pathology</topic><topic>Prognosis</topic><topic>Squamous cell carcinoma</topic><topic>Squamous Cell Carcinoma of Head and Neck - metabolism</topic><topic>Squamous Cell Carcinoma of Head and Neck - pathology</topic><topic>Squamous Cell Carcinoma of Head and Neck - virology</topic><topic>Surgery</topic><topic>Survival</topic><topic>Survival Analysis</topic><topic>Throat cancer</topic><topic>tumor</topic><topic>tumor staging</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Freitag, Josefine</creatorcontrib><creatorcontrib>Wald, Theresa</creatorcontrib><creatorcontrib>Kuhnt, Thomas</creatorcontrib><creatorcontrib>Gradistanac, Tanja</creatorcontrib><creatorcontrib>Kolb, Marlen</creatorcontrib><creatorcontrib>Dietz, Andreas</creatorcontrib><creatorcontrib>Wiegand, Susanne</creatorcontrib><creatorcontrib>Wichmann, Gunnar</creatorcontrib><collection>Open Access: Wiley-Blackwell Open Access Journals</collection><collection>Wiley-Blackwell Free Backfiles(OpenAccess)</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Environmental Sciences and Pollution Management</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Premium</collection><jtitle>Cancer</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Freitag, Josefine</au><au>Wald, Theresa</au><au>Kuhnt, Thomas</au><au>Gradistanac, Tanja</au><au>Kolb, Marlen</au><au>Dietz, Andreas</au><au>Wiegand, Susanne</au><au>Wichmann, Gunnar</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Extracapsular extension of neck nodes and absence of human papillomavirus 16‐DNA are predictors of impaired survival in p16‐positive oropharyngeal squamous cell carcinoma</atitle><jtitle>Cancer</jtitle><addtitle>Cancer</addtitle><date>2020-05-01</date><risdate>2020</risdate><volume>126</volume><issue>9</issue><spage>1856</spage><epage>1872</epage><pages>1856-1872</pages><issn>0008-543X</issn><eissn>1097-0142</eissn><abstract>Background
Human papillomavirus (HPV)‐driven oropharyngeal squamous cell carcinomas (OPSCCs) demonstrate superior outcome compared with HPV‐negative OPSCCs. The eighth edition of the American Joint Committee on Cancer/Union for International Cancer Control (AJCC/UICC) tumor, lymph node, metastasis (TNM) classification (TNM 2017) modifies OPSCC staging based on p16 positivity as a surrogate for HPV‐driven disease. In p16‐negative OPSCCs, lymph node (N) categories include extracapsular/extranodal extension (ECE); and, in p16‐positive OPSCCs, N categories are based on the number of positive neck lymph nodes omitting ECE status. The objective of the current study was to assess the prognostic impact of positive ECE status and the detection of HPV16 DNA in patients with p16‐positive OPSCC.
Methods
In a cohort of 92 patients with p16‐positive, lymph node (N)‐positive (stage III‐IVB) OPSCC who underwent surgery and neck dissection, allowing for a pathologic examination of positive lymph nodes, 66 of 92 patients (71.4%) were p16‐positive/HPV16 DNA‐positive, 62 of 92 (67%) were ECE‐positive, and 45 of 62 (72.6%) were ECE‐positive, p16‐positive, and HPV16 DNA‐positive. Differences in outcome were assessed using Kaplan‐Meier plots and Cox proportional hazard regression (CoxR) for tumor‐specific survival and overall survival (OS).
Results
The mean numbers of positive lymph nodes in ECE‐positive patients (5.0 positive lymph nodes; 95% CI, 3.8‐6.4 positive lymph nodes) and ECE‐negative patients (2.4 positive lymph nodes; 95% CI, 1.8‐2.9 positive lymph nodes) were different (P = .0007). ECE affected OS and tumor‐specific survival in p16‐positive patients (P = .007 and P = .047, respectively) and in p16‐positive/HPV16 DNA‐positive patients (P = .013 and P = .026, respectively). Related to the unequal distributions of ECE‐positive/HPV16 DNA‐negative tumors, the TNM 2017 failed to discriminate OS in patients with UICC stage I, II, and III disease (mean OS, 54.5, 73.4, and 45 months, respectively; median OS, 64.7 months, not reached, and 41.1 months, respectively). According to a univariate CoxR, the presence of ECE predicted impaired OS in patients with p16‐positive OPSCC (hazard ratio, 3.40; 95% CI, 1.17‐9.89; P = .025) and even greater impaired OS in those with p16‐positive/HPV16 DNA‐positive OPSCC (HR, 8.64; 95% CI, 1.12‐66.40; P = .038). Multivariate CoxR confirmed ECE and HPV16 DNA detection as independent predictors.
Conclusions
ECE and HPV16 DNA status should be included in the prognostic staging of patients with p16‐positive OPSCC because several lines of evidence demonstrate their impact on survival.
In a consecutive sample of 92 patients with p16‐positive oropharyngeal squamous cell carcinoma who underwent surgery with or without adjuvant radiotherapy/chemotherapy, extracapsular extension of neck lymph nodes and the absence of detectable human papillomavirus (HPV) subtype 16 DNA are linked to impaired outcomes. The staging of these patients should not omit but, rather, should include an assessment of HPV type 16 DNA and extracapsular extension because both are independent prognostic factors for overall survival and other outcome measures.</abstract><cop>United States</cop><pub>Wiley Subscription Services, Inc</pub><pmid>32032442</pmid><doi>10.1002/cncr.32667</doi><tpages>17</tpages><orcidid>https://orcid.org/0000-0001-6191-2095</orcidid><oa>free_for_read</oa></addata></record> |
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| recordid | cdi_proquest_journals_2389187452 |
| source | Wiley; EZB Electronic Journals Library |
| subjects | Adult Aged Cancer Cyclin-Dependent Kinase Inhibitor p16 - metabolism Deoxyribonucleic acid DNA DNA, Viral - genetics extracapsular extension (ECE) Extranodal Extension - pathology Female Head & neck cancer head and neck squamous cell carcinoma (HNSCC) Health hazards Human papillomavirus human papillomavirus (HPV) Human papillomavirus 16 - genetics Humans independent predictor lymph node Lymph nodes Lymphatic system Male Metastases metastasis (TNM) classification Middle Aged multivariate regression analysis Neck Neoplasm Staging Nodes Oncology Oropharyngeal Neoplasms - metabolism Oropharyngeal Neoplasms - pathology Oropharyngeal Neoplasms - virology oropharyngeal squamous cell carcinoma (OPSCC) Oropharyngolaryngeal carcinoma p16 expression Papillomavirus Infections - metabolism Papillomavirus Infections - pathology Prognosis Squamous cell carcinoma Squamous Cell Carcinoma of Head and Neck - metabolism Squamous Cell Carcinoma of Head and Neck - pathology Squamous Cell Carcinoma of Head and Neck - virology Surgery Survival Survival Analysis Throat cancer tumor tumor staging Tumors |
| title | Extracapsular extension of neck nodes and absence of human papillomavirus 16‐DNA are predictors of impaired survival in p16‐positive oropharyngeal squamous cell carcinoma |
| url | http://sfxeu10.hosted.exlibrisgroup.com/loughborough?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-29T11%3A49%3A09IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Extracapsular%20extension%20of%20neck%20nodes%20and%20absence%20of%20human%20papillomavirus%2016%E2%80%90DNA%20are%20predictors%20of%20impaired%20survival%20in%20p16%E2%80%90positive%20oropharyngeal%20squamous%20cell%20carcinoma&rft.jtitle=Cancer&rft.au=Freitag,%20Josefine&rft.date=2020-05-01&rft.volume=126&rft.issue=9&rft.spage=1856&rft.epage=1872&rft.pages=1856-1872&rft.issn=0008-543X&rft.eissn=1097-0142&rft_id=info:doi/10.1002/cncr.32667&rft_dat=%3Cproquest_cross%3E2389187452%3C/proquest_cross%3E%3Cgrp_id%3Ecdi_FETCH-LOGICAL-c3607-7b5853d5ec1888d4eca0bff41c08affd1ce5ade29b7647046f8402892019529e3%3C/grp_id%3E%3Coa%3E%3C/oa%3E%3Curl%3E%3C/url%3E&rft_id=info:oai/&rft_pqid=2389187452&rft_id=info:pmid/32032442&rfr_iscdi=true |