African Americans with oropharyngeal carcinoma have significantly poorer outcomes despite similar rates of human papillomavirus–mediated carcinogenesis
Summary We examined racial disparities among 102 oropharyngeal carcinoma (OPC) patients (30 African Americans and 72 whites) comparing rates of transcriptionally active human papillomavirus (HPV)16/18 and p16INK4a overexpression, with times to disease progression and disease-specific survival (DSS)....
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creator | Isayeva, Tatyana, MD, PhD Xu, Jie, MD, PhD Dai, Qian, MD, PhD Whitley, Alex C., MD, PhD Bonner, James, MD Nabell, Lisle, MD Spencer, Sharon, MD Carroll, William, MD Jones, Giera, MS Ragin, Camille, PhD, MPH Brandwein-Gensler, Margaret, MD |
description | Summary We examined racial disparities among 102 oropharyngeal carcinoma (OPC) patients (30 African Americans and 72 whites) comparing rates of transcriptionally active human papillomavirus (HPV)16/18 and p16INK4a overexpression, with times to disease progression and disease-specific survival (DSS). Expression of HPV16/18 transcripts was assessed by reverse transcription and polymerase chain reaction using type-specific E6/E7 primers; p16INK4a was evaluated by immunohistochemistry. African Americans were significantly more likely to present with high T stage disease and receive nonsurgical treatment. HPV16/18 was present in 63% of patients; no racial differences were observed. Silenced p16INK4a in OPC was significantly more common in African Americans (15/24) than in whites (20/69) ( P = .004) and in HPV16+ African Americans (6/24) than in HPV+ whites (2/42) ( P = .023). Kaplan-Meier analysis for DSS revealed a protective effect for p16INK4a overexpression ( P = .0028; hazard ratio [HR], 0.23), HPV16+ ( P = .036; HR, 0.38), and whites ( P = .0039; HR, 0.27). Shorter DSS was associated with primary definitive chemoradiation ( P = .019; HR, 3.49) and T3/T4 disease ( P = .0001; HR, 7.75). A protective effect with respect to disease progression was observed for HPV16+ ( P = .007; HR, 0.27), whites ( P = .0006; HR, 0.197), and p16INK4a overexpression ( P = .0001; HR, 0.116). African Americans with OPC experience poorer outcomes likely due to p16INK4a silencing, higher T stage, and nonsurgical treatment but not lower rates of transcriptionally active HPV16/18. |
doi_str_mv | 10.1016/j.humpath.2013.09.006 |
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Expression of HPV16/18 transcripts was assessed by reverse transcription and polymerase chain reaction using type-specific E6/E7 primers; p16INK4a was evaluated by immunohistochemistry. African Americans were significantly more likely to present with high T stage disease and receive nonsurgical treatment. HPV16/18 was present in 63% of patients; no racial differences were observed. Silenced p16INK4a in OPC was significantly more common in African Americans (15/24) than in whites (20/69) ( P = .004) and in HPV16+ African Americans (6/24) than in HPV+ whites (2/42) ( P = .023). Kaplan-Meier analysis for DSS revealed a protective effect for p16INK4a overexpression ( P = .0028; hazard ratio [HR], 0.23), HPV16+ ( P = .036; HR, 0.38), and whites ( P = .0039; HR, 0.27). Shorter DSS was associated with primary definitive chemoradiation ( P = .019; HR, 3.49) and T3/T4 disease ( P = .0001; HR, 7.75). A protective effect with respect to disease progression was observed for HPV16+ ( P = .007; HR, 0.27), whites ( P = .0006; HR, 0.197), and p16INK4a overexpression ( P = .0001; HR, 0.116). African Americans with OPC experience poorer outcomes likely due to p16INK4a silencing, higher T stage, and nonsurgical treatment but not lower rates of transcriptionally active HPV16/18.</description><identifier>ISSN: 0046-8177</identifier><identifier>EISSN: 1532-8392</identifier><identifier>DOI: 10.1016/j.humpath.2013.09.006</identifier><identifier>PMID: 24355195</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Adult ; African Americans ; Aged ; Alcohol use ; Carcinogenesis ; Confidence intervals ; Cyclin-Dependent Kinase Inhibitor p16 - biosynthesis ; Cyclin-dependent kinases ; Deoxyribonucleic acid ; Disparity ; DNA ; Female ; Gene Silencing ; HPV ; Human papillomavirus ; Human papillomavirus 16 - genetics ; Human papillomavirus 18 - genetics ; Humans ; Infections ; Kaplan-Meier Estimate ; Male ; Middle Aged ; Oropharyngeal ; Oropharyngeal Neoplasms - ethnology ; Oropharyngeal Neoplasms - genetics ; Oropharyngeal Neoplasms - mortality ; Oropharyngeal Neoplasms - therapy ; Oropharynx ; Outcome ; p16 ; Papillomaviridae - metabolism ; Papillomavirus Infections - complications ; Pathology ; Surgery</subject><ispartof>Human pathology, 2014-02, Vol.45 (2), p.310-319</ispartof><rights>Elsevier Inc.</rights><rights>2014 Elsevier Inc.</rights><rights>2014.</rights><rights>Copyright Elsevier Limited Feb 2014</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c481t-9019721f331a8c1019b67472b5ebda600535526dc431ae31c88cd68e921827a63</citedby><cites>FETCH-LOGICAL-c481t-9019721f331a8c1019b67472b5ebda600535526dc431ae31c88cd68e921827a63</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0046817713003894$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24355195$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Isayeva, Tatyana, MD, PhD</creatorcontrib><creatorcontrib>Xu, Jie, MD, PhD</creatorcontrib><creatorcontrib>Dai, Qian, MD, PhD</creatorcontrib><creatorcontrib>Whitley, Alex C., MD, PhD</creatorcontrib><creatorcontrib>Bonner, James, MD</creatorcontrib><creatorcontrib>Nabell, Lisle, MD</creatorcontrib><creatorcontrib>Spencer, Sharon, MD</creatorcontrib><creatorcontrib>Carroll, William, MD</creatorcontrib><creatorcontrib>Jones, Giera, MS</creatorcontrib><creatorcontrib>Ragin, Camille, PhD, MPH</creatorcontrib><creatorcontrib>Brandwein-Gensler, Margaret, MD</creatorcontrib><title>African Americans with oropharyngeal carcinoma have significantly poorer outcomes despite similar rates of human papillomavirus–mediated carcinogenesis</title><title>Human pathology</title><addtitle>Hum Pathol</addtitle><description>Summary We examined racial disparities among 102 oropharyngeal carcinoma (OPC) patients (30 African Americans and 72 whites) comparing rates of transcriptionally active human papillomavirus (HPV)16/18 and p16INK4a overexpression, with times to disease progression and disease-specific survival (DSS). Expression of HPV16/18 transcripts was assessed by reverse transcription and polymerase chain reaction using type-specific E6/E7 primers; p16INK4a was evaluated by immunohistochemistry. African Americans were significantly more likely to present with high T stage disease and receive nonsurgical treatment. HPV16/18 was present in 63% of patients; no racial differences were observed. Silenced p16INK4a in OPC was significantly more common in African Americans (15/24) than in whites (20/69) ( P = .004) and in HPV16+ African Americans (6/24) than in HPV+ whites (2/42) ( P = .023). Kaplan-Meier analysis for DSS revealed a protective effect for p16INK4a overexpression ( P = .0028; hazard ratio [HR], 0.23), HPV16+ ( P = .036; HR, 0.38), and whites ( P = .0039; HR, 0.27). Shorter DSS was associated with primary definitive chemoradiation ( P = .019; HR, 3.49) and T3/T4 disease ( P = .0001; HR, 7.75). A protective effect with respect to disease progression was observed for HPV16+ ( P = .007; HR, 0.27), whites ( P = .0006; HR, 0.197), and p16INK4a overexpression ( P = .0001; HR, 0.116). African Americans with OPC experience poorer outcomes likely due to p16INK4a silencing, higher T stage, and nonsurgical treatment but not lower rates of transcriptionally active HPV16/18.</description><subject>Adult</subject><subject>African Americans</subject><subject>Aged</subject><subject>Alcohol use</subject><subject>Carcinogenesis</subject><subject>Confidence intervals</subject><subject>Cyclin-Dependent Kinase Inhibitor p16 - biosynthesis</subject><subject>Cyclin-dependent kinases</subject><subject>Deoxyribonucleic acid</subject><subject>Disparity</subject><subject>DNA</subject><subject>Female</subject><subject>Gene Silencing</subject><subject>HPV</subject><subject>Human papillomavirus</subject><subject>Human papillomavirus 16 - genetics</subject><subject>Human papillomavirus 18 - genetics</subject><subject>Humans</subject><subject>Infections</subject><subject>Kaplan-Meier Estimate</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Oropharyngeal</subject><subject>Oropharyngeal Neoplasms - ethnology</subject><subject>Oropharyngeal Neoplasms - genetics</subject><subject>Oropharyngeal Neoplasms - mortality</subject><subject>Oropharyngeal Neoplasms - therapy</subject><subject>Oropharynx</subject><subject>Outcome</subject><subject>p16</subject><subject>Papillomaviridae - metabolism</subject><subject>Papillomavirus Infections - complications</subject><subject>Pathology</subject><subject>Surgery</subject><issn>0046-8177</issn><issn>1532-8392</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFksuO1DAQRS0EYpqBTwBZYsMmwY887A2oNeIljcQCWFtup9LtJomDnfSod_wDK36PL6FC94A0G1a2rFO3qu41IU85yznj1ct9vpv70U67XDAuc6Zzxqp7ZMVLKTIltbhPVowVVaZ4XV-QRyntGeO8LMqH5EIUsiy5Llfk57qN3tmBrnv4c0n0xk87GmIYdzYehy3YjjobnR9Cb-nOHoAmvx18u9BTd6RjCBEiDfPkQg-JNpBGPy1U7zsbabQTvoaW4sDYaLSj7zrUOvg4p1_ff_TQeESa2y5bGCD59Jg8aG2X4Mn5vCRf3r75fPU-u_747sPV-jpzheJTphnXteCtlNwqh9boTVUXtdiUsGlsxViJq4qqcQUCILlTyjWVAi24ErWt5CV5cdIdY_g2Q5pM75ODrrMDhDkZXuhKaYUwos_voPswxwGnQ6quEWFyocoT5WJIKUJrxuh79NJwZpbszN6cszNLdoZpg9lh3bOz-rxBT_5W3YaFwOsTAGjHwUM0yXkYHPoXwU2mCf6_LV7dUXCdHzDI7iscIf3bxiRhmPm0fKDl_3DJmFS6kL8B-KnGTQ</recordid><startdate>20140201</startdate><enddate>20140201</enddate><creator>Isayeva, Tatyana, MD, PhD</creator><creator>Xu, Jie, MD, PhD</creator><creator>Dai, Qian, MD, PhD</creator><creator>Whitley, Alex C., MD, PhD</creator><creator>Bonner, James, MD</creator><creator>Nabell, Lisle, MD</creator><creator>Spencer, Sharon, MD</creator><creator>Carroll, William, MD</creator><creator>Jones, Giera, MS</creator><creator>Ragin, Camille, PhD, MPH</creator><creator>Brandwein-Gensler, Margaret, MD</creator><general>Elsevier Inc</general><general>Elsevier Limited</general><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>K9.</scope><scope>7U9</scope><scope>H94</scope></search><sort><creationdate>20140201</creationdate><title>African Americans with oropharyngeal carcinoma have significantly poorer outcomes despite similar rates of human papillomavirus–mediated carcinogenesis</title><author>Isayeva, Tatyana, MD, PhD ; Xu, Jie, MD, PhD ; Dai, Qian, MD, PhD ; Whitley, Alex C., MD, PhD ; Bonner, James, MD ; Nabell, Lisle, MD ; Spencer, Sharon, MD ; Carroll, William, MD ; Jones, Giera, MS ; Ragin, Camille, PhD, MPH ; Brandwein-Gensler, Margaret, MD</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c481t-9019721f331a8c1019b67472b5ebda600535526dc431ae31c88cd68e921827a63</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Adult</topic><topic>African Americans</topic><topic>Aged</topic><topic>Alcohol use</topic><topic>Carcinogenesis</topic><topic>Confidence intervals</topic><topic>Cyclin-Dependent Kinase Inhibitor p16 - biosynthesis</topic><topic>Cyclin-dependent kinases</topic><topic>Deoxyribonucleic acid</topic><topic>Disparity</topic><topic>DNA</topic><topic>Female</topic><topic>Gene Silencing</topic><topic>HPV</topic><topic>Human papillomavirus</topic><topic>Human papillomavirus 16 - genetics</topic><topic>Human papillomavirus 18 - genetics</topic><topic>Humans</topic><topic>Infections</topic><topic>Kaplan-Meier Estimate</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Oropharyngeal</topic><topic>Oropharyngeal Neoplasms - ethnology</topic><topic>Oropharyngeal Neoplasms - genetics</topic><topic>Oropharyngeal Neoplasms - mortality</topic><topic>Oropharyngeal Neoplasms - therapy</topic><topic>Oropharynx</topic><topic>Outcome</topic><topic>p16</topic><topic>Papillomaviridae - metabolism</topic><topic>Papillomavirus Infections - complications</topic><topic>Pathology</topic><topic>Surgery</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Isayeva, Tatyana, MD, PhD</creatorcontrib><creatorcontrib>Xu, Jie, MD, PhD</creatorcontrib><creatorcontrib>Dai, Qian, MD, PhD</creatorcontrib><creatorcontrib>Whitley, Alex C., MD, PhD</creatorcontrib><creatorcontrib>Bonner, James, MD</creatorcontrib><creatorcontrib>Nabell, Lisle, MD</creatorcontrib><creatorcontrib>Spencer, Sharon, MD</creatorcontrib><creatorcontrib>Carroll, William, MD</creatorcontrib><creatorcontrib>Jones, Giera, MS</creatorcontrib><creatorcontrib>Ragin, Camille, PhD, MPH</creatorcontrib><creatorcontrib>Brandwein-Gensler, Margaret, MD</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Virology and AIDS Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><jtitle>Human pathology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Isayeva, Tatyana, MD, PhD</au><au>Xu, Jie, MD, PhD</au><au>Dai, Qian, MD, PhD</au><au>Whitley, Alex C., MD, PhD</au><au>Bonner, James, MD</au><au>Nabell, Lisle, MD</au><au>Spencer, Sharon, MD</au><au>Carroll, William, MD</au><au>Jones, Giera, MS</au><au>Ragin, Camille, PhD, MPH</au><au>Brandwein-Gensler, Margaret, MD</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>African Americans with oropharyngeal carcinoma have significantly poorer outcomes despite similar rates of human papillomavirus–mediated carcinogenesis</atitle><jtitle>Human pathology</jtitle><addtitle>Hum Pathol</addtitle><date>2014-02-01</date><risdate>2014</risdate><volume>45</volume><issue>2</issue><spage>310</spage><epage>319</epage><pages>310-319</pages><issn>0046-8177</issn><eissn>1532-8392</eissn><abstract>Summary We examined racial disparities among 102 oropharyngeal carcinoma (OPC) patients (30 African Americans and 72 whites) comparing rates of transcriptionally active human papillomavirus (HPV)16/18 and p16INK4a overexpression, with times to disease progression and disease-specific survival (DSS). Expression of HPV16/18 transcripts was assessed by reverse transcription and polymerase chain reaction using type-specific E6/E7 primers; p16INK4a was evaluated by immunohistochemistry. African Americans were significantly more likely to present with high T stage disease and receive nonsurgical treatment. HPV16/18 was present in 63% of patients; no racial differences were observed. Silenced p16INK4a in OPC was significantly more common in African Americans (15/24) than in whites (20/69) ( P = .004) and in HPV16+ African Americans (6/24) than in HPV+ whites (2/42) ( P = .023). Kaplan-Meier analysis for DSS revealed a protective effect for p16INK4a overexpression ( P = .0028; hazard ratio [HR], 0.23), HPV16+ ( P = .036; HR, 0.38), and whites ( P = .0039; HR, 0.27). Shorter DSS was associated with primary definitive chemoradiation ( P = .019; HR, 3.49) and T3/T4 disease ( P = .0001; HR, 7.75). A protective effect with respect to disease progression was observed for HPV16+ ( P = .007; HR, 0.27), whites ( P = .0006; HR, 0.197), and p16INK4a overexpression ( P = .0001; HR, 0.116). African Americans with OPC experience poorer outcomes likely due to p16INK4a silencing, higher T stage, and nonsurgical treatment but not lower rates of transcriptionally active HPV16/18.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>24355195</pmid><doi>10.1016/j.humpath.2013.09.006</doi><tpages>10</tpages></addata></record> |
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subjects | Adult African Americans Aged Alcohol use Carcinogenesis Confidence intervals Cyclin-Dependent Kinase Inhibitor p16 - biosynthesis Cyclin-dependent kinases Deoxyribonucleic acid Disparity DNA Female Gene Silencing HPV Human papillomavirus Human papillomavirus 16 - genetics Human papillomavirus 18 - genetics Humans Infections Kaplan-Meier Estimate Male Middle Aged Oropharyngeal Oropharyngeal Neoplasms - ethnology Oropharyngeal Neoplasms - genetics Oropharyngeal Neoplasms - mortality Oropharyngeal Neoplasms - therapy Oropharynx Outcome p16 Papillomaviridae - metabolism Papillomavirus Infections - complications Pathology Surgery |
title | African Americans with oropharyngeal carcinoma have significantly poorer outcomes despite similar rates of human papillomavirus–mediated carcinogenesis |
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