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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Veröffentlicht in:Human pathology 2014-02, Vol.45 (2), p.310-319
Hauptverfasser: 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
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container_end_page 319
container_issue 2
container_start_page 310
container_title Human pathology
container_volume 45
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 ; 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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.</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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