The Clinical Value of Measuring Circulating HPV DNA during Chemo-Radiotherapy in Squamous Cell Carcinoma of the Anus
Background and purpose: Circulating tumor DNA (ctDNA) is investigated in various cancers. In squamous cell carcinoma of the anus (SCCA) infection with human papilloma virus (HPV) is found in around 90% of cases and here, plasma HPV (pHPV) can be used as ctDNA. Preliminary data have proved the abilit...
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description | Background and purpose: Circulating tumor DNA (ctDNA) is investigated in various cancers. In squamous cell carcinoma of the anus (SCCA) infection with human papilloma virus (HPV) is found in around 90% of cases and here, plasma HPV (pHPV) can be used as ctDNA. Preliminary data have proved the ability to detect pHPV16 and -18 in SCCA. We have developed a highly sensitive method for measurement of six relevant pHPV subtypes, to investigate the elimination pattern of pHPV during chemo-radiotherapy (CRT) for SCCA and its clinical value. Material and methods: Patients treated at Aarhus University Hospital from 2016–2020 were included. P16 status in the primary biopsy was measured and 82% of patients had P16 positive tumor. Blood samples were collected prior to treatment (PT), mid treatment (MT), end of therapy (EOT), and during follow-up (FU). An in-house multiplex digital droplet PCR method measured pHPV subtypes 16, 18, 31, 33, 51, 58. Results: Samples from 88 patients were drawn PT (n = 73), MT (n = 72), EOT (n = 64) and during FU (n = 41). Plasma HPV was detectable in 52 patients and PT pHPV levels correlated to tumor stages. Three elimination patterns were observed during CRT with correlation to outcome: fast responders with no local or distant failures (0/12); slow responders with high risk of local failures (4/20), no distant failures; persistent molecular responders with high risk of distant failures (4/13), but no local failures, p < 0.01. Conclusion: During CRT, pHPV can divide patients with SCCA into three groups with significantly different risk of failure. The use of pHPV can potentially assist in clinical treatment decision. |
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P. ; Spindler, Karen-Lise G.</creator><creatorcontrib>Lefèvre, Anna C. ; Pallisgaard, Niels ; Kronborg, Camilla ; Wind, Karen L. ; Krag, Søren R. P. ; Spindler, Karen-Lise G.</creatorcontrib><description>Background and purpose: Circulating tumor DNA (ctDNA) is investigated in various cancers. In squamous cell carcinoma of the anus (SCCA) infection with human papilloma virus (HPV) is found in around 90% of cases and here, plasma HPV (pHPV) can be used as ctDNA. Preliminary data have proved the ability to detect pHPV16 and -18 in SCCA. We have developed a highly sensitive method for measurement of six relevant pHPV subtypes, to investigate the elimination pattern of pHPV during chemo-radiotherapy (CRT) for SCCA and its clinical value. Material and methods: Patients treated at Aarhus University Hospital from 2016–2020 were included. P16 status in the primary biopsy was measured and 82% of patients had P16 positive tumor. Blood samples were collected prior to treatment (PT), mid treatment (MT), end of therapy (EOT), and during follow-up (FU). An in-house multiplex digital droplet PCR method measured pHPV subtypes 16, 18, 31, 33, 51, 58. Results: Samples from 88 patients were drawn PT (n = 73), MT (n = 72), EOT (n = 64) and during FU (n = 41). Plasma HPV was detectable in 52 patients and PT pHPV levels correlated to tumor stages. Three elimination patterns were observed during CRT with correlation to outcome: fast responders with no local or distant failures (0/12); slow responders with high risk of local failures (4/20), no distant failures; persistent molecular responders with high risk of distant failures (4/13), but no local failures, p < 0.01. Conclusion: During CRT, pHPV can divide patients with SCCA into three groups with significantly different risk of failure. The use of pHPV can potentially assist in clinical treatment decision.</description><identifier>ISSN: 2072-6694</identifier><identifier>EISSN: 2072-6694</identifier><identifier>DOI: 10.3390/cancers13102451</identifier><identifier>PMID: 34070045</identifier><language>eng</language><publisher>Basel: MDPI AG</publisher><subject>Anus ; Biopsy ; Blood ; Cancer therapies ; Cell division ; Chemoradiotherapy ; Deoxyribonucleic acid ; DNA ; Genes ; Genomes ; Human papillomavirus ; Medical prognosis ; Patients ; Pelvis ; Plasma ; Radiation therapy ; Squamous cell carcinoma ; Tumors</subject><ispartof>Cancers, 2021-05, Vol.13 (10), p.2451</ispartof><rights>2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2021 by the authors. 2021</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c398t-76bd81c9339901fe5bfd98e3c994f6f4815d35edc5ba197c776c71d2b39404403</citedby><cites>FETCH-LOGICAL-c398t-76bd81c9339901fe5bfd98e3c994f6f4815d35edc5ba197c776c71d2b39404403</cites><orcidid>0000-0002-2937-4677</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8158133/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8158133/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,27901,27902,53766,53768</link.rule.ids></links><search><creatorcontrib>Lefèvre, Anna C.</creatorcontrib><creatorcontrib>Pallisgaard, Niels</creatorcontrib><creatorcontrib>Kronborg, Camilla</creatorcontrib><creatorcontrib>Wind, Karen L.</creatorcontrib><creatorcontrib>Krag, Søren R. P.</creatorcontrib><creatorcontrib>Spindler, Karen-Lise G.</creatorcontrib><title>The Clinical Value of Measuring Circulating HPV DNA during Chemo-Radiotherapy in Squamous Cell Carcinoma of the Anus</title><title>Cancers</title><description>Background and purpose: Circulating tumor DNA (ctDNA) is investigated in various cancers. In squamous cell carcinoma of the anus (SCCA) infection with human papilloma virus (HPV) is found in around 90% of cases and here, plasma HPV (pHPV) can be used as ctDNA. Preliminary data have proved the ability to detect pHPV16 and -18 in SCCA. We have developed a highly sensitive method for measurement of six relevant pHPV subtypes, to investigate the elimination pattern of pHPV during chemo-radiotherapy (CRT) for SCCA and its clinical value. Material and methods: Patients treated at Aarhus University Hospital from 2016–2020 were included. P16 status in the primary biopsy was measured and 82% of patients had P16 positive tumor. Blood samples were collected prior to treatment (PT), mid treatment (MT), end of therapy (EOT), and during follow-up (FU). An in-house multiplex digital droplet PCR method measured pHPV subtypes 16, 18, 31, 33, 51, 58. Results: Samples from 88 patients were drawn PT (n = 73), MT (n = 72), EOT (n = 64) and during FU (n = 41). Plasma HPV was detectable in 52 patients and PT pHPV levels correlated to tumor stages. Three elimination patterns were observed during CRT with correlation to outcome: fast responders with no local or distant failures (0/12); slow responders with high risk of local failures (4/20), no distant failures; persistent molecular responders with high risk of distant failures (4/13), but no local failures, p < 0.01. Conclusion: During CRT, pHPV can divide patients with SCCA into three groups with significantly different risk of failure. The use of pHPV can potentially assist in clinical treatment decision.</description><subject>Anus</subject><subject>Biopsy</subject><subject>Blood</subject><subject>Cancer therapies</subject><subject>Cell division</subject><subject>Chemoradiotherapy</subject><subject>Deoxyribonucleic acid</subject><subject>DNA</subject><subject>Genes</subject><subject>Genomes</subject><subject>Human papillomavirus</subject><subject>Medical prognosis</subject><subject>Patients</subject><subject>Pelvis</subject><subject>Plasma</subject><subject>Radiation therapy</subject><subject>Squamous cell carcinoma</subject><subject>Tumors</subject><issn>2072-6694</issn><issn>2072-6694</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>8G5</sourceid><sourceid>BENPR</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNpdkU1LxDAQhoMoKurZa8CLl2rSpE1zEZb6CX6h615DmqZuljbZTRrBf28WF1HnMgPz8DAvA8AxRmeEcHSupFXaB0wwymmBt8B-jlielSWn27_mPXAUwgKlIgSzku2CPUIRQ4gW-2CczjWse2ONkj2cyT5q6Dr4oGWI3th3WBuvYi_H9Xz7PIOXjxPYblZzPbjsRbbGjXPt5fITGgtfV1EOLgZY676HtfTKWDfItTVRcGJjOAQ7neyDPtr0A_B2fTWtb7P7p5u7enKfKcKrMWNl01ZY8RSWI9zpoulaXmmiOKdd2dEKFy0pdKuKRmLOFGOlYrjNG8IpohSRA3Dx7V3GZkictqOXvVh6M0j_KZw04u_Gmrl4dx8imStMSBKcbgTeraIOoxhMUCmXtDpFFHlBSlpVBOOEnvxDFy56m-KtqZxSXOYsUefflPIuBK-7n2MwEuunin9PJV-jsZR6</recordid><startdate>20210518</startdate><enddate>20210518</enddate><creator>Lefèvre, Anna C.</creator><creator>Pallisgaard, Niels</creator><creator>Kronborg, Camilla</creator><creator>Wind, Karen L.</creator><creator>Krag, Søren R. P.</creator><creator>Spindler, Karen-Lise G.</creator><general>MDPI AG</general><general>MDPI</general><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7T5</scope><scope>7TO</scope><scope>7XB</scope><scope>8FE</scope><scope>8FH</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>H94</scope><scope>HCIFZ</scope><scope>LK8</scope><scope>M2O</scope><scope>M7P</scope><scope>MBDVC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-2937-4677</orcidid></search><sort><creationdate>20210518</creationdate><title>The Clinical Value of Measuring Circulating HPV DNA during Chemo-Radiotherapy in Squamous Cell Carcinoma of the Anus</title><author>Lefèvre, Anna C. ; Pallisgaard, Niels ; Kronborg, Camilla ; Wind, Karen L. ; Krag, Søren R. P. ; Spindler, Karen-Lise G.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c398t-76bd81c9339901fe5bfd98e3c994f6f4815d35edc5ba197c776c71d2b39404403</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Anus</topic><topic>Biopsy</topic><topic>Blood</topic><topic>Cancer therapies</topic><topic>Cell division</topic><topic>Chemoradiotherapy</topic><topic>Deoxyribonucleic acid</topic><topic>DNA</topic><topic>Genes</topic><topic>Genomes</topic><topic>Human papillomavirus</topic><topic>Medical prognosis</topic><topic>Patients</topic><topic>Pelvis</topic><topic>Plasma</topic><topic>Radiation therapy</topic><topic>Squamous cell carcinoma</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Lefèvre, Anna C.</creatorcontrib><creatorcontrib>Pallisgaard, Niels</creatorcontrib><creatorcontrib>Kronborg, Camilla</creatorcontrib><creatorcontrib>Wind, Karen L.</creatorcontrib><creatorcontrib>Krag, Søren R. P.</creatorcontrib><creatorcontrib>Spindler, Karen-Lise G.</creatorcontrib><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Immunology Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Research Library (Alumni Edition)</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>ProQuest Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central</collection><collection>ProQuest Central Student</collection><collection>Research Library Prep</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>Biological Sciences</collection><collection>Research Library</collection><collection>Biological Science Database</collection><collection>Research Library (Corporate)</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>ProQuest Central Basic</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Cancers</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lefèvre, Anna C.</au><au>Pallisgaard, Niels</au><au>Kronborg, Camilla</au><au>Wind, Karen L.</au><au>Krag, Søren R. P.</au><au>Spindler, Karen-Lise G.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The Clinical Value of Measuring Circulating HPV DNA during Chemo-Radiotherapy in Squamous Cell Carcinoma of the Anus</atitle><jtitle>Cancers</jtitle><date>2021-05-18</date><risdate>2021</risdate><volume>13</volume><issue>10</issue><spage>2451</spage><pages>2451-</pages><issn>2072-6694</issn><eissn>2072-6694</eissn><abstract>Background and purpose: Circulating tumor DNA (ctDNA) is investigated in various cancers. In squamous cell carcinoma of the anus (SCCA) infection with human papilloma virus (HPV) is found in around 90% of cases and here, plasma HPV (pHPV) can be used as ctDNA. Preliminary data have proved the ability to detect pHPV16 and -18 in SCCA. We have developed a highly sensitive method for measurement of six relevant pHPV subtypes, to investigate the elimination pattern of pHPV during chemo-radiotherapy (CRT) for SCCA and its clinical value. Material and methods: Patients treated at Aarhus University Hospital from 2016–2020 were included. P16 status in the primary biopsy was measured and 82% of patients had P16 positive tumor. Blood samples were collected prior to treatment (PT), mid treatment (MT), end of therapy (EOT), and during follow-up (FU). An in-house multiplex digital droplet PCR method measured pHPV subtypes 16, 18, 31, 33, 51, 58. Results: Samples from 88 patients were drawn PT (n = 73), MT (n = 72), EOT (n = 64) and during FU (n = 41). Plasma HPV was detectable in 52 patients and PT pHPV levels correlated to tumor stages. Three elimination patterns were observed during CRT with correlation to outcome: fast responders with no local or distant failures (0/12); slow responders with high risk of local failures (4/20), no distant failures; persistent molecular responders with high risk of distant failures (4/13), but no local failures, p < 0.01. Conclusion: During CRT, pHPV can divide patients with SCCA into three groups with significantly different risk of failure. The use of pHPV can potentially assist in clinical treatment decision.</abstract><cop>Basel</cop><pub>MDPI AG</pub><pmid>34070045</pmid><doi>10.3390/cancers13102451</doi><orcidid>https://orcid.org/0000-0002-2937-4677</orcidid><oa>free_for_read</oa></addata></record> |
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subjects | Anus Biopsy Blood Cancer therapies Cell division Chemoradiotherapy Deoxyribonucleic acid DNA Genes Genomes Human papillomavirus Medical prognosis Patients Pelvis Plasma Radiation therapy Squamous cell carcinoma Tumors |
title | The Clinical Value of Measuring Circulating HPV DNA during Chemo-Radiotherapy in Squamous Cell Carcinoma of the Anus |
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