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Digital droplet PCR-based quantification of ccfHPV-DNA as liquid biopsy in HPV-driven cervical and vulvar cancer
Purpose More than 99% of cervical cancers and up to 40% of vulvar cancers are human papillomavirus (HPV) related. HPV 16 and 18 are the most relevant subtypes. Novel technologies allow the detection of minimal amounts of circulating cell-free HPV DNA (ccfHPV-DNA). The aim of this study was to evalua...
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| Published in: | Journal of cancer research and clinical oncology 2023-11, Vol.149 (14), p.12597-12604 |
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| creator | Thangarajah, Fabinshy Busshoff, Jana Salamon, Janina Pruss, Marie-Sandrine Lenz, Caroline Morgenstern, Bernd Hellmich, Martin Schlößer, Hans Anton Lenz, Maximilian Domröse, Christian Mallmann, Michael R. Mallmann, Peter Weiß, Jonathan Franzen, Fabian Merkelbach-Bruse, Sabine Binot, Elke Eich, Marie-Lisa Büttner, Reinhardt Schultheis, Anne Maria Alidousty, Christina |
| description | Purpose
More than 99% of cervical cancers and up to 40% of vulvar cancers are human papillomavirus (HPV) related. HPV 16 and 18 are the most relevant subtypes. Novel technologies allow the detection of minimal amounts of circulating cell-free HPV DNA (ccfHPV-DNA). The aim of this study was to evaluate ccfHPV-DNA assessed by droplet digital PCR (ddPCR) as a biomarker for molecular therapy monitoring in early, advanced, relapsed and metastatic HPV-driven cervical and vulvar cancer.
Methods
Inclusion criteria of the study were histologically proven HPV 16/18-driven cervical and vulvar cancer with first diagnosed disease, newly diagnosed recurrence, or progression of disease. Blood samples were taken pre- and post-therapeutically. Circulating cell-free HPV DNA was quantified using ddPCR and the results were correlated with clinical data.
Results
The mean copy number of ccfHPV-DNA was 838.6 (± 3089.1) in pretreatment and 2.3 (± 6.4) in post-treatment samples (
p
|
| doi_str_mv | 10.1007/s00432-023-05077-3 |
| format | article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_10587338</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2838251727</sourcerecordid><originalsourceid>FETCH-LOGICAL-c475t-e970f4cf1a95054958f62603d45712f6a6080b81531948394ac254d47610f64a3</originalsourceid><addsrcrecordid>eNp9kUtv1DAUhS0EokPhD7BAlth0Y7h-xckKVVOgSBVUCNhaHsceXGXsjJ1E6r_Hw5TyWLCyfM93jn11EHpO4RUFUK8LgOCMAOMEJChF-AO0oocR5Vw-RCugihLJaHOCnpRyA_UuFXuMTrgSkjFgKzRehG2YzID7nMbBTfh6_ZlsTHE93s8mTsEHa6aQIk4eW-svr7-Ri4_n2BQ8hP0cerwJaSy3OER80PocFhexdXmpxgGb2ONlHhaTsTWxjp-iR94MxT27O0_R13dvv6wvydWn9x_W51fECiUn4joFXlhPTSdBik62vmEN8F5IRZlvTAMtbFoqOe1EyzthLJOiF6qh4Bth-Cl6c8wd583O9dbFKZtBjznsTL7VyQT9txLDd71Ni6YgW8V5WxPO7hJy2s-uTHoXinXDYKJLc9Gs5S2TVDFV0Zf_oDdpzrHuVynVdlQKySvFjpTNqZTs_P1vKOhDo_rYqK6N6p-N6oPpxZ973Ft-VVgBfgRKleLW5d9v_yf2B24Pqk4</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2878915453</pqid></control><display><type>article</type><title>Digital droplet PCR-based quantification of ccfHPV-DNA as liquid biopsy in HPV-driven cervical and vulvar cancer</title><source>Springer Link</source><creator>Thangarajah, Fabinshy ; Busshoff, Jana ; Salamon, Janina ; Pruss, Marie-Sandrine ; Lenz, Caroline ; Morgenstern, Bernd ; Hellmich, Martin ; Schlößer, Hans Anton ; Lenz, Maximilian ; Domröse, Christian ; Mallmann, Michael R. ; Mallmann, Peter ; Weiß, Jonathan ; Franzen, Fabian ; Merkelbach-Bruse, Sabine ; Binot, Elke ; Eich, Marie-Lisa ; Büttner, Reinhardt ; Schultheis, Anne Maria ; Alidousty, Christina</creator><creatorcontrib>Thangarajah, Fabinshy ; Busshoff, Jana ; Salamon, Janina ; Pruss, Marie-Sandrine ; Lenz, Caroline ; Morgenstern, Bernd ; Hellmich, Martin ; Schlößer, Hans Anton ; Lenz, Maximilian ; Domröse, Christian ; Mallmann, Michael R. ; Mallmann, Peter ; Weiß, Jonathan ; Franzen, Fabian ; Merkelbach-Bruse, Sabine ; Binot, Elke ; Eich, Marie-Lisa ; Büttner, Reinhardt ; Schultheis, Anne Maria ; Alidousty, Christina</creatorcontrib><description>Purpose
More than 99% of cervical cancers and up to 40% of vulvar cancers are human papillomavirus (HPV) related. HPV 16 and 18 are the most relevant subtypes. Novel technologies allow the detection of minimal amounts of circulating cell-free HPV DNA (ccfHPV-DNA). The aim of this study was to evaluate ccfHPV-DNA assessed by droplet digital PCR (ddPCR) as a biomarker for molecular therapy monitoring in early, advanced, relapsed and metastatic HPV-driven cervical and vulvar cancer.
Methods
Inclusion criteria of the study were histologically proven HPV 16/18-driven cervical and vulvar cancer with first diagnosed disease, newly diagnosed recurrence, or progression of disease. Blood samples were taken pre- and post-therapeutically. Circulating cell-free HPV DNA was quantified using ddPCR and the results were correlated with clinical data.
Results
The mean copy number of ccfHPV-DNA was 838.6 (± 3089.1) in pretreatment and 2.3 (± 6.4) in post-treatment samples (
p
< 0.05). The copy number of ccfHPV-DNA increased with higher FIGO stages (
p
< 0.05), which are commonly used for clinical staging/assessment. Furthermore, we compared the distribution of copy numbers between T-stage 1 versus T-stage 2/3. We could show higher copy number level of ccfHPV-DNA in T-stage 2/3 (
p
< 0.05).
Conclusions
Therapy monitoring with determination of ccfHPV-DNA by ddPCR with a small amount of plasma reflects response to therapy and appears feasible for patients in advanced cancer stages of cervical and vulvar cancer. This promising tool should be examined as marker of therapy monitoring in particular in novel HPV-directed therapies.</description><identifier>ISSN: 0171-5216</identifier><identifier>EISSN: 1432-1335</identifier><identifier>DOI: 10.1007/s00432-023-05077-3</identifier><identifier>PMID: 37452202</identifier><language>eng</language><publisher>Berlin/Heidelberg: Springer Berlin Heidelberg</publisher><subject>Biopsy ; Cancer Research ; Cervical cancer ; Copy number ; Deoxyribonucleic acid ; DNA ; Genital cancers ; Hematology ; Human papillomavirus ; Internal Medicine ; Medicine ; Medicine & Public Health ; Metastases ; Oncology ; Polymerase chain reaction</subject><ispartof>Journal of cancer research and clinical oncology, 2023-11, Vol.149 (14), p.12597-12604</ispartof><rights>The Author(s) 2023</rights><rights>2023. The Author(s).</rights><rights>The Author(s) 2023. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c475t-e970f4cf1a95054958f62603d45712f6a6080b81531948394ac254d47610f64a3</citedby><cites>FETCH-LOGICAL-c475t-e970f4cf1a95054958f62603d45712f6a6080b81531948394ac254d47610f64a3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,780,784,885,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/37452202$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Thangarajah, Fabinshy</creatorcontrib><creatorcontrib>Busshoff, Jana</creatorcontrib><creatorcontrib>Salamon, Janina</creatorcontrib><creatorcontrib>Pruss, Marie-Sandrine</creatorcontrib><creatorcontrib>Lenz, Caroline</creatorcontrib><creatorcontrib>Morgenstern, Bernd</creatorcontrib><creatorcontrib>Hellmich, Martin</creatorcontrib><creatorcontrib>Schlößer, Hans Anton</creatorcontrib><creatorcontrib>Lenz, Maximilian</creatorcontrib><creatorcontrib>Domröse, Christian</creatorcontrib><creatorcontrib>Mallmann, Michael R.</creatorcontrib><creatorcontrib>Mallmann, Peter</creatorcontrib><creatorcontrib>Weiß, Jonathan</creatorcontrib><creatorcontrib>Franzen, Fabian</creatorcontrib><creatorcontrib>Merkelbach-Bruse, Sabine</creatorcontrib><creatorcontrib>Binot, Elke</creatorcontrib><creatorcontrib>Eich, Marie-Lisa</creatorcontrib><creatorcontrib>Büttner, Reinhardt</creatorcontrib><creatorcontrib>Schultheis, Anne Maria</creatorcontrib><creatorcontrib>Alidousty, Christina</creatorcontrib><title>Digital droplet PCR-based quantification of ccfHPV-DNA as liquid biopsy in HPV-driven cervical and vulvar cancer</title><title>Journal of cancer research and clinical oncology</title><addtitle>J Cancer Res Clin Oncol</addtitle><addtitle>J Cancer Res Clin Oncol</addtitle><description>Purpose
More than 99% of cervical cancers and up to 40% of vulvar cancers are human papillomavirus (HPV) related. HPV 16 and 18 are the most relevant subtypes. Novel technologies allow the detection of minimal amounts of circulating cell-free HPV DNA (ccfHPV-DNA). The aim of this study was to evaluate ccfHPV-DNA assessed by droplet digital PCR (ddPCR) as a biomarker for molecular therapy monitoring in early, advanced, relapsed and metastatic HPV-driven cervical and vulvar cancer.
Methods
Inclusion criteria of the study were histologically proven HPV 16/18-driven cervical and vulvar cancer with first diagnosed disease, newly diagnosed recurrence, or progression of disease. Blood samples were taken pre- and post-therapeutically. Circulating cell-free HPV DNA was quantified using ddPCR and the results were correlated with clinical data.
Results
The mean copy number of ccfHPV-DNA was 838.6 (± 3089.1) in pretreatment and 2.3 (± 6.4) in post-treatment samples (
p
< 0.05). The copy number of ccfHPV-DNA increased with higher FIGO stages (
p
< 0.05), which are commonly used for clinical staging/assessment. Furthermore, we compared the distribution of copy numbers between T-stage 1 versus T-stage 2/3. We could show higher copy number level of ccfHPV-DNA in T-stage 2/3 (
p
< 0.05).
Conclusions
Therapy monitoring with determination of ccfHPV-DNA by ddPCR with a small amount of plasma reflects response to therapy and appears feasible for patients in advanced cancer stages of cervical and vulvar cancer. This promising tool should be examined as marker of therapy monitoring in particular in novel HPV-directed therapies.</description><subject>Biopsy</subject><subject>Cancer Research</subject><subject>Cervical cancer</subject><subject>Copy number</subject><subject>Deoxyribonucleic acid</subject><subject>DNA</subject><subject>Genital cancers</subject><subject>Hematology</subject><subject>Human papillomavirus</subject><subject>Internal Medicine</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Metastases</subject><subject>Oncology</subject><subject>Polymerase chain 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B.V</general><scope>C6C</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7TO</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>H94</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>M2O</scope><scope>MBDVC</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>Q9U</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20231101</creationdate><title>Digital droplet PCR-based quantification of ccfHPV-DNA as liquid biopsy in HPV-driven cervical and vulvar cancer</title><author>Thangarajah, Fabinshy ; Busshoff, Jana ; Salamon, Janina ; Pruss, Marie-Sandrine ; Lenz, Caroline ; Morgenstern, Bernd ; Hellmich, Martin ; Schlößer, Hans Anton ; Lenz, Maximilian ; Domröse, Christian ; Mallmann, Michael R. ; Mallmann, Peter ; Weiß, Jonathan ; Franzen, Fabian ; Merkelbach-Bruse, Sabine ; Binot, Elke ; Eich, Marie-Lisa ; Büttner, Reinhardt ; Schultheis, Anne Maria ; Alidousty, Christina</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c475t-e970f4cf1a95054958f62603d45712f6a6080b81531948394ac254d47610f64a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><topic>Biopsy</topic><topic>Cancer Research</topic><topic>Cervical cancer</topic><topic>Copy number</topic><topic>Deoxyribonucleic acid</topic><topic>DNA</topic><topic>Genital cancers</topic><topic>Hematology</topic><topic>Human papillomavirus</topic><topic>Internal Medicine</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Metastases</topic><topic>Oncology</topic><topic>Polymerase chain reaction</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Thangarajah, Fabinshy</creatorcontrib><creatorcontrib>Busshoff, Jana</creatorcontrib><creatorcontrib>Salamon, Janina</creatorcontrib><creatorcontrib>Pruss, Marie-Sandrine</creatorcontrib><creatorcontrib>Lenz, Caroline</creatorcontrib><creatorcontrib>Morgenstern, Bernd</creatorcontrib><creatorcontrib>Hellmich, Martin</creatorcontrib><creatorcontrib>Schlößer, Hans Anton</creatorcontrib><creatorcontrib>Lenz, Maximilian</creatorcontrib><creatorcontrib>Domröse, Christian</creatorcontrib><creatorcontrib>Mallmann, Michael R.</creatorcontrib><creatorcontrib>Mallmann, Peter</creatorcontrib><creatorcontrib>Weiß, Jonathan</creatorcontrib><creatorcontrib>Franzen, Fabian</creatorcontrib><creatorcontrib>Merkelbach-Bruse, Sabine</creatorcontrib><creatorcontrib>Binot, Elke</creatorcontrib><creatorcontrib>Eich, Marie-Lisa</creatorcontrib><creatorcontrib>Büttner, Reinhardt</creatorcontrib><creatorcontrib>Schultheis, Anne Maria</creatorcontrib><creatorcontrib>Alidousty, Christina</creatorcontrib><collection>SpringerOpen</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>ProQuest Health and Medical</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Research Library (Alumni Edition)</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest Central</collection><collection>ProQuest Central 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Basic</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Journal of cancer research and clinical oncology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Thangarajah, Fabinshy</au><au>Busshoff, Jana</au><au>Salamon, Janina</au><au>Pruss, Marie-Sandrine</au><au>Lenz, Caroline</au><au>Morgenstern, Bernd</au><au>Hellmich, Martin</au><au>Schlößer, Hans Anton</au><au>Lenz, Maximilian</au><au>Domröse, Christian</au><au>Mallmann, Michael R.</au><au>Mallmann, Peter</au><au>Weiß, Jonathan</au><au>Franzen, Fabian</au><au>Merkelbach-Bruse, Sabine</au><au>Binot, Elke</au><au>Eich, Marie-Lisa</au><au>Büttner, Reinhardt</au><au>Schultheis, Anne Maria</au><au>Alidousty, Christina</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Digital droplet PCR-based quantification of ccfHPV-DNA as liquid biopsy in HPV-driven cervical and vulvar cancer</atitle><jtitle>Journal of cancer research and clinical oncology</jtitle><stitle>J Cancer Res Clin Oncol</stitle><addtitle>J Cancer Res Clin Oncol</addtitle><date>2023-11-01</date><risdate>2023</risdate><volume>149</volume><issue>14</issue><spage>12597</spage><epage>12604</epage><pages>12597-12604</pages><issn>0171-5216</issn><eissn>1432-1335</eissn><abstract>Purpose
More than 99% of cervical cancers and up to 40% of vulvar cancers are human papillomavirus (HPV) related. HPV 16 and 18 are the most relevant subtypes. Novel technologies allow the detection of minimal amounts of circulating cell-free HPV DNA (ccfHPV-DNA). The aim of this study was to evaluate ccfHPV-DNA assessed by droplet digital PCR (ddPCR) as a biomarker for molecular therapy monitoring in early, advanced, relapsed and metastatic HPV-driven cervical and vulvar cancer.
Methods
Inclusion criteria of the study were histologically proven HPV 16/18-driven cervical and vulvar cancer with first diagnosed disease, newly diagnosed recurrence, or progression of disease. Blood samples were taken pre- and post-therapeutically. Circulating cell-free HPV DNA was quantified using ddPCR and the results were correlated with clinical data.
Results
The mean copy number of ccfHPV-DNA was 838.6 (± 3089.1) in pretreatment and 2.3 (± 6.4) in post-treatment samples (
p
< 0.05). The copy number of ccfHPV-DNA increased with higher FIGO stages (
p
< 0.05), which are commonly used for clinical staging/assessment. Furthermore, we compared the distribution of copy numbers between T-stage 1 versus T-stage 2/3. We could show higher copy number level of ccfHPV-DNA in T-stage 2/3 (
p
< 0.05).
Conclusions
Therapy monitoring with determination of ccfHPV-DNA by ddPCR with a small amount of plasma reflects response to therapy and appears feasible for patients in advanced cancer stages of cervical and vulvar cancer. This promising tool should be examined as marker of therapy monitoring in particular in novel HPV-directed therapies.</abstract><cop>Berlin/Heidelberg</cop><pub>Springer Berlin Heidelberg</pub><pmid>37452202</pmid><doi>10.1007/s00432-023-05077-3</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
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| issn | 0171-5216 1432-1335 |
| language | eng |
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| source | Springer Link |
| subjects | Biopsy Cancer Research Cervical cancer Copy number Deoxyribonucleic acid DNA Genital cancers Hematology Human papillomavirus Internal Medicine Medicine Medicine & Public Health Metastases Oncology Polymerase chain reaction |
| title | Digital droplet PCR-based quantification of ccfHPV-DNA as liquid biopsy in HPV-driven cervical and vulvar cancer |
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