Double positivity for HPV-DNA/p16(ink4a) is the biomarker with strongest diagnostic accuracy and prognostic value for human papillomavirus related oropharyngeal cancer patients
Background: The etiologic role of human papillomaviruses (HPV) in oropharyngeal cancer (OPC) is well established. Nevertheless, information on survival differences by anatomic sub-site or treatment remains scarce, and it is still unclear the HPV-relatedness definition with best diagnostic accuracy a...
| Autores: | , , , , , , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Tipo de recurso: | artículo |
| Estado: | Versión aceptada para publicación |
| Fecha de publicación: | 2018 |
| País: | España |
| Institución: | Universidad de Barcelona |
| Repositorio: | Dipòsit Digital de la UB |
| OAI Identifier: | oai:diposit.ub.edu:2445/172839 |
| Acceso en línea: | https://hdl.handle.net/2445/172839 |
| Access Level: | acceso abierto |
| Palabra clave: | Papil·lomavirus Càncer de boca Papillomaviruses Mouth cancer |
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Double positivity for HPV-DNA/p16(ink4a) is the biomarker with strongest diagnostic accuracy and prognostic value for human papillomavirus related oropharyngeal cancer patientsMena Cervigón, MarisaTaberna, MirenTous, SaraClavero, OmarQuiros, BeatrizLloveras Rubio, BetlemAlejo, MariaLeon, XavierQuer, MiquelBague, SilviaMesía Nin, RicardNogues, JulioGomà, MontseAguilà, AntonBonfill, TeresaBlazquez, CarmenGuix, MartaHijano, RafaelTorres, MontserratHolzinger, DanaPawlita, MichaelPavón Ribas, Miquel ÀngelBravo, Ignacio G.Sanjosé Llongueras, Silvia deBosch José, Francesc Xavier, 1947-Alemany i Vilches, LaiaMarquez, SandraPapil·lomavirusCàncer de bocaPapillomavirusesMouth cancerBackground: The etiologic role of human papillomaviruses (HPV) in oropharyngeal cancer (OPC) is well established. Nevertheless, information on survival differences by anatomic sub-site or treatment remains scarce, and it is still unclear the HPV-relatedness definition with best diagnostic accuracy and prognostic value. Methods: We conducted a retrospective cohort study of all patients diagnosed with a primary OPC in four Catalonian hospitals from 1990 to 2013. Formalin-fixed, paraffin-embedded cancer tissues were subjected to histopathological evaluation, DNA quality control, HPV-DNA detection, and p16(INK4a)/pRb/p53/Cyclin-D1 immunohistochemistry. HPV-DNA positive and a random sample of HPV-DNA negative cases were subjected to HPV-E6*I mRNA detection. Demographic, tobacco/alcohol use, clinical and follow-up data were collected. Multivariate models were used to evaluate factors associated with HPV positivity as defined by four different HPV-relatedness definitions. Proportional-hazards models were used to compare the risk of death and recurrence among HPV-related and non-related OPC. Results: 788 patients yielded a valid HPV-DNA result. The percentage of positive cases was 10.9%, 10.2%, 8.5% and 7.4% for p16(INK4a), HPV-DNA, HPV-DNA/HPV-E6*I mRNA, and HPV-DNA/p16(INK4a), respectively. Being nonsmoker or non-drinker was consistently associated across HPV-relatedness definitions with HPV positivity. A suggestion of survival differences between anatomic sub-sites and treatments was observed. Double positivity for HPV-DNA/p16(INK4a) showed strongest diagnostic accuracy and prognostic value. Conclusions: Double positivity for HPV-DNA/p16(INK4a), a test that can be easily implemented in the clinical practice, has optimal diagnostic accuracy and prognostic value. Our results have strong clinical implications for patients' classification and handling and also suggest that not all the HPV-related OPC behave similarly.Elsevier Science Bv2018info:eu-repo/semantics/articleinfo:eu-repo/semantics/acceptedVersionapplication/pdfhttps://hdl.handle.net/2445/172839Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))reponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaInglésVersió postprint del document publicat a: https://doi.org/10.1016/j.oraloncology.2018.01.010Oral Oncology, 2018, vol. 78, p. 137-144https://doi.org/10.1016/j.oraloncology.2018.01.010(c) Elsevier Science Bv, 2018info:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/1728392026-05-27T06:46:51Z |
| dc.title.none.fl_str_mv |
Double positivity for HPV-DNA/p16(ink4a) is the biomarker with strongest diagnostic accuracy and prognostic value for human papillomavirus related oropharyngeal cancer patients |
| title |
Double positivity for HPV-DNA/p16(ink4a) is the biomarker with strongest diagnostic accuracy and prognostic value for human papillomavirus related oropharyngeal cancer patients |
| spellingShingle |
Double positivity for HPV-DNA/p16(ink4a) is the biomarker with strongest diagnostic accuracy and prognostic value for human papillomavirus related oropharyngeal cancer patients Mena Cervigón, Marisa Papil·lomavirus Càncer de boca Papillomaviruses Mouth cancer |
| title_short |
Double positivity for HPV-DNA/p16(ink4a) is the biomarker with strongest diagnostic accuracy and prognostic value for human papillomavirus related oropharyngeal cancer patients |
| title_full |
Double positivity for HPV-DNA/p16(ink4a) is the biomarker with strongest diagnostic accuracy and prognostic value for human papillomavirus related oropharyngeal cancer patients |
| title_fullStr |
Double positivity for HPV-DNA/p16(ink4a) is the biomarker with strongest diagnostic accuracy and prognostic value for human papillomavirus related oropharyngeal cancer patients |
| title_full_unstemmed |
Double positivity for HPV-DNA/p16(ink4a) is the biomarker with strongest diagnostic accuracy and prognostic value for human papillomavirus related oropharyngeal cancer patients |
| title_sort |
Double positivity for HPV-DNA/p16(ink4a) is the biomarker with strongest diagnostic accuracy and prognostic value for human papillomavirus related oropharyngeal cancer patients |
| dc.creator.none.fl_str_mv |
Mena Cervigón, Marisa Taberna, Miren Tous, Sara Clavero, Omar Quiros, Beatriz Lloveras Rubio, Betlem Alejo, Maria Leon, Xavier Quer, Miquel Bague, Silvia Mesía Nin, Ricard Nogues, Julio Gomà, Montse Aguilà, Anton Bonfill, Teresa Blazquez, Carmen Guix, Marta Hijano, Rafael Torres, Montserrat Holzinger, Dana Pawlita, Michael Pavón Ribas, Miquel Àngel Bravo, Ignacio G. Sanjosé Llongueras, Silvia de Bosch José, Francesc Xavier, 1947- Alemany i Vilches, Laia Marquez, Sandra |
| author |
Mena Cervigón, Marisa |
| author_facet |
Mena Cervigón, Marisa Taberna, Miren Tous, Sara Clavero, Omar Quiros, Beatriz Lloveras Rubio, Betlem Alejo, Maria Leon, Xavier Quer, Miquel Bague, Silvia Mesía Nin, Ricard Nogues, Julio Gomà, Montse Aguilà, Anton Bonfill, Teresa Blazquez, Carmen Guix, Marta Hijano, Rafael Torres, Montserrat Holzinger, Dana Pawlita, Michael Pavón Ribas, Miquel Àngel Bravo, Ignacio G. Sanjosé Llongueras, Silvia de Bosch José, Francesc Xavier, 1947- Alemany i Vilches, Laia Marquez, Sandra |
| author_role |
author |
| author2 |
Taberna, Miren Tous, Sara Clavero, Omar Quiros, Beatriz Lloveras Rubio, Betlem Alejo, Maria Leon, Xavier Quer, Miquel Bague, Silvia Mesía Nin, Ricard Nogues, Julio Gomà, Montse Aguilà, Anton Bonfill, Teresa Blazquez, Carmen Guix, Marta Hijano, Rafael Torres, Montserrat Holzinger, Dana Pawlita, Michael Pavón Ribas, Miquel Àngel Bravo, Ignacio G. Sanjosé Llongueras, Silvia de Bosch José, Francesc Xavier, 1947- Alemany i Vilches, Laia Marquez, Sandra |
| author2_role |
author author author author author author author author author author author author author author author author author author author author author author author author author author |
| dc.subject.none.fl_str_mv |
Papil·lomavirus Càncer de boca Papillomaviruses Mouth cancer |
| topic |
Papil·lomavirus Càncer de boca Papillomaviruses Mouth cancer |
| description |
Background: The etiologic role of human papillomaviruses (HPV) in oropharyngeal cancer (OPC) is well established. Nevertheless, information on survival differences by anatomic sub-site or treatment remains scarce, and it is still unclear the HPV-relatedness definition with best diagnostic accuracy and prognostic value. Methods: We conducted a retrospective cohort study of all patients diagnosed with a primary OPC in four Catalonian hospitals from 1990 to 2013. Formalin-fixed, paraffin-embedded cancer tissues were subjected to histopathological evaluation, DNA quality control, HPV-DNA detection, and p16(INK4a)/pRb/p53/Cyclin-D1 immunohistochemistry. HPV-DNA positive and a random sample of HPV-DNA negative cases were subjected to HPV-E6*I mRNA detection. Demographic, tobacco/alcohol use, clinical and follow-up data were collected. Multivariate models were used to evaluate factors associated with HPV positivity as defined by four different HPV-relatedness definitions. Proportional-hazards models were used to compare the risk of death and recurrence among HPV-related and non-related OPC. Results: 788 patients yielded a valid HPV-DNA result. The percentage of positive cases was 10.9%, 10.2%, 8.5% and 7.4% for p16(INK4a), HPV-DNA, HPV-DNA/HPV-E6*I mRNA, and HPV-DNA/p16(INK4a), respectively. Being nonsmoker or non-drinker was consistently associated across HPV-relatedness definitions with HPV positivity. A suggestion of survival differences between anatomic sub-sites and treatments was observed. Double positivity for HPV-DNA/p16(INK4a) showed strongest diagnostic accuracy and prognostic value. Conclusions: Double positivity for HPV-DNA/p16(INK4a), a test that can be easily implemented in the clinical practice, has optimal diagnostic accuracy and prognostic value. Our results have strong clinical implications for patients' classification and handling and also suggest that not all the HPV-related OPC behave similarly. |
| publishDate |
2018 |
| dc.date.none.fl_str_mv |
2018 |
| dc.type.none.fl_str_mv |
info:eu-repo/semantics/article info:eu-repo/semantics/acceptedVersion |
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article |
| status_str |
acceptedVersion |
| dc.identifier.none.fl_str_mv |
https://hdl.handle.net/2445/172839 |
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https://hdl.handle.net/2445/172839 |
| dc.language.none.fl_str_mv |
Inglés |
| language_invalid_str_mv |
Inglés |
| dc.relation.none.fl_str_mv |
Versió postprint del document publicat a: https://doi.org/10.1016/j.oraloncology.2018.01.010 Oral Oncology, 2018, vol. 78, p. 137-144 https://doi.org/10.1016/j.oraloncology.2018.01.010 |
| dc.rights.none.fl_str_mv |
(c) Elsevier Science Bv, 2018 info:eu-repo/semantics/openAccess |
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(c) Elsevier Science Bv, 2018 |
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openAccess |
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application/pdf |
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Elsevier Science Bv |
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Elsevier Science Bv |
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Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL)) reponame:Dipòsit Digital de la UB instname:Universidad de Barcelona |
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Universidad de Barcelona |
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Dipòsit Digital de la UB |
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Dipòsit Digital de la UB |
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