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PD-L1 protein expression and copy number gains in HIV-positive locally advanced cervical cancer
BACKGROUND: The programmed death-1/programmed death-ligand-1 (PD-1/PD-L1) axis may represent a target for cervical cancer; however, it is poorly understood in human immunodeficiency virus (HIV)-infected patients. METHODS: We evaluated HIV-positive (n = 42) and HIV-negative (n = 110) women with locall...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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SAGE Publications
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7580136/ https://www.ncbi.nlm.nih.gov/pubmed/33149767 http://dx.doi.org/10.1177/1758835920963001 |
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author | Loharamtaweethong, Kongsak Puripat, Napaporn Praditphol, Niphon Thammasiri, Jidapa Tangitgamol, Siriwan |
author_facet | Loharamtaweethong, Kongsak Puripat, Napaporn Praditphol, Niphon Thammasiri, Jidapa Tangitgamol, Siriwan |
author_sort | Loharamtaweethong, Kongsak |
collection | PubMed |
description | BACKGROUND: The programmed death-1/programmed death-ligand-1 (PD-1/PD-L1) axis may represent a target for cervical cancer; however, it is poorly understood in human immunodeficiency virus (HIV)-infected patients. METHODS: We evaluated HIV-positive (n = 42) and HIV-negative (n = 110) women with locally advanced cervical cancer regarding their PD-L1 expression, determined by combined positive score (CPS) ⩾ 1 and tumor proportion score (TPS) ⩾ 25%, and PD-L1 copy number alterations, assessed by fluorescence in situ hybridization. RESULTS: Regardless of HIV status, 84.9% and 44.8% of cases were PD-L1-positive according to CPS ⩾ 1 and TPS ⩾ 25%. Per CPS ⩾ 1, PD-L1 positive rate was similar between HIV-positive and HIV-negative women, whereas a significant difference was seen per TPS ⩾ 25%. Tumor size and parametrial invasion were correlated with PD-L1 positivity in HIV-negative women, whereas anti-retroviral therapy (ART) was correlated with TPS < 25%. Low CD4-positive cell counts were associated with CPS < 1 in HIV-positive women. No significant difference was observed in PD-L1 copy number status between HIV-positive and HIV-negative women. PD-L1 amplification and polysomy were independently associated with TPS ⩾ 25%, whereas the presence of parametrial invasion was independently associated with CPS ⩾ 1. Cancer stage and PD-L1 amplification were identified as independent predictors of recurrence-free survival [hazard ratio (HR) = 2.40 (1.32–4.36) and HR = 5.33 (1.94–14.61)] and cancer-specific survival [HR = 13.62 (5.1–36.38) and HR = 3.53 (1.43–8.69)]. PD-L1 polysomy was an independent predictor of locoregional recurrence-free survival [HR = 3.27 (1.27–8.41)]. HIV status and PD-L1 expression (CPS ⩾ 1 or TPS ⩾ 25%) were not associated with poor patient outcomes. CONCLUSION: PD-L1 amplification and polysomy are the strongest drivers of PD-L1 expression in cervical cancer, and could represent prognostic biomarkers for anti-PD-1/PD-L1 therapy. Cervical cancer biology may be modulated by HIV infection, CD4-positive cells, and HIV treatments. |
format | Online Article Text |
id | pubmed-7580136 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | SAGE Publications |
record_format | MEDLINE/PubMed |
spelling | pubmed-75801362020-11-03 PD-L1 protein expression and copy number gains in HIV-positive locally advanced cervical cancer Loharamtaweethong, Kongsak Puripat, Napaporn Praditphol, Niphon Thammasiri, Jidapa Tangitgamol, Siriwan Ther Adv Med Oncol Original Research BACKGROUND: The programmed death-1/programmed death-ligand-1 (PD-1/PD-L1) axis may represent a target for cervical cancer; however, it is poorly understood in human immunodeficiency virus (HIV)-infected patients. METHODS: We evaluated HIV-positive (n = 42) and HIV-negative (n = 110) women with locally advanced cervical cancer regarding their PD-L1 expression, determined by combined positive score (CPS) ⩾ 1 and tumor proportion score (TPS) ⩾ 25%, and PD-L1 copy number alterations, assessed by fluorescence in situ hybridization. RESULTS: Regardless of HIV status, 84.9% and 44.8% of cases were PD-L1-positive according to CPS ⩾ 1 and TPS ⩾ 25%. Per CPS ⩾ 1, PD-L1 positive rate was similar between HIV-positive and HIV-negative women, whereas a significant difference was seen per TPS ⩾ 25%. Tumor size and parametrial invasion were correlated with PD-L1 positivity in HIV-negative women, whereas anti-retroviral therapy (ART) was correlated with TPS < 25%. Low CD4-positive cell counts were associated with CPS < 1 in HIV-positive women. No significant difference was observed in PD-L1 copy number status between HIV-positive and HIV-negative women. PD-L1 amplification and polysomy were independently associated with TPS ⩾ 25%, whereas the presence of parametrial invasion was independently associated with CPS ⩾ 1. Cancer stage and PD-L1 amplification were identified as independent predictors of recurrence-free survival [hazard ratio (HR) = 2.40 (1.32–4.36) and HR = 5.33 (1.94–14.61)] and cancer-specific survival [HR = 13.62 (5.1–36.38) and HR = 3.53 (1.43–8.69)]. PD-L1 polysomy was an independent predictor of locoregional recurrence-free survival [HR = 3.27 (1.27–8.41)]. HIV status and PD-L1 expression (CPS ⩾ 1 or TPS ⩾ 25%) were not associated with poor patient outcomes. CONCLUSION: PD-L1 amplification and polysomy are the strongest drivers of PD-L1 expression in cervical cancer, and could represent prognostic biomarkers for anti-PD-1/PD-L1 therapy. Cervical cancer biology may be modulated by HIV infection, CD4-positive cells, and HIV treatments. SAGE Publications 2020-10-16 /pmc/articles/PMC7580136/ /pubmed/33149767 http://dx.doi.org/10.1177/1758835920963001 Text en © The Author(s), 2020 https://creativecommons.org/licenses/by-nc/4.0/ This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License (https://creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages (https://us.sagepub.com/en-us/nam/open-access-at-sage). |
spellingShingle | Original Research Loharamtaweethong, Kongsak Puripat, Napaporn Praditphol, Niphon Thammasiri, Jidapa Tangitgamol, Siriwan PD-L1 protein expression and copy number gains in HIV-positive locally advanced cervical cancer |
title | PD-L1 protein expression and copy number gains in HIV-positive locally advanced cervical cancer |
title_full | PD-L1 protein expression and copy number gains in HIV-positive locally advanced cervical cancer |
title_fullStr | PD-L1 protein expression and copy number gains in HIV-positive locally advanced cervical cancer |
title_full_unstemmed | PD-L1 protein expression and copy number gains in HIV-positive locally advanced cervical cancer |
title_short | PD-L1 protein expression and copy number gains in HIV-positive locally advanced cervical cancer |
title_sort | pd-l1 protein expression and copy number gains in hiv-positive locally advanced cervical cancer |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7580136/ https://www.ncbi.nlm.nih.gov/pubmed/33149767 http://dx.doi.org/10.1177/1758835920963001 |
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