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High-risk human papillomavirus status and prognosis in invasive cervical cancer: A nationwide cohort study
BACKGROUND: High-risk human papillomavirus (hrHPV) infection is established as the major cause of invasive cervical cancer (ICC). However, whether hrHPV status in the tumor is associated with subsequent prognosis of ICC is controversial. We aim to evaluate the association between tumor hrHPV status...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6166926/ https://www.ncbi.nlm.nih.gov/pubmed/30273338 http://dx.doi.org/10.1371/journal.pmed.1002666 |
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author | Lei, Jiayao Ploner, Alexander Lagheden, Camilla Eklund, Carina Nordqvist Kleppe, Sara Andrae, Bengt Elfström, K. Miriam Dillner, Joakim Sparén, Pär Sundström, Karin |
author_facet | Lei, Jiayao Ploner, Alexander Lagheden, Camilla Eklund, Carina Nordqvist Kleppe, Sara Andrae, Bengt Elfström, K. Miriam Dillner, Joakim Sparén, Pär Sundström, Karin |
author_sort | Lei, Jiayao |
collection | PubMed |
description | BACKGROUND: High-risk human papillomavirus (hrHPV) infection is established as the major cause of invasive cervical cancer (ICC). However, whether hrHPV status in the tumor is associated with subsequent prognosis of ICC is controversial. We aim to evaluate the association between tumor hrHPV status and ICC prognosis using national registers and comprehensive human papillomavirus (HPV) genotyping. METHODS AND FINDINGS: In this nationwide population-based cohort study, we identified all ICC diagnosed in Sweden during the years 2002–2011 (4,254 confirmed cases), requested all archival formalin-fixed paraffin-embedded blocks, and performed HPV genotyping. Twenty out of 25 pathology biobanks agreed to the study, yielding a total of 2,845 confirmed cases with valid HPV results. Cases were prospectively followed up from date of cancer diagnosis to 31 December 2015, migration from Sweden, or death, whichever occurred first. The main exposure was tumor hrHPV status classified as hrHPV-positive and hrHPV-negative. The primary outcome was all-cause mortality by 31 December 2015. Five-year relative survival ratios (RSRs) were calculated, and excess hazard ratios (EHRs) with 95% confidence intervals (CIs) were estimated using Poisson regression, adjusting for education, time since cancer diagnosis, and clinical factors including age at cancer diagnosis and International Federation of Gynecology and Obstetrics (FIGO) stage. Of the 2,845 included cases, hrHPV was detected in 2,293 (80.6%), and we observed 1,131 (39.8%) deaths during an average of 6.2 years follow-up. The majority of ICC cases were diagnosed at age 30–59 years (57.5%) and classified as stage IB (40.7%). hrHPV positivity was significantly associated with screen-detected tumors, young age, high education level, and early stage at diagnosis (p < 0.001). The 5-year RSR compared to the general female population was 0.74 (95% CI 0.72–0.76) for hrHPV-positive cases and 0.54 (95% CI 0.50–0.59) for hrHPV-negative cases, yielding a crude EHR of 0.45 (95% CI 0.38–0.52) and an adjusted EHR of 0.61 (95% CI 0.52–0.71). Risk of all-cause mortality as measured by EHR was consistently and statistically significantly lower for cases with hrHPV-positive tumors for each age group above 29 years and each FIGO stage above IA. The difference in prognosis by hrHPV status was highly robust, regardless of the clinical, histological, and educational characteristics of the cases. The main limitation was that, except for education, we were not able to adjust for lifestyle factors or other unmeasured confounders. CONCLUSIONS: In this study, women with hrHPV-positive cervical tumors had a substantially better prognosis than women with hrHPV-negative tumors. hrHPV appears to be a biomarker for better prognosis in cervical cancer independent of age, FIGO stage, and histological type, extending information from already established prognostic factors. The underlying biological mechanisms relating lack of detectable tumor hrHPV to considerably worse prognosis are not known and should be further investigated. |
format | Online Article Text |
id | pubmed-6166926 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-61669262018-10-19 High-risk human papillomavirus status and prognosis in invasive cervical cancer: A nationwide cohort study Lei, Jiayao Ploner, Alexander Lagheden, Camilla Eklund, Carina Nordqvist Kleppe, Sara Andrae, Bengt Elfström, K. Miriam Dillner, Joakim Sparén, Pär Sundström, Karin PLoS Med Research Article BACKGROUND: High-risk human papillomavirus (hrHPV) infection is established as the major cause of invasive cervical cancer (ICC). However, whether hrHPV status in the tumor is associated with subsequent prognosis of ICC is controversial. We aim to evaluate the association between tumor hrHPV status and ICC prognosis using national registers and comprehensive human papillomavirus (HPV) genotyping. METHODS AND FINDINGS: In this nationwide population-based cohort study, we identified all ICC diagnosed in Sweden during the years 2002–2011 (4,254 confirmed cases), requested all archival formalin-fixed paraffin-embedded blocks, and performed HPV genotyping. Twenty out of 25 pathology biobanks agreed to the study, yielding a total of 2,845 confirmed cases with valid HPV results. Cases were prospectively followed up from date of cancer diagnosis to 31 December 2015, migration from Sweden, or death, whichever occurred first. The main exposure was tumor hrHPV status classified as hrHPV-positive and hrHPV-negative. The primary outcome was all-cause mortality by 31 December 2015. Five-year relative survival ratios (RSRs) were calculated, and excess hazard ratios (EHRs) with 95% confidence intervals (CIs) were estimated using Poisson regression, adjusting for education, time since cancer diagnosis, and clinical factors including age at cancer diagnosis and International Federation of Gynecology and Obstetrics (FIGO) stage. Of the 2,845 included cases, hrHPV was detected in 2,293 (80.6%), and we observed 1,131 (39.8%) deaths during an average of 6.2 years follow-up. The majority of ICC cases were diagnosed at age 30–59 years (57.5%) and classified as stage IB (40.7%). hrHPV positivity was significantly associated with screen-detected tumors, young age, high education level, and early stage at diagnosis (p < 0.001). The 5-year RSR compared to the general female population was 0.74 (95% CI 0.72–0.76) for hrHPV-positive cases and 0.54 (95% CI 0.50–0.59) for hrHPV-negative cases, yielding a crude EHR of 0.45 (95% CI 0.38–0.52) and an adjusted EHR of 0.61 (95% CI 0.52–0.71). Risk of all-cause mortality as measured by EHR was consistently and statistically significantly lower for cases with hrHPV-positive tumors for each age group above 29 years and each FIGO stage above IA. The difference in prognosis by hrHPV status was highly robust, regardless of the clinical, histological, and educational characteristics of the cases. The main limitation was that, except for education, we were not able to adjust for lifestyle factors or other unmeasured confounders. CONCLUSIONS: In this study, women with hrHPV-positive cervical tumors had a substantially better prognosis than women with hrHPV-negative tumors. hrHPV appears to be a biomarker for better prognosis in cervical cancer independent of age, FIGO stage, and histological type, extending information from already established prognostic factors. The underlying biological mechanisms relating lack of detectable tumor hrHPV to considerably worse prognosis are not known and should be further investigated. Public Library of Science 2018-10-01 /pmc/articles/PMC6166926/ /pubmed/30273338 http://dx.doi.org/10.1371/journal.pmed.1002666 Text en © 2018 Lei et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Lei, Jiayao Ploner, Alexander Lagheden, Camilla Eklund, Carina Nordqvist Kleppe, Sara Andrae, Bengt Elfström, K. Miriam Dillner, Joakim Sparén, Pär Sundström, Karin High-risk human papillomavirus status and prognosis in invasive cervical cancer: A nationwide cohort study |
title | High-risk human papillomavirus status and prognosis in invasive cervical cancer: A nationwide cohort study |
title_full | High-risk human papillomavirus status and prognosis in invasive cervical cancer: A nationwide cohort study |
title_fullStr | High-risk human papillomavirus status and prognosis in invasive cervical cancer: A nationwide cohort study |
title_full_unstemmed | High-risk human papillomavirus status and prognosis in invasive cervical cancer: A nationwide cohort study |
title_short | High-risk human papillomavirus status and prognosis in invasive cervical cancer: A nationwide cohort study |
title_sort | high-risk human papillomavirus status and prognosis in invasive cervical cancer: a nationwide cohort study |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6166926/ https://www.ncbi.nlm.nih.gov/pubmed/30273338 http://dx.doi.org/10.1371/journal.pmed.1002666 |
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