A novel sequencing-based vaginal health assay combining self-sampling, HPV detection and genotyping, STI detection, and vaginal microbiome analysis

Elisabeth M. Bik, Sara W. Bird, Juan P. Bustamante, Luis E. Leon, Pamela A. Nieto, Kwasi Addae, Víctor Alegría-Mera, Cristian Bravo, Denisse Bravo, Juan P. Cardenas, Glenn A. Carson, Adam Caughey, Paulo C. Covarrubias, José Pérez-Donoso, Graham Gass, Sarah L. Gupta, Kira Harman, Donna Marie B. Hongo, Juan C. Jiménez, Laurens Kraal & 20 otros Felipe Melis-Arcos, Eduardo H. Morales, Amanda Morton, Camila F. Navas, Harold Nuñez, Eduardo Olivares, Nicolás Órdenes-Aenishanslins, Francisco J. Ossandon, Richard Phan, Raul Pino, Katia Soto-Liebe, Ignacio Varas, Patricia Vera-Wolf, Nathaniel A. Walton, Daniel E. Almonacid, Audrey D. Goddard, Juan A. Ugalde, Susan Zneimer, Jessica Richman, Zachary S. Apte

Resultado de la investigación: Article

Resumen

The composition of the vaginal microbiome, including both the presence of pathogens involved in sexually transmitted infections (STI) as well as commensal microbiota, has been shown to have important associations for a woman’s reproductive and general health. Currently, healthcare providers cannot offer comprehensive vaginal microbiome screening, but are limited to the detection of individual pathogens, such as high-risk human papillomavirus (hrHPV), the predominant cause of cervical cancer. There is no single test on the market that combines HPV, STI, and microbiome screening. Here, we describe a novel inclusive vaginal health assay that combines self-sampling with sequencing-based HPV detection and genotyping, vaginal microbiome analysis, and STI-associated pathogen detection. The assay includes genotyping and detection of 14 hrHPV types, 5 low-risk HPV types (lrHPV), as well as the relative abundance of 31 bacterial taxa of clinical importance, including Lactobacillus, Sneathia, Gardnerella, and 3 pathogens involved in STI, with high sensitivity, specificity, and reproducibility. For each of these taxa, reference ranges were determined in a group of 50 self-reported healthy women. The HPV sequencing portion of the test was evaluated against the digene High-Risk HPV HC2 DNA test. For hrHPV genotyping, agreement was 95.3% with a kappa of 0.804 (601 samples); after removal of samples in which the digene hrHPV probe showed cross-reactivity with lrHPV types, the sensitivity and specificity of the hrHPV genotyping assay were 94.5% and 96.6%, respectively, with a kappa of 0.841. For lrHPV genotyping, agreement was 93.9% with a kappa of 0.788 (148 samples), while sensitivity and specificity were 100% and 92.9%, respectively. This novel assay could be used to complement conventional cervical cancer screening, because its self-sampling format can expand access among women who would otherwise not participate, and because of its additional information about the composition of the vaginal microbiome and the presence of pathogens.

Idioma originalEnglish
Número de artículoe0215945
PublicaciónPLoS ONE
Volumen14
N.º5
DOI
EstadoPublished - 1 may 2019

Huella dactilar

sexually transmitted diseases
Microbiota
Sexually Transmitted Diseases
genotyping
Assays
Health
Sampling
Papillomaviridae
Pathogens
assays
sampling
Screening
uterine cervical neoplasms
pathogens
screening
Sensitivity and Specificity
Uterine Cervical Neoplasms
Gardnerella
Human Papillomavirus DNA Tests
microbial detection

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Citar esto

Bik, Elisabeth M. ; Bird, Sara W. ; Bustamante, Juan P. ; Leon, Luis E. ; Nieto, Pamela A. ; Addae, Kwasi ; Alegría-Mera, Víctor ; Bravo, Cristian ; Bravo, Denisse ; Cardenas, Juan P. ; Carson, Glenn A. ; Caughey, Adam ; Covarrubias, Paulo C. ; Pérez-Donoso, José ; Gass, Graham ; Gupta, Sarah L. ; Harman, Kira ; Hongo, Donna Marie B. ; Jiménez, Juan C. ; Kraal, Laurens ; Melis-Arcos, Felipe ; Morales, Eduardo H. ; Morton, Amanda ; Navas, Camila F. ; Nuñez, Harold ; Olivares, Eduardo ; Órdenes-Aenishanslins, Nicolás ; Ossandon, Francisco J. ; Phan, Richard ; Pino, Raul ; Soto-Liebe, Katia ; Varas, Ignacio ; Vera-Wolf, Patricia ; Walton, Nathaniel A. ; Almonacid, Daniel E. ; Goddard, Audrey D. ; Ugalde, Juan A. ; Zneimer, Susan ; Richman, Jessica ; Apte, Zachary S. / A novel sequencing-based vaginal health assay combining self-sampling, HPV detection and genotyping, STI detection, and vaginal microbiome analysis. En: PLoS ONE. 2019 ; Vol. 14, N.º 5.
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abstract = "The composition of the vaginal microbiome, including both the presence of pathogens involved in sexually transmitted infections (STI) as well as commensal microbiota, has been shown to have important associations for a woman’s reproductive and general health. Currently, healthcare providers cannot offer comprehensive vaginal microbiome screening, but are limited to the detection of individual pathogens, such as high-risk human papillomavirus (hrHPV), the predominant cause of cervical cancer. There is no single test on the market that combines HPV, STI, and microbiome screening. Here, we describe a novel inclusive vaginal health assay that combines self-sampling with sequencing-based HPV detection and genotyping, vaginal microbiome analysis, and STI-associated pathogen detection. The assay includes genotyping and detection of 14 hrHPV types, 5 low-risk HPV types (lrHPV), as well as the relative abundance of 31 bacterial taxa of clinical importance, including Lactobacillus, Sneathia, Gardnerella, and 3 pathogens involved in STI, with high sensitivity, specificity, and reproducibility. For each of these taxa, reference ranges were determined in a group of 50 self-reported healthy women. The HPV sequencing portion of the test was evaluated against the digene High-Risk HPV HC2 DNA test. For hrHPV genotyping, agreement was 95.3{\%} with a kappa of 0.804 (601 samples); after removal of samples in which the digene hrHPV probe showed cross-reactivity with lrHPV types, the sensitivity and specificity of the hrHPV genotyping assay were 94.5{\%} and 96.6{\%}, respectively, with a kappa of 0.841. For lrHPV genotyping, agreement was 93.9{\%} with a kappa of 0.788 (148 samples), while sensitivity and specificity were 100{\%} and 92.9{\%}, respectively. This novel assay could be used to complement conventional cervical cancer screening, because its self-sampling format can expand access among women who would otherwise not participate, and because of its additional information about the composition of the vaginal microbiome and the presence of pathogens.",
author = "Bik, {Elisabeth M.} and Bird, {Sara W.} and Bustamante, {Juan P.} and Leon, {Luis E.} and Nieto, {Pamela A.} and Kwasi Addae and V{\'i}ctor Alegr{\'i}a-Mera and Cristian Bravo and Denisse Bravo and Cardenas, {Juan P.} and Carson, {Glenn A.} and Adam Caughey and Covarrubias, {Paulo C.} and Jos{\'e} P{\'e}rez-Donoso and Graham Gass and Gupta, {Sarah L.} and Kira Harman and Hongo, {Donna Marie B.} and Jim{\'e}nez, {Juan C.} and Laurens Kraal and Felipe Melis-Arcos and Morales, {Eduardo H.} and Amanda Morton and Navas, {Camila F.} and Harold Nu{\~n}ez and Eduardo Olivares and Nicol{\'a}s {\'O}rdenes-Aenishanslins and Ossandon, {Francisco J.} and Richard Phan and Raul Pino and Katia Soto-Liebe and Ignacio Varas and Patricia Vera-Wolf and Walton, {Nathaniel A.} and Almonacid, {Daniel E.} and Goddard, {Audrey D.} and Ugalde, {Juan A.} and Susan Zneimer and Jessica Richman and Apte, {Zachary S.}",
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Bik, EM, Bird, SW, Bustamante, JP, Leon, LE, Nieto, PA, Addae, K, Alegría-Mera, V, Bravo, C, Bravo, D, Cardenas, JP, Carson, GA, Caughey, A, Covarrubias, PC, Pérez-Donoso, J, Gass, G, Gupta, SL, Harman, K, Hongo, DMB, Jiménez, JC, Kraal, L, Melis-Arcos, F, Morales, EH, Morton, A, Navas, CF, Nuñez, H, Olivares, E, Órdenes-Aenishanslins, N, Ossandon, FJ, Phan, R, Pino, R, Soto-Liebe, K, Varas, I, Vera-Wolf, P, Walton, NA, Almonacid, DE, Goddard, AD, Ugalde, JA, Zneimer, S, Richman, J & Apte, ZS 2019, 'A novel sequencing-based vaginal health assay combining self-sampling, HPV detection and genotyping, STI detection, and vaginal microbiome analysis', PLoS ONE, vol. 14, n.º 5, e0215945. https://doi.org/10.1371/journal.pone.0215945

A novel sequencing-based vaginal health assay combining self-sampling, HPV detection and genotyping, STI detection, and vaginal microbiome analysis. / Bik, Elisabeth M.; Bird, Sara W.; Bustamante, Juan P.; Leon, Luis E.; Nieto, Pamela A.; Addae, Kwasi; Alegría-Mera, Víctor; Bravo, Cristian; Bravo, Denisse; Cardenas, Juan P.; Carson, Glenn A.; Caughey, Adam; Covarrubias, Paulo C.; Pérez-Donoso, José; Gass, Graham; Gupta, Sarah L.; Harman, Kira; Hongo, Donna Marie B.; Jiménez, Juan C.; Kraal, Laurens; Melis-Arcos, Felipe; Morales, Eduardo H.; Morton, Amanda; Navas, Camila F.; Nuñez, Harold; Olivares, Eduardo; Órdenes-Aenishanslins, Nicolás; Ossandon, Francisco J.; Phan, Richard; Pino, Raul; Soto-Liebe, Katia; Varas, Ignacio; Vera-Wolf, Patricia; Walton, Nathaniel A.; Almonacid, Daniel E.; Goddard, Audrey D.; Ugalde, Juan A.; Zneimer, Susan; Richman, Jessica; Apte, Zachary S.

En: PLoS ONE, Vol. 14, N.º 5, e0215945, 01.05.2019.

Resultado de la investigación: Article

TY - JOUR

T1 - A novel sequencing-based vaginal health assay combining self-sampling, HPV detection and genotyping, STI detection, and vaginal microbiome analysis

AU - Bik, Elisabeth M.

AU - Bird, Sara W.

AU - Bustamante, Juan P.

AU - Leon, Luis E.

AU - Nieto, Pamela A.

AU - Addae, Kwasi

AU - Alegría-Mera, Víctor

AU - Bravo, Cristian

AU - Bravo, Denisse

AU - Cardenas, Juan P.

AU - Carson, Glenn A.

AU - Caughey, Adam

AU - Covarrubias, Paulo C.

AU - Pérez-Donoso, José

AU - Gass, Graham

AU - Gupta, Sarah L.

AU - Harman, Kira

AU - Hongo, Donna Marie B.

AU - Jiménez, Juan C.

AU - Kraal, Laurens

AU - Melis-Arcos, Felipe

AU - Morales, Eduardo H.

AU - Morton, Amanda

AU - Navas, Camila F.

AU - Nuñez, Harold

AU - Olivares, Eduardo

AU - Órdenes-Aenishanslins, Nicolás

AU - Ossandon, Francisco J.

AU - Phan, Richard

AU - Pino, Raul

AU - Soto-Liebe, Katia

AU - Varas, Ignacio

AU - Vera-Wolf, Patricia

AU - Walton, Nathaniel A.

AU - Almonacid, Daniel E.

AU - Goddard, Audrey D.

AU - Ugalde, Juan A.

AU - Zneimer, Susan

AU - Richman, Jessica

AU - Apte, Zachary S.

PY - 2019/5/1

Y1 - 2019/5/1

N2 - The composition of the vaginal microbiome, including both the presence of pathogens involved in sexually transmitted infections (STI) as well as commensal microbiota, has been shown to have important associations for a woman’s reproductive and general health. Currently, healthcare providers cannot offer comprehensive vaginal microbiome screening, but are limited to the detection of individual pathogens, such as high-risk human papillomavirus (hrHPV), the predominant cause of cervical cancer. There is no single test on the market that combines HPV, STI, and microbiome screening. Here, we describe a novel inclusive vaginal health assay that combines self-sampling with sequencing-based HPV detection and genotyping, vaginal microbiome analysis, and STI-associated pathogen detection. The assay includes genotyping and detection of 14 hrHPV types, 5 low-risk HPV types (lrHPV), as well as the relative abundance of 31 bacterial taxa of clinical importance, including Lactobacillus, Sneathia, Gardnerella, and 3 pathogens involved in STI, with high sensitivity, specificity, and reproducibility. For each of these taxa, reference ranges were determined in a group of 50 self-reported healthy women. The HPV sequencing portion of the test was evaluated against the digene High-Risk HPV HC2 DNA test. For hrHPV genotyping, agreement was 95.3% with a kappa of 0.804 (601 samples); after removal of samples in which the digene hrHPV probe showed cross-reactivity with lrHPV types, the sensitivity and specificity of the hrHPV genotyping assay were 94.5% and 96.6%, respectively, with a kappa of 0.841. For lrHPV genotyping, agreement was 93.9% with a kappa of 0.788 (148 samples), while sensitivity and specificity were 100% and 92.9%, respectively. This novel assay could be used to complement conventional cervical cancer screening, because its self-sampling format can expand access among women who would otherwise not participate, and because of its additional information about the composition of the vaginal microbiome and the presence of pathogens.

AB - The composition of the vaginal microbiome, including both the presence of pathogens involved in sexually transmitted infections (STI) as well as commensal microbiota, has been shown to have important associations for a woman’s reproductive and general health. Currently, healthcare providers cannot offer comprehensive vaginal microbiome screening, but are limited to the detection of individual pathogens, such as high-risk human papillomavirus (hrHPV), the predominant cause of cervical cancer. There is no single test on the market that combines HPV, STI, and microbiome screening. Here, we describe a novel inclusive vaginal health assay that combines self-sampling with sequencing-based HPV detection and genotyping, vaginal microbiome analysis, and STI-associated pathogen detection. The assay includes genotyping and detection of 14 hrHPV types, 5 low-risk HPV types (lrHPV), as well as the relative abundance of 31 bacterial taxa of clinical importance, including Lactobacillus, Sneathia, Gardnerella, and 3 pathogens involved in STI, with high sensitivity, specificity, and reproducibility. For each of these taxa, reference ranges were determined in a group of 50 self-reported healthy women. The HPV sequencing portion of the test was evaluated against the digene High-Risk HPV HC2 DNA test. For hrHPV genotyping, agreement was 95.3% with a kappa of 0.804 (601 samples); after removal of samples in which the digene hrHPV probe showed cross-reactivity with lrHPV types, the sensitivity and specificity of the hrHPV genotyping assay were 94.5% and 96.6%, respectively, with a kappa of 0.841. For lrHPV genotyping, agreement was 93.9% with a kappa of 0.788 (148 samples), while sensitivity and specificity were 100% and 92.9%, respectively. This novel assay could be used to complement conventional cervical cancer screening, because its self-sampling format can expand access among women who would otherwise not participate, and because of its additional information about the composition of the vaginal microbiome and the presence of pathogens.

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U2 - 10.1371/journal.pone.0215945

DO - 10.1371/journal.pone.0215945

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VL - 14

JO - PLoS ONE

JF - PLoS ONE

SN - 1932-6203

IS - 5

M1 - e0215945

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