Vaginal microbiome community state types and high-risk human papillomaviruses in cervical precancer and cancer in North-central Nigeria

Jonah Musa; Mamoudou Maiga; Stefan J. Green; Francis A. Magaji; Ali J. Maryam; Mark Okolo; Chuwang J. Nyam; Nanma T. Cosmas; Olugbenga A. Silas; Godwin E. Imade; Yinan Zheng; Brian T. Joyce; Brehima Diakite; Imran Morhason-Bello; Chad J. Achenbach; Atiene S. Sagay; Innocent A.O. Ujah; Robert L. Murphy; Lifang Hou; Supriya Dinesh Mehta

doi:10.1186/s12885-023-11187-5

Vaginal microbiome community state types and high-risk human papillomaviruses in cervical precancer and cancer in North-central Nigeria

Jonah Musa^*, Mamoudou Maiga, Stefan J. Green, Francis A. Magaji, Ali J. Maryam, Mark Okolo, Chuwang J. Nyam, Nanma T. Cosmas, Olugbenga A. Silas, Godwin E. Imade, Yinan Zheng, Brian T. Joyce, Brehima Diakite, Imran Morhason-Bello, Chad J. Achenbach, Atiene S. Sagay, Innocent A.O. Ujah, Robert L. Murphy, Lifang Hou, Supriya Dinesh Mehta

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

7 Scopus citations

Abstract

Background: High risk human papillomaviruses (HR-HPV) have a causal role in cervical oncogenesis, and HIV-mediated immune suppression allows HR-HPV to persist. We studied whether vaginal microbiome community state types (CSTs) are associated with high-grade precancer and/or invasive cervical cancer (HSIL/ICC). Methods: This was a cross-sectional study of adult women with cervical cancer screening (CCS) at the Jos University Teaching Hospital (JUTH) in Jos, Nigeria, between January 2020 and February 2022. Cervical swabs underwent HPV genotyping (Anyplex™ II HPV28). Cervico-vaginal lavage (CVL) sample was collected for 16 S rRNA gene amplicon sequencing. We used multivariable logistic regression modelling to assess associations between CSTs and other factors associated with HSIL/ICC. Results: We enrolled 155 eligible participants, 151 with microbiome data for this analysis. Women were median age 52 (IQR:43–58), 47.7% HIV positive, and 58.1% with HSIL/ICC. Of the 138 with HPV data, 40.6% were negative for HPV, 10.1% had low-risk HPV, 26.8% had single HR-HPV, and 22.5% had multiple HR-HPV types. The overall prevalence of any HR-HPV type (single and multiple) was 49.3%, with a higher proportion in women with HSIL/ICC (NILM 31.6%, LSIL 46.5%, HSIL 40.8%, and 81.5% ICC; p = 0.007). Women with HIV were more likely to have HSIL/ICC (70.3% vs. 29.7% among women without HIV). In crude and multivariable analysis CST was not associated with cervical pathology (CST-III aOR = 1.13, CST-IV aOR = 1.31). However, in the presence of HR-HPV CST-III (aOR = 6.7) and CST-IV (aOR = 3.6) showed positive association with HSIL/ICC. Conclusion: Vaginal microbiome CSTs were not significantly associated with HSIL/ICC. Our findings suggest however, that CST could be helpful in identifying women with HSIL/ICC and particularly those with HR-HPV. Characterization of CSTs using point-of-care molecular testing in women with HR-HPV should be studied as an approach to improve early detection and cervical cancer prevention. Future longitudinal research will improve our understanding of the temporal effect of non-optimal CST, HR-HPV, and other factors in cervical cancer development, prevention, and control.

Original language	English (US)
Article number	683
Journal	BMC cancer
Volume	23
Issue number	1
DOIs	https://doi.org/10.1186/s12885-023-11187-5
State	Published - Dec 2023

Funding

The contributions of Joyce Asufi, RN, BNsc, Maryam shuaibu, RN, and Patricia Asemota, RN, BNsc, of the Nursing department and the “Operation Stop” Cervical Cancer Unit of Jos University Teaching Hospital, Jos, Nigeria is hereby acknowledged. I acknowledged the contributions and dedication of the laboratory staff (Mr. Acheng Shedrach Yakubu, Mr. Rapp Chuwang Nyam, Mr. Michael Eshioramhe, Mrs. Flavia Godfrey Lamo, Mrs. Tsok Yop Gwom, and Jacob Bwalsim) of the genomics and postgraduate core facility of the College of Health Sciences, University of Jos. I acknowledge the funding support from the Strohm’s family through the Robert J. Havey MD Institute for Global Health to provide access to cervical cancer screening for indigent women through the community cervical cancer screening project in Jos Nigeria. The NIH/Fogarty international center provided funding support for this research and the research-protected time for writing this manuscript under the award number: K43TW011416 . The NIH/NCI funded U54CA221205 provided institutional support facilities for the conduct of this research in Jos Nigeria. JM, FJM, CJN, and OAS acknowledges training support as Fogarty fellows under the NIH/FIC D43TW009575, while YZ and OAS acknowledged funding support from NIH/FIC R21TW12092. The findings and views expressed in this manuscript are those of the authors and do not necessarily represent the views of the Fogarty International Center or the National Institutes of Health. I acknowledge the funding support from the Strohm’s family through the Robert J. Havey MD Institute for Global Health to provide access to cervical cancer screening for indigent women through the community cervical cancer screening project in Jos Nigeria.

Keywords

Cervical precancer and cancer
HIV
High-risk HPV
Vaginal microbiome

ASJC Scopus subject areas

Oncology
Genetics
Cancer Research

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1186/s12885-023-11187-5

Cite this

Musa, J., Maiga, M., Green, S. J., Magaji, F. A., Maryam, A. J., Okolo, M., Nyam, C. J., Cosmas, N. T., Silas, O. A., Imade, G. E., Zheng, Y., Joyce, B. T., Diakite, B., Morhason-Bello, I., Achenbach, C. J., Sagay, A. S., Ujah, I. A. O., Murphy, R. L., Hou, L., & Mehta, S. D. (2023). Vaginal microbiome community state types and high-risk human papillomaviruses in cervical precancer and cancer in North-central Nigeria. BMC cancer, 23(1), Article 683. https://doi.org/10.1186/s12885-023-11187-5

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title = "Vaginal microbiome community state types and high-risk human papillomaviruses in cervical precancer and cancer in North-central Nigeria",

abstract = "Background: High risk human papillomaviruses (HR-HPV) have a causal role in cervical oncogenesis, and HIV-mediated immune suppression allows HR-HPV to persist. We studied whether vaginal microbiome community state types (CSTs) are associated with high-grade precancer and/or invasive cervical cancer (HSIL/ICC). Methods: This was a cross-sectional study of adult women with cervical cancer screening (CCS) at the Jos University Teaching Hospital (JUTH) in Jos, Nigeria, between January 2020 and February 2022. Cervical swabs underwent HPV genotyping (Anyplex{\texttrademark} II HPV28). Cervico-vaginal lavage (CVL) sample was collected for 16 S rRNA gene amplicon sequencing. We used multivariable logistic regression modelling to assess associations between CSTs and other factors associated with HSIL/ICC. Results: We enrolled 155 eligible participants, 151 with microbiome data for this analysis. Women were median age 52 (IQR:43–58), 47.7% HIV positive, and 58.1% with HSIL/ICC. Of the 138 with HPV data, 40.6% were negative for HPV, 10.1% had low-risk HPV, 26.8% had single HR-HPV, and 22.5% had multiple HR-HPV types. The overall prevalence of any HR-HPV type (single and multiple) was 49.3%, with a higher proportion in women with HSIL/ICC (NILM 31.6%, LSIL 46.5%, HSIL 40.8%, and 81.5% ICC; p = 0.007). Women with HIV were more likely to have HSIL/ICC (70.3% vs. 29.7% among women without HIV). In crude and multivariable analysis CST was not associated with cervical pathology (CST-III aOR = 1.13, CST-IV aOR = 1.31). However, in the presence of HR-HPV CST-III (aOR = 6.7) and CST-IV (aOR = 3.6) showed positive association with HSIL/ICC. Conclusion: Vaginal microbiome CSTs were not significantly associated with HSIL/ICC. Our findings suggest however, that CST could be helpful in identifying women with HSIL/ICC and particularly those with HR-HPV. Characterization of CSTs using point-of-care molecular testing in women with HR-HPV should be studied as an approach to improve early detection and cervical cancer prevention. Future longitudinal research will improve our understanding of the temporal effect of non-optimal CST, HR-HPV, and other factors in cervical cancer development, prevention, and control.",

keywords = "Cervical precancer and cancer, HIV, High-risk HPV, Vaginal microbiome",

author = "Jonah Musa and Mamoudou Maiga and Green, {Stefan J.} and Magaji, {Francis A.} and Maryam, {Ali J.} and Mark Okolo and Nyam, {Chuwang J.} and Cosmas, {Nanma T.} and Silas, {Olugbenga A.} and Imade, {Godwin E.} and Yinan Zheng and Joyce, {Brian T.} and Brehima Diakite and Imran Morhason-Bello and Achenbach, {Chad J.} and Sagay, {Atiene S.} and Ujah, {Innocent A.O.} and Murphy, {Robert L.} and Lifang Hou and Mehta, {Supriya Dinesh}",

note = "Publisher Copyright: {\textcopyright} 2023, The Author(s).",

year = "2023",

month = dec,

doi = "10.1186/s12885-023-11187-5",

language = "English (US)",

volume = "23",

journal = "BMC cancer",

issn = "1471-2407",

publisher = "BioMed Central",

number = "1",

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Musa, J, Maiga, M, Green, SJ, Magaji, FA, Maryam, AJ, Okolo, M, Nyam, CJ, Cosmas, NT, Silas, OA, Imade, GE, Zheng, Y , Joyce, BT, Diakite, B, Morhason-Bello, I, Achenbach, CJ, Sagay, AS, Ujah, IAO, Murphy, RL , Hou, L & Mehta, SD 2023, 'Vaginal microbiome community state types and high-risk human papillomaviruses in cervical precancer and cancer in North-central Nigeria', BMC cancer, vol. 23, no. 1, 683. https://doi.org/10.1186/s12885-023-11187-5

TY - JOUR

T1 - Vaginal microbiome community state types and high-risk human papillomaviruses in cervical precancer and cancer in North-central Nigeria

AU - Musa, Jonah

AU - Maiga, Mamoudou

AU - Green, Stefan J.

AU - Magaji, Francis A.

AU - Maryam, Ali J.

AU - Okolo, Mark

AU - Nyam, Chuwang J.

AU - Cosmas, Nanma T.

AU - Silas, Olugbenga A.

AU - Imade, Godwin E.

AU - Zheng, Yinan

AU - Joyce, Brian T.

AU - Diakite, Brehima

AU - Morhason-Bello, Imran

AU - Achenbach, Chad J.

AU - Sagay, Atiene S.

AU - Ujah, Innocent A.O.

AU - Murphy, Robert L.

AU - Hou, Lifang

AU - Mehta, Supriya Dinesh

PY - 2023/12

Y1 - 2023/12

N2 - Background: High risk human papillomaviruses (HR-HPV) have a causal role in cervical oncogenesis, and HIV-mediated immune suppression allows HR-HPV to persist. We studied whether vaginal microbiome community state types (CSTs) are associated with high-grade precancer and/or invasive cervical cancer (HSIL/ICC). Methods: This was a cross-sectional study of adult women with cervical cancer screening (CCS) at the Jos University Teaching Hospital (JUTH) in Jos, Nigeria, between January 2020 and February 2022. Cervical swabs underwent HPV genotyping (Anyplex™ II HPV28). Cervico-vaginal lavage (CVL) sample was collected for 16 S rRNA gene amplicon sequencing. We used multivariable logistic regression modelling to assess associations between CSTs and other factors associated with HSIL/ICC. Results: We enrolled 155 eligible participants, 151 with microbiome data for this analysis. Women were median age 52 (IQR:43–58), 47.7% HIV positive, and 58.1% with HSIL/ICC. Of the 138 with HPV data, 40.6% were negative for HPV, 10.1% had low-risk HPV, 26.8% had single HR-HPV, and 22.5% had multiple HR-HPV types. The overall prevalence of any HR-HPV type (single and multiple) was 49.3%, with a higher proportion in women with HSIL/ICC (NILM 31.6%, LSIL 46.5%, HSIL 40.8%, and 81.5% ICC; p = 0.007). Women with HIV were more likely to have HSIL/ICC (70.3% vs. 29.7% among women without HIV). In crude and multivariable analysis CST was not associated with cervical pathology (CST-III aOR = 1.13, CST-IV aOR = 1.31). However, in the presence of HR-HPV CST-III (aOR = 6.7) and CST-IV (aOR = 3.6) showed positive association with HSIL/ICC. Conclusion: Vaginal microbiome CSTs were not significantly associated with HSIL/ICC. Our findings suggest however, that CST could be helpful in identifying women with HSIL/ICC and particularly those with HR-HPV. Characterization of CSTs using point-of-care molecular testing in women with HR-HPV should be studied as an approach to improve early detection and cervical cancer prevention. Future longitudinal research will improve our understanding of the temporal effect of non-optimal CST, HR-HPV, and other factors in cervical cancer development, prevention, and control.

AB - Background: High risk human papillomaviruses (HR-HPV) have a causal role in cervical oncogenesis, and HIV-mediated immune suppression allows HR-HPV to persist. We studied whether vaginal microbiome community state types (CSTs) are associated with high-grade precancer and/or invasive cervical cancer (HSIL/ICC). Methods: This was a cross-sectional study of adult women with cervical cancer screening (CCS) at the Jos University Teaching Hospital (JUTH) in Jos, Nigeria, between January 2020 and February 2022. Cervical swabs underwent HPV genotyping (Anyplex™ II HPV28). Cervico-vaginal lavage (CVL) sample was collected for 16 S rRNA gene amplicon sequencing. We used multivariable logistic regression modelling to assess associations between CSTs and other factors associated with HSIL/ICC. Results: We enrolled 155 eligible participants, 151 with microbiome data for this analysis. Women were median age 52 (IQR:43–58), 47.7% HIV positive, and 58.1% with HSIL/ICC. Of the 138 with HPV data, 40.6% were negative for HPV, 10.1% had low-risk HPV, 26.8% had single HR-HPV, and 22.5% had multiple HR-HPV types. The overall prevalence of any HR-HPV type (single and multiple) was 49.3%, with a higher proportion in women with HSIL/ICC (NILM 31.6%, LSIL 46.5%, HSIL 40.8%, and 81.5% ICC; p = 0.007). Women with HIV were more likely to have HSIL/ICC (70.3% vs. 29.7% among women without HIV). In crude and multivariable analysis CST was not associated with cervical pathology (CST-III aOR = 1.13, CST-IV aOR = 1.31). However, in the presence of HR-HPV CST-III (aOR = 6.7) and CST-IV (aOR = 3.6) showed positive association with HSIL/ICC. Conclusion: Vaginal microbiome CSTs were not significantly associated with HSIL/ICC. Our findings suggest however, that CST could be helpful in identifying women with HSIL/ICC and particularly those with HR-HPV. Characterization of CSTs using point-of-care molecular testing in women with HR-HPV should be studied as an approach to improve early detection and cervical cancer prevention. Future longitudinal research will improve our understanding of the temporal effect of non-optimal CST, HR-HPV, and other factors in cervical cancer development, prevention, and control.

KW - Cervical precancer and cancer

KW - HIV

KW - High-risk HPV

KW - Vaginal microbiome

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UR - http://www.scopus.com/inward/citedby.url?scp=85165479266&partnerID=8YFLogxK

U2 - 10.1186/s12885-023-11187-5

DO - 10.1186/s12885-023-11187-5

M3 - Article

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AN - SCOPUS:85165479266

SN - 1471-2407

VL - 23

JO - BMC cancer

JF - BMC cancer

IS - 1

M1 - 683

ER -

Vaginal microbiome community state types and high-risk human papillomaviruses in cervical precancer and cancer in North-central Nigeria

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