T cell receptor repertoire among women who cleared and failed to clear cervical human papillomavirus infection: An exploratory proof-of-principle study

Krystle A. Lang Kuhs, Shih Wen Lin, Xing Hua, Mark Schiffman, Robert D. Burk, Ana Cecilia Rodriguez, Rolando Herrero, Christian C. Abnet, Neal D. Freedman, Ligia A. Pinto, David Hamm, Harlan Robins, Allan Hildesheim, Jianxin Shi, Mahboobeh Safaeian

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Background It is unknown why a minority of women fail to clear human papillomavirus (HPV) and develop precancer/cancer. Differences in T-cell receptor (TCR) repertoires may identify HPV16-infected women at highest-risk for progression to cancer. We conducted a proof-of-principle study nested within the Guanacaste HPV Natural History Study to evaluate the utility of next-generation sequencing for interrogating the TCR repertoires among women who cleared and failed to clear cervical HPV16. Methods TCR repertoires of women with HPV16-related intraepithelial neoplasia grade 3 or higher (CIN3+; n = 25) were compared to women who cleared an incident HPV16 infection without developing precancer/cancer (n = 25). TCR diversity (richness and evenness) and relative abundance (RA) of gene segment (V [n = 51], D [n = 2], J [n = 13]) usage was evaluated; receiver operating curve analysis assessed the ability to differentiate case-control status. Results TCR repertoire richness was associated with CIN3+ status (P = 0.001). Relative abundance (RA) of V-gene segments was enriched for associations between cases and controls. A single V-gene (TRBV6-7) was significantly associated with CIN3+ status (RA = 0.11%, 0.16%, among cases and controls, respectively, Bonferroni P = 0.0008). The estimated area under the curve using richness and V-gene segment RA was 0.83 (95% confidence interval: 0.73–0.90). Conclusions Substantial differences in TCR repertoire among women with CIN3+ compared to women who cleared infection were observed.

Original languageEnglish (US)
Article numbere0178167
JournalPLoS One
Volume13
Issue number1
DOIs
StatePublished - Jan 1 2018

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Papillomavirus Infections
Papillomaviridae
T-Cell Antigen Receptor
T-lymphocytes
receptors
Genes
infection
neoplasms
Neoplasms
genes
Infection
Natural History
natural history
Area Under Curve
confidence interval
Confidence Intervals

ASJC Scopus subject areas

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

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T cell receptor repertoire among women who cleared and failed to clear cervical human papillomavirus infection : An exploratory proof-of-principle study. / Lang Kuhs, Krystle A.; Lin, Shih Wen; Hua, Xing; Schiffman, Mark; Burk, Robert D.; Rodriguez, Ana Cecilia; Herrero, Rolando; Abnet, Christian C.; Freedman, Neal D.; Pinto, Ligia A.; Hamm, David; Robins, Harlan; Hildesheim, Allan; Shi, Jianxin; Safaeian, Mahboobeh.

In: PLoS One, Vol. 13, No. 1, e0178167, 01.01.2018.

Research output: Contribution to journalArticle

Lang Kuhs, KA, Lin, SW, Hua, X, Schiffman, M, Burk, RD, Rodriguez, AC, Herrero, R, Abnet, CC, Freedman, ND, Pinto, LA, Hamm, D, Robins, H, Hildesheim, A, Shi, J & Safaeian, M 2018, 'T cell receptor repertoire among women who cleared and failed to clear cervical human papillomavirus infection: An exploratory proof-of-principle study', PLoS One, vol. 13, no. 1, e0178167. https://doi.org/10.1371/journal.pone.0178167
Lang Kuhs, Krystle A. ; Lin, Shih Wen ; Hua, Xing ; Schiffman, Mark ; Burk, Robert D. ; Rodriguez, Ana Cecilia ; Herrero, Rolando ; Abnet, Christian C. ; Freedman, Neal D. ; Pinto, Ligia A. ; Hamm, David ; Robins, Harlan ; Hildesheim, Allan ; Shi, Jianxin ; Safaeian, Mahboobeh. / T cell receptor repertoire among women who cleared and failed to clear cervical human papillomavirus infection : An exploratory proof-of-principle study. In: PLoS One. 2018 ; Vol. 13, No. 1.
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abstract = "Background It is unknown why a minority of women fail to clear human papillomavirus (HPV) and develop precancer/cancer. Differences in T-cell receptor (TCR) repertoires may identify HPV16-infected women at highest-risk for progression to cancer. We conducted a proof-of-principle study nested within the Guanacaste HPV Natural History Study to evaluate the utility of next-generation sequencing for interrogating the TCR repertoires among women who cleared and failed to clear cervical HPV16. Methods TCR repertoires of women with HPV16-related intraepithelial neoplasia grade 3 or higher (CIN3+; n = 25) were compared to women who cleared an incident HPV16 infection without developing precancer/cancer (n = 25). TCR diversity (richness and evenness) and relative abundance (RA) of gene segment (V [n = 51], D [n = 2], J [n = 13]) usage was evaluated; receiver operating curve analysis assessed the ability to differentiate case-control status. Results TCR repertoire richness was associated with CIN3+ status (P = 0.001). Relative abundance (RA) of V-gene segments was enriched for associations between cases and controls. A single V-gene (TRBV6-7) was significantly associated with CIN3+ status (RA = 0.11{\%}, 0.16{\%}, among cases and controls, respectively, Bonferroni P = 0.0008). The estimated area under the curve using richness and V-gene segment RA was 0.83 (95{\%} confidence interval: 0.73–0.90). Conclusions Substantial differences in TCR repertoire among women with CIN3+ compared to women who cleared infection were observed.",
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T1 - T cell receptor repertoire among women who cleared and failed to clear cervical human papillomavirus infection

T2 - An exploratory proof-of-principle study

AU - Lang Kuhs, Krystle A.

AU - Lin, Shih Wen

AU - Hua, Xing

AU - Schiffman, Mark

AU - Burk, Robert D.

AU - Rodriguez, Ana Cecilia

AU - Herrero, Rolando

AU - Abnet, Christian C.

AU - Freedman, Neal D.

AU - Pinto, Ligia A.

AU - Hamm, David

AU - Robins, Harlan

AU - Hildesheim, Allan

AU - Shi, Jianxin

AU - Safaeian, Mahboobeh

PY - 2018/1/1

Y1 - 2018/1/1

N2 - Background It is unknown why a minority of women fail to clear human papillomavirus (HPV) and develop precancer/cancer. Differences in T-cell receptor (TCR) repertoires may identify HPV16-infected women at highest-risk for progression to cancer. We conducted a proof-of-principle study nested within the Guanacaste HPV Natural History Study to evaluate the utility of next-generation sequencing for interrogating the TCR repertoires among women who cleared and failed to clear cervical HPV16. Methods TCR repertoires of women with HPV16-related intraepithelial neoplasia grade 3 or higher (CIN3+; n = 25) were compared to women who cleared an incident HPV16 infection without developing precancer/cancer (n = 25). TCR diversity (richness and evenness) and relative abundance (RA) of gene segment (V [n = 51], D [n = 2], J [n = 13]) usage was evaluated; receiver operating curve analysis assessed the ability to differentiate case-control status. Results TCR repertoire richness was associated with CIN3+ status (P = 0.001). Relative abundance (RA) of V-gene segments was enriched for associations between cases and controls. A single V-gene (TRBV6-7) was significantly associated with CIN3+ status (RA = 0.11%, 0.16%, among cases and controls, respectively, Bonferroni P = 0.0008). The estimated area under the curve using richness and V-gene segment RA was 0.83 (95% confidence interval: 0.73–0.90). Conclusions Substantial differences in TCR repertoire among women with CIN3+ compared to women who cleared infection were observed.

AB - Background It is unknown why a minority of women fail to clear human papillomavirus (HPV) and develop precancer/cancer. Differences in T-cell receptor (TCR) repertoires may identify HPV16-infected women at highest-risk for progression to cancer. We conducted a proof-of-principle study nested within the Guanacaste HPV Natural History Study to evaluate the utility of next-generation sequencing for interrogating the TCR repertoires among women who cleared and failed to clear cervical HPV16. Methods TCR repertoires of women with HPV16-related intraepithelial neoplasia grade 3 or higher (CIN3+; n = 25) were compared to women who cleared an incident HPV16 infection without developing precancer/cancer (n = 25). TCR diversity (richness and evenness) and relative abundance (RA) of gene segment (V [n = 51], D [n = 2], J [n = 13]) usage was evaluated; receiver operating curve analysis assessed the ability to differentiate case-control status. Results TCR repertoire richness was associated with CIN3+ status (P = 0.001). Relative abundance (RA) of V-gene segments was enriched for associations between cases and controls. A single V-gene (TRBV6-7) was significantly associated with CIN3+ status (RA = 0.11%, 0.16%, among cases and controls, respectively, Bonferroni P = 0.0008). The estimated area under the curve using richness and V-gene segment RA was 0.83 (95% confidence interval: 0.73–0.90). Conclusions Substantial differences in TCR repertoire among women with CIN3+ compared to women who cleared infection were observed.

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