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

PLoS One. 2018 Jan 31;13(1):e0178167. doi: 10.1371/journal.pone.0178167. eCollection 2018.


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.

Impact: This is the first study to use next-generation sequencing to investigate TCR repertoire in the context of HPV infection. These findings suggest that women with HPV16-associated cervical lesions have significantly different TCR repertoires from disease-free women who cleared HPV16 infection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Case-Control Studies
  • Cohort Studies
  • Female
  • Human papillomavirus 16 / immunology*
  • Humans
  • Papillomavirus Infections / immunology*
  • Papillomavirus Infections / virology
  • Receptors, Antigen, T-Cell / immunology*
  • Reproducibility of Results
  • Uterine Cervical Dysplasia / immunology*
  • Uterine Cervical Dysplasia / virology
  • Uterine Cervical Neoplasms / immunology*
  • Uterine Cervical Neoplasms / virology
  • VDJ Recombinases / genetics


  • Receptors, Antigen, T-Cell
  • VDJ Recombinases