Open AccessT cell receptor repertoire among women who cleared and failed to clear cervical human papillomavirus infection: An exploratory proof-of-principle study
Author(s) -
Krystle A. Lang Kuhs,
Shih Wen Lin,
Xing Hua,
Mark Schiffman,
Robert D. Burk,
Ana Cecilia Rodríguez,
Rolando Herrero,
Christian C. Abnet,
Neal D. Freedman,
Lígia A. Pinto,
David Hamm,
Harlan Robins,
Allan Hildesheim,
Jianxin Shi,
Mahboobeh Safaeian
Publication year - 2018
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0178167
Subject(s) - t cell receptor , cervical intraepithelial neoplasia , context (archaeology) , biology , squamous intraepithelial lesion , cervical cancer , species richness , clearance , immunology , confidence interval , cancer , oncology , medicine , genetics , t cell , immune system , ecology , paleontology , urology
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.