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Winnie W. Y. Tong, Kelsee Shepherd, Suzanne Garland, Alan Meagher, David J. Templeton, Christopher K. Fairley, Fengyi Jin, I. Mary Poynten, John Zaunders, Richard J. Hillman, Andrew E. Grulich, Anthony D. Kelleher, Andrew Carr, Study of the Prevention of Anal Cancer (SPANC) team, Human Papillomavirus 16–Specific T-Cell Responses and Spontaneous Regression of Anal High-Grade Squamous Intraepithelial Lesions, The Journal of Infectious Diseases, Volume 211, Issue 3, 1 February 2015, Pages 405–415, https://doi.org/10.1093/infdis/jiu461
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Abstract
Background. Most anal cancers are attributable to persistent human papillomavirus type 16 (HPV-16) infection. The anal cancer precursor, high-grade squamous intraepithelial lesion (HSIL), frequently regresses spontaneously. We hypothesized that T-cell responses are associated with HSIL regression.
Methods. In men who have sex with men undergoing anal cytology and high-resolution anoscopy, we measured responses to HPV-16 oncogenic proteins E6 and E7, using the CD25/CD134 assay for CD4+ antigen–specific T cells and intracellular cytokine staining for CD4+ and CD8+ antigen–specific T cells.
Results. Of 134 participants (mean [SD] age, 51 [9.3] years; 31 [23.1%] infected with human immunodeficiency virus), 51 (38.1%) had HSIL. E6- and E7-specific CD4+ T-cell responses were detected in 80 (59.7%) and 40 (29.9%) of the participants, respectively, and E6- and E7-specific CD8+ T-cell responses were each detected in 25 (18.7%). HSIL was significantly associated with E7-specific CD8+ T-cell responses (odds ratio, 4.09 [95% confidence interval, 1.55–10.77], P = .004), but not with any CD4+ T-cell response (P ≥ .09). Twenty-six participants had HSIL a mean of 1 year before measurement of T-cell responses, and 6 (23%) of them were regressors. Five regressors (83%) had E6-specific CD4+ T-cell responses vs 7 of 20 (35%) nonregressors (Pexact = .065).
Conclusions. Systemic HPV-16 E6- and E7-specific T-cell responses were common in men who have sex with men. E6-specific CD4+ T-cell responses may be associated with recent HSIL regression.
Clinical Trials Registration. NCT02007421.
