Human Papillomavirus 16–Specific T-Cell Responses and Spontaneous Regression of Anal High-Grade Squamous Intraepithelial Lesions

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.