Human Papillomavirus 16–Specific T-Cell Responses and Spontaneous Regression of Anal High-Grade Squamous Intraepithelial Lesions
| Autor: | Fengyi Jin, Christopher K Fairley, Andrew Carr, Kelsee Shepherd, John Zaunders, Anthony D. Kelleher, Winnie Tong, Alan K Meagher, Richard J. Hillman, Andrew E. Grulich, David J Templeton, Suzanne M. Garland, Mary Poynten |
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| Rok vydání: | 2014 |
| Předmět: |
CD4-Positive T-Lymphocytes
Male medicine.medical_specialty Cellular immunity Pathology Papillomavirus E7 Proteins Anal Canal Uterine Cervical Neoplasms CD8-Positive T-Lymphocytes Biology Gastroenterology Men who have sex with men Internal medicine medicine Humans Immunology and Allergy Anal cancer Homosexuality Male Human papillomavirus 16 Intraepithelial neoplasia medicine.diagnostic_test Papillomavirus Infections Anoscopy Oncogene Proteins Viral Odds ratio Middle Aged Anal canal Anus Neoplasms medicine.disease Repressor Proteins Squamous intraepithelial lesion Infectious Diseases medicine.anatomical_structure Female Squamous Intraepithelial Lesions of the Cervix |
| Zdroj: | Journal of Infectious Diseases. 211:405-415 |
| ISSN: | 1537-6613 0022-1899 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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