Human papillomavirus 16-specific T-cell responses and spontaneous regression of anal high-grade squamous intraepithelial lesions

J Infect Dis. 2015 Feb 1;211(3):405-15. doi: 10.1093/infdis/jiu461. Epub 2014 Aug 19.


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.

Keywords: HIV; T-lymphocytes; anal canal; cellular immunity; flow cytometry; human papillomavirus; intraepithelial neoplasia; precancerous conditions; spontaneous neoplasm regression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anal Canal / immunology
  • Anal Canal / virology
  • Anus Neoplasms / immunology
  • Anus Neoplasms / virology
  • CD4-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / virology
  • Female
  • Homosexuality, Male
  • Human papillomavirus 16 / immunology*
  • Humans
  • Male
  • Middle Aged
  • Oncogene Proteins, Viral / immunology
  • Papillomavirus E7 Proteins / immunology
  • Papillomavirus Infections / immunology*
  • Papillomavirus Infections / virology
  • Repressor Proteins / immunology
  • Squamous Intraepithelial Lesions of the Cervix / immunology*
  • Squamous Intraepithelial Lesions of the Cervix / virology
  • Uterine Cervical Neoplasms / immunology
  • Uterine Cervical Neoplasms / virology


  • E6 protein, Human papillomavirus type 16
  • Oncogene Proteins, Viral
  • Papillomavirus E7 Proteins
  • Repressor Proteins
  • oncogene protein E7, Human papillomavirus type 16

Associated data