title: Human papillomavirus 16-specific T-cell responses and spontaneous regression of anal high-grade squamous intraepithelial lesions.
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.
  
  
  BACKGROUND
  NCT02007421.
authors.affiliation: Centre for Applied Medical Research, St Vincent's Hospital, Darlinghurst.
authors.forename: Winnie W Y
authors.initials: WW
authors.lastname: Tong
authors.affiliation: Centre for Applied Medical Research, St Vincent's Hospital, Darlinghurst.
authors.forename: Kelsee
authors.initials: K
authors.lastname: Shepherd
authors.affiliation: Royal Women's Hospital and University of Melbourne, Parkville.
authors.forename: Suzanne
authors.initials: S
authors.lastname: Garland
authors.affiliation: Centre for Applied Medical Research, St Vincent's Hospital, Darlinghurst.
authors.forename: Alan
authors.initials: A
authors.lastname: Meagher
authors.affiliation: The Kirby Institute, UNSW Australia, Sydney RPA Sexual Health, Royal Prince Alfred Hospital, Camperdown.
authors.forename: David J
authors.initials: DJ
authors.lastname: Templeton
authors.affiliation: Melbourne Sexual Health Centre and University of Melbourne, Carlton, Victoria, Australia.
authors.forename: Christopher K
authors.initials: CK
authors.lastname: Fairley
authors.affiliation: The Kirby Institute, UNSW Australia, Sydney.
authors.forename: Fengyi
authors.initials: F
authors.lastname: Jin
authors.affiliation: The Kirby Institute, UNSW Australia, Sydney.
authors.forename: I Mary
authors.initials: IM
authors.lastname: Poynten
authors.affiliation: Centre for Applied Medical Research, St Vincent's Hospital, Darlinghurst The Kirby Institute, UNSW Australia, Sydney.
authors.forename: John
authors.initials: J
authors.lastname: Zaunders
authors.affiliation: Centre for Applied Medical Research, St Vincent's Hospital, Darlinghurst Western Sydney Sexual Health Centre and University of Sydney, Westmead, New South Wales.
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Hillman
authors.affiliation: The Kirby Institute, UNSW Australia, Sydney.
authors.forename: Andrew E
authors.initials: AE
authors.lastname: Grulich
authors.affiliation: Centre for Applied Medical Research, St Vincent's Hospital, Darlinghurst The Kirby Institute, UNSW Australia, Sydney.
authors.forename: Anthony D
authors.initials: AD
authors.lastname: Kelleher
authors.affiliation: Centre for Applied Medical Research, St Vincent's Hospital, Darlinghurst.
authors.forename: Andrew
authors.initials: A
authors.lastname: Carr
mesh_terms: D001003:Anal Canal / Q000276:immunology / Q000821:virology; D001005:Anus Neoplasms / Q000276:immunology / Q000821:virology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology; D005260:Female; D018451:Homosexuality, Male; D052162:Human papillomavirus 16 / Q000276:immunology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009856:Oncogene Proteins, Viral / Q000276:immunology; D050725:Papillomavirus E7 Proteins / Q000276:immunology; D030361:Papillomavirus Infections / Q000276:immunology* / Q000821:virology; D012097:Repressor Proteins / Q000276:immunology; D065310:Squamous Intraepithelial Lesions of the Cervix / Q000276:immunology* / Q000821:virology; D002583:Uterine Cervical Neoplasms / Q000276:immunology / Q000821:virology
chemical_list: C068651:E6 protein, Human papillomavirus type 16; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D012097:Repressor Proteins; C059731:oncogene protein E7, Human papillomavirus type 16
keywords: HIV; T-lymphocytes; anal canal; cellular immunity; flow cytometry; human papillomavirus; intraepithelial neoplasia; precancerous conditions; spontaneous neoplasm regression