title: Human papillomavirus type 16 E6/E7-specific cytotoxic T lymphocytes in women with cervical neoplasia.
abstract: Infection with oncogenic human papillomavirus (HPV) types is associated with the development of cervical neoplasia (CIN). The E6 and E7 oncoproteins are constitutively expressed in these lesions and are therefore putative targets for the immune response against HPV. The relation between HPV 16-specific memory cytotoxic T-cell precursor (mCTLp) activity to both oncoproteins and the natural course of cervical dysplasia was analyzed in 38 patients participating in a nonintervention cohort study of women with CIN and 11 HPV 16-positive cervical carcinoma patients. In a cross-sectional study at the end of follow-up prior to biopsy, 8 of 20 patients with a persistent HPV 16 infection had specific mCTLp against at least one of the two oncoproteins. By contrast, no specific mCTLp activity was detected in 11 HPV-negative patients or in 7 patients who had cleared an HPV 16 infection at the end of follow-up. However, 5 of 11 cervical carcinoma patients showed mCTLp activity against the E7 protein only. This study demonstrates that HPV 16 oncogene-specific mCTLp are present in women with HPV 16-positive CIN prior to any intervention. Since HPV-specific mCTLp were detected predominantly in women with high-grade lesions or invasive cervical carcinoma and not in women who cleared the virus, the role of naturally occurring mCTLp in the protection against HPV-associated cervical neoplasia remains to be established.
authors.affiliation: Department of Pathology, Academisch Ziekenhuis Vrije Universiteit, Amsterdam, the Netherlands.
authors.forename: H J
authors.initials: HJ
authors.lastname: Bontkes
authors.forename: T D
authors.initials: TD
authors.lastname: de Gruijl
authors.forename: A J
authors.initials: AJ
authors.lastname: van den Muysenberg
authors.forename: R H
authors.initials: RH
authors.lastname: Verheijen
authors.forename: M J
authors.initials: MJ
authors.lastname: Stukart
authors.forename: C J
authors.initials: CJ
authors.lastname: Meijer
authors.forename: R J
authors.initials: RJ
authors.lastname: Scheper
authors.forename: S N
authors.initials: SN
authors.lastname: Stacey
authors.forename: M F
authors.initials: MF
authors.lastname: Duggan-Keen
authors.forename: P L
authors.initials: PL
authors.lastname: Stern
authors.forename: S
authors.initials: S
authors.lastname: Man
authors.forename: L K
authors.initials: LK
authors.lastname: Borysiewicz
authors.forename: J M
authors.initials: JM
authors.lastname: Walboomers
mesh_terms: D015331:Cohort Studies; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D007156:Immunologic Memory / Q000276:immunology; D007376:Interleukin-2 / Q000096:biosynthesis / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D008875:Middle Aged; D009856:Oncogene Proteins, Viral / Q000276:immunology*; D027383:Papillomaviridae / Q000276:immunology*; D030361:Papillomavirus Infections / Q000276:immunology* / Q000821:virology; D012097:Repressor Proteins; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology; D014412:Tumor Virus Infections / Q000276:immunology* / Q000821:virology; D002583:Uterine Cervical Neoplasms / Q000276:immunology / Q000821:virology*; D002578:Uterine Cervical Dysplasia / Q000276:immunology / Q000821:virology*
chemical_list: C068651:E6 protein, Human papillomavirus type 16; D007376:Interleukin-2; D009856:Oncogene Proteins, Viral; D012097:Repressor Proteins; C062495:oncogene protein E7, Human papillomavirus type 6