Differential T helper cell responses to human papillomavirus type 16 E7 related to viral clearance or persistence in patients with cervical neoplasia: a longitudinal study.
AuthorsDe Gruijl, T D
Bontkes, H J
Walboomers, J M
Stukart, M J
Doekhie, F S
Remmink, A J
Helmerhorst, T J
Verheijen, R H
Duggan-Keen, Margaret F
Stern, Peter L
Meijer, C J
Scheper, R J
AffiliationDepartment of Pathology, Free University Hospital, Amsterdam, The Netherlands.
MetadataShow full item record
AbstractT-cell-mediated immune responses against oncogenic human papillomaviruses (HPVs) are believed to play a role in the prevention of cervical carcinogenesis. The in vitro production of interleukin 2 by CD4+ T helper (Th) cells in response to overlapping 20-mer peptides covering the HPV-16 E7 oncoprotein sequence was determined in 72 women with cytological evidence of premalignant cervical intraepithelial neoplasia (CIN) who participated in a nonintervention follow-up (FU) study. In addition, 15 HPV-16 + cervical carcinoma patients were tested. Positive Th cell reactivity was restricted to patients infected by HPV-16 and related types and showed a strong association with viral persistence and disease progression, as evidenced by the high frequency of positive responders among women with persistent HPV-16 infections who ended FU with high-grade CIN III lesions [14 of 15 (93%)]. Women with cervical carcinoma showed responses at a significantly reduced rate [7 of 15 (47%); P = 0.014]. Over the FU period (10-34 months), the level of E7-induced interleukin 2 production from the lymphocytes of CIN patients who had cleared HPV-16 infection showed an inverse correlation with time relative to the last positive HPV DNA test, with 8 of 13 of these patients showing positive responses after clearance. By contrast, among women with persistent HPV-16 infections and developing CIN III lesions (n = 8), there was a rise in Th cell activity over the course of FU. The majority of women responded to an immunogenic region in the carboxyl terminus of the E7 protein (amino acids 67-98). The observed HPV-16 E7-specific Th cell responses may develop as a consequence of increased antigen availability resulting either from clearance or from progression of cervical lesions.
CitationDifferential T helper cell responses to human papillomavirus type 16 E7 related to viral clearance or persistence in patients with cervical neoplasia: a longitudinal study. 1998, 58 (8):1700-6 Cancer Res.
- Interleukin 2 production in vitro by peripheral lymphocytes in response to human papillomavirus-derived peptides: correlation with cervical pathology.
- Authors: Tsukui T, Hildesheim A, Schiffman MH, Lucci J 3rd, Contois D, Lawler P, Rush BB, Lorincz AT, Corrigan A, Burk RD, Qu W, Marshall MA, Mann D, Carrington M, Clerici M, Shearer GM, Carbone DP, Scott DR, Houghten RA, Berzofsky JA
- Issue date: 1996 Sep 1
- A phase I trial of a human papillomavirus (HPV) peptide vaccine for women with high-grade cervical and vulvar intraepithelial neoplasia who are HPV 16 positive.
- Authors: Muderspach L, Wilczynski S, Roman L, Bade L, Felix J, Small LA, Kast WM, Fascio G, Marty V, Weber J
- Issue date: 2000 Sep
- Inverse correlation of cellular immune responses specific to synthetic peptides from the E6 and E7 oncoproteins of HPV-16 with recurrence of cervical intraepithelial neoplasia in a cross-sectional study.
- Authors: Sarkar AK, Tortolero-Luna G, Follen M, Sastry KJ
- Issue date: 2005 Dec
- Disease-stage variance in functional CD4(+) T-cell responses against novel pan-human leukocyte antigen-D region presented human papillomavirus-16 E7 epitopes.
- Authors: Warrino DE, Olson WC, Knapp WT, Scarrow MI, D'Ambrosio-Brennan LJ, Guido RS, Edwards RP, Kast WM, Storkus WJ
- Issue date: 2004 May 15
- A phase II study of Hsp-7 (SGN-00101) in women with high-grade cervical intraepithelial neoplasia.
- Authors: Roman LD, Wilczynski S, Muderspach LI, Burnett AF, O'Meara A, Brinkman JA, Kast WM, Facio G, Felix JC, Aldana M, Weber JS
- Issue date: 2007 Sep