Human papillomavirus type 16 E6/E7-specific cytotoxic T lymphocytes in women with cervical neoplasia
Hetty J. Bontkes
Department of Pathology, Academisch Ziekenhuis Vrije Universiteit, Amsterdam, the Netherlands
Search for more papers by this authorTanja D. de Gruijl
Department of Pathology, Academisch Ziekenhuis Vrije Universiteit, Amsterdam, the Netherlands
Search for more papers by this authorAdrie J.C. van den Muysenberg
Department of Pathology, Academisch Ziekenhuis Vrije Universiteit, Amsterdam, the Netherlands
Search for more papers by this authorRené H.M. Verheijen
Department of Obstetrics and Gynaecology, Academisch Ziekenhuis Vrije Universiteit, Amsterdam, the Netherlands
Search for more papers by this authorMarij J. Stukart
Department of Pathology, Academisch Ziekenhuis Vrije Universiteit, Amsterdam, the Netherlands
Search for more papers by this authorCorresponding Author
Chris J.L.M. Meijer
Department of Pathology, Academisch Ziekenhuis Vrije Universiteit, Amsterdam, the Netherlands
Department of Pathology, Academisch Ziekenhuis Vrije Universiteit, P.O. Box 7057, 1007 MB Amsterdam, the Netherlands. Fax: 31-20-4442964Search for more papers by this authorRik J. Scheper
Department of Pathology, Academisch Ziekenhuis Vrije Universiteit, Amsterdam, the Netherlands
Search for more papers by this authorSimon N. Stacey
Department of Molecular Biology, Cancer Research Campaign, Paterson Institute for Cancer Research, Christie Hospital National Health Service Trust, Manchester, United Kingdom
Search for more papers by this authorMargaret F. Duggan-Keen
Department of Immunology, Cancer Research Campaign, Paterson Institute for Cancer Research, Christie Hospital National Health Service Trust, Manchester, United Kingdom
Search for more papers by this authorPeter L. Stern
Department of Immunology, Cancer Research Campaign, Paterson Institute for Cancer Research, Christie Hospital National Health Service Trust, Manchester, United Kingdom
Search for more papers by this authorStephen Man
Department of Medicine, University of Wales College of Medicine, Cardiff, Wales, United Kingdom
Search for more papers by this authorLeszek K. Borysiewicz
Department of Medicine, University of Wales College of Medicine, Cardiff, Wales, United Kingdom
Search for more papers by this authorJan M.M. Walboomers
Department of Pathology, Academisch Ziekenhuis Vrije Universiteit, Amsterdam, the Netherlands
Search for more papers by this authorHetty J. Bontkes
Department of Pathology, Academisch Ziekenhuis Vrije Universiteit, Amsterdam, the Netherlands
Search for more papers by this authorTanja D. de Gruijl
Department of Pathology, Academisch Ziekenhuis Vrije Universiteit, Amsterdam, the Netherlands
Search for more papers by this authorAdrie J.C. van den Muysenberg
Department of Pathology, Academisch Ziekenhuis Vrije Universiteit, Amsterdam, the Netherlands
Search for more papers by this authorRené H.M. Verheijen
Department of Obstetrics and Gynaecology, Academisch Ziekenhuis Vrije Universiteit, Amsterdam, the Netherlands
Search for more papers by this authorMarij J. Stukart
Department of Pathology, Academisch Ziekenhuis Vrije Universiteit, Amsterdam, the Netherlands
Search for more papers by this authorCorresponding Author
Chris J.L.M. Meijer
Department of Pathology, Academisch Ziekenhuis Vrije Universiteit, Amsterdam, the Netherlands
Department of Pathology, Academisch Ziekenhuis Vrije Universiteit, P.O. Box 7057, 1007 MB Amsterdam, the Netherlands. Fax: 31-20-4442964Search for more papers by this authorRik J. Scheper
Department of Pathology, Academisch Ziekenhuis Vrije Universiteit, Amsterdam, the Netherlands
Search for more papers by this authorSimon N. Stacey
Department of Molecular Biology, Cancer Research Campaign, Paterson Institute for Cancer Research, Christie Hospital National Health Service Trust, Manchester, United Kingdom
Search for more papers by this authorMargaret F. Duggan-Keen
Department of Immunology, Cancer Research Campaign, Paterson Institute for Cancer Research, Christie Hospital National Health Service Trust, Manchester, United Kingdom
Search for more papers by this authorPeter L. Stern
Department of Immunology, Cancer Research Campaign, Paterson Institute for Cancer Research, Christie Hospital National Health Service Trust, Manchester, United Kingdom
Search for more papers by this authorStephen Man
Department of Medicine, University of Wales College of Medicine, Cardiff, Wales, United Kingdom
Search for more papers by this authorLeszek K. Borysiewicz
Department of Medicine, University of Wales College of Medicine, Cardiff, Wales, United Kingdom
Search for more papers by this authorJan M.M. Walboomers
Department of Pathology, Academisch Ziekenhuis Vrije Universiteit, Amsterdam, the Netherlands
Search for more papers by this authorAbstract
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. Int. J. Cancer 88:92–98, 2000. © 2000 Wiley-Liss, Inc.
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