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Title: Cytokine gene polymorphism analysis and HPV typing in low grade cervical lesions
Author: Kirkpatrick, Alison
Awarding Body: UCL (University College London)
Current Institution: University College London (University of London)
Date of Award: 2007
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Persistent high-risk human papillomavirus infection (HPVI) of the uterine cervix is associated with squamous intraepithelial lesions (SIL) and cervical cancer. Low-grade SIL (LSIL) is common but factors determining the outcome are incompletely understood and the management is controversial. The infecting HPV type and the host response to HPVI are thought to be important. Genetic polymorphisms in the regulatory sequences of genes have been identified that are associated with different levels of cytokine expression. These include interieukin 1 alpha (IL-1alpha, 46 base pair VNTR in intron 6), interieukin 1 receptor antagonist (IL-1Ralpha, 86 bp VNTR in intron 2) and tumour necrosis factor alpha (TNFalpha, single nucleotide polymorphisms at -308 and -238). Cytokine gene polymorphisms and HPV types were investigated in 209 women presenting to colposcopy clinic with smears suggesting LSIL and compared to controls with normal cervix and those with high-grade SIL (HSIL). Twelve month follow up showed 9% progression to HSIL, 15% persistence of LSIL, 56% regression and 21% loss to follow up. High risk HPVI was common (62%) in women with smears suggesting LSIL but more so in those with co-existing HSIL (85%). HPV 16 was the most common infecting type but 14 infecting high-risk HPV types were seen. The risks of progressing or regressing were not influenced by the presence of HR HPV in this study. Screening for HPV types 16 and 18 alone would miss 36% of disease progression. The low secretor phenotype of TNFalpha -308 was associated with all grades of SIL but most strongly with LSIL (p=0.004). The low secretor phenotype of IL-1alpha was associated with LSIL (p=0.031) but not with HSIL. No associations were demonstrated between IL-1Ralpha polymorphism and cervical disease. No associations were shown between cytokine polymorphisms and HPVI or disease outcome.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available