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Title: Studies on common genital HPV types, HPV variants and HPV integration in the development of cervical carcinoma
Author: Donaldson, Yvonne K.
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 1993
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There has been considerable epidemiological and experimental evidence to support a role for human papillomavirus (HPV) in the development of cervical cancer, however, the precise contribution of HPV remains controversial. Variation in prevalence of HPV types in cervical lesions have been found and there have been reports of a high prevalence of HPV in normal tissue. These variable findings have been attributed to several factors including the different detection and cervical sampling techniques used. In this study a PCR based assay for the detection of the common genital HPV types 6b, 11, 16, 18 and 33 was designed and optimised for both sensitivity and specificity. The assay was applied to 24 normal control cases, 20 cases each of cervical intraepithelial neoplasia (CIN) 1, CIN 2 and CIN 3, 26 cases of squamous carcinoma, 16 cases of adenocarcinoma and 4 cases of mixed adenosquamous carcinoma. HPV DNA was found in 25% of CIN 1 cases, 60% of both CIN 2 and CIN 3 cases and in 80% of the cervical carcinomas. A novel finding was that no HPV DNA was detected in the normal control cases. No HPV 6 or 33 DNA was found and HPV 11 DNA was detected in only 5% of CIN 1 cases. HPV 16 and HPV 18 DNA was seen with increasing frequency though the spectrum of cervical disease. The results of this assay support a role for HPV 16 and 18 in neoplastic progression and emphasise the biological similarity of CIN 2 and CIN 3 and their divergence from CIN 1. The prevalence of HPV 16 and HPV 18 in cervical neoplasms was compared. HPV 16 was found in more squamous carcinomas (58%) than HPV 18 (23%), whereas in adenocarcinomas - which have a poorer prognosis than squamous carcinomas - both HPV types showed an equal prevalence (44%). Thus, in terms of cancer cell differentiation HPV 16 appeared to confer a better prognosis than HPV 18. The frequency of HPV 16 in all cancers and CINs gave a CANCER:CIN prevalence ratio of 1.4 (54% /38%) as compared to one of 3.75 (30% /8%) for HPV 18 - a 2.6 fold difference - indicating either a greater risk of, or more rapid progression to malignancy associated with HPV 18. These findings suggest that HPV 18 is more aggressive than HPV 16.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available