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The aims of this thesis were to investigate (1) the prevalence of high-risk HPV infection in UK women and factors associated with infection risk; and (2) the value of a single high-risk HPV test in identifying women with CIN2 or more severe disease.  Data from the UK TOMBOLA trial were used.  TOMBOLA recruited women aged 20-59 years, who were resident in Grampian, Tayside or Nottingham with a recent low-grade abnormal cervical smear.  Women underwent HPV testing using PCR methodology. The prevalence of high-risk HPV infection increased with increasing smear severity (16% among those with a current normal and previous BNA, 34-35% among those with a current BNA smear; 60-69% among those with a current mild smear depending whether the woman had had a previous BNA or not), and decreased with increasing age.  After taking into account these strong associations, and interactions, between HPV status and smear severity and age, modest associations between several lifestyle factors and prevalence of high-risk HPV infection remained. In women with a mild smear, sensitivity in terms of identifying women with CIN2 or more severe disease was 75.2% (95% CI 68.8-81.0) and specificity 46.9% (95% CI 42.2-51.6).  In those with a BNA smear, sensitivity was 69.9% (95% CI 61.7-7-77.3%) and specificity 71.3% (95% CI 68.5-74.1).  The negative predictive values were high (mild 80.5%, 95% CI 75.2-85.1%; BNA 94.5%, 95% CI 92.6-96.0) suggesting that HPV testing may be promising in avoiding referral to colposcopy, particularly among women with a BNA smear. Both analyses are relevant to the debate on HPV testing in a triage of women with low-grade cytological abnormalities.  The epidemiological data from the first aim is also relevant to the development of strategies for the delivery of HPV vaccination programmes.

This thesis evaluates the role, safety, and side effects of misoprostol in the evacuation of the pregnant uterus. Chapter 1 includes a discussion and literature review of the status of abortion practice in the world and the magnitude of the associated morbidity and mortality. The place of misoprostol among other prostaglandin agents, as well as its development, safety and applications are reviewed. The rationale and aims of the thesis are explained. Chapter 2 describes two open studies examining the place and applicability of misoprostol in the evacuation of the pregnant uterus in cases of miscarriage. The first study examines the place of misoprostol in the evacuation of the uterus in cases of anembryonic pregnancy and missed abortion in women pretreated with mifepristone. The second study describes the sole use of misoprostol in the management of incomplete abortions. Chapter 3 describes a randomised study examining the efficacy and side effects of two misoprostol dose regimens in the induction of abortion prior to 56 days amenorrhea in women pretreated with mifepristone. Chapter 4 examines the place of the vaginal administration of misoprostol to induce abortion in women prior to 63 days of amenorrhea and pretreated with mifepristone. Two studies are presented. The first is an open study examining this approach and the second is a randomised study evaluating the oral versus vaginal administration of the drug. Chapter 5 examines the place of misoprostol in the management of second trimester pregnancy. Two randomised studies are described. They evaluate different regimens of misoprostol when administered orally and vaginally after mifepristone treatment. Chapter 6 assesses the place of misoprostal as a cervical priming agent prior to surgical termination of pregnancy. A randomised study evaluating the biophysical and histochemical changes induced in the cervix is described.

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