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The object of our study is to project the impact of a prophylactic vaccine against persistent human papillomavirus (HPV)-16/18 infection on age-specific incidence of invasive cervical cancer. We developed a computer-based mathematical model of the natural history of cervical carcinogenesis to incorporate the underlying type-specific HPV distribution within precancerous lesions and invasive cancer. After defining plausible ranges for each parameter based on a comprehensive literature review, the model was calibrated to the best available population-based data. We projected the age-specific reduction in cervical cancer that would occur with a vaccine that reduced the probability of acquiring persistent infection with HPV 16/18, and explored the impact of alternative assumptions about vaccine efficacy and coverage, waning immunity and competing risks associated with non-16/18 HPV types in vaccinated women. The model predicted a peak age-specific cancer incidence of 90 per 100,000 in the 6th decade, a lifetime cancer risk of 3.7% and a reproducible representation of type-specific HPV within low and high-grade cervical precancerous lesions and cervical cancer. A vaccine that prevented 98% of persistent HPV 16/18 was associated with an approximate equivalent reduction in 16/18-associated cancer and a 51% reduction in total cervical cancer; the effect on total cancer was attenuated due to the competing risks associated with other oncogenic non-16/18 types. A vaccine that prevented 75% of persistent HPV 16/18 was associated with a 70% to 83% reduction in HPV-16/18 cancer cases. Similar effects were observed with high-grade squamous intraepithelial lesions (HSIL) although the impact of vaccination on the overall prevalence of HPV and low-grade squamous intraepithelial lesions (LSIL) was minimal. In conclusion, a prophylactic vaccine that prevents persistent HPV-16/18 infection can be expected to significantly reduce HPV-16/18-associated LSIL, HSIL and cervical cancer. The impact on overall prevalence of HPV or LSIL, however, may be minimal. Based on the relative importance of different parameters in the model, several priorities for future research were identified. These include a better understanding of the heterogeneity of vaccine response, the effect of type-specific vaccination on other HPV types and the degree to which vaccination effect persists over time. © 2003 Wiley-Liss, Inc. Key words: HPV; cervical cancer precursors; invasive cervical cancer; vaccine; modeling In the past several years there have been substantial advances in our understanding of the epidemiology of cervical carcinogenesis and the causal role of oncogenic human papillomavirus (HPV). [1][2][3] Despite this scientific progress, cervical cancer continues to have a devastating impact on women worldwide, with an estimated 400,000 women developing cervical cancer and 200,000 dying from this disease each year. 4 -7 From the perspective of developing countries, where less than 5% of women are ever screened, the development of a preventive vacci...

To predict the public health impact on cervical disease by introducing human papillomavirus (HPV) vaccination in the United Kingdom, we developed a mathematical model that can be used to reflect the impact of vaccination in different countries with existing screening programmes. Its use is discussed in the context of the United Kingdom. The model was calibrated with published data. The impact of vaccination on cervical cancer and deaths, precancerous lesions and screening outcomes were estimated for a vaccinated cohort of 12-year-old girls, among which it is estimated that there would be a reduction of 66% in the prevalence of high-grade precancerous lesions and a 76% reduction in cervical cancer deaths. Estimates for various other measures of the population effects of vaccination are also presented. We concluded that it is feasible to forecast the potential effects of HPV vaccination in the context of an existing national screening programme. Results suggest a sizable reduction in the incidence of cervical cancer and related deaths. Areas for future research include investigation of the beneficial effects of HPV vaccination on infection transmission and epidemic dynamics, as well as HPV-related neoplasms in other sites.

Our analysis suggests that adding ezetimibe to atorvastatin for patients not achieving treatment goals with their current atorvastatin dose produces greater clinical benefits than treatment with a fixed-dose atorvastatin or atorvastatin titration at an increased overall cost. The cost-effectiveness ratios provide strong evidence for the adoption of ezetimibe within the Canadian healthcare system.

This manuscript has been reproduoed from the microfilm rnaster. UMI films the text directly from the original or copy submitted. Thus. some thesis and dissertation copies are in typewriter face, while others may be from any type of cornputer printer.The quality of this reproduction is dependent upon the quality of the copy submitted. Broken or indistinct print. colored or poor quality illustrations and photographs, print bleedthrough, substandard margins, and improper alignment can adversely affect reproduction.In the unlikely event that the author did not send UMI a wmplete manuscript and there are missing pages, these will be noted. Also, if unauthorized copyright rnaterial had to be removed, a note will indicate the deletion.Oversize materials (e-g., maps, drawings, charts) are reproduoed by sedioning the original. beginning at the upper lefl-hand corner and continuing from left to right in equal sections with small overlaps. Each original is also photographed in one exposure and is induded in reduced f o m at the back of the book.Photographs induded in the original manuscript have been reproduced xerographically in this copy. Higher quality 6" x 9" black and white photographie prints are available for any photographs or illustrations appearing in this copy for an additional charge. Contact UMI directly to order. Canada canadaThe author has granted a nonexclusive licence allowing the National Libmy of Canada to reproduce, loan, distribute or sell copies of this thesis in microfonn, paper or electronic formats.The author retains ownership of the copyright in this thesis. Neither the thesis nor substantial extracts fkom it may be printed or otherwise reproduced without the author's permission.L'auteur a accordé une licence non exclusive permettant à la Bibliothèque nationale du Canada de reproduire, prêter, distribuer ou vendre des copies de cette thèse sous la forme de microfiche/fdm, de reproduction sur papier ou sur format électronique.L'auteur conserve la propriété du droit d'auteur qui protège cette thèse. Ni la thèse ni des extraits substantiels de celle-ci ne doivent être imprimés ou autrement reproduits sans son autorisation. A RISK INDEX FOR STERNAL SURGICAL WOUND INFECTION AFTERCAmIovASCULAR SURGERY Masters of Science, Epidemiology Mïchele Kohli Graduate Department of Community HealthUniversity of TorontoThe purpose of this study was to look at factors that increase the risk of stemal wgicai wound infection d e r cardiovasmlar surgery and to develop a clinical index to identie patients who are at high risk of infection. This study was based on data fiom 1 1,508 cardiac nirgery patients at the Toronto Hospital and emplo yed stepwise logistic regression techniques. The data were split into 3 groups so that validation could be done on new, independent data sets. The study found that reoperation due to complication, diabetes, more than 3 days in the intensive care unit and use of the interna1 mammary artery for revascularization were significant risk factors and these factors were included in the index. ...

The addition of PCR to the standard screening questionnaire is economically attractive compared to the current standard screening questionnaire.