Browsing by Subject "Cervical cancer"

Now showing 1 - 6 of 6
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    Cervical Cancer in Women with HIV in A Setting with High Smoking: Implications for Prevention
    (2021-12) Zhao, Ran
    In China, cervical cancer is recognized as a major public health problem. Human papillomavirus (HPV) infections cause almost all cases of cervical cancer. Tobacco smoking and co-infection with human immunodeficiency virus (HIV) are two independent risk factors for cervical cancer. Women living with HIV (WLWH) have been shown to have higher risks of HPV infection, precancerous lesions, and cervical cancer. Similarly, smoking negatively impacts the immune system and increases the risk of cervical cancer. Routine cervical cancer screening followed by early treatment is effective in reducing the burden of cervical cancer. In 2009, the Chinese government launched a population-based cervical cancer screening program in rural China as the first step towards implementing national population-based cervical cancer screening. Cervical cancer incidence among Chinese WLWH is estimated to be 47.6 per 100,000, compared to 15.5 per 100,000 in the general population. Considering their excess risk of developing cervical cancer, current screening coverage remains low. Moreover, the current cervical cancer screening guidelines for China do not provide separate screening recommendations for WLWH to account for their increased risk. The aims of this dissertation are to provide evidence to support tailored cervical cancer screening programs for WLWH in Guangxi, a region with a high prevalence of HIV in China. Since smoking control is a challenge in China, and more than 70% of adults are exposed to secondhand smoke in a typical week, we specifically consider the additional risk of cervical cancer associated with smoking exposure. In particular, we (1) surveyed WLWH in Guangxi regarding their knowledge about cervical cancer screening and risk factors for cervical cancer, (2) systematically summarized the literature on the effect of smoking exposure on cervical abnormalities among WLWH, and (3) evaluated the benefits and the harms associated with cytology-based cervical cancer screening tailored to WLWH in Guangxi using decision modeling.
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    HPV Treatment: What’s the next step?
    (2012-07-26) Vallera, Vincent
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    HPV Vaccination
    (2012-07-26) Houghton, Andrew
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    The "Not-So-Scary Pap-Smear" Guide
    (2012-09-24) Redland, Kelsey
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    Pap Tests: What? Why? When?
    (2012-07-26) Dirlam, Carly
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    Role of equilibrative nucleoside transporters 1 and 2 in the transport and disposition of gemcitabine and its metabolites in cervical carcinoma.
    (2010-08) Hodge, Lucy Sahr
    Gemcitabine is a nucleoside analog used as a radiosensitizer for the treatment of locally advanced cervical carcinoma. Yet, despite its efficacy when administered concomitantly with radiation, gemcitabine therapy is not without side effects. The utility of delivering gemcitabine directly to the cervix was explored through the use of a novel drug delivery device, CerviPrep(TM). Local administration to the cervix led to clinically relevant concentrations of gemcitabine in cervical tissue and plasma, while no gemcitabine was detected in the systemic circulation and no side effects were reported. Our data suggest that targeting gemcitabine delivery to the cervix can limit systemic exposure and toxicity while achieving cytotoxic concentrations of drug at the target site. Despite its widespread use in cervical carcinoma, little is known about the disposition of gemcitabine in this tissue. As a nucleoside analog, gemcitabine is a substrate for the equilibrative nucleoside transporters (hENT), and patient response to gemcitabine therapy has been associated with the expression of these proteins. A characterization of hENT1 and hENT2 in both malignant and normal cervical tissue was undertaken, and while no effect of malignancy was observed on hENT1 protein expression, hENT2 protein was nearly three-fold higher in malignant cervical tissue when compared to normal tissue. Expression of hENT mRNA was highly variable and not associated with malignancy. We also examined the effect of dFdU on gemcitabine disposition, as this relatively inactive metabolite is present at much higher concentrations in the plasma than gemcitabine following intravenous administration of the parent compound. We report a novel interaction between dFdU and gemcitabine whereby dFdU competes with gemcitabine for transport via hENT1 and hENT2. The presence of dFdU appears to enhance the retention of gemcitabine intracellularly leading to an increase in the amount of active gemcitabine triphosphate. As more gemcitabine is phosphorylated in the presence of dFdU, a "metabolic sink" is created, further increasing gemcitabine uptake into the cell via hENT1 and hENT2. These data suggest that both transport and intracellular metabolism are equally important components of gemcitabine disposition and cytotoxic potential, and that the presence of dFdU increases intracellular exposure to this nucleoside analog.