Depressed type 1 cytokine synthesis by superantigen-activated CD4+ T cells of women with human papillomavirus-related high-grade squamous intraepithelial lesions.

Carcinoma of the cervix is causally related to infection with the human papillomavirus (HPV), and T cells play a pivotal role in the immune response of the host to rid itself of HPV infection. Therefore, we assessed the T-cell function of women with HPV-related cervical neoplasia against a superantigen, Staphylococcus enterotoxin B (SEB). Each woman provided a cervical brush specimen for HPV DNA testing and Papanicolaou (Pap) smears for the staging of cervical lesions. They also provided a blood specimen for determination of the ability of CD4(+) T and CD8(+) T cells to synthesize Th1 (interleukin-2 [IL-2], gamma interferon [IFN-gamma], and tumor necrosis factor alpha [TNF-alpha]) and Th2 (IL-10) cytokines in response to activation with SEB. Compared with control subjects with self-attested negative Pap smears, women with high-grade squamous intraepithelial lesions (HSIL) had significantly lower percentages of activated CD4(+) T cells that produced IL-2 (P = 0.045), IFN-gamma (P = 0.040), and TNF-alpha (P = 0.015) and a significantly lower percentage of activated CD8(+) T cells that produced IL-2 (P < 0.01). These data indicate that women with HPV-related cervical HSIL show a decrease in Th1 cytokine production by activated CD4(+) T cells and suggested that compromised T-helper functions may negatively impact the function of cytotoxic CD8(+) T cells.

Development and evaluation of a cervical cancer screening program for Chinese women

Despite of the proven efficacy of the Pap test, Asian populations still have low Pap screening compliance. The purpose of this dissertation was to investigate factors that influencing women's decision to obtain a Pap test, and to describe the development and evaluation of a cervical cancer educational program promoting the Pap screening behavior among women in Taiwan. ^ The first study examined factors associated with Pap screening compliance. Psychometric properties of measurement instruments were also assessed. The scale reliabilities were as the follows: Cronbach alpha 0.70 for knowledge scale, 0.88 for pros scale, 0.68 for cons scale, and 0.72 for perceived norms scale. Results from multiple logistic regression analysis, after adjusted for marital status, showed women who compliant to Pap screening guidelines had significantly higher knowledge, higher perceived benefits (pros), lower perceived barriers (cons), and higher perceived norms to receive a Pap test. ^ The second study described the development of a program called “Love yourself before you take care of your family”, designed to increase Pap screening behavior among women in Taiwan. The development of this program was guided by Intervention Mapping (IM), an innovative process of intervention design. The program used methods such as information transmission, modeling, persuasion, and facilitation. Strategies included direct mail campaigns, role model stories with women's testimonials, and phone intervention. ^ The third study examined the effectiveness of a randomized trial of the carefully-designed intervention (N = 424). Participants were female family members of inpatients admitted to one of the major teaching hospitals in Taiwan during August and September 1999. Women in the intervention group reported a higher rate of receiving a Pap test than women in the control group (50% versus 32%) after a three-month intervention (p = 0.002). Women in the intervention group showed increased knowledge (p = .016), perceived pros (p = 0.008), and susceptibility (p = .011) between baseline and follow-up. They also showed higher perceived pros of Pap tests than women in control group at follow-up (p = .031). This result suggested that program development based on theories and evidences could maximize the intervention impact for a specific target population. ^

RNA binding characteristics and overall topology of the vaccinia virus polyadenylation complex

mRNA 3′ polyadenylation is central to mRNA biogenesis in prokaryotes and eukaryotes, and is implicated in numerous aspects of mRNA metabolism, including efficiency of mRNA export from the nucleus, message stability, and initiation of translation. However, due to the great complexity of the eukaryotic polyadenylation apparatus, the mechanisms of RNA 3 ′ end processing have remained elusive. Although the RNA processing reactions leading to polyadenylated messenger RNA have been studied in many systems, and much progress has been made, a complete understanding of the biochemistry of the poly(A) polymerase enzyme is still lacking. My research uses Vaccinia virus as a model system to gain a better understanding of this complicated polyadenylation process, which consist of RNA binding, catalysis and polymerase translocation. ^ Vaccinia virus replicates in the cytoplasm of its host cell, so it must employ its own poly(A) polymerase (PAP), a heterodimer of two virus encoded proteins, VP55 and VP39. VP55 is the catalytic subunit, adding 30 adenylates to a non-polyadenylated RNA in a rapid processive manner before abruptly changing to a slow, non-processive mode of adenylate addition and dissociating from the RNA. VP39 is the stimulatory subunit. It has no polyadenylation catalytic activity by itself, but when associated with VP55 it facilitates the semi-processive synthesis of tails several hundred adenylates in length. ^ Oligonucleotide selection and competition studies have shown that the heterodimer binds a minimal motif of (rU)2 (N)25 U, the “heterodimer binding motif”, within an oligonucleotide, and its primer selection for polyadenylation is base-type specific. ^ Crosslinking studies using photosensitive uridylate analogs show that within a VP55-VP39-primer ternary complex, VP55 comes into contact with all three required uridylates, while VP39 only contacts the downstream uridylate. Further studies, using a backbone-anchored photosensitive crosslinker show that both PAP subunits are in close proximity to the downstream −10 to −21 region of 50mer model primers containing the heterodimer binding motif. This equal crosslinking to both subunits suggests that the dimerization of VP55 and VP39 creates either a cleft or a channel between the two subunits through which this region of RNA passes. ^ Peptide mapping studies of VP39 covalently crosslinked to the oligonucleotide have identified residue R107 as the amino acid in close proximity to the −10 uridylate. This helps us project a conceptual model onto the known physical surface of this subunit. In the absence of any tertiary structural data for VP55, we have used a series of oligonucleotide selection assays, as well as crosslinking, nucleotide transfer assays, and gel shift assays to gain insight into the requirements for binding, polyadenylation and translocation. Collectively, these data allow us to put together a comprehensive model of the structure and function of the polyadenylation ternary complex consisting of VP39, VP55 and RNA. ^

Cervical cancer screening in Hispanic women as compared with other ethnic groups on an urban campus

Although Pap screening has decreased morbidity and mortality from cervical cancer, reported statistics indicate that among ethnic groups, Hispanic women are one of the least likely to follow screening guidelines. Human papillomavirus (HPV), a major risk factor for cervical cancer, as well as pre-cancerous lesions, may be detected by early Pap screening. With a reported 43% prevalence of HPV infection in college women, regular Pap screening is important. The purpose of this descriptive, cross-sectional survey was to examine self-reported cervical cancer screening rates in a target population of primarily Mexican-American college women, and to discover if recognized correlates for screening behavior explained differences in screening rates between this and two other predominant groups on the University of Houston Downtown campus, non-Hispanic white and African-American. The sample size consisted of 613 women recruited from summer 2003 classes. A survey, adapted from an earlier El Paso study, and based on constructs of the Health Belief Model (HBM), was administered to women ages 18 and older. It was found that although screening rates were similar across ethnic groups, overall, the Hispanic group obtained screening less frequently, though this did not reach statistical significance. However, a significant difference in lower screening rates was found in Mexican American women ages <25. Additionally, of the predicted correlates, the construct of perceived barriers from the HBM was most significant for the Mexican American group for non-screening. For all groups, knowledge about cervical cancer was negatively correlated with ever obtaining Pap screening and screening within the past year. This implies that if health counseling is given at the time of women's screening visits, both adherence to appropriate screening intervals and risk factor avoidance may be more likely. Studies such as these are needed to address both screening behaviors and likelihood of follow-up for abnormal results in populations of multicultural, urban college women. ^

The use of culturally related health practices and health care utilization among Hispanic women in farmworker communities

Breast and cervical cancer screening rates continue to be lower in Hispanic women than other ethnic subgroups. Several factors have been identified that influence health care utilization. The use of preventive services (cancer screenings and adherence) in addition to yearly doctor visits are often used to measure health care utilization. A secondary analysis of an existing dataset containing baseline survey data collected from participants of an intervention trial to test the Cultivando La Salud (CLS) program was used to analyze the association between cultural health practice use (use of curandero,s obador, and herbal remedies) and health care utilization. The sample consisted of women 50 years of age and older living in farmer communities in four sites: Eagle Pass, TX, Anthony, NM, Merced, CA, and Watsonville, CA (n=708). Participants reported using a curandero (5.67%), sobador (29.79%), and herbal remedies (46.65%) at some point in their lives. The use of cultural health practices was found to significantly influence utilization of certain health care services: use of herbal remedies influence doctor visits, adherence to mammography screening and adherence to Pap test screening; use of a curandero influenced ever having a mammogram; use of a sobador influenced ever having a mammogram, ever having a Pap test, and Pap test adherence. In addition, women reporting use of curandero or herbal remedies were found to be more avoidant of the health care system than those that reported not using them. Further research is needed to further analyze the influence of cultural health practices on health care utilization. ^

Determinants of cervical cancer screening among women workers in Monterrey, Mexico

Introduction. Cervical cancer is the most common and lethal cancer among Mexican women. A nationwide cervical cancer screening program established in 1974 has had little impact on cervical cancer incidence or mortality rates. This case-control study was designed to determine the association between knowledge factors and structural, organizational, and sociocultural perceptions related to adherence to cervical cancer screening guidelines among women living and working in Monterrey, Mexico.^ Methods. Cases were defined as sexually active female store clerks ages 18-64 who do not adhere to cervical cancer screening guidelines in accordance with the Official Mexican Standard (Norma Oficial Mexicana, NOM 014-SSA2-1994). Controls were defined as sexually active female store clerks ages 18-64 who do adhere to cervical cancer screening guidelines in accordance with the NOM. Participants (N = 229) answered survey questions regarding cervical cancer screening practices as well as their knowledge and perceptions about screening for cervical cancer. Two multivariate logistic regression models were built to analyze (1) knowledge factors and (2) perceptions significantly associated with adherence in univariate analysis.^ Results. Having no or inaccurate knowledge of national cervical cancer screening guidelines (OR = 11.05, 95%CI: 4.28, 28.54) and no knowledge of the utility of the Papanicolaou (Pap) exam (OR = 6.77, 95%CI: 0.99, 46.43) were risk factors for non-adherence to cervical cancer screening guidelines. Perceptions of fear or embarrassment of the Pap exam (OR = 16.17, 95%CI: 5.08, 51.49) and lower levels of spousal or partner acceptance of the Pap exam (OR = 5.82, 95%CI: 1.34, 25.31) were risk factors for non-adherence to cervical cancer screening guidelines.^ Conclusion. Knowledge factors and sociocultural perceptions related to cervical cancer screening were strong predictors of adherence to screening guidelines. Future studies may be able to further explore these findings with larger sample sizes and in other populations in Mexico. By identifying these factors, future population-specific recommendations and interventions to increase screening rates can be formulated with the long-term goal of reducing morbidity and mortality from cervical cancer among Mexican women.^

Exploring the use of pharmaceutical patient assistance programs as an option to improve access to and affordability of prescription drugs

Background. Pharmaceutical-sponsored patient assistance programs (PAPs) are charity programs that provide free or reduced-priced medications to eligible patients. PAPs have the potential to improve prescription drug accessibility for patients but currently there is limited information about their use and effectiveness. ^ Objectives and methods. This dissertation described the use of PAPs in the U.S. through the conduct of two studies: (1) a systematic review of primary studies of PAPs from commercially-published and “grey” literature sources; and (2) a retrospective, cross-sectional study of cancer patients' use of PAPs at a tertiary care cancer outpatient center. ^ Results. (1) The systematic review identified 33 studies: 15 evaluated the impact of PAP enrollment assistance programs on patient healthcare outcomes; 7 assessed institutional costs of providing enrollment assistance; 7 surveyed stakeholders; 4 examined other aspects. Standardized mean differences calculated for disease indicator outcomes (most of which were single group, pre-posttest designs) showed significant decreases in glycemic and lipid control, and inconsistent results for blood pressure. Grey literature abstracts reported insufficient statistics for calculations. Study heterogeneity made weighted summary estimates inappropriate. Economic analyses indicated positive financial benefits to institutions providing enrollment assistance (cost) compared to the wholesale value of the medications provided (benefit); analyses did not value health outcomes. Mean quality of reporting scores were higher for observational studies in commercially-published articles versus full text, grey literature reports. (2) The cross-sectional study found that PAP outpatients were significantly more likely to be uninsured, indigent, and < 65 years old than non-PAP patients. Nearly all non-PAP and PAP prescriptions were for non-cancer conditions, either for co-morbidities (e.g., hypertension) or the management of treatment side effects (e.g., pain). Oral chemotherapies from PAPs were significantly more likely to be for breast versus other cancers, and be a newer, targeted versus traditional chemotherapy.^ Conclusions. In outpatient settings, PAP enrollment assistance plus additional medication services (e.g., counseling, reminders, and free samples) is associated with improved disease indicators for patients. Healthcare institutions, including cancer centers, can offset financial losses from uncompensated drug costs and recoup costs invested in enrollment assistance programs by procuring free PAP medications. Cancer patients who are indigent and uninsured may be able to access more outpatient medications for their supportive care needs through PAPs, than for cancer treatment options like oral chemotherapies. Because of the selective availability of drugs through PAPs, there may be more options for newer, oral, targeted chemotherapies for the treatment breast cancer versus other for other cancers.^

For health's sake: Cervical and breast cancer screening

African-Americans make up twelve percent of the United States population, yet they experience morbidity and mortality at a rate that, in some cases, is disproportionate to their numbers. There are numerous health areas, including cancer, in which disparities exist. There are also numerous reasons which have been suggested to explain the high rates of cancer morbidity and mortality experienced by African-Americans. Among the reasons given to explain these differences are lack of knowledge and lack of access to medical care (1). This study sought to increase the knowledge, attitudes, and behavioral intentions of African-American women attending a Baptist church in Houston with regard to cervical cancer, breast cancer, Pap smear, and mammography. It was hypothesized that a church-based cancer education program would produce the desired change in knowledge, attitudes, and behavioral intentions.^ The quasi-experimental design of the study was untreated control group with pretest and posttest and untreated control group with posttest only. Female members of Mount Ararat Baptist Church took part in an eight-week, cancer education program based on social cognitive theory. Baseline data were collected before the start of the program at Mount Ararat and at Solid Rock Baptist Church, control group one. At the end of the program, the follow-up survey was administered at the program church, control church one, and in a third church, Damascus Missionary Baptist Church, which served as the posttest only group. The data were analyzed by Fisher's exact and paired t-test to determine if the program supported the project's hypotheses.^ Results of data analyses supported the major study hypotheses, the exception being behavioral intention to have Pap smear performed. Although the program appeared to have generally influenced changes in the desired direction, the results are limited due to the quasi-experimental design and small sample size. Longer term studies with larger sample sizes are needed to more fully develop and evaluate programs which impact the health of African-Americans. ^

Information sources influencing urban Mexican-American women's cancer screening participation

Breast and cervical cancer, though less common in Mexican-American than in Anglo women, are more likely to go undetected in Mexican-American women, leaving them more vulnerable to advanced disease and death. Although highly effective screening tests--the Pap smear and the mammogram--can detect these cancers early, many Mexican-American women do not regularly undergo these preventive screening tests.^ To explore the differential influence of encouraging sources of health information, this investigation examined the relationship between encouragement from a "peer"--husband or partner, child or children, other family members, or close friends--and a "health professional"--a doctor, a nurse, or another health professional--on Mexican-American women's cancer screening intentions and behaviors. Furthermore, this research explored whether the sources' influence on cancer screening intentions and behaviors differed depending on level of acculturation.^ One thousand seven hundred eleven surveys of Mexican-American women were analyzed to identify the source that most effectively encourages these women to participate in cancer screening. The data provided evidence that health professionals strongly influenced this population's cancer screening intentions and behaviors. Evidence for peer influence was also found; however, it was usually weaker, and, in some cases, negligible. Peer encouragement was related to Pap test behaviors and mammogram intentions, but not to Pap test intentions or mammogram behaviors. Consistently, women reported greater intentions and screening behaviors when encouraged from a health professional than from a peer. Acculturation was not found to be a modifying variable related to the relationship between sources of information and Pap test or mammogram intentions and behaviors.^ Because health professionals were identified as strongly influencing both intentions and behaviors for Pap tests and mammograms, further efforts should be undertaken to urge them to encourage their clients to obtain cancer screening. Failure to provide this encouragement leads to missed opportunities. Enlisting support from peers also may help to increase cancer screening participation in urban Mexican-American women; however, the consistently greater intentions and behaviors related to a health professional's encouragement indicated the greater power of the latter. ^

Anal warts and their predictors among HIV-infected women

Human papillomavirus (HPV) is a necessary cause of cervical cancer and is also strongly associated with anal cancer. While different factors such as CD4+ cell count, HIV RNA viral load, smoking status, and cytological screening results have been identified as risk factors for the infection of HPV high-risk types and associated cancers, much less is known about the association between those risk factors and the infection of HPV low-risk types and anogential warts. In this dissertation, a public dataset (release P09) obtained from the Women's Interagency HIV Study (WIHS) was used to examine the effects of those risk factors on the size of the largest anal warts in HIV-infected women in the United States. Linear mixed modeling was used to address this research question. ^ The prevalence of anal warts at baseline for WIHS participants was higher than other populations. Incidence of anal warts in HIV-infected women was significantly higher than that of HIV-uninfected women [4.15 cases per 100 person-years (95% CI: 3.83–4.77) vs. 1.30 cases per 100 person-years (95% CI: 1.00–1.58), respectively]. There appeared to be an inverse association between the size of the largest anal wart and CD4+ cell count at baseline visit, however it was not statistically significant. There was no association between size of the largest anal wart and CD4+ cell count or HIV RNA viral load over time among HIV-infected women. There was also no association between the size of the largest anal wart and current smoking over time in HIV-infected women, even though smokers had larger warts at baseline than non-smokers. Finally, even though a woman with Pap smear results of ASCUS/LGSIL was found to have an anal wart larger than a woman with normal cervical Pap smear results the relationship between the size of the largest anal wart with cervical Pap smear results over time remains unclear. ^ Although the associations between these risk factors and the size of the largest anal wart over time in HIV-infected women could not be firmly established, this dissertation poses several questions concerning anal wart development for further exploration: (1) the role of immune function (i.e., CD4+ cell count), (2) the role of smoking status and the interaction between smoking status with other risk factors (e.g., CD4+ cell count or HIV RNA viral load), (3) the molecular mechanism of smoking on anal warts over time, (4) the potential for development of a screening program using anal Pap smear in HIV-infected women, and (5) how cost-effective and efficacious would an anal Pap smear screening program be in this high-risk population. ^

Cancer screening behaviors among Asian Americans in Houston, Texas

Background: Cancer is the second-leading cause of death in the United States, and Asian Americans/Pacific Islanders are the only racial/ethnic group for which cancer is the leading cause of death. Regular cancer screenings help to identify precancerous lesions and cancer at an earlier stage, when the cancer is more treatable. Ethnic disparities in participation in cancer screenings are also striking, and evidence indicates that Asian Americans may have lower rates of cancer screening participation than other racial/ethnic groups. The Health of Houston Survey 2010 (HHS 2010) is an address-based survey, administered via telephone, website, and mail, of over 5,000 respondents in Houston and Harris County that provides recent data on the health status and needs of the Houston community. HHS 2010 researchers oversampled for Asians and Vietnamese Americans in order to obtain a sample size large enough to obtain statistical power. This dataset provides a unique opportunity to examine the cancer screening behaviors and predictors of Vietnamese and Chinese Americans living in Houston, Texas.^ Methods: This study was a secondary data analysis of HHS 2010 data. The data were analyzed to compare the breast, cervical, and colorectal cancer screening compliance rates of Vietnamese and Chinese Americans with other racial/ethnic groups in Houston, Texas. Key predictors of participation and barriers to cancer screening were identified.^ Results: The results of this study indicate that in Houston, Vietnamese Americans and Asian Americans as a whole have strikingly lower rates of participation in cancer screenings compared to other ethnic groups. Chinese Americans had the highest rate of noncompliance for mammography of all ethnic groups; Asian Americans and Vietnamese Americans also had high rates of noncompliance. Similarly, Vietnamese and Asian Americans had high rates of noncompliance with colorectal cancer screening recommendations. Importantly, Vietnamese, Chinese, and Asian Americans had by far the worst pap test participation, with noncompliance rates more than double that of all other racial/ethnic groups. In general, the findings indicated several key predictors in cancer screening behaviors, including English language proficiency, years lived in the United States, health insurance, college education, and income; however, the significance and patterns of these variables varied by ethnic group as well as cancer site.^ Conclusions: This secondary analysis highlights the disparities in cancer screening participation among Vietnamese, Chinese, and Asian Americans in Houston, Texas and indicate the need to identify Asian Americans as a high-risk group in need of health promotion attention. Barriers to screening and educational needs appear to be specific to each target ethnic group. Thus, health educators and health professionals in Houston must focus on the specific educational needs of the key ethnic groups that make up the Houston population. Further, more ethnic-specific research is needed to examine the health behaviors and needs of Houston's Asian American subgroups.^

Classification of cellular malignancy associated changes in cervical cancer

Cervical cancer is the leading cause of death and disease from malignant neoplasms among women in developing countries. Even though the Pap smear has significantly decreased the number of deaths from cervical cancer in the past years, it has its limitations. Researchers have developed an automated screening machine which can potentially detect abnormal cases that are overlooked by conventional screening. The goal of quantitative cytology is to classify the patient's tissue sample based on quantitative measurements of the individual cells. It is also much cheaper and potentially can take less time. One of the major challenges of collecting cells with a cytobrush is the possibility of not sampling any existing dysplastic cells on the cervix. Being able to correctly classify patients who have disease without the presence of dysplastic cells could improve the accuracy of quantitative cytology algorithms. Subtle morphologic changes in normal-appearing tissues adjacent to or distant from malignant tumors have been shown to exist, but a comparison of various statistical methods, including many recent advances in the statistical learning field, has not previously been done. The objective of this thesis is to use different classification methods applied to quantitative cytology data for the detection of malignancy associated changes (MACs). In this thesis, Elastic Net is the best algorithm. When we applied the Elastic Net algorithm to the test set, we combined the training set and validation set as "training" set and used 5-fold cross validation to choose the parameter for Elastic Net. It has a sensitivity of 47% at 80% specificity, an AUC 0.52, and a partial AUC 0.10 (95% CI 0.09-0.11).^