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Item Association of human papillomavirus vaccination with exposure to dental or medical visits(Wiley, 2020) Shukla, Anubhuti; McKenna, Maria; Hayes, Catherine; Klevens, Ruth Monina; Cariology, Operative Dentistry and Dental Public Health, School of DentistryBackground Human papillomavirus (HPV) infection is associated with oropharyngeal cancers. The Centers for Disease Control and Prevention (CDC) estimate that >15,000 new cases of HPV-associated oropharyngeal cancers are diagnosed in the United States annually. We evaluated an association between HPV vaccination and dental visits in the previous year. Methods Data were analyzed from the 2012, 2014, and 2016 Massachusetts Behavioral Risk Factor Surveillance System (MA-BRFSS) datasets. We created four categories of exposures to healthcare services in the past 12 months: a) both medical and dental visits, b) medical visit only, c) dental visit only, d) neither. Outcomes were HPV vaccination ever or influenza vaccination within the past 12 months. Logistic regression, controlled for race and education, was used to measure the association between medical/dental visits and vaccination status. Separate models were generated by sex. Results Crude and adjusted odds ratio of influenza and HPV vaccination were highest among males and females with both medical and dental visits. Women with both medical and dental provider visits had 3.7 times higher odds of being vaccinated for influenza and 1.7 times higher odds of being vaccinated for HPV. There were no differences in crude or adjusted odds among both males and females if the type of healthcare visits were only medical or only dental. Conclusion No difference in association between vaccination and medical or dental healthcare exposures suggests that oral health professionals might partner in promotion of positive health behaviors, including HPV vaccination. The type of provider did not affect the outcome as per this study.Item Characterizing U.S. mothers with high human papillomavirus vaccine intent yet unvaccinated adolescents(Elsevier, 2023-04) Srivastava, Tuhina; Head, Katharine J.; O'Dell, Sean; Feemster, Kristen A.; Panozzo, Catherine A.; Zimet, Gregory D.; Kornides, Melanie L.; Communication Studies, School of Liberal ArtsHPV vaccination rates remain suboptimal in the United States. While the current literature focuses on expressly hesitant parents, few studies have examined parents with “high intent”, or those indicating they definitely will vaccinate and have had the opportunity but not yet vaccinated their adolescents. Our objective was to differentiate characteristics of mothers with high intent from those who already vaccinated their adolescents using various socioeconomic, previous vaccine decision-making, and healthcare provider relationship-related variables. English-speaking mothers or female guardians of adolescents ages 11–14 years living in low HPV vaccine uptake states within the U.S. in September 2018 were recruited from a national survey panel as part of a larger study. We assessed HPV vaccine status of their adolescents and categorized respondents into two categories: Already Vaccinated and High Intent. We assessed differences using a multivariable logistic regression model. Among 2406 mothers, 18% reported high intent vs. 82% already having vaccinated. Mothers with high intent were more likely to identify as non-Hispanic White (p = 0.01), to have a younger adolescent (p < 0.001), and to report not receiving a provider HPV vaccination recommendation (p < 0.001). Mothers who estimated that half/more (vs. less) of their child's friends have received/will receive the vaccine had higher odds of already vaccinating (p < 0.001). Our findings suggest that clinicians may be able to improve HPV vaccination uptake within their practices by giving repeated, high-quality recommendations to parents of children who are not yet vaccinated. Additionally, these findings indicate perceived social norms may play a large role in on-time vaccine uptake. Reassuring hesitant parents that most parents accept the vaccine may also improve uptake in clinical practice.Item Factors Associated with Home Based Self-Collection for Human Papillomavirus (HPV) Testing(2021-09) Biederman, Erika Brooke; Champion, Victoria; Zimet, Gregory; Draucker, Claire; Han, JialiWomen who are medically underserved may be less likely to obtain provider-based cervical cancer screening because of structural and intrapersonal barriers. Self-collection for human papillomavirus (HPV) testing, a method for women to collect their own sample through a vaginal swab or urine collection, has accuracy comparable to provider-based cervico-vaginal HPV testing and may be useful in overcoming barriers to provider-based cervical cancer screening. The purpose of this dissertation study is to examine factors associated with self-collection for HPV testing, psychometrically test Diffusion of Innovations (DOI) instruments, and identify preferences for self-collection for HPV testing. Three distinct aims were developed: 1) factors (sociodemographic, health-related, and theoretical variables) associated with mailed return of vaginal self-collection for HPV testing, 2) psychometric examination of DOI ÷instruments (relative advantages and complexity), and 3) dimensions of self-collection and characteristic preferences to self-collection for HPV testing stratified by age cohorts. This dissertation involved two cross-sectional studies. In Chapters 2-3, data were collected from women (n=168) at food pantries and online. Women were eligible if they were: 1) female, 2) between the ages of 30-65, 3) could read and speak English, and 4) at 2019 federal poverty guidelines for income and family size as defined by the Department of Health and Human Services. Women were not eligible if they had a history of hysterectomy or were adherent to cervical cancer screening guidelines. Logistic regression analyses, item analysis, Cronbach’s alpha, exploratory factor analysis, and tests were used to analyze data. Chapter 4 involved collection of data from an online survey with a sample (n=878) provided by Dynata. Participants evaluated 9 scenarios that varied along 4 attributes: HPV self-collection kit type (vaginal swab or urine collection), HPV self-collection kit delivery (mail, pharmacy pick-up, or clinic pick-up), HPV self-collection kit return (mail, pharmacy drop-off, or clinic drop-off), and HPV test result communication (mail, phone call, or text message). Ratings-based conjoint analysis (RBCA) determined how each attribute influenced the ratings of each scenario.Item Factors associated with human papillomavirus (HPV) test acceptability in primary screening for cervical cancer: A mixed methods research synthesis(Elsevier, 2018) Tatar, Ovidiu; Thompson, Erika; Naz, Anila; Perez, Samara; Shapiro, Gilla K.; Wade, Kristina; Zimet, Gregory D.; Gilca, Vladimir; Janda, Monika; Kahn, Jessica; Daley, Ellen; Rosberger, Zeev; Pediatrics, School of MedicinePrimary screening for cervical cancer is transitioning from the longstanding Pap smear towards implementation of an HPV-DNA test, which is more sensitive than Pap cytology in detecting high-risk lesions and offers greater protection against invasive cervical carcinomas. Based on these results, many countries are recommending and implementing HPV testing-based screening programs. Understanding what factors (e.g., knowledge, attitudes) will impact on HPV test acceptability by women is crucial for ensuring adequate public health practices to optimize cervical screening uptake. We used mixed methods research synthesis to provide a categorization of the relevant factors related to HPV primary screening for cervical cancer and describe their influence on women's acceptability of HPV testing. We searched Medline, Embase, PsycINFO, CINAHL, Global Health and Web of Science for journal articles between January 1, 1980 and October 31, 2017 and retained 22 empirical articles. Our results show that while most factors associated with HPV test acceptability are included in the Health Belief Model and/or Theory of Planned Behavior (e.g., attitudes, knowledge), other important factors are not encompassed by these theoretical frameworks (e.g., health behaviors, negative emotional reactions related to HPV testing). The direction of influence of psychosocial factors on HPV test acceptability was synthesized based on 14 quantitative studies as: facilitators (e.g., high perceived HPV test benefits), barriers (e.g., negative attitudes towards increased screening intervals), contradictory evidence (e.g., sexual history) and no impact (e.g., high perceived severity of HPV infection). Further population-based studies are needed to confirm the impact of these factors on HPV-based screening acceptability.Item Factors associated with the human papillomavirus (HPV) vaccination across three countries following vaccination introduction(Elsevier, 2017-11) Nickel, Brooke; Dodd, Rachael H.; Turner, Robin M.; Waller, Jo; Marlow, Laura; Zimet, Gregory; Ostini, Remo; McCaffery, Kirsten; Pediatrics, School of MedicineDirect international comparisons which aim to understand how factors associated with human papillomavirus (HPV) vaccine initiation and attitudes towards the HPV vaccination in parents differ are scarce. Parents (n = 179) of daughters aged 9–17 years in the US, UK and Australia completed an online survey in 2011 with questions measuring daughters' HPV vaccination status, HPV knowledge, HPV vaccination knowledge, and statements assessing attitude towards the HPV vaccine. The strongest factor associated with vaccination status across all countries was parental HPV knowledge (p < 0.001). Parents with both very low and very high knowledge scores were less likely to have vaccinated their daughters. Parents with higher HPV vaccination knowledge scores intended to vaccinate their daughters (if not already vaccinated) for protective reasons (p < 0.001), while those whose daughters were already vaccinated understood that vaccination protection was not 100% and that their daughters may still be at risk of getting HPV (p < 0.05). Compared to the UK and Australia, a higher proportion of parents with unvaccinated daughters from the US were worried about the side-effects of the HPV vaccination (US: 60.5%, UK: 36.4%, AUS: 15.4%; p < 0.05), believed that getting the vaccination might be a hassle (US: 21.1%, UK: 0%, AUS: 7.7%; p < 0.05), and that the vaccine was too new (US: 44.7%, UK: 22.7%, AUS: 7.7%; p < 0.05). This study adds to the understanding of how parents may influence vaccination uptake by demonstrating the effect of knowledge and the parental attitudes towards HPV vaccination across three countries.Item Florida physicians' reported use of AFIX-based strategies for human papillomavirus vaccination(Elsevier, 2018-11) Kasting, Monica L.; Christy, Shannon M.; Sutton, Steven K.; Lake, Paige; Malo, Teri L.; Roetzheim, Richard G.; Schechtman, Tommy; Zimet, Gregory D.; Walkosz, Barbara J.; Salmon, Daniel; Kahn, Jessica A.; Giuliano, Anna R.; Vadaparampil, Susan T.; Pediatrics, School of MedicineHPV vaccination rates in Florida are low. To increase rates, the CDC recommends clinics adhere to components of their evidence-based quality improvement program, AFIX (Assessment, Feedback, Incentives, and eXchange of information). We explored factors associated with engaging in HPV-specific AFIX-related activities. In 2016, we conducted a cross-sectional survey of a representative sample of 770 pediatric and family medicine physicians in Florida and assessed vaccination practices, clinic characteristics, and HPV-related knowledge. Data were analyzed in 2017. The primary outcome was whether physicians' clinics engaged in ≥1 AFIX activity. We stratified by physician specialty and developed multivariable models using a backward selection approach. Of the participants in the analytic sample (n = 340), 52% were male, 60% were White of any ethnicity, and 55% were non-Hispanic. Pediatricians and family medicine physicians differed on: years practicing medicine (p < 0.001), HPV-related knowledge (p < 0.001), and VFC provider status (p < 0.001), among others. Only 39% of physicians reported engaging in ≥1 AFIX activity. In the stratified multivariable model for pediatricians, AFIX activity was significantly associated with HPV-related knowledge (aOR = 1.33;95%CI = 1.08–1.63) and provider use of vaccine reminder prompts (aOR = 3.61;95%CI = 1.02–12.77). For family medicine physicians, HPV-related knowledge was significant (aOR = 1.57;95%CI = 1.20–2.05) as was majority race of patient population (non-Hispanic White vs. Other: aOR = 3.02;95%CI = 1.08–8.43), daily patient load (<20 vs. 20–24: aOR = 9.05;95%CI = 2.72–30.10), and vaccine administration to male patients (aOR = 2.98;95%CI = 1.11–8.02). Fewer than half of Florida pediatric and family medicine physicians engaged in any AFIX activities. Future interventions to increase AFIX engagement should focus on implementing and evaluating AFIX activities in groups identified as having low engagement in AFIX activities.Item Genes Regulated by HPV 16 E6 and High Expression of NFX1-123 in Cervical Cancers(Dove Press, 2020-06-26) Chintala, Sreenivasulu; Levan, Justine; Robinson, Kristin; Quist, Kevin; Katzenellenbogen, Rachel A.; Pediatrics, School of MedicinePurpose High-risk human papillomaviruses (HR HPV) cause cervical cancer, and in these cancers, HPV type 16 is the most common HR type. The HR viral oncogenes E6 and E7 partner with cellular proteins to drive cancer and modulate immune pathways; previously, we demonstrated in keratinocytes that HPV 16 E6 and high expression of the endogenous host protein partner NFX1-123 led to the increased expression of multiple genes, including Notch1, secretory leukocyte peptidase inhibitor (SLPI), and retinoic acid early transcript 1G (RAET1G). The present study was conducted to determine if NFX1-123 was highly expressed in cervical cancer and if genes increased by NFX1-123 and 16E6 in keratinocytes were also increased in cervical cancers. Materials and Methods The Cancer Genome Atlas (TCGA) database and The Human Protein Atlas database were used to compare relative mRNA and protein gene expression, respectively, in the normal cervix and cervical cancers. Formalin-fixed paraffin-embedded (FFPE) normal cervix and HPV 16 positive cervical cancer samples were analyzed for relative protein expression by immunohistochemical staining. Protein expression of a subset of regulated genes was quantified by Western blot of HPV positive and negative cell lines. Results Immunohistochemical staining of HPV 16 positive cervical dysplasias and cancers revealed high NFX1-123, Ki67, and Notch1 expression. NFX1 and NFX1L1 mRNA levels were increased in cervical cancers compared to normal cervix in the TCGA database. Fourteen genes previously identified as upregulated in keratinocytes with 16E6 and overexpressed NFX1-123 also had high mRNA expression and selected genes had high protein expression in cervical cancers and cell lines. Conclusion In cervical cancer, NFX1-123 is highly expressed, and 16E6 and NFX1-123 together alter the expression of a wide set of genes. The involvement of these genes in cell proliferation, differentiation, invasion, and metastasis provides further insight into potential ways that HR HPVs promote cancer initiation and maintenance.Item Global Delivery of Human Papillomavirus Vaccines(Elsevier, 2016-02) Wigle, Jannah; Fontenot, Holly B.; Zimet, Gregory D.; Department of Pediatrics, IU School of MedicineWorldwide, cervical cancer is the fourth most common cancer among women, with over half a million women diagnosed with cervical cancer in 2012. Human papillomavirus (HPV) vaccination, if broadly implemented, has the potential to significantly reduce global rates of morbidity and mortality associated with cervical and other HPV-related cancers. Over 100 countries around the world have licensed HPV vaccines. As of February, 2015, there were an estimated 80 national HPV immunization programs and 37 pilot programs, including many implemented in low- and middle-income countries. In this article, global implementation of HPV vaccination programs is discussed, including successes and ongoing challenges. Issues such as vaccine financing and different approaches to HPV vaccine delivery are presented.Item Human papillomavirus (HPV)-induced neoplasia in the urinary bladder: a missing link?(2016) Alexander, Riley E.; Wang, Lisha; Lopez-Beltran, Antonio; Emerson, Robert E.; Montironi, Rodolfo; Pedrosa, Jose A.; Kaimakliotis, Hristos Z.; Koch, Michael O.; Cheng, Liang; Department of Pathology and Laboratory Medicine, IU School of MedicineThe discovery that the role human papillomavirus (HPV) plays in the induction of human cancer represents an important achievement in oncologic research. It has taken on even greater importance since the development of vaccines, which promise the hope of preventing these cancers from ever occurring. Because of these important implications, many have attempted to determine a possible role for the virus in cancers of the urinary bladder-an organ in close anatomic proximity to the primary sites of HPV-induced neoplasia and one which already has an established oncogenic infectious agent in Schistosoma haematobium. Here we review the current literature exploring this possible role in the most common subtype of cancer of the urinary bladder, urothelial carcinoma, and two much more rare histologic subtypes that have well established roles for HPV-induced neoplasia in other anatomic sites-squamous cell carcinoma and adenocarcinoma.Item Human papillomavirus detection in cervical neoplasia attributed to 12 high-risk human papillomavirus genotypes by region(Elsevier, 2016-12) Castellsagué, Xavier; Ault, Kevin A.; Bosch, F. Xavier; Brown, Darron; Cuzick, Jack; Ferris, Daron G.; Jours, Elmar A.; Garland, Suzanne M.; Giuliano, Anna R.; Hernandez-Avila, Mauricio; Huh, Warner; Iversen, Ole-Erik; Kjaer, Susanne K.; Luna, Joaquin; Monsonego, Joseph; Muñoz, Nubia; Myers, Evan; Paavonen, Jorma; Pitisuttihum, Punnee; Steben, Marc; Wheeler, Cosette M.; Perez, Gonzalo; Saah, Alfred; Luxembourg, Alain; Sings, Heather L.; Velicer, Christine; Department of Medicine, IU School of MedicineBackground We estimated the proportion of cervical intraepithelial neoplasia (CIN) cases attributed to 14 HPV types, including quadrivalent (qHPV) (6/11/16/18) and 9-valent (9vHPV) (6/11/16/18/31/33/45/52/58) vaccine types, by region Methods Women ages 15–26 and 24–45 years from 5 regions were enrolled in qHPV vaccine clinical trials. Among 10,706 women (placebo arms), 1539 CIN1, 945 CIN2/3, and 24 adenocarcinoma in situ (AIS) cases were diagnosed by pathology panel consensus. Results Predominant HPV types were 16/51/52/56 (anogenital infection), 16/39/51/52/56 (CIN1), and 16/31/52/58 (CIN2/3). In regions with largest sample sizes, minimal regional variation was observed in 9vHPV type prevalence in CIN1 (~50%) and CIN2/3 (81–85%). Types 31/33/45/52/58 accounted for 25–30% of CIN1 in Latin America and Europe, but 14–18% in North America and Asia. Types 31/33/45/52/58 accounted for 33–38% of CIN2/3 in Latin America (younger women), Europe, and Asia, but 17–18% of CIN2/3 in Latin America (older women) and North America. Non-vaccine HPV types 35/39/51/56/59 had similar or higher prevalence than qHPV types in CIN1 and were attributed to 2–11% of CIN2/3. Conclusions The 9vHPV vaccine could potentially prevent the majority of CIN1-3, irrespective of geographic region. Notwithstanding, non-vaccine types 35/39/51/56/59 may still be responsible for some CIN1, and to a lesser extent CIN2/3.
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