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Item Association between intrauterine device use and endometrial, cervical, and ovarian cancer: an expert review(Elsevier, 2023-08) Minalt, Nicole; Caldwell, Amy; Yedlicka, Grace M.; Joseph, Sophia; Robertson, Sharon E.; Landrum, Lisa M.; Peipert, Jeffrey F.; Obstetrics and Gynecology, School of MedicineThe intrauterine device is one of the most effective forms of contraception. Use of the intrauterine device has increased in the United States over the last 2 decades. Two formulations are commercially available in the United States: the levonorgestrel-releasing intrauterine device and the copper intrauterine device. The levonorgestrel intrauterine device releases progestin, causing endometrial suppression and cervical mucus thickening, whereas the primary mechanism of action of the copper intrauterine device is to create a local inflammatory response to prevent fertilization. Whereas the protective effects of combined hormonal contraception against ovarian and endometrial cancer, and of tubal sterilization against ovarian cancer are generally accepted, less is known about the effects of modern intrauterine devices on the development of gynecologic malignancies. The best evidence for a protective effect of intrauterine device use against cancer incidence pertains to levonorgestrel intrauterine devices and endometrial cancer, although studies suggest that both copper intrauterine devices and levonorgestrel intrauterine devices reduce endometrial cancer risk. This is supported by the proposed dual mechanisms of action including both endometrial suppression and a local inflammatory response. Studies on the relationship between intrauterine device use and ovarian cancer risk show conflicting results, although most data suggest reduced risk of ovarian cancer in intrauterine device users. The proposed biological mechanisms of ovarian cancer reduction (foreign-body inflammatory response, increased pH, antiestrogenic effect, ovulation suppression) vary by type of intrauterine device. Whereas it has been well established that use of copper intrauterine devices confers a lower risk of cervical intraepithelial neoplasms, the effect of levonorgestrel intrauterine device use on cervical cancer remains unclear. Older studies have linked its use to a higher incidence of cervical dysplasia, but more recent literature has found a decrease in cervical cancer with intrauterine device use. Various mechanisms of protection are postulated, including device-related inflammatory response in the endocervical canal and prostaglandin-mediated immunosurveillance. Overall, the available evidence suggests that both levonorgestrel intrauterine devices and copper intrauterine devices reduce gynecologic cancer risk. Whereas there is support for the reduction of endometrial cancer risk with hormonal and copper intrauterine device use, and reduction of cervical cancer risk with copper intrauterine device use, evidence in support of risk reduction with levonorgestrel intrauterine device use for cervical and ovarian cancers is less consistent.Item Cervical cancer data and data systems in limited-resource settings: Challenges and opportunities(Wiley, 2017-07) Drummond, Jennifer L.; Were, Martin C.; Arrossi, Silvina; Wools-Kaloustian, Kara; Medicine, School of MedicineAppropriate collection and use of health information is critical to the planning, scaling up, and improvement of cervical cancer programs. The health information systems implementation landscape is unique to each country; however, systems serving cervical cancer programs in low-resource settings share characteristics that present common challenges. In response, many programs have taken innovative approaches to generating the quality information needed for decision making. Recent advances in health information technology also provide feasible solutions to challenges. This article draws from the experiences of the authors and from current literature to describe outstanding challenges and promising practices in the implementation of cervical cancer data systems, and to make recommendations for next steps. Recommendations include engaging all stakeholders—including providers, program managers, implementing partners, and donors—in promoting national, district, and community information systems; building on existing systems and processes, as well as introducing new technologies; and evolving data collection and data systems as programs advance.Item Cervical cancer metastasis to the brain: A case report and review of literature(Medknow Publications, 2017-08-09) Fetcko, Kaleigh; Gondim, Dibson D.; Bonnin, Jose M.; Dey, Mahua; Neurological Surgery, School of MedicineBackground: Intracranial metastasis from cervical cancer is a rare occurrence. Methods: In this study we describe a case of cervical cancer metastasis to the brain and perform an extensive review of literature from 1956 to 2016, to characterize clearly the clinical presentation, treatment options, molecular markers, targeted therapies, and survival of patients with this condition. Results: An elderly woman with history of cervical cancer in remission, presented 2 years later with a right temporo-parietal tumor, which was treated with surgery and subsequent stereotactic radiosurgery (SRS) to the resection cavity. She then returned 5 months later with a second solitary right lesion; she again underwent surgery and SRS to the resection cavity with no signs of recurrence 6 months later. According to the reviewed literature, the most common clinical presentation included females with median age of 48 years; presenting symptoms such as headache, weakness/hemiplegia/hemiparesis, seizure, and altered mental status (AMS)/confusion; multiple lesions mostly supratentorially located; poorly differentiated squamous cell carcinoma; and additional recurrences at other sites. The best approach to treatment is a multimodal plan, consisting of SRS or whole brain radiation therapy (WBRT) for solitary brain metastases followed by chemotherapy for systemic disease, surgery and WBRT for solitary brain lesions without systemic disease, and SRS or WBRT followed by chemotherapy for palliative care. The overall prognosis is poor with a mean and median survival time from diagnosis of brain metastasis of 7 and 4.6 months, respectively. Conclusion: Future efforts through large prospective randomized trials are warranted to better describe the clinical presentation and identify more effective treatment plans.Item County-level correlates of completed HPV vaccination in Indiana(Elsevier, 2023-09) Enujioke, Sharon C.; Shedd-Steele, Rivienne; Daggy, Joanne; Burney, Heather N.; Head, Katharine J.; Kasting, Monica L.; Zimet, Gregory; Communication Studies, School of Liberal ArtsThe Healthy People 2030 goal is for 80% of all adolescents to complete their HPV vaccination series. Per the 2021, National Immunization Survey-Teen (NIS-Teen), 61.7% of adolescents have completed the series, and Indiana lags below the national average (55.2%). The present study estimated the 2-dose HPV vaccine series completion rates across Indiana counties among individuals aged 9–14 years who received their first dose of vaccine and determined what factors were associated with series completion at the county level. The association of county-level sociodemographic and health measures with series completion was also examined. Data were extracted from the Indiana Immunization Information System (IIS), administered by the Indiana Department of Health. All vaccine providers are required to report all immunizations to the system for any patient under age 19 years. All Indiana children ages 9–14 years at the time of first dose who had initiated HPV vaccination in 2017 or 2018 were included. Two-dose series completion was evaluated through October of 2020, allowing a minimum gap of 22 months from first dose administration. All statistical analyses were conducted at the county-level. The Indiana HPV vaccination series completion rate among individuals that received the first dose was on average 73% across counties, ranging from 55.7% to 90.4%. Higher series completion was positively associated with primary care providers per capita, participation in mammography screening among Medicare enrollees, median household income, life expectancy, percentage of residents with some college, percentage of adults up-to-date with colonoscopy screening, and percentage of adults with flu vaccine. There was wide variability in series completion across Indiana counties. HPV series completion was associated with county-level sociodemographic and health measures, particularly variables reflecting difficulties with access to care and lack of financial resources.Item The effect of distance from cancer facility on advanced clinical stage at diagnosis in patients with cervical cancer(Elsevier, 2020) Steele, Ethan M.; Robertson, Sharon E.; Holmes, Jordan A.; Radiation Oncology, School of MedicinePurpose/Objectives In the United States, cervical cancer remains a significant cause of morbidity and mortality. The effect of distance has a complicated relationship with disease characteristics and outcomes in other cancers. The purpose of this study is to investigate the relationship between distance from cancer facility on clinical stage at diagnosis in women with cervical cancer. Materials/Methods Data were obtained from the National Cancer Database which include patient demographics, disease characteristics, and treatment details. Persons diagnosed with cervical cancer from 2004 to 2015 were included. Subjects were excluded if they had missing information, variant histology, or lived >1,000 miles from their facility resulting in 51,413 persons. Disease was classified as localized (stage 1a-2a) or advanced (stage 2b-4b). Univariate comparisons were performed using analysis of variance and chi-square test. Multivariable logistic regression was used to investigate the effect of distance quartiles on advanced stage while adjusting for other significant variables. Results Mean age was 51.0 years, 16.9% of women were black, 14.7% were Hispanic, 45.0% had private insurance, and 10.7% were uninsured. Overall, 50.9% of women presented with advanced disease. In multivariable analysis, greater distance demonstrated a stepwise risk reduction of advanced disease where those in the farthest quartile had odds ratio of 0.73 (p<0.001) relative to the closest. Additionally, age, race, income, and insurance status significantly affected risk of advanced disease. Conclusions Distance from cancer facility resulted in lower risk of advanced stage disease at diagnosis. Additional research could elucidate the nuanced relationship between distance, disease characteristics and outcomes in cervical cancer.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 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.Item Increasing Efforts to Reduce Cervical Cancer Through State-Level Comprehensive Cancer Control Planning(2015-07) Meyerson, Beth E.; Zimet, Gregory D.; Multani, Gurprit S.; Levell, Caleb; Lawrence, Carrie A.; Smith, Jennifer S.; Department of Medicine, IU School of MedicineReducing cervical cancer disparities in the United States requires intentional focus on structural barriers such as systems and policy that impact access to human papillomavirus (HPV) vaccination, cervical cancer screening, and treatment. Such changes are difficult and often politicized. State comprehensive cancer control (CCC) plans are vehicles that, if designed well, can help build collective focus on structural changes. Study objectives were to identify the prioritization of cervical cancer in state CCC plans, the conceptualization of HPV within these plans, and the focus of plans on structural changes to reduce cervical cancer disparities. Data were gathered by systematic content analysis of CCC plans from 50 states and the District of Columbia from February–June 2014 for evidence of cervical cancer prioritization, conceptualization of HPV, and focus on structural barriers to cervical cancer vaccination, screening or treatment. Findings indicate that prioritization of cervical cancer within state CCC plans may not be a strong indicator of state efforts to reduce screening and treatment disparities. While a majority of plans reflected scientific evidence that HPV causes cervical and other cancers, they did not focus on structural elements impacting access to evidence-based interventions. Opportunities exist to improve state CCC plans by increasing their focus on structural interventions that impact cervical cancer prevention, detection, and treatment, particularly for the 41% of plans ending in 2015 and the 31% ending between 2016 and 2020. Future studies should focus on the use of policy tools in state CCC plans and their application to cervical cancer prevention and treatment.Item Invasive cervical cancers in the United States, Botswana and Kenya: HPV type distribution and health policy implications(BioMed Central, 2016) Ermel, Aaron; Qadadri, Brahim; Tong, Yan; Orang’o, Omenge; Macharia, Benson; Ramogola-Masire, Doreen; Zetola, Nicola M.; Brown, Darron R.; Department of Medicine, School of MedicineBackground More deaths occur in African women from invasive cervical cancer (ICC) than from any other malignancy. ICC is caused by infection with oncogenic types of human papillomavirus (HPV). Co-infection with the human immunodeficiency virus (HIV) accelerates the natural history of ICC, and may influence the HPV type distribution. Because HPV vaccines are available, this malignancy is theoretically preventable, but the vaccines are largely type-specific in protection against infection. Data on specific HPV types causing ICC in African women is limited, and many studies utilized swab samples rather than actual cancer tissue. A previous study using archived, ICC tissue from women in Botswana identified an unusual HPV type distribution. A similar study was therefore performed in a second sub-Saharan country to provide additional information on the HPV type distribution in ICC. Methods Archived, formalin-fixed, paraffin-embedded ICCs were acquired from women in the United States, Kenya, or Botswana. DNA was extracted and HPV genotyping performed by Roche Linear Array. HIV sequences were identified in ICCs by PCR. Results HPV types 16 or 18 (HPV 16/18) were identified in 93.5 % of HPV-positive ICCs from the U.S., 93.8 % from Kenya, and 61.8 % from Botswana (p < 0.0001). Non-HPV 16/18 types were detected in 10.9 % of HPV-positive cancers from the U.S., 17.2 % from Kenya, and 47.8 % from Botswana (p < 0.0001). HIV was detected in 2.2, 31.5, and 32.4 % from ICCs from the U.S., Kenya, or Botswana, respectively (p = 0.0002). The distribution of HPV types was not significantly different between HIVinfected or HIV-uninfected women. The percentages of ICCs theoretically covered by the bivalent/quadrivalent HPV vaccines were 93.5, 93.9, and 61.8 % from the U.S., Kenya and Botswana, respectively, and increased to 100, 98, and 77.8 % for the nanovalent vaccine. Conclusions HPV 16/18 caused most ICCs from the U.S. and western Kenya. Fewer ICCs contained HPV 16/18 in Botswana. HIV co-infection did not influence the HPV type distribution in ICCs from African women from the two countries. Available HPV vaccines should provide protection against most ICCs in the U.S. and Kenya. The recently developed nanovalent vaccine may be more suitable for countries where non-HPV 16/18 types are frequently detected in ICC.Item Patient knowledge and attitudes toward cervical cancer screening after the 2012 screening guidelines(Elsevier, 2018) Clay, Jayanti M.; Daggy, Joanne K.; Fluellen, Sunetris; Edmonds, Brownsyne Tucker; Obstetrics and Gynecology, School of MedicineObjective To assess women’s attitudes and preferences related to recent changes in cervical cancer screening guidelines. Methods We distributed 380 surveys in three University based and Community clinics. Study participants anonymously completed surveys, which included questions related to demographics, cervical cancer, screening practices, risk perception and attitudes towards changing practices. Results 315 women agreed to participate (83%). 60% (185/310) of participants had some college education or higher and 12% (36/305) worked in the medical field. On average, participants answered 4.1 (SD = 1.3) of the 8 knowledge questions correctly. Knowledge scores significantly increased with education level (Kruskal-Wallis test p-value < 0.001). The majority (72%, n = 228) reported that they should be screened annually, and that screening should be initiated with the onset of sexual activity (63%, n = 197). Participants that were more knowledgeable of current screening practices were more comfortable extending screening intervals (Kruskal-Wallis test p < 0.001). Conclusion Even among a relatively highly educated population of women, participants had limited knowledge of cervical cancer and current screening guidelines. Many participants reported discomfort with less frequent screening intervals. Practice implications This study supports the need for improvement in cervical cancer prevention education especially with regards to the new screening guidelines.