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Item Are Boys Ready for Human Papillomavirus Vaccine? A National Study of Boys in Malaysia(Wolters Kluwer, 2019-09) Wong, L. P.; Alias, H.; Yusoff, R. N. A. R. M.; Sam, I. C.; Zimet, G. D.; Pediatrics, School of MedicineBackground The aim of this study was to investigate factors associated with the willingness of boys to accept the human papillomavirus (HPV) vaccine. Methods A nationwide cross-sectional survey among Secondary One male students in Malaysia. Results Among 2823 respondents, knowledge about HPV infection and the HPV vaccine was extremely poor. The mean total knowledge score was only 3.17 (SD ± 2.14), out of a possible score of 10. The majority of respondents were unaware that vaccinating boys can help protect girls against HPV infection (81.6%), and HPV is a sexually transmitted infection (70.1%). Many had the misconception that only females get HPV (78.9%). In multivariable analysis, the factors associated with the intention to receive the HPV vaccination were: agreeing boys need to be vaccinated against HPV infection (odds ratio [OR], 2.05; 95% confidence interval [CI], 1.57–2.68), perceiving their parents might allow them to get the HPV vaccine (OR, 1.66; 95% CI, 1.18–2.34), perceived susceptibility to HPV infection (OR, 1.63; 95% CI, 1.06–2.52), and attending a rural school (OR, 1.49; 95% CI, 1.14–1.95). Conclusions Public health educational programs that are focused and tailored on parents consenting to HPV vaccination for boys at a young age can be useful in improving HPV vaccination rates among boys. There is also a pressing need to educate boys about the benefits of HPV vaccination in males and about HPV disease susceptibility to facilitate adoption of the HPV vaccine by young adults in the future.Item Attitudes toward Adolescent HPV Vaccination after the COVID-19 Pandemic: A National Survey of Mothers(MDPI, 2024-08-28) Glauberman, Gary; Liebermann, Erica; Kornides, Melanie L.; Matsunaga, Masako; Lim, Eunjung; Zimet, Gregory; Fontenot, Holly B.; Pediatrics, School of MedicineIn the United States, vaccination rates for many routinely recommended vaccines have recovered to pre-pandemic levels, yet human papillomavirus (HPV) vaccination rates still lag pre-pandemic levels. This study sought to uncover the potential effects of the pandemic on attitudes about the HPV vaccine, and factors associated with changes in attitudes. We conducted a national survey (n = 3968) of U.S. mothers with children aged 9-17 years. Outcome variables measured changes in attitude toward the HPV vaccine following the pandemic. Two logistic regression models identified predictors of (1) those who did not have attitude changes (always negative vs. always positive), and (2) those who reported attitude changes (change to negative vs. change to positive). Attitudes toward the HPV vaccine remained unchanged in 78.9% of participants (58.1% positive, 20.8% negative). Of the 21.1% reporting changed attitudes, 9.6% changed to positive and 11.5% to negative. Those reporting changing to a negative attitude had a greater odds of reporting conservative political views, and being unsure/undecided about vaccinating their child against HPV compared to those who reported changing to a positive attitude. Targeted strategies are needed to address erosion in confidence in the HPV vaccine and other vaccines resulting from mis- and disinformation associated with the COVID-19 pandemic and future pandemics.Item Attitudinal Correlates of HPV Vaccination in College Women(SAGE, 2022) Kasting, Monica L.; Christy, Shannon M.; Stout, Madison E.; Zimet, Gregory D.; Mosher, Catherine E.This study examined associations between general attitudes toward seeking medical care, attitudes about vaccines/fear of shots, and human papillomavirus (HPV) vaccine uptake and intentions in college women. Hypothesized associations were framed by the Theory of Planned Behavior (TPB). Participants (N = 330, mean age = 18.9 years, 75% White) completed a one-time survey. The majority (61%; n = 201) had received ≥1 HPV vaccine dose. Hierarchical logistic regression examined relationships between attitudes and vaccine uptake. Pearson correlation coefficients and Kruskal-Wallis tests examined associations between attitudes and vaccine intentions. Results were partially consistent with the TPB. In the final model, perceived benefits, but not fear of shots, were associated with vaccine uptake. Among the unvaccinated, perceived benefits, but not fear of shots, were associated with vaccine intentions. Provider recommendation was the strongest predictor of vaccine uptake. Findings suggest interventions incorporating discussion of perceived benefits and provider recommendation may improve HPV vaccine receipt among college women.Item Awareness data on cervical cancer among females of rural and urban areas of Haryana, India(Elsevier, 2024-02-07) Yadav, Ritu; Chauhan, Meenakshi B.; Yadav, Chetna; Ranga, Shalu; Ahuja, Parul; Tanwar, Mukesh; Balhara, Nikita; Kadian, Lokesh; Chauhan, Preeti; Tanwar, Neha; Ahlawat, Chavi; Medicine, School of MedicineA cross-sectional study was done to assess the degree of current awareness and behaviors about cervical cancer among females in urban and rural areas of North India. This survey was conducted on one thousand females (500 rural and 500 urban). A well-structured questionnaire was designed to collect information about participants’ knowledge on cancer of cervix uteri such as age, height and weight measurements, marital status, menstrual status, personal hygiene, age at menarche, sexual history, pregnancy and abortion history, use of contraceptive pills for birth-control, smoking, alcohol consumption, and other relevant information. The data was collected by conducting face-to-face interviews after obtaining the verbal consent of the participants. The data has the potential to reduce disease burden by spreading awareness about symptoms and risk factors of cervical cancer as well as implementation of effective early screening strategies.Item Comparison of Xpert® HPV and Hybrid Capture® 2 DNA Test™ for detection of high-risk HPV infection in cervical atypical squamous cells of undetermined significance(Elsevier, 2017-03) Rabaan, Ali A.; Taylor, Donald R.; Dawamneh, Mohammed F.; Al-Tawfiq, Jaffar A.; Department of Medicine, School of MedicineThis study compares Xpert® HPV and Hybrid Capture® 2 High-Risk HPV DNA Test™ (hc2) for the detection of high-risk HPV infection in cervical smears. Papanicolaou smears with atypical squamous cells of undetermined significance (ASC-US) constituted the study specimens. Of the 168 ASC-US samples, 134 (79.8%) were from Saudi patients. The hc2 test was positive in 33 (19.6%) of the total patients, 20% among Saudi patients, and 17.6% among non-Saudi patients. Xpert® HPV produced positive results in 30 (17.8%) of the samples. The overall concordance rate between the two tests was 98.2%, and the positive concordance rate was 91%. There were three samples tested positive by hc2 that tested negative by Xpert® HPV. HPV 16, HPV 18/45 and HPV other types were the most common types. Both tests have a reasonable positive concordance rate, although hc2 detected more cases than Xpert® HPV. Xpert® HPV provides a viable alternative to the hc2 test with similar detection results for samples with ASC-US.Item Conserved Residues in Murine Papillomavirus E2 Regulate the Viral Life Cycle(2024-12) Gonzalez, Jessica Kay; Androphy, Elliot J.; Dong, X. Charlie; Katzenellenbogen, Rachel; Robinson, ChristopherPapillomaviruses (PVs) are small, non-enveloped DNA viruses that infect the stratified epithelia. Once an infection is initiated, the virus must successfully navigate the three stages of its life cycle: establishment, maintenance, and vegetative amplification. A major mechanism of regulating this viral program is post-translational modification on the viral E2 protein, which is responsible for orchestrating viral transcription, replication, and genome partitioning. The hypothesis underscoring this work is that residues in E2 are highly conserved across PV types because they serve some structural or functional purpose for the virus. A targeted mutant library was generated in E2 from murine papillomavirus (MmuPV1) to investigate conserved residues that have been shown to be post-translationally modified in the E2 of other PVs, including BPV-1 and high-risk HPV-31. In the transactivation domain (TAD) tyrosine 102 and the lysine 112/113 motif were modified to their constitutively modified (phosphorylated and acetylated, respectively) or unmodified states, while cysteine 307 in the DNA binding and dimerization domain (DBD) was mutated to a less-reactive serine or DNA binding defective phenylalanine mutant. We characterized how mutation at each of these conserved sites alters E2 function using a battery of in vitro assays to assess for transcription and replication ability. We also studied how each mutant contributes to disease progression using an immunocompromised mouse model assessing cutaneous disease. We demonstrate that mutants which fail to replicate transiently in vitro will also fail to induce proliferative wart formation, establishing a predictive link between in vitro and in vivo experiments. Taken together, our findings suggest that modifications on conserved residues in E2 act as molecular switches that regulate E2 activity throughout the cellular and viral life cycle.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 East Africa Consortium for human papillomavirus and cervical cancer in women living with HIV/AIDS(Taylor & Francis, 2022) Tong, Y.; Orang’o, E.; Nakalembe, M.; Tonui, P.; Itsura, P.; Muthoka, K.; Titus, M.; Kiptoo, S.; Mwangi, A.; Ong’echa, J.; Tonui, R.; Odongo, B.; Mpamani, C.; Rosen, B.; Moormann, A.; Cu-Uvin, S.; Bailey, J.A.; Oduor, C.I.; Ermel, A.; Yiannoutsos, C.; Musick, B.; Sang, E.; Ngeresa, A.; Banturaki, G.; Kiragga, A.; Zhang, J.; Song, Y.; Chintala, S.; Katzenellenbogen, R.; Loehrer, P.; Brown, D.R.; Biostatistics and Health Data Science, School of MedicineThe East Africa Consortium was formed to study the epidemiology of human papillomavirus (HPV) infections and cervical cancer and the influence of human immunodeficiency virus (HIV) infection on HPV and cervical cancer, and to encourage collaborations between researchers in North America and East African countries. To date, studies have led to a better understanding of the influence of HIV infection on the detection and persistence of oncogenic HPV, the effects of dietary aflatoxin on the persistence of HPV, the benefits of antiretroviral therapy on HPV persistence, and the differences in HPV detections among HIV-infected and HIV-uninfected women undergoing treatment for cervical dysplasia by either cryotherapy or LEEP. It will now be determined how HPV testing fits into cervical cancer screening programs in Kenya and Uganda, how aflatoxin influences immunological control of HIV, how HPV alters certain genes involved in the growth of tumours in HIV-infected women. Although there have been challenges in performing this research, with time, this work should help to reduce the burden of cervical cancer and other cancers related to HIV infection in people living in sub-Saharan Africa, as well as optimized processes to better facilitate research as well as patient autonomy and safety. KEY MESSAGESThe East Africa Consortium was formed to study the epidemiology of human papillomavirus (HPV) infections and cervical cancer and the influence of human immunodeficiency virus (HIV) infection on HPV and cervical cancer.Collaborations have been established between researchers in North America and East African countries for these studies.Studies have led to a better understanding of the influence of HIV infection on the detection and persistence of oncogenic HPV, the effects of dietary aflatoxin on HPV detection, the benefits of antiretroviral therapy on HPV persistence, and the differences in HPV detections among HIV-infected and HIV-uninfected women undergoing treatment for cervical dysplasia by either cryotherapy or LEEP.Item An Educational Intervention to Improve HPV Vaccination: A Cluster Randomized Trial(AAP, 2019-01) Dixon, Brian E.; Zimet, Gregory D.; Xiao, Shan; Tu, Wanzhu; Lindsay, Brianna; Church, Abby; Downs, Stephen M.; Epidemiology, School of Public HealthBackground: Human Papillomavirus (HPV) infection can lead to serious health issues and remains the most common sexually transmitted infection. Despite availability of effective vaccines, HPV vaccination rates are suboptimal. Methods: In a cluster randomized trial, an intervention targeting parents of adolescents (11-17 years) eligible for a dose of HPV vaccine was tested in pediatric clinics part of an urban health system. Parents watched a digital video outlining the risks and benefits of vaccine using a tablet in the exam room. The primary outcome was change in HPV vaccine status two weeks after the clinic visit. An intention to treat analysis for the primary outcome utilized generalized estimating equations to accommodate the potential cluster effect of clinics. Results: A total of 1596 eligible adolescents were observed during the 7-month trial. One-third of adolescents visited an intervention clinic. Adolescents who attended an intervention clinic were more likely to be younger (11-12 years) than those who attended a control clinic (72.4% versus 49.8%; p<0.001). No differences in race or gender were observed. The proportion of adolescents with an observed change in vaccine status was higher for those attending an intervention clinic (64.8%) versus control clinic (50.1%; OR=1.82; 95% CI=1.47-2.25; p<0.001). Adolescents whose parents watched the video had a three times greater odds of receiving a dose of the HPV vaccine (78.0%; OR=3.07; 95% CI=1.47-6.42; p=0.003). Conclusions: Educational interventions delivered within a clinical setting hold promise to improve vaccination behaviors.Item Effects of Caffeine, a DNA Damage Response Inhibitor, on Papillomavirus Genome Replication(MDPI, 2022-11-05) Kanginakudru, Sriramana; Gilson, Timra; Jose, Leny; Androphy, Elliot J.; Dermatology, School of MedicineEpidemiological studies have revealed that caffeinated coffee imparts a reduced risk of oropharyngeal cancer, of which human papillomavirus (HPV) is one of the causative agents. Caffeine is a known inhibitor of the DNA damage response (DDR) pathway. We sought to test the effects of caffeine on the early replication of the HPV31 virus. It has been reported that the inhibition of several factors necessary for the DDR during the differentiation-dependent stage of HPV block genome amplification, while the HPV genome maintenance replication was unaffected. We first studied the effects of caffeine in the earliest stages of viral infection. Using pseudo-virions (PsV) expressing an m-Cherry reporter gene and quasi-virions (QsV) containing HPV31 genomes to mediate the infection, we found no evidence that caffeine impeded the viral entry; however, the infected cells displayed a reduced HPV copy number. In contrast, caffeine exposure increased the copy number of HPV31 episomes in the transient transfection assays and in the CIN612E cells that stably maintain viral episomes. There was a concomitant increase in the steady state levels of the HPV31 E1 and E2 transcripts, along with increased E2 loading at the viral origin of replication (ori). These results suggest that the caffeine-mediated inhibition of the DDR reduces viral genome replication in the early stage of infection, in contrast to the maintenance stage, in which the inhibition of the DDR may lead to an increase in viral amplicon replication.