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The Centers for Disease Control and Prevention (CDC) recommends recombinant zoster vaccination (RZV) for adults ≥ 50 years to prevent herpes zoster (HZ) and its sequelae. Initially, no distinct recommendation was made for immunocompromised adults, who experience higher HZ rates and more severe outcomes. We characterized receipt of first RZV dose (initiation) and both doses (completion) over time, and the impact of immune function on RZV uptake among adults aged 50-64 years in the United States.We identified RZV claims from the IBM MarketScan database between 1/1/2018 and 12/31/2019. We characterized immunocompromised enrollees as having malignancy, HIV, solid organ transplant, primary immunosuppression, or medication-induced immunosuppression using inpatient, outpatient, and prescription claims in the 6 months prior to study start. We evaluated patterns of vaccine uptake by demographic and healthcare access characteristics and immune status.The cumulative incidence of RZV initiation during the study period was 10.0%. Incidence increased with age and number of medical office visits, and was higher among women, urban residents, high-deductible insurance beneficiaries, and those who were immunocompromised compared to immunocompetent. Among immunocompromised adults, RZV initiation was highest among those with HIV and primary immunodeficiencies. Of those who initiated RZV, 89.5% received both doses. RZV completion was highest among those who received the first dose at a pharmacy. Most enrollees (88.6%) who completed RZV vaccination did so within the recommended dosing schedule.RZV uptake was low in the two years since the CDC recommendation, and differed by demographic, healthcare access, and clinical characteristics. Initiation rates were higher among immunocompromised adults compared to immunocompetent adults, despite no CDC recommendation for vaccination in these groups during the study period. The CDC has since recommended RZV for immunocompromised individuals, and our findings may inform efforts to increase RZV uptake in individuals at higher risk of severe disease.

Cervical cancer is the leading cause of cancer mortality among Malawian women, despite being preventable through screening and preventive therapy. In 2004, Malawi implemented a national screening program, using visual inspection with acetic acid (VIA) and cryotherapy, but its success has been limited due to equipment and human resources challenges. Since the development of that program, new technologies for screening and treatment that are less resource-intensive and more scalable have become available. GeneXpert systems provide fast, accurate HPV results and are increasingly available in low-income countries. Self-collection for human papillomavirus (HPV) testing is a validated method for screening and improves uptake. Thermal ablation provides an alternative ablative treatment that is simpler to use than cryotherapy and can be performed with portable devices. Meanwhile, urine HPV testing methods provide promising options for primary screening. We designed a single-arm prospective study to investigate a novel HPV screen-triage-treat strategy among 1250 women in Lilongwe, Malawi. Our proposed strategy consists of (1) Xpert HPV testing of self-collected samples, (2) VIA and colposcopy for HPV-positive women, and (3) thermal ablation for HPV-positive/ablation-eligible women. We will collect cervical biopsies, Pap smears, and endocervical samples to validate the HPV results and VIA/colposcopy findings against endpoints of high-grade cervical intraepithelial neoplasia or cancer (CIN2+). We will evaluate same-day completion of our algorithm, its performance in triaging women for treatment, and 24-week treatment efficacy of thermal ablation. We will also explore the performance of HPV and methylation tests in urine samples, as compared to provider- and self-collected cervicovaginal samples.

Overuse of clinical preventive services increases healthcare costs and may deprive underserved patients of necessary care. Up to 45% of cervical cancer screening is overuse. We conducted a systematic review of correlates of overuse of cervical cancer screening and interventions to reduce overuse. The search identified 25 studies (20 observational; 5 intervention). Correlates varied by the type of overuse measured (i.e., too frequent, before/after recommended age to start or stop screening, after hysterectomy), the most common correlates of overuse related to patient age (n = 7), OBGYN practice or provider (n = 5), location (n = 4), and marital status (n = 4). Six observational studies reported a decrease in overuse over time. Screening overuse decreased in all intervention studies, which used before-after designs with no control or comparison groups. Observational studies suggest potential targets for de-escalating overuse. Randomized clinical trials are needed to establish best practices for reducing overuse.

ASCCP cervical cancer screening guidelines recommend triaging high-risk human papillomavirus (hrHPV) positive women with cytology and genotyping, but cytology is often unavailable in resource-limited areas. We compared the long-term risk of cervical cancer and precancers among type-specific hrHPV-positive women triaged by viral load to cytology and visual inspection with acetic acid (VIA).A cohort of 1742 Chinese women was screened with cytology, VIA, and Hybrid Capture 2 (HC2) test and followed for ten years. All HC2-positive samples were genotyped. Viral load was measured by HC2 relative light units/cutoff (RLU/CO). Ten-year cumulative incidence rate (CIR) of cervical intraepithelial neoplasia grade 2 or worse (CIN2+) for type-specific hrHPV viral load was estimated using Kaplan-Meier methods.Baseline hrHPV viral load stratified by specific genotypes was positively correlated with prevalent cytological lesions. Ten-year CIR of CIN2+ was associated with cytological lesions and viral load. Among HPV 16/18-positive women, ten-year CIR of CIN2+ was high, even with normal cytology (15.3%), normal VIA (32.4%), viral load with RLU/CO10 (23.6%) or RLU/CO100 (33.8%). Among non-16/18 hrHPV positive women, ten-year CIR of CIN2+ was significantly stratified by cytology grade of atypical squamous cell of undetermined significance or higher (2.0% VS. 34.6%), viral load cutoffs at 10 RLU/CO (5.1% VS. 27.2%), at 100 RLU/CO (11.0% VS. 35.5%), but not by VIA (19.1% VS. 19.0%).Our findings support the guidelines in referring all HPV16/18 positive women to colposcopy and suggest triaging non-16/18 hrHPV positive women using viral loads in resource-limited areas where cytology screening was inaccessible.

Purpose The purpose of the study was to describe the patterns of use of universally recommended adolescent vaccines in the United States. Methods We identified 11-year-olds using the MarketScan insurance claims database (2009–2014). Human papillomavirus (HPV), tetanus-diphtheria-acellular pertussis (Tdap), and meningococcal (MenACWY) vaccination claims were identified using diagnosis and procedure codes. Generalized linear models estimated vaccination incidence rates and correlates of adolescent vaccination and timely vaccination. Results Among 1,691,223 adolescents, receipt of Tdap (52.1%) and MenACWY (45.8%) vaccinations exceeded receipt of HPV vaccination (18.4%). While both sexes had similar Tdap and MenACWY vaccination proportions, girls received HPV vaccination more frequently than boys (21.9% vs. 15.1%). Adolescents received HPV vaccination later (mean age: 11.8 years) than Tdap or MenACWY vaccination (mean age: 11.2 years for both). Half of vaccinated adolescents received Tdap and MenACWY vaccination only; however, coadministration with HPV vaccine increased with birth cohort. Western adolescents had the highest incidence rates of HPV vaccination, and Southern adolescents had the lowest. Rural adolescents were less likely than urban adolescents to receive each vaccination except in the Northeast, where they were more likely to receive HPV vaccination (incidence rate ratio: 1.09, 95% confidence interval: 1.2005–1.13). Timely HPV vaccination was associated with female sex, urbanicity, Western residence, and later birth cohort. Conclusions HPV vaccination occurred later than Tdap or MenACWY vaccination and was less frequent in boys and rural adolescents. Girls, Western and urban residents, and younger birth cohorts were more likely to receive timely HPV vaccination. Vaccine coadministration increased over time and may encourage timely and complete vaccination coverage.

Introduction Multipurpose vaccines (MPVs) could be formulated to prevent multiple sexually transmitted infections simultaneously. Little is known about acceptability of MPVs among vaccine health care providers (HCPs) or mothers of adolescent girls. Methods 151 adolescent vaccine providers and 118 mothers of adolescent girls aged 9–14 were recruited from five geographically-diverse countries: Argentina, Malaysia, South Africa, South Korea, and Spain. We assessed providers’ preferences for single-purpose human papillomavirus (HPV) vaccine versus MPVs (including HPV+herpes simplex virus (HSV)−2, HPV+HIV, or HPV+HSV-2+HIV) via quantitative surveys. Maternal MPV attitudes were assessed in four focus group discussions (FGDs) in each country. Results Most providers preferred MPVs over single-purpose HPV vaccination, with preference ranging from 61% in Malaysia to 96% in South Africa. HPV+HSV-2+HIV was the most preferred MPV formulation (56–82%). Overall, 53% of the mothers preferred MPVs over single-purpose HPV vaccines, with strongest support in South Africa (90%) and lowest support in South Korea (29%). Convenience and trust in the health care system were commonly-cited reasons for MPV acceptability. Safety and efficacy concerns were common barriers to accepting MPVs, though specific concerns differed by country. Across FGDs, additional safety and efficacy information on MPVs were requested, particularly from trusted sources like HCPs. Conclusions Though maternal acceptability of MPVs varied by country, MPV acceptability would be enhanced by having HCPs provide parents with additional MPV vaccine safety and efficacy information. While most providers preferred MPVs, future health behavior research should identify acceptability barriers, and targeted provider interventions should equip providers to improve vaccination discussions with parents., Highlights • We gauged acceptance of a multipurpose vaccine (MPV) concept to prevent HPV and STIs. • Most vaccine providers were willing to administer an MPV for HPV, HSV-2, and HIV. • Mothers of teen girls desired safety and efficacy evidence before accepting MPVs. • In mothers, MPV acceptability differed by region and daughter's vaccination history.

Background Urine testing for high-risk human papillomavirus (HR-HPV) detection could provide a non-invasive, simple method for cervical cancer screening. Objectives We examined whether HR-HPV detection is affected by urine collection time, portion of urine stream, or urine fraction tested, and assessed the performance of HR-HPV testing in urine for detection of cervical intraepithelial neoplasia grade II or worse (CIN2+). Study design A total of 37 female colposcopy clinic attendees, ≥30 years, provided three urine samples: “first void” urine collected at home, and “initial stream” and “mid-stream” urine samples collected at the clinic later in the day. Self- and physician-collected brush specimens were obtained at the same clinic visit. Colposcopy was performed and directed biopsies obtained if clinically indicated. For each urine sample, HR-HPV DNA testing was conducted for unfractionated, pellet, and supernatant fractions using the Trovagene test. HR-HPV mRNA testing was performed on brush specimens using the Aptima HPV assay. Results HR-HPV prevalence was similar in unfractionated and pellet fractions of all urine samples. For supernatant urine fractions, HR-HPV prevalence appeared lower in mid-stream urine (56.8%[40.8–72.7%]) than in initial stream urine (75.7%[61.9–89.5%]). Sensitivity of CIN2+ detection was identical for initial stream urine and physician-collected cervical specimen (89.9%[95%CI = 62.7–99.6%]), and similar to self-collected vaginal specimen (79.1%[48.1–96.6%]). Conclusion This is among the first studies to compare methodologies for collection and processing of urine for HR-HPV detection. HR-HPV prevalence was similar in first void and initial stream urine, and was highly sensitive for CIN2+ detection. Additional research in a larger and general screening population is needed.

To compare the consistency of HPV genotype and viral loads among different sites within the female genital tract, and to correlate these with clinical outcomes.2646 previously unscreened rural women were enrolled in this population-based, cross-sectional study between May 2006 and April 2007. Physician-collected samples from lower vagina, upper vagina, cervix, and one self-collected sample were taken from each woman. Viral load was assessed by HC2 using the relative light unit/cutoff ratio (RLU/CO), and HPV genotyping was tested by Linear Array.The low risk HPV positive rate was highest in lower vagina samples and lowest in cervix samples. Overall kappa values of high risk HPV types between various anatomic sampling sites showed substantial or almost perfect agreement among women with normal pathology, CIN1, and CIN2+. In the CIN2+ population, high risk HPV viral load for cervix samples (557.25 RLU/CO) were much higher than upper vagina samples (96.43 RLU/CO, P0.001), lower vagina samples (36.51 RLU/CO, P0.001), and self-collected (206.83RLU/CO, P=0.003) samples.Although the distribution of high risk HPV genotypes was fairly equivalent across different genital sites, particularly for CIN2+ lesions, viral loads were largely variable. The findings may affect the cervical cancer screening methods using self-collected samples, particularly in resource-challenged areas.

Objective Hispanic women in Texas have among the highest rates of cervical cancer incidence and mortality in the country. Increasing regular Papanicolaou test screening and HPV vaccination are crucial to reduce the burden of cervical cancer among Hispanics. This paper presents lessons learned from community-based cervical cancer control programs for Hispanics and highlights effective intervention programs, methods and strategies. Methods We reviewed and summarized cervical cancer control efforts targeting Hispanic women, focusing on interventions developed by researchers at the University of Texas, School of Public Health. We identified commonalities across programs, highlighted effective methods, and summarized lessons learned to help guide future intervention efforts. Results Community–academic partnerships were fundamental in all steps of program development and implementation. Programs reviewed addressed psychosocial, cultural, and access barriers to cervical cancer control among low-income Hispanic women. Intervention approaches included lay health worker (LHW) and navigation models and used print media, interactive tailored media, photonovellas, client reminders, one-on-one and group education sessions. Conclusions Small media materials combined with LHW and navigation approaches were effective in delivering Pap test screening and HPV vaccination messages and in linking women to services. Common theoretical methods included in these approaches were modeling, verbal persuasion, and facilitating access. Adaptation of programs to an urban environment revealed that intensive navigation was needed to link women with multiple access barriers to health services. Collectively, this review reveals 1) the importance of using a systematic approach for planning and adapting cervical cancer control programs; 2) advantages of collaborative academic–community partnerships to develop feasible interventions with broad reach; 3) the use of small media and LHW approaches and the need for tailored phone navigation in urban settings; and 4) coordination and technical assistance of community-based efforts as a way to maximize resources.

Objectives While the provision of cervical cancer prevention services in the United States has expanded to new settings beyond clinics that give Pap smears, prevention efforts are being hampered by relatively low human papillomavirus (HPV) vaccine coverage. Pharmacies are an underused setting to deliver HPV vaccine. To better understand this opportunity, we sought to classify pharmacists' authority to administer HPV vaccine in each US state. Methods For each US state and the District of Columbia (for simplicity, we refer to these 51 regions as states), we interviewed a member of the state's pharmacy association, member of the state board of pharmacy, or a faculty member at a school or college of pharmacy. Results Most states (80%) allowed pharmacists to provide HPV vaccine to adult women ages 19 and older, and 61% of states allowed provision to girls age 12. The mechanism for pharmacists to immunize was highly variable across states. For example, a 12year-old girl seeking HPV vaccine could receive it from a pharmacist in 31% of states under a protocol between a specific physician and pharmacist, in 24% with an HPV vaccine prescription, and in 6% without prior physician approval. Pharmacists' authority was broadest on the west coast and limited on the east coast. Pharmacist authority to provide HPV, Tdap, and meningitis vaccines was very similar, but it was highly dependent on patient age. Conclusions US states' laws governing pharmacists' ability to offer HPV vaccine varied widely. One consequence is that newly expanded cervical prevention efforts underuse pharmacists.

Objectives Despite the Advisory Committee on Immunization Practices (ACIP) recommendations for young adult females and males to receive the three-dose human papillomavirus (HPV) vaccine, most recent findings show that only 30% of the U.S. females aged 19–26, 2.8% of males aged 19–21, and only 1.7% of males aged 22–26 are initiating vaccination. This study evaluates the effects of a brief (5–10min) group HPV educational intervention on knowledge and intent to vaccinate among young adults. Methods A sample of 131 18–26year old females and males was recruited from the 2012 INShape Black and Minority Health Fair in Indiana. We randomized participants into one of two groups: (1) survey completion prior to education (control group) or (2) survey completion following education (intervention group). Written surveys assessed HPV knowledge, vaccination history, and vaccination intent (for unvaccinated participants). Results Respondents were primarily female (70%), single (85%), and the majority self-identified as non-Hispanic Black (77%). Thirty-seven percent had initiated HPV vaccination (≥1 dose) and 19% had completed the series. The intervention group had higher HPV knowledge scores (M=9.1; SD=1.8) than the control group (M=7.0; SD=2.9; F=22.53). Among unvaccinated individuals (n=79), the intervention group had higher HPV vaccination intent (86%) compared to the control group (67%) (OR=3.09; 95%CI=1.02–9.36). Conclusions Despite ACIP recommendations, young adults continue to have low awareness of vaccine benefits and low vaccination rates. This study suggests that educational interventions to increase HPV awareness and vaccination may help to boost vaccination rates.

Innovative screening methods such as self-testing for human papillomavirus (HPV) may alleviate barriers to cervical cancer screening. The purpose of this exploratory study was to determine whether Appalachian Kentucky women would be amenable to self-collecting a cervico-vaginal specimen for HPV testing.Women aged 30-64 who were overdue for guideline-recommended cervical cancer screening were recruited from a primary care clinic in southeastern Kentucky. The women were asked to self-collect a specimen, using a cervico-vaginal brush, based on verbal and printed directions provided by a research nurse. All study participants, regardless of laboratory-confirmed HPV status, received the same counseling on the importance of cervical cancer screening and offered navigation to follow-up Pap testing at the local health department.Thirty-one women were approached and recruited to participate in the study, indicating a 100% acceptance rate of HPV self-testing. Of the 31 women, 26 tested negative for high-risk HPV and five tested positive. All of the women with negative results declined nurse navigation to Pap testing, whereas four of the five women with positive results accepted nurse navigation and received subsequent Pap smear screenings (all results were normal).Among this sample of Appalachian Kentucky women, self-collecting a cervico-vaginal specimen for HPV testing was highly acceptable. This exploratory study provides impetus for larger studies among high-risk, medically underserved women in rural communities. Tailoring alternative cancer screening strategies to meet the complex needs of rural women is likely to lead to reductions in cervical cancer incidence and mortality among this vulnerable population.

Infection with human papillomavirus (HPV) is recognized as one of the major causes of infection-related cancer worldwide, as well as the causal factor in other diseases. Strong evidence for a causal etiology with HPV has been stated by the International Agency for Research on Cancer for cancers of the cervix uteri, penis, vulva, vagina, anus and oropharynx (including base of the tongue and tonsils). Of the estimated 12.7 million new cancers occurring in 2008 worldwide, 4.8% were attributable to HPV infection, with substantially higher incidence and mortality rates seen in developing versus developed countries. In recent years, we have gained tremendous knowledge about HPVs and their interactions with host cells, tissues and the immune system; have validated and implemented strategies for safe and efficacious prophylactic vaccination against HPV infections; have developed increasingly sensitive and specific molecular diagnostic tools for HPV detection for use in cervical cancer screening; and have substantially increased global awareness of HPV and its many associated diseases in women, men, and children. While these achievements exemplify the success of biomedical research in generating important public health interventions, they also generate new and daunting challenges: costs of HPV prevention and medical care, the implementation of what is technically possible, socio-political resistance to prevention opportunities, and the very wide ranges of national economic capabilities and health care systems. Gains and challenges faced in the quest for comprehensive control of HPV infection and HPV-related cancers and other disease are summarized in this review. The information presented may be viewed in terms of a reframed paradigm of prevention of cervical cancer and other HPV-related diseases that will include strategic combinations of at least four major components: 1) routine introduction of HPV vaccines to women in all countries, 2) extension and simplification of existing screening programs using HPV-based technology, 3) extension of adapted screening programs to developing populations, and 4) consideration of the broader spectrum of cancers and other diseases preventable by HPV vaccination in women, as well as in men. Despite the huge advances already achieved, there must be ongoing efforts including international advocacy to achieve widespread-optimally universal-implementation of HPV prevention strategies in both developed and developing countries. This article summarizes information from the chapters presented in a special ICO Monograph 'Comprehensive Control of HPV Infections and Related Diseases' Vaccine Volume 30, Supplement 5, 2012. Additional details on each subtopic and full information regarding the supporting literature references may be found in the original chapters. (C) 2013 Elsevier Ltd. All rights reserved.

Resume Objectif Le but de cette etude est de determiner la prevalence des virus du papillome humain (HPV) et la distribution des genotypes HPV en fonction de l’âge, de la cytologie et de l’histologie chez les femmes ayant eu un examen gynecologique de routine et l’impact sur les strategies de prevention. Patientes et methodes Les prelevements cytologiques ont ete testes pour la presence de l’ADN, l’ARN et les genotypes d’HPV. Les femmes ayant une cytologie ASC-US+ et/ou un test HPV positif ont ete evaluees en colposcopie. Chez les femmes ayant une colposcopie normale, deux biopsies ont ete effectuees systematiquement sur la zone de transformation a six et 12 heures. Resultats Au total, 515 (10,3 %) des 5002 femmes avaient moins de 25 ans et 4487 (89,7 %) 25 ans ou plus. La prevalence de l’HPV etait de 10,1 % a 16,1 % suivant le test HPV utilise. La prevalence de l’HPV etait plus elevee que celle de la cytologie. La prevalence des HPV 16/18 etait de 5,2 % et 2,7 %, respectivement, chez les femmes de moins de 25 ans et 25 ans ou plus. Plus de deux partenaires sexuels les 12 derniers mois est le facteur de risque le plus eleve pour l’exposition aux HPV (odds ratio [OR] superieur a 3,60). Compare aux autres types d’HPV, l’HPV 16 est l’indicateur de risque le plus eleve des CIN3+ (OR = 11,64 ; p Discussion et conclusion Ces resultats indiquent que la plupart des jeunes femmes pourrait beneficier de la vaccination prophylactique contre les HPV, mais confirme l’importance du depistage et souligne la necessite de developper des vaccins incluant le plus possible de types d’HPV.

A series of (S)-2-(2-(diethylamino)-5-(N-alkyl-N-sulfonamido)pyrimidin-4-ylamino)-3-(4-(carbamoyloxy)phenyl)propanoic acid is discovered as orally available VLA-4 antagonists. Representative compounds 11b and 11p showed efficacy in multiple in vivo animal models. The in vitro selectivity of 11p is also described.

Cancer is an important cause of premature death in low- and middle-income countries (LMIC). Two preventive tools are available that have the potential together to sharply decrease the impact of cervical cancer in LMIC. The combination of human papillomavirus (HPV) vaccination and cervical cancer screening within existing programs is possible. Although there is a great deal of concern about introducing and strengthening HPV prevention efforts in LMIC, recent projects have demonstrated feasibility. Thus, with appropriate prioritization and resources, HPV prevention can be introduced and scaled up. Comprehensive HPV prevention strategies, mainly those geared at preventing cervical cancer, should include both vaccination and screening. The integration of both screening and vaccination will save the most lives, and such strategies are endorsed by many international organizations. However, some vaccine and screening programs are financed almost entirely by special externally-based programs. These more closely resemble demonstration exercises than sustainable national programs. In order for successful demonstration projects to have a broad impact on prevention, sustainable national funding based on strong commitments is essential. There may be challenges to implementing HPV prevention programs, but none should be considered insurmountable. Many LMIC have successfully adopted an HPV prevention agenda despite prevailing pessimism. Failure to act on this issue can perpetuate inequity in sexually transmitted infection and cancer prevention. This article forms part of a special supplement entitled "Comprehensive Control of HPV Infections and Related Diseases" Vaccine Volume 30, Supplement 5, 2012.

Objective New commercial HPV RNA assays require further validation studies in population-based cervical cancer screening settings. To assess the performance of (FDA-approved) APTIMA® HPV Assay (AHPV), Hybrid Capture 2 (HC2), in-house PCR genotyping, and ThinPrep LBC in population-based screening, stratified by three histological gold standards. Study design A multi-center trial in 5006 women undergoing routine screening in France was designed to compare the absolute and relative risks of diagnosing CIN3+ and CIN2+ lesions by different diagnostic tests. Results Reproducibility between the primary and second pathology reading was excellent for CIN3+ and CIN2+ endpoints (Cohen's kappa 0.948 and 0.854). Absolute risks (PPV) of different tests (AHPV, HC2, PCR genotyping, LBC) in diagnosing CIN2+ (15–20%) and CIN3+ (4–6%) were similar for the first, second, and consensus pathology readings. The relative risks of diagnosing these lesions by the four tests were also similar when the first, second or third pathology readings were employed. AHPV had the highest absolute risk of both histological endpoints, and detects 5% to 15% more CIN3+ and CIN2+ lesions, respectively, than LBC. Compared with HC2 assay, the relative risk of AHPV is 24% to 29% higher, with a significant difference in CIN2+ detection. With LBC as reference, AHPV had the best sensitivity/specificity balance measured by AUC (area under ROC curve) comparison test (significant for CIN2+), and the colposcopy referral rate (9.2%) comparable to that of LBC (8.7%). Conclusions These data corroborate the suitability of AHPV for the primary cervical cancer screening.

Objective Cervical cancer causes over 4000 deaths yearly in the United States, although highly preventable through vaccination, screening, and early treatment. We aimed to determine demographic correlates for cervical cancer in North Carolina to identify target populations for interventions and to create a framework for state-level analyses. Method Data on all reported invasive cervical cancer cases from 1998 to 2007 were obtained from the North Carolina Central Cancer Registry. Age-adjusted incidence and mortality rates were estimated using population data from the National Center for Health Statistics. Results Cervical cancer incidence and mortality rates varied greatly by county and were inversely associated with county prosperity. Hispanic women had the highest incidence rate, black women the highest mortality rate, although white women accounted for most cases. Incidence rates remained fairly steady above age 35 and mortality rates steadily increased with age. A later stage at diagnosis was more common for older women and for women without private insurance. Conclusion Registry-based assessment illustrates the economic, racial, and age disparities associated with cervical cancer. This localized focus on demographic correlates is an important step toward eliminating this preventable disease and offers a template for cervical cancer prevention programs in other states.

Purpose Global data on human papillomavirus (HPV) serological and deoxyribonucleic acid (DNA) prevalence are essential to optimize HPV prophylactic vaccination strategies. Methods We conducted a global review of age-specific HPV antibody and studies with both antibody and DNA prevalence for HPV-16, −18, −6, and −11. Results One hundred seventeen studies were included; participants' ages ranged from several hours to >90 years. HPV-16 seroprevalence was generally higher in Africa, Central and South America, and North America, more prevalent among women than among men, and peaked around ages 25–40 years. HPV-18 seroprevalence was generally lower than HPV-16 with a later age peak. Data were limited for HPV-6 and −11, both of which peaked at ages similar to HPV-18. Among 9–26-year-old females, HPV-16 seroprevalence ranged from 0%–31% in North America, 21%–30% in Africa, 0%–23% in Asia/Australia, 0%–33% in Europe, and 13%–43% in Central and South America. HPV-16/-18 DNA prevalence peaked 10–15 years before corresponding HPV-16/-18 antibody prevalence. Conclusions Females within the HPV vaccine-eligible age-group (9–26 years) had a range of dual HPV-16 DNA and serology negativity from 81%–87%, whereas 90%–98% were HPV-16 DNA negative. Serology and DNA data are lacking worldwide for females younger than age 15 years, the prime target group for vaccination.

Rapid and accurate identification of disease progression are key factors in testing novel vaccines and antivirals against encephalitic alphaviruses. Typical efficacy studies utilize a large number of animals and severe morbidity or mortality as an endpoint. New technologies provide a means to reduce and refine the animal use as proposed in Hume’s 3Rs (replacement, reduction, refinement) described by Russel and Burch. In vivo imaging systems (IVIS) and bioluminescent enzyme technologies accomplish the reduction of animal requirements while shortening the experimental time and improving the accuracy in localizing active virus replication. In the case of murine models of viral encephalitis in which central nervous system (CNS) viral invasion occurs rapidly but the disease development is relatively slow, we visualized the initial brain infection and enhance the data collection process required for efficacy studies on antivirals or vaccines that are aimed at preventing brain infection. Accordingly, we infected mice through intranasal inoculation with the genetically modified pathogen, Venezuelan equine encephalitis, which expresses a luciferase gene. In this study, we were able to identify the invasion of the CNS at least 3 days before any clinical signs of disease, allowing for reduction of animal morbidity providing a humane means of disease and vaccine research while obtaining scientific data accurately and more rapidly. Based on our data from the imaging model, we confirmed the usefulness of this technology in preclinical research by demonstrating the efficacy of Ampligen, a TLR-3 agonist, in preventing CNS invasion.

Purpose Global data on age-specific prevalence of human papillomavirus (HPV) infection in males, especially for oncogenic HPV types 16 and 18, are essential for future efforts to prevent HPV-related diseases, including expanded access to HPV prophylactic vaccines for boys and young men. Methods A systematic review of peer-reviewed publications was conducted to summarize worldwide data on genital HPV-DNA prevalence in men. Studies using polymerase chain reaction or hybrid capture detection assays were included. Results Approximately 6,600 abstracts were identified. Of them, 64 reported age-specific HPV prevalence and were included in the review. Of these, 38 were from populations at high risk of HPV infections, such as sexually transmitted infection clinic attendees, human immunodeficiency virus-positive males, and male partners of women with HPV infection or abnormal cytology. The largest proportions of studies were from Europe (38%) and North America (25%), with smaller proportions from Central and South America (19%), Asia (11%), and Africa (5%). Across all regions, data on HPV prevalence were generally limited to men >18 years of age. HPV prevalence was high among sexually active men in all regions but with considerable variation, from 1% to 84% among low-risk men and from 2% to 93% among high-risk men. Peak HPV prevalence spanned a wide range of ages and was generally not concentrated in the younger age groups. Age-specific prevalence curves were relatively flat or declined only slightly following peak prevalence. Conclusions Genital HPV infection in men varies widely, both between and within high- and low-risk groups and by geographic region. Compared with that in women, HPV prevalence in men seems to peak at slightly older ages and remains constant or decreases slightly with increasing age, suggesting persistent HPV infection or a higher rate of reinfection.

Objective To determine herpes simplex virus (HSV)-2 and HSV-1 seroprevalence in women and men in Romania. Methods A cross-sectional seroprevalence survey was conducted between 2004 and 2005 on a total of 1058 women and men representative of the population of Bucharest. All participants were aged 15–44 years and completed a structured questionnaire. A blood sample was collected to detect IgG anti-HSV-1 and HSV-2 serum antibodies using the HerpeSelect ELISA (Focus Diagnostics). Results A total of 761 women (median age 29 years) and 297 men (median age 29 years) were included. Overall, HSV-2 seroprevalence (15.2%) increased with age. Among women, HSV-2 seroprevalence increased from 11.0% in 15–19-year-olds to 38.3% in 40–44-year-olds. Among men, seroprevalence increased from 4.0% in 20–24-year-olds to 27.1% in 40–44-year-olds. HSV-2 seroprevalence was significantly higher among women than men (17.0% vs. 10.8%). HSV-1 seropositivity was high (87.2%) in all age groups, with no clear trend by age or by sex. In addition to older age and female sex, risk factors for HSV-2 included greater number of lifetime sexual partners, lower educational attainment, and history of genital vesicles. Lower educational level and rural residence were associated with a higher risk of HSV-1 seropositivity. Conclusions In Romania, HSV-2 seroprevalence was higher in women than men, and was within European limits and lower than that in Africa and the USA. In contrast, HSV-1 seroprevalence was generally higher than that previously recorded in similarly aged populations in Western Europe.

As human papillomavirus (HPV) vaccines become available in less-developed countries, understanding women's attitudes towards HPV vaccines can help guide approaches to immunization programs. We assessed knowledge and interest in prophylactic HPV vaccines among Kenyan women seeking women's health services (N=147). They knew little about cervical cancer or HPV vaccine. Most women (95%, 95% confidence interval [CI]: 92%, 99%), however, were willing to have their daughters vaccinated with a vaccine that would prevent cervical cancer, with preference for an inexpensive vaccine requiring fewer doses.

We examined the prevalence of reported pain following human papillomavirus (HPV) vaccination and whether it differed from that for other adolescent vaccines or affected completion of the HPV vaccine regimen. In 2008, we conducted cross-sectional surveys with parents of adolescent girls aged 11-20 living in areas of North Carolina with elevated cervical cancer rates who had received at least one dose of HPV vaccine. Pain from HPV vaccination, while commonly reported by parents, was less frequent compared to other adolescent vaccines and did not appear to affect vaccine regimen completion. These findings may be important to increase HPV vaccination coverage.

While two prophylactic HPV vaccines have been proven notably efficacious in clinical trials, the effectiveness of these vaccines at the population level remains to be evaluated. To lay the foundation for understanding the strengths and limitations of different endpoints for future effectiveness research, we present a comprehensive review of HPV-related clinical outcomes, including: (i) HPV type-specific positivity and persistence, (ii) Pap diagnoses (ASC-US, LSIL, and HSIL), (iii) histologic cervical cancer precursor lesions (i.e., CIN1, CIN2, and CIN3), (iv) invasive cervical cancer (ICC), (v) anogenital warts, (vi) recurrent respiratory papillomatosis (RRP), and (vii) other HPV-associated cancers (vulvar, vaginal, anal, penile, and oropharyngeal). While research on the vaccines' effects on these HPV clinical outcomes in the general population is presently limited, numerous large trials will soon be completed, making a priori discussion of these potential outcomes especially urgent. Furthermore, population level systems to track HPV-associated clinical outcomes may need to be developed for HPV vaccine effectiveness evaluation.

Asia accounts for more than half of all cases of cervical cancer registered globally and improving prevention is urgently needed. A range of tools and strategies is now available to effectively prevent this disease, including two new prophylactic HPV vaccines approved and recommended for adolescents and young women. However, without communication these tools may have little impact on disease burden. The conferences of the Asia Oceania Research Organisation in Genital Infection and Neoplasia (AOGIN) bring together clinicians and scientists whose work is related to genital infections, particularly HPV, cervical dysplasia and neoplasia, as well as other anogenital cancers, with the aim of improving communication on prevention through human papillomavirus (HPV) vaccination and screening in Asian countries. The scope of this year's AOGIN conference was to extend education to include health workers, family doctors, paediatricians, governmental health agencies, and the general public through patients' testimonials that can reach out to women raising awareness of this silent disease. Community based initiatives and awareness campaigns were also reported, and can empower the people to engage in a dialog with local governments towards prioritization of cancer prevention programs, achieving more for the public than isolated actions. Parents and teachers are encouraged to communicate about these issues within families and schools. Evidence was discussed that males can participate in cervical cancer control as well, and prevention programs involving men should not be neglected as they may reduce genital disease burden in women. Opinion leaders proposed prevention measures to be considered for governmental decisions. While each country develops a locally appropriate policy for cervical cancer control there is a need to revise these programs regularly, as knowledge increases in response to public need, as well as to gather evidence about disease burden and the effectiveness of education and interventions. In conclusion, AOGIN is committed to improve communication with patients, health authorities, professional organizations and opinion leaders towards strengthening cervical cancer prevention in Asia, to achieve a timely steep reduction in this cancer.

Purpose Potential barriers to widespread vaccination of adolescent girls against human papillomavirus (HPV) infection are poorly understood. We provide an overview of potential barriers to provision of HPV vaccine and empirical data on the concerns of medical practices that may inhibit HPV vaccine provision. Method We conducted phone interviews with medical practices in rural areas in southeastern North Carolina with high rates of cervical cancer to assess 10 potential concerns about HPV vaccine provision. Results Concerns most commonly reported by medical practices (N = 71) were inadequate reimbursement (68%), high cost of the vaccine to patients (66%), and burden of determining insurance coverage (66%). Practices that were not providing the vaccine reported more concerns about HPV vaccine provision on average than practices providing the vaccine (6.0 vs. 4.5 concerns, p Conclusions Medical practices' concerns about the HPV vaccine may be barriers to stocking it and, thus, to providing it to adolescents. Even providers who stock the vaccine reported concerns. Research is needed to address ways to ameliorate these medical practices' concerns and also to understand other potential barriers to vaccine coverage.

To develop a comprehensive intervention policy for future management of cervical cancer in China and Mongolia, it is essential to review the prevalence of human papillomavirus (HPV) infection, cervical cancer incidence and mortality, status of cervical screening and issues related to prophylactic HPV vaccines. Invasive cervical cancer (ICC) remains an important health problem among women in both China and Mongolia. However, a significant proportion of the burden is observed in rural settings. In areas of China and Mongolia where data are available, HPV prevalence is relatively high, with sexual activity being the most important risk factor. Nationwide programs for cervical cancer screening do not exist, and the majority of women have never been screened. However, government and non-governmental organizations have been collaborating to establish demonstration centers in both high- and low-resource settings to provide screening and obtain geographic specific data. To date, the prophylactic HPV vaccines are not licensed in China or Mongolia, although with wide coverage, the HPV vaccine could potentially prevent as much as three quarters of ICC cases among Chinese and Mongolian women. Ultimately, the introduction of HPV vaccination will present specific challenges, as well as opportunities, for developing advocacy, information and communication strategies that will involve policymakers and the general public.

With the approval of a vaccine to prevent human papillomavirus (HPV) infection and the pending approval of a second vaccine, an exciting era has dawned that provides clinicians the opportunity to prevent a majority of lower genital tract cancers. Herein, we describe the quadrivalent and bivalent prophylactic HPV vaccines and examine how they can be incorporated into clinical practice. Efficacy and safety of the vaccines are discussed as are potential barriers to vaccination. Future questions and challenges are also reviewed. A quadrivalent virus-like particle vaccine has now been approved for use in girls and women ages 9–26 years. A second bivalent vaccine could be available soon. The development of these vaccines targeted against 2 oncogenic types of HPV infection (HPV 16 and 18) has made it possible to eliminate approximately 70% of all invasive cervical cancers in women worldwide and decrease the incidence of other lower genital tract cancers and precancers. Vaccine efficacy in clinical trials has been outstanding, with nearly 100% protection against high-grade lesions because of HPV vaccine types. It is extremely important that vaccinated and unvaccinated women continue with recommended cervical cancer screening because not all oncogenic HPV types are covered in currently developed vaccines. Prevention of most cervical cancer and a notable proportion of cervical precancers and other lower genital tract cancers is now possible with the clinical availability of prophylactic vaccination for girls and young women. Prevention of genital warts is also possible with the quadrivalent vaccine. However, knowledge about HPV infection and cervical cancer as well as the need to vaccinate against oncogenic HPV infection is still lacking among women and physicians; thus, continued education of patients and clinicians is necessary to optimize vaccine use and assure ongoing cytologic screening.

With the introduction of cervical screening programs, the incidence and mortality of cervical cancer has been drastically reduced. Techniques such as the traditional Papanicolaou test and the newer liquid-based cytology allow for the early detection of cervical abnormalities prior to the development of invasive cervical cancer. As oncogenic human papillomavirus (HPV) infection is necessary for cervical cancer, HPV-DNA testing has also been proposed as a routine screening method for the general population. Screening limitations, such as adherence, test sensitivity and specificity, access, and cost-effectiveness are reflected in current screening guidelines. The development of prophylactic cervical cancer vaccines is a major milestone in cervical cancer prevention. These vaccines protect against the initial infection of certain oncogenic HPV types, and therefore prevent the development of cervical dysplasia, precancerous lesions, and cervical cancer. Considering routine cervical cancer vaccination in adolescent girls, screening guidelines must adapt in order to retain efficient and cost-effective prevention measures. Although the true epidemiological and economic impact of cervical cancer vaccines cannot be immediately realized, mathematical models predict various scenarios in which vaccination, in addition to cervical screening, will be cost-effective and further reduce cervical cancer disease.

and extended hospital stays. Non-serious complications included formation of a hematoma, discoloration, oozing, swelling, or bleeding at the entry site. P values < 0.05 were considered significant. Results: An independent T-test indicated a significant (p < .001) increase in the mean percentage in the number of reused SUDs at BBH. There was no difference in the number of complications that developed after surgery between the hospitals, despite the significant difference in the number of SUDs per procedure. When analyzing length of stay, the results showed significant (p < .001) increase in the average mean stay for patients in BBH which may be attributed to the initial health status of patients. No significant differences were found between hospitals in the severity of complications was analyzed (serious vs. non-serious). Conclusion: There was no significant correlation between the reuse of single use medical devices and adverse outcomes for PTCA at either of the two hospitals in which the study took place. Funding: No funding listed. Abstract #: 02NCD005

The aim of the present study was to evaluate the first void urine (FVU) as a non-invasive sampling method for HPV detection and genotyping in a high-risk population. Men presenting with HPV associated penile lesions or HPV positive partners attending a urological department in La Plata, Argentina were enrolled for HPV detection and genotyping. DNA from 185 first-void urine samples was evaluated for the presence of HPV by nested polymerase chain reaction using MY09/11 and GP05/06 primers. The viral genotype was analyzed by means of the single-stranded conformation polymorphisms (SSCP) method. Seventy-three percent (135/185) of the FVU specimens were positive for HPV-DNA. The viral prevalence in patients with HPV-DNA positive partners was 68.8% (77/112), and 79.5% (58/73) of patients with penile lesions were found to be HPV positive. The most frequent viral type was HPV-11 (26.7%), followed by HPV-6 (23%), HPV-16 (21.5%), HPV-18 (6%), and HPV-31 (4.4%). In this study, 11.1% (15/135) of the HPV positive specimens were double infections. These results indicate that high-risk HPVs can be found in clinical lesions in a high percentage (43.8%), as simple or double infections. In this sense, the male population represents an important reservoir for the virus and may play a role in the transmission and perpetuation of the infection in the general population. The method described below provides a tool for detection and typing of HPV-DNA using samples obtained by non-invasive techniques and thus easy to obtain. Fil: Golijow, Carlos Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico CONICET- La Plata. Instituto de Genética Veterinaria "Ing. Fernando Noel Dulout". Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias. Instituto de Genética Veterinaria; Argentina Fil: Perez, Luis Orlando. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico CONICET- La Plata. Instituto de Genética Veterinaria "Ing. Fernando Noel Dulout". Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias. Instituto de Genética Veterinaria; Argentina Fil: Smith, Jennifer S.. University of North Carolina; Estados Unidos Fil: Abba, Martín Carlos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico CONICET- La Plata. Instituto de Genética Veterinaria "Ing. Fernando Noel Dulout". Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias. Instituto de Genética Veterinaria; Argentina

Objectives. To examine the prevalence of Human papillomavirus and Chlamydia trachomatis DNA in cervical samples among women with normal and abnormal cervical cytology from La Plata, Argentina. Methods. Two hundred and seventy-nine women (200 with cervical neoplasia or ICC and 79 women with normal cytology) provided cervical samples for the detection of HPV and C. trachomatis DNA by PCR-based assays. Results. HPV DNA increased with the cervical lesion severity, ranging from 30% among women with normal cytology to 99–100% among women with HSIL or ICC. C. trachomatis DNA prevalence increased from low levels in women with normal cytology (11%) to 47% in those with HSIL, but was uncommon among ICC patients (20%). Among women with normal cytology, C. trachomatis prevalence was higher in HPV DNA positive (12.5%) than HPV DNA negative women (10.9%), but this difference was not significant. Conclusions. HPV prevalence in the general population is slightly higher than those reported for other developing countries. C. trachomatis DNA positivity was associated with a higher risk of both LSIL and HSIL lesions, but not with ICC.

A series of oxadiazole-substituted α-isopropoxy phenylpropanoic acids with dual agonist activity on PPARα and PPARγ is described. Several of these compounds also showed partial agonist activity on PPARδ. Resolution of one analogue showed that PPARα and PPARγ activity resided in mainly one enantiomer, whereas PPARδ activity was retained in both enantiomers.

s The Journal of Pain S35 (236) African Americans are at increased risk of developing chronic pain and itch at the site of tissue autograft following major thermal burn injury A Liu, A Bermudez, J Hu, S Jones, J Hwang, J Smith, L Ballina, A Patel, T Tran, R Karlnoski, D Smith, B Cairns, and S McLean; University of North Carolina

The objective of the study was to evaluate the efficacy of intravaginal application of 5% 5-fluorouracil (5-FU) for the treatment of cervical intraepithelial neoplasia (CIN) 2 in women.Women aged 18-29 years with CIN 2 were recruited for this randomized controlled trial of observation vs treatment with intravaginal 5-FU. Women in the observation group returned in 6 months for a Papanicolaou smear, colposcopy, and a human papillomavirus (HPV) deoxyribonucleic acid test. Women in the 5-FU group were treated with intravaginal 5-FU once every 2 weeks for a total of 16 weeks and were similarly evaluated at 6 months. All women who had a baseline visit were included in the intention-to-treat analysis. Values of P.05 were considered statistically significant.Between August 2010 and June 2013, 60 women were randomized and had a baseline visit for intervention (n = 31) vs observation (n = 29). Of women who had cervical biopsy results at 6 months, regression of disease was demonstrated in 93% of women in the 5-FU group (26 of 28) and 56% of women in the observation group (15 of 27). Under the intention-to-treat analysis, a relative risk for cervical disease regression of 1.62 (95% confidence interval [CI], 1.10-2.56) was found between the 5-FU and observation arms (P = .01). When the cervical biopsy, Papanicolaou smear, and HPV results were combined for the 6 month follow-up visit, 50% of the 5-FU group (14 of 28) had a documented normal biopsy, normal Papanicolaou smear, and negative HPV test compared with 22% in the observation group (6 of 27) (relative risk, 2.25; 95% confidence interval, 1.05-5.09; P.05). There were no moderate or severe side effects in the intervention group.Topical 5-FU appears to be an effective medical therapy for CIN 2 in young women. 5-FU is readily available and may be considered as an off-label treatment option for young women with CIN 2 who are interested in the treatment of disease but want to avoid excisional procedures.

a Division of Clinical and Epidemiological Research, Department of Obstetrics and Gynecology, DUMC 3279, 244 Baker House, Duke University Medical Center, Durham, NC 27710, USA b Obstetrics and Gynecology, UAB Hospital, Birmingham, AL 35233, USA c Columbia University, Division of Gynecologic Oncology, 161 Fort Washington Avenue, Suite 843, 8th Floor, New York, NY 10032, USA d University of North Carolina, Department of Epidemiology, 2103 McGavran-Greenberg Hall, CB# 7435, Chapel Hill, NC, USA