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Find video protocols related to scientific articles indexed in Pubmed.
Effect of different human papillomavirus serological and DNA criteria on vaccine efficacy estimates.
Am. J. Epidemiol.
PUBLISHED: 08-19-2014
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Two trials of clinically approved human papillomavirus (HPV) vaccines, Females United to Unilaterally Reduce Endo/Ectocervical Disease (FUTURE I/II) and the Papilloma Trial Against Cancer in Young Adults (PATRICIA), reported a 22% difference in vaccine efficacy (VE) against cervical intraepithelial neoplasia grade 2 or worse in HPV-naïve subcohorts; however, serological testing methods and the HPV DNA criteria used to define HPV-unexposed women differed between the studies. We applied previously described methods to simulate these HPV-naïve subcohorts within the Costa Rica HPV16/18 Vaccine Trial and assessed how these criteria affect the estimation of VE. We applied 2 enzyme-linked immunosorbent assay (ELISA) thresholds for HPV16 and HPV18 seropositivity (8 and 7 ELISA units/mL, respectively, for PATRICIA; 54 and 65 ELISA units/mL, respectively, for FUTURE I/II (to approximate the competitive Luminex immunoassay)) and 2 criteria for HPV DNA positivity (12 oncogenic HPV types, plus HPV66 and 68/73 for PATRICIA; or plus HPV6 and 11 for FUTURE I/II). VE was computed in the 2 naïve subcohorts. Using the FUTURE I/II and PATRICIA criteria, VE estimates against cervical intraepithelial neoplasia grade 2 or worse, regardless of HPV type, were 69.0% (95% confidence interval: 40.3%, 84.9%) and 80.8% (95% confidence interval: 52.6%, 93.5%), respectively (P = 0.1). Although the application of FUTURE I/II criteria to our cohort resulted in the inclusion of more sexually experienced women, methodological differences did not fully explain the VE differences.
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An updated natural history model of cervical cancer: derivation of model parameters.
Am. J. Epidemiol.
PUBLISHED: 07-31-2014
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Mathematical models of cervical cancer have been widely used to evaluate the comparative effectiveness and cost-effectiveness of preventive strategies. Major advances in the understanding of cervical carcinogenesis motivate the creation of a new disease paradigm in such models. To keep pace with the most recent evidence, we updated a previously developed microsimulation model of human papillomavirus (HPV) infection and cervical cancer to reflect 1) a shift towards health states based on HPV rather than poorly reproducible histological diagnoses and 2) HPV clearance and progression to precancer as a function of infection duration and genotype, as derived from the control arm of the Costa Rica Vaccine Trial (2004-2010). The model was calibrated leveraging empirical data from the New Mexico Surveillance, Epidemiology, and End Results Registry (1980-1999) and a state-of-the-art cervical cancer screening registry in New Mexico (2007-2009). The calibrated model had good correspondence with data on genotype- and age-specific HPV prevalence, genotype frequency in precancer and cancer, and age-specific cancer incidence. We present this model in response to a call for new natural history models of cervical cancer intended for decision analysis and economic evaluation at a time when global cervical cancer prevention policy continues to evolve and evidence of the long-term health effects of cervical interventions remains critical.
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Immunosuppression in cervical cancer with special reference to arginase activity.
Gynecol. Oncol.
PUBLISHED: 06-09-2014
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Cervical cancer is characterized by an immunosuppressive microenvironment and a Th2-type cytokine profile. Expression of arginase (ASE), the enzyme that converts l-arginine into l-ornithine and urea, is stimulated by Th2-type cytokines.
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Efficacy of the HPV-16/18 vaccine: final according to protocol results from the blinded phase of the randomized Costa Rica HPV-16/18 vaccine trial.
Vaccine
PUBLISHED: 05-16-2014
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A community-based randomized trial was conducted in Costa Rica to evaluate the HPV-16/18 AS04-adjuvanted vaccine (NCT00128661). The primary objective was to evaluate efficacy of the vaccine to prevent cervical intraepithelial neoplasia 2 or more severe disease (CIN2+) associated with incident HPV-16/18 cervical infections. Secondary objectives were to evaluate efficacy against CIN2+ associated with incident cervical infection by any oncogenic HPVs and to evaluate duration of protection against incident cervical infection with HPV-16/18. Vaccine safety and immunogenicity over the 4-year follow-up were also evaluated.
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Antibodies against high-risk human papillomavirus proteins as markers for invasive cervical cancer.
Int. J. Cancer
PUBLISHED: 03-13-2014
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Different human papillomavirus (HPV) genes are expressed during the various phases of the HPV life cycle and may elicit immune responses in the process towards malignancy. To evaluate their association with cervical cancer, antibodies against proteins from HPV16 (L1, E1, E2, E4, E6 and E7) and HPV18/31/33/35/45/52/58 (L1, E6 and E7) were measured in serum of 307 invasive cervical cancer cases and 327 controls from Algeria and India. Antibody response was evaluated using a glutathione S-transferase-based multiplex serology assay and HPV DNA detected from exfoliated cervical cells using a GP5+/6+-mediated PCR assay. Among HPV16 DNA-positive cases, seroprevalence of HPV16 antibodies ranged from 16% for HPV16 E1 to 50% for HPV16 E6 and all were significantly higher than controls. Seroprevalence of E6, E7 and L1 antibodies for HPV18 and for at least one of HPV31/33/35/45/52/58 were also higher in cases positive for DNA of the corresponding type (50% and 30% for E6 of HPV18 and HPV31/33/35/45/52/58 combined, respectively). E6 and E7 antibodies were rarely found in controls, but cross-reactivity was evident among cancer cases positive for DNA of closely phylogenetically-related HPV types. E6 or E7 antibodies against any of the eight HPV types were detected in 66.1% of all cervical cancer cases, as compared to 10.1% of controls. E6, and to a lesser extent E7, antibodies appear to be specific markers of HPV-related malignancy. However, even among cases positive for the same type of HPV DNA, approximately one-third of cervical cancer cases show no detectable immune response to either E6 or E7.
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Glutathione S-transferase L1 multiplex serology as a measure of cumulative infection with human papillomavirus.
BMC Infect. Dis.
PUBLISHED: 02-26-2014
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Several assays are used to measure type-specific serological responses to human papillomavirus (HPV), including the bead-based glutathione S-transferase (GST)-L1 multiplex serology assay and virus-like particle (VLP)-based ELISA. We evaluated the high-throughput GST-L1, which is increasingly used in epidemiologic research, as a measure of cumulative HPV infection and future immune protection among HPV-unvaccinated women.
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Estimating and explaining the effect of education and income on head and neck cancer risk: INHANCE consortium pooled analysis of 31 case-control studies from 27 countries.
Int. J. Cancer
PUBLISHED: 02-21-2014
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Low socioeconomic status has been reported to be associated with head and neck cancer risk. However, previous studies have been too small to examine the associations by cancer subsite, age, sex, global region and calendar time and to explain the association in terms of behavioral risk factors. Individual participant data of 23,964 cases with head and neck cancer and 31,954 controls from 31 studies in 27 countries pooled with random effects models. Overall, low education was associated with an increased risk of head and neck cancer (OR = 2.50; 95% CI = 2.02 - 3.09). Overall one-third of the increased risk was not explained by differences in the distribution of cigarette smoking and alcohol behaviors; and it remained elevated among never users of tobacco and nondrinkers (OR = 1.61; 95% CI = 1.13 - 2.31). More of the estimated education effect was not explained by cigarette smoking and alcohol behaviors: in women than in men, in older than younger groups, in the oropharynx than in other sites, in South/Central America than in Europe/North America and was strongest in countries with greater income inequality. Similar findings were observed for the estimated effect of low versus high household income. The lowest levels of income and educational attainment were associated with more than 2-fold increased risk of head and neck cancer, which is not entirely explained by differences in the distributions of behavioral risk factors for these cancers and which varies across cancer sites, sexes, countries and country income inequality levels.
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Management of Helicobacter pylori infection in Latin America: a Delphi technique-based consensus.
World J. Gastroenterol.
PUBLISHED: 01-14-2014
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To optimize diagnosis and treatment guidelines for this geographic region, a panel of gastroenterologists, epidemiologists, and basic scientists carried out a structured evaluation of available literature.
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Comparison of antibody responses to human papillomavirus vaccination as measured by three assays.
Front Oncol
PUBLISHED: 01-13-2014
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Different assays, including the competitive Luminex immunoassay (cLIA), secreted alkaline phosphatase neutralization assay (SEAP-NA), and virus-like particle-based ELISA, are commonly used to measure antibody responses after human papillomavirus (HPV) vaccination. Direct assay comparisons aid interpretation of immunogenicity data evaluated by different assays.
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Genetic variants in nicotine addiction and alcohol metabolism genes, oral cancer risk and the propensity to smoke and drink alcohol: a replication study in India.
PLoS ONE
PUBLISHED: 01-01-2014
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Genetic variants in nicotinic acetylcholine receptor and alcohol metabolism genes have been associated with propensity to smoke tobacco and drink alcohol, respectively, and also implicated in genetic susceptibility to head and neck cancer. In addition to smoking and alcohol, tobacco chewing is an important oral cancer risk factor in India. It is not known if these genetic variants influence propensity or oral cancer susceptibility in the context of this distinct etiology.
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Durable antibody responses following one dose of the bivalent human papillomavirus L1 virus-like particle vaccine in the Costa Rica Vaccine Trial.
Cancer Prev Res (Phila)
PUBLISHED: 11-06-2013
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The Costa Rica HPV16/18 Vaccine Trial (CVT) showed that four-year vaccine efficacy against 12-month HPV16/18 persistent infection was similarly high among women who received one, two, or the recommended three doses of the bivalent HPV16/18 L1 virus-like particle (VLP) vaccine. Live-attenuated viral vaccines, but not simple-subunit vaccines, usually induce durable lifelong antibody responses after a single dose. It is unclear whether noninfectious VLP vaccines behave more like live-virus or simple-subunit vaccines in this regard. To explore the likelihood that efficacy will persist longer term, we investigated the magnitude and durability of antibodies to this vaccine by measuring HPV16- and HPV18-specific antibodies by VLP-ELISA using serum from enrollment, vaccination, and annual visits through four years in four vaccinated groups; one-dose (n = 78), two-doses separated by one month (n = 140), two doses separated by six months (n = 52), and three scheduled doses (n = 120, randomly selected). We also tested enrollment sera from n = 113 HPV16- or HPV18 L1-seropositive women prevaccination, presumably from natural infection. At four years, 100% of women in all groups remained HPV16/18 seropositive; both HPV16/18 geometric mean titers (GMT) among the extended two-dose group were non-inferior to the three-dose group, and ELISA titers were highly correlated with neutralization titers in all groups. Compared with the natural infection group, HPV16/18 GMTs were, respectively, at least 24 and 14 times higher among the two-dose and 9 and 5 times higher among one-dose vaccinees. Antibody levels following one-dose remained stable from month 6 through month 48. Results raise the possibility that even a single dose of HPV VLPs will induce long-term protection.
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Helicobacter pylori eradication in the prevention of gastric cancer: are more trials needed?
Curr Oncol Rep
PUBLISHED: 10-09-2013
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The incidence of gastric cancer has decreased in much of the world, but gastric cancer remains the second leading cause of cancer death globally, and the burden is growing in many countries in East Asia and Latin America. Chronic infection with Helicobacter pylori is the dominant cause of gastric cancer, and two recent randomized trials showed that H. pylori eradication significantly decreased gastric cancer risk. Population screening and treating individuals for H. pylori also appears to be cost-effective. Nevertheless, current clinical guidelines differ as to whether asymptomatic adults should be screened and treated for H. pylori, and no countries have yet implemented eradication programs. Some of this inaction may reflect lingering doubts about the effectiveness of H. pylori eradication in preventing gastric cancer, but there is also uncertainty about possible risks of mass antibiotic treatment and its impact on gut flora. Appropriately designed studies will help address these issues and hasten the implementation of population-wide prevention programs.
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Overcoming barriers to HPV vaccination: Non-inferiority of antibody response to human papillomavirus 16/18 vaccine in adolescents vaccinated with a two-dose vs. a three-dose schedule at 21 months.
Vaccine
PUBLISHED: 08-05-2013
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For middle and low-income countries, the cost of HPV vaccines remains challenging. We conducted an open-label nonrandomized clinical trial evaluating immune response to the HPV-16/18 AS04-adjuvanted vaccine administered on a standard (months (M) 0-1-6) versus extended schedule (M 0-6-60) at 7, 21, 60, 72 and 120 months post-vaccination. Participants were females recruited in Morelos, Mexico: 474 girls aged 9-10 years and 500 women aged 18-24 years receiving a standard schedule, and 1026 girls aged 9-10 years receiving an extended schedule (currently the girls in the extended schedule had received only the first 2 doses). This report presents the interim analysis results for non-inferiority between the regimes conducted with the current available data at 21 months after the first dose, with serum antibodies assessed by ELISA. A pre-stated margin of non-inferiority was defined by post-vaccination geometric mean titer (GMT) ratio (upper 95% confidence interval [CI]?2.0) between the standard and the two-dose schedule in girls at month 21. Immune response to the vaccine was strongest in adolescent girls and in the 3-dose group. Statistical non-inferiority of the two-dose versus three-dose groups was demonstrated. At 21 months, comparing the adolescent 2-dose versus 3-dose groups, the GMT ratio and 95% CI were 1.66 (1.55-1.81) and 1.67 (1.51-1.86) for HPV16 and 18, respectively. The two-dose regimen was non-inferior when compared to the three-dose response in same-age girls and with women aged 18-24 years after 21 months of follow-up. The reduction in the number of doses from the current three-dose schedule may lower overall costs associated with the vaccination and increase accessibility and compliance with the recommended dosing of the HPV vaccine.
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Impact of human papillomavirus vaccination on cervical cytology screening, colposcopy, and treatment.
Am. J. Epidemiol.
PUBLISHED: 07-10-2013
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The impact of human papillomavirus (HPV) vaccination on cervical screening, colposcopy, and treatment is incompletely understood. In 2004-2005, investigators in the Costa Rica Vaccine Trial randomized 7,466 women aged 18-25 years, 1:1, to receive HPV vaccination or hepatitis A vaccination. The worst-ever cytology diagnosis and the 4-year cumulative proportions of colposcopy referral and treatment by vaccination arm were compared for 2 cohorts. The total vaccinated cohort included 6,844 women who provided cervical samples. The naive cohort included 2,284 women with no evidence of previous HPV exposure. In the total vaccinated cohort, HPV-vaccinated women had a significant (P = 0.01) reduction in cytological abnormalities: 12.4% for high-grade lesions and 5.9% for minor lesions. Colposcopy referral was reduced by 7.9% (P = 0.03) and treatment by 11.3% (P = 0.24). Greater relative reductions in abnormal cytology (P < 0.001) were observed for HPV-vaccinated women in the naive cohort: 49.2% for high-grade lesions and 18.1% for minor lesions. Colposcopy referral and treatment were reduced by 21.3% (P = 0.01) and 45.6% (P = 0.08), respectively, in the naive cohort. The overall impact on health services will be modest in the first years after vaccine introduction among young adult women, even in regions with high coverage.
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Cigarette, cigar, and pipe smoking and the risk of head and neck cancers: pooled analysis in the International Head and Neck Cancer Epidemiology Consortium.
Am. J. Epidemiol.
PUBLISHED: 06-30-2013
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Cigar and pipe smoking are considered risk factors for head and neck cancers, but the magnitude of effect estimates for these products has been imprecisely estimated. By using pooled data from the International Head and Neck Cancer Epidemiology (INHANCE) Consortium (comprising 13,935 cases and 18,691 controls in 19 studies from 1981 to 2007), we applied hierarchical logistic regression to more precisely estimate odds ratios and 95% confidence intervals for cigarette, cigar, and pipe smoking separately, compared with reference groups of those who had never smoked each single product. Odds ratios for cigar and pipe smoking were stratified by ever cigarette smoking. We also considered effect estimates of smoking a single product exclusively versus never having smoked any product (reference group). Among never cigarette smokers, the odds ratio for ever cigar smoking was 2.54 (95% confidence interval (CI): 1.93, 3.34), and the odds ratio for ever pipe smoking was 2.08 (95% CI: 1.55, 2.81). These odds ratios increased with increasing frequency and duration of smoking (Ptrend ? 0.0001). Odds ratios for cigar and pipe smoking were not elevated among ever cigarette smokers. Head and neck cancer risk was elevated for those who reported exclusive cigar smoking (odds ratio = 3.49, 95% CI: 2.58, 4.73) or exclusive pipe smoking (odds ratio = 3.71, 95% CI: 2.59, 5.33). These results suggest that cigar and pipe smoking are independently associated with increased risk of head and neck cancers.
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Cross-protective vaccine efficacy of the bivalent HPV vaccine against HPV31 is associated with humoral immune responses: results from the Costa Rica Vaccine Trial.
Hum Vaccin Immunother
PUBLISHED: 04-09-2013
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We investigated the role of antibody responses as potential mechanism for the cross-protective vaccine-efficacies (VE) observed from randomized clinical trials of the HPV16/18 bivalent vaccine. Results HPV31 cases had lower HPV16 antibody levels than controls (OR 4th quartile compared with 1st quartile = 0.63; 95%CI: 0.36-1.08; p-trend = 0.03). HPV31 cases were also less likely to have detectable HPV31 neutralization, and HPV16 avidity than controls. No statistically significant differences by HPV18 antibody or HPV45 neutralization were observed among HPV45 cases and controls. Protection against HPV58 was not associated with any of the markers, confirming the specificity of our findings.
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Adult height and head and neck cancer: a pooled analysis within the INHANCE Consortium.
Eur. J. Epidemiol.
PUBLISHED: 02-28-2013
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Several epidemiological studies have shown a positive association between adult height and cancer incidence. The only study conducted among women on mouth and pharynx cancer risk, however, reported an inverse association. This study aims to investigate the association between height and the risk of head and neck cancer (HNC) within a large international consortium of HNC. We analyzed pooled individual-level data from 24 case-control studies participating in the International Head and Neck Cancer Epidemiology Consortium. Odds ratios (ORs) and 95 % confidence intervals (CIs) were estimated separately for men and women for associations between height and HNC risk. Educational level, tobacco smoking, and alcohol consumption were included in all regression models. Stratified analyses by HNC subsites were performed. This project included 17,666 cases and 28,198 controls. We found an inverse association between height and HNC (adjusted OR per 10 cm height = 0.91, 95 % CI 0.86-0.95 for men; adjusted OR = 0.86, 95 % CI 0.79-0.93 for women). In men, the estimated OR did vary by educational level, smoking status, geographic area, and control source. No differences by subsites were detected. Adult height is inversely associated with HNC risk. As height can be considered a marker of childhood illness and low energy intake, the inverse association is consistent with prior studies showing that HNC occur more frequently among deprived individuals. Further studies designed to elucidate the mechanism of such association would be warranted.
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HPV16 seropositivity and subsequent HPV16 infection risk in a naturally infected population: comparison of serological assays.
PLoS ONE
PUBLISHED: 01-02-2013
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Several serological assays have been developed to detect antibodies elicited against infections with oncogenic human papillomavirus (HPV) type 16. The association between antibody levels measured by various assays and subsequent HPV infection risk may differ. We compared HPV16-specific antibody levels previously measured by a virus-like particle (VLP)-based direct enzyme-linked immunoassay (ELISA) with levels measured by additional assays and evaluated the protection against HPV16 infection conferred at different levels of the assays.
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Evolution and taxonomic classification of alphapapillomavirus 7 complete genomes: HPV18, HPV39, HPV45, HPV59, HPV68 and HPV70.
PLoS ONE
PUBLISHED: 01-01-2013
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The species Alphapapillomavirus 7 (alpha-7) contains human papillomavirus genotypes that account for 15% of invasive cervical cancers and are disproportionately associated with adenocarcinoma of the cervix. Complete genome analyses enable identification and nomenclature of variant lineages and sublineages.
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Reduced prevalence of oral human papillomavirus (HPV) 4 years after bivalent HPV vaccination in a randomized clinical trial in Costa Rica.
PLoS ONE
PUBLISHED: 01-01-2013
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Human papillomavirus (HPV) infection, particularly with type 16, causes a growing fraction of oropharyngeal cancers, whose incidence is increasing, mainly in developed countries. In a double-blind controlled trial conducted to investigate vaccine efficacy (VE) of the bivalent HPV 16/18 vaccine against cervical infections and lesions, we estimated VE against prevalent oral HPV infections 4 years after vaccination.
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Longitudinal analysis of carcinogenic human papillomavirus infection and associated cytologic abnormalities in the Guanacaste natural history study: looking ahead to cotesting.
J. Infect. Dis.
PUBLISHED: 12-05-2011
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Few studies have addressed the timing of cervical cytologic abnormalities and human papillomavirus (HPV) positivity during the course of an infection. It remains largely unknown how infections detected by HPV and cytology wax and wane relative to each other. The aim of this analysis was to assess the longitudinal relationship of abnormal cytology and HPV positivity in a 7-year prospective study of 2500 women in Guanacaste, Costa Rica.
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Evaluation of the polyclonal ELISA HPV serology assay as a biomarker for human papillomavirus exposure.
Sex Transm Dis
PUBLISHED: 09-22-2011
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Seropositivity to human papillomavirus (HPV)16 and 18 antibodies is used as a measure of cumulative HPV exposure and as a stratifier of HPV exposure for vaccine efficacy analyses. Overall performance of these assays, as a measure of HPV exposure, has not been evaluated.
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Intrauterine device use, cervical infection with human papillomavirus, and risk of cervical cancer: a pooled analysis of 26 epidemiological studies.
Lancet Oncol.
PUBLISHED: 09-12-2011
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Intrauterine device (IUD) use has been shown to reduce the risk of endometrial cancer, but little is known about its association with cervical cancer risk. We assessed whether IUD use affects cervical human papillomavirus (HPV) infection and the risk of developing cervical cancer.
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Prevention of persistent human papillomavirus infection by an HPV16/18 vaccine: a community-based randomized clinical trial in Guanacaste, Costa Rica.
Cancer Discov
PUBLISHED: 09-09-2011
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Target groups for human papillomavirus (HPV) vaccination are controversial. We evaluated vaccine efficacy (VE) against 1-year persistent infection, stratified by age and sexual behavior, among young women in Costa Rica. We randomized 7,466 healthy women 18 to 25 years of age to HPV16/18 or hepatitis A vaccine (follow-up, 50.4 months). According-to-protocol (ATP) cohorts included compliant HPV-negative women; intention-to-treat (ITT) included all randomized women. ATP VE was 90.9% (95% CI, 82.0-95.9) against HPV16/18 infections, 44.5% against HPV31/33/45 (95% CI, 17.5-63.1), and 12.4% (95% CI, -3.2 to 25.6) against any oncogenic infection. Overall ITT VE against HPV16/18 infections was 49.0%, but ATP and ITT VE almost reached 100% in year 4 of follow-up. ATP efficacy against HPV16/18 was similar by age, but ITT VE was greatest among youngest women (68.9% among those 18-19 years of age; 21.8% among those 24-25 years of age) and 79.8% among virgins. Among previously unexposed women, vaccination is highly efficacious against HPV16/18 and partially against HPV31/33/45. Vaccination is most effective in women and girls before they initiate sexual activity, with programmatic and individual decision implications.
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Proof-of-principle evaluation of the efficacy of fewer than three doses of a bivalent HPV16/18 vaccine.
J. Natl. Cancer Inst.
PUBLISHED: 09-09-2011
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Three-dose regimens for human papillomavirus (HPV) vaccines are expensive and difficult to complete, especially in settings where the need for cervical cancer prevention is greatest.
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Efficacy of a bivalent HPV 16/18 vaccine against anal HPV 16/18 infection among young women: a nested analysis within the Costa Rica Vaccine Trial.
Lancet Oncol.
PUBLISHED: 08-22-2011
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Anal cancer remains rare (incidence of about 1·5 per 100,000 women yearly), but rates are increasing in many countries. Human papillomavirus (HPV) 16 and 18 infections cause most cases of anal cancer. We assessed efficacy of an AS04-adjuvanted HPV 16 and HPV 18 vaccine against anal infection with HPV 16, HPV 18, or both (HPV 16/18).
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The oral cavity contains abundant known and novel human papillomaviruses from the Betapapillomavirus and Gammapapillomavirus genera.
J. Infect. Dis.
PUBLISHED: 08-17-2011
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Human papillomaviruses (HPVs) primarily sort into 3 genera: Alphapapillomavirus (?-HPV), predominantly isolated from mucosa, and Betapapillomavirus (?-HPV) and Gammapapillomavirus (?-HPV), predominantly isolated from skin. HPV types might infect body sites that are different from those from which they were originally isolated.
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14-day triple, 5-day concomitant, and 10-day sequential therapies for Helicobacter pylori infection in seven Latin American sites: a randomised trial.
Lancet
PUBLISHED: 07-21-2011
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Evidence from Europe, Asia, and North America suggests that standard three-drug regimens of a proton-pump inhibitor plus amoxicillin and clarithromycin are significantly less effective for eradication of Helicobacter pylori infection than are 5-day concomitant and 10-day sequential four-drug regimens that include a nitroimidazole. These four-drug regimens also entail fewer antibiotic doses than do three-drug regimens and thus could be suitable for eradication programmes in low-resource settings. Few studies in Latin America have been done, where the burden of H pylori-associated diseases is high. We therefore did a randomised trial in Latin America comparing the effectiveness of four-drug regimens given concomitantly or sequentially with that of a standard 14-day regimen of triple therapy.
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Clustering of multiple human papillomavirus infections in women from a population-based study in Guanacaste, Costa Rica.
J. Infect. Dis.
PUBLISHED: 07-12-2011
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To evaluate clustering patterns of prevalent infection with multiple human papillomavirus (HPV) types in 8365 nonhysterectomized women from the Guanacaste Study of HPV Natural History.
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A competitive serological assay shows naturally acquired immunity to human papillomavirus infections in the Guanacaste Natural History Study.
J. Infect. Dis.
PUBLISHED: 06-02-2011
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A competitive Luminex Immunoassay (cLIA) has been developed to measure neutralizing antibodies against human papillomavirus (HPV) types 6, 11, 16 and 18.
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Smoking and passive smoking in cervical cancer risk: pooled analysis of couples from the IARC multicentric case-control studies.
Cancer Epidemiol. Biomarkers Prev.
PUBLISHED: 05-24-2011
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The independent role of tobacco smoking in invasive cervical cancer (ICC) has been established. We evaluated the potential impact of passive smoking (PS).
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Diet and the risk of head and neck cancer: a pooled analysis in the INHANCE consortium.
Cancer Causes Control
PUBLISHED: 05-11-2011
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We investigated the association between diet and head and neck cancer (HNC) risk using data from the International Head and Neck Cancer Epidemiology (INHANCE) consortium. The INHANCE pooled data included 22 case-control studies with 14,520 cases and 22,737 controls. Center-specific quartiles among the controls were used for food groups, and frequencies per week were used for single food items. A dietary pattern score combining high fruit and vegetable intake and low red meat intake was created. Odds ratios (OR) and 95% confidence intervals (CI) for the dietary items on the risk of HNC were estimated with a two-stage random-effects logistic regression model. An inverse association was observed for higher-frequency intake of fruit (4th vs. 1st quartile OR = 0.52, 95% CI = 0.43-0.62, p (trend) < 0.01) and vegetables (OR = 0.66, 95% CI = 0.49-0.90, p (trend) = 0.01). Intake of red meat (OR = 1.40, 95% CI = 1.13-1.74, p (trend) = 0.13) and processed meat (OR = 1.37, 95% CI = 1.14-1.65, p (trend) < 0.01) was positively associated with HNC risk. Higher dietary pattern scores, reflecting high fruit/vegetable and low red meat intake, were associated with reduced HNC risk (per score increment OR = 0.90, 95% CI = 0.84-0.97).
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Switch from cytology-based to human papillomavirus test-based cervical screening: implications for colposcopy.
Int. J. Cancer
PUBLISHED: 03-25-2011
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Human papillomavirus (HPV) testing is more sensitive than cytology; some cervical cancer prevention programs will switch from cytology to carcinogenic HPV test-based screening. The objective of our study is to evaluate the clinical implications of a switch to HPV test-based screening on performance and workload of colposcopy. Women in the population-based, 7-year Guanacaste cohort study were screened at enrollment using cytology. We also took another specimen for HPV DNA testing and collected magnified cervical photographic images (cervigrams). A final case diagnosis (?cervical intraepithelial neoplasia [CIN] grade 3, CIN2,
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Human papillomavirus infection with multiple types: pattern of coinfection and risk of cervical disease.
J. Infect. Dis.
PUBLISHED: 03-16-2011
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We investigated coinfection patterns for 25 human papillomavirus (HPV) types and assessed the risk conferred by multiple HPV types toward cervical disease.
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Long-term persistence of prevalently detected human papillomavirus infections in the absence of detectable cervical precancer and cancer.
J. Infect. Dis.
PUBLISHED: 02-24-2011
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Detailed descriptions of long-term persistence of human papillomavirus (HPV) in the absence of cervical precancer are lacking.
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A sex-specific association between a 15q25 variant and upper aerodigestive tract cancers.
Cancer Epidemiol. Biomarkers Prev.
PUBLISHED: 02-18-2011
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Sequence variants located at 15q25 have been associated with lung cancer and propensity to smoke. We recently reported an association between rs16969968 and risk of upper aerodigestive tract (UADT) cancers (oral cavity, oropharynx, hypopharynx, larynx, and esophagus) in women (OR = 1.24, P = 0.003) with little effect in men (OR = 1.04, P = 0.35).
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Long-term risk of recurrent cervical human papillomavirus infection and precancer and cancer following excisional treatment.
Int. J. Cancer
PUBLISHED: 02-14-2011
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Risk of recurrent CIN2+ (including cervical intraepithelial neoplasia grade 2 [CIN2], CIN3, carcinoma and in situ, adenocarcinoma in situ or cancer) remains elevated for years following treatment. The role of long-term post-treatment human papillomavirus (HPV) presence on subsequent risk of CIN2+ was evaluated in the 10,049-women Guanacaste cohort. Six hundred eighty-one women were referred to colposcopy because of high-grade cytology, positive cervicography and/or suspicion of cancer based on visual assessment; 486 were judged to require treatment. After excluding women with <12 months of follow-up (N = 88), prior cancer or hysterectomy (N = 37) or other reasons (N = 14), 347 were included in the analysis. Infections were categorized as persistent if present at both pre- and post-treatment visits and new if detected only post-treatment. Median time between the treatment and post-treatment visits was 6.7 years (interquartile range 3.8-7.8). At the post-treatment visit, 8 (2.4%), 2 (0.6%) and 8 (2.4%) of the 347 treated women had persistent HPV16, HPV18 or other carcinogenic HPV, respectively. Two (0.8%), 3 (1.0%) and 13 (4.0%) had new HPV16, HPV18 and other carcinogenic HPV, respectively. Six CIN2+ cases were identified at the post-treatment visit, all with persistent infections (three HPV16, one HPV18 and two other carcinogenic HPV). No recurrent disease was observed among women with new HPV infections during the follow-up period. Thus, persistence of HPV infection a median of six years after treatment was uncommon but, when present, posed a substantial risk of subsequent CIN2+. Serial follow-up data from other studies would further strengthen these conclusions.
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A genome-wide association study of upper aerodigestive tract cancers conducted within the INHANCE consortium.
James D McKay, Thérèse Truong, Valerie Gaborieau, Amélie Chabrier, Shu-Chun Chuang, Graham Byrnes, David Zaridze, Oxana Shangina, Neonila Szeszenia-Dabrowska, Jolanta Lissowska, Peter Rudnai, Eleonóra Fabiánová, Alexandru Bucur, Vladimír Bencko, Ivana Holcatova, Vladimir Janout, Lenka Foretova, Pagona Lagiou, Dimitrios Trichopoulos, Simone Benhamou, Christine Bouchardy, Wolfgang Ahrens, Franco Merletti, Lorenzo Richiardi, Renato Talamini, Luigi Barzan, Kristina Kjaerheim, Gary J Macfarlane, Tatiana V Macfarlane, Lorenzo Simonato, Cristina Canova, Antonio Agudo, Xavier Castellsague, Ray Lowry, David I Conway, Patricia A McKinney, Claire M Healy, Mary E Toner, Ariana Znaor, María Paula Curado, Sergio Koifman, Ana Menezes, Victor Wünsch-Filho, Jose Eluf Neto, Leticia Fernández Garrote, Stefania Boccia, Gabriella Cadoni, Dario Arzani, Andrew F Olshan, Mark C Weissler, William K Funkhouser, Jingchun Luo, Jan Lubiński, Joanna Trubicka, Marcin Lener, Dorota Oszutowska, Stephen M Schwartz, Chu Chen, Sherianne Fish, David R Doody, Joshua E Muscat, Philip Lazarus, Carla J Gallagher, Shen-Chih Chang, Zuo-Feng Zhang, Qingyi Wei, Erich M Sturgis, Li-E Wang, Silvia Franceschi, Rolando Herrero, Karl T Kelsey, Michael D McClean, Carmen J Marsit, Heather H Nelson, Marjorie Romkes, Shama Buch, Tomoko Nukui, Shilong Zhong, Martin Lacko, Johannes J Manni, Wilbert H M Peters, Rayjean J Hung, John Mclaughlin, Lars Vatten, Inger Njølstad, Gary E Goodman, John K Field, Triantafillos Liloglou, Paolo Vineis, Francoise Clavel-Chapelon, Domenico Palli, Rosario Tumino, Vittorio Krogh, Salvatore Panico, Carlos A González, J Ramon Quiros, Carmen Martínez, Carmen Navarro, Eva Ardanaz, Nerea Larranaga, Kay-Tee Khaw, Timothy Key, H Bas Bueno-de-Mesquita, Petra H M Peeters, Antonia Trichopoulou, Jakob Linseisen, Heiner Boeing, Göran Hallmans, Kim Overvad, Anne Tjønneland, Merethe Kumle, Elio Riboli, Kristjan Välk, Tõnu Vooder, Tõnu Voodern, Andres Metspalu, Diana Zelenika, Anne Boland, Marc Delepine, Mario Foglio, Doris Lechner, Hélène Blanché, Ivo G Gut, Pilar Galán, Simon Heath, Mia Hashibe, Richard B Hayes, Paolo Boffetta, Mark Lathrop, Paul Brennan.
PLoS Genet.
PUBLISHED: 02-11-2011
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Genome-wide association studies (GWAS) have been successful in identifying common genetic variation involved in susceptibility to etiologically complex disease. We conducted a GWAS to identify common genetic variation involved in susceptibility to upper aero-digestive tract (UADT) cancers. Genome-wide genotyping was carried out using the Illumina HumanHap300 beadchips in 2,091 UADT cancer cases and 3,513 controls from two large European multi-centre UADT cancer studies, as well as 4,821 generic controls. The 19 top-ranked variants were investigated further in an additional 6,514 UADT cancer cases and 7,892 controls of European descent from an additional 13 UADT cancer studies participating in the INHANCE consortium. Five common variants presented evidence for significant association in the combined analysis (p ? 5 × 10??). Two novel variants were identified, a 4q21 variant (rs1494961, p?=?1×10??) located near DNA repair related genes HEL308 and FAM175A (or Abraxas) and a 12q24 variant (rs4767364, p =2 × 10??) located in an extended linkage disequilibrium region that contains multiple genes including the aldehyde dehydrogenase 2 (ALDH2) gene. Three remaining variants are located in the ADH gene cluster and were identified previously in a candidate gene study involving some of these samples. The association between these three variants and UADT cancers was independently replicated in 5,092 UADT cancer cases and 6,794 controls non-overlapping samples presented here (rs1573496-ADH7, p = 5 × 10??); rs1229984-ADH1B, p = 7 × 10??; and rs698-ADH1C, p = 0.02). These results implicate two variants at 4q21 and 12q24 and further highlight three ADH variants in UADT cancer susceptibility.
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Sequence imputation of HPV16 genomes for genetic association studies.
PLoS ONE
PUBLISHED: 01-21-2011
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Human Papillomavirus type 16 (HPV16) causes over half of all cervical cancer and some HPV16 variants are more oncogenic than others. The genetic basis for the extraordinary oncogenic properties of HPV16 compared to other HPVs is unknown. In addition, we neither know which nucleotides vary across and within HPV types and lineages, nor which of the single nucleotide polymorphisms (SNPs) determine oncogenicity.
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Persistence of concurrent infections with multiple human papillomavirus types: a population-based cohort study.
J. Infect. Dis.
PUBLISHED: 01-21-2011
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The presence of more than one human papillomavirus (HPV) genotype may influence the duration of prevalently detected infections. This analysis included 1,646 infections detected at enrollment in 980 women from the Guanacaste, Costa Rica, cohort who were actively followed up every 6-12 months for up to 8 years. We categorized HPV infections as single or multiple types. Persistence of infections was estimated using discrete-time survival analysis. The difference between the duration of single and that of concurrent multiple type-specific prevalent HPV infections was not significant (P = .9; log-rank test). Concurrent, prevalent detection of additional HPV types did not change the likelihood of viral persistence.
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Evolution and taxonomic classification of human papillomavirus 16 (HPV16)-related variant genomes: HPV31, HPV33, HPV35, HPV52, HPV58 and HPV67.
PLoS ONE
PUBLISHED: 01-18-2011
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Human papillomavirus 16 (HPV16) species group (alpha-9) of the Alphapapillomavirus genus contains HPV16, HPV31, HPV33, HPV35, HPV52, HPV58 and HPV67. These HPVs account for 75% of invasive cervical cancers worldwide. Viral variants of these HPVs differ in evolutionary history and pathogenicity. Moreover, a comprehensive nomenclature system for HPV variants is lacking, limiting comparisons between studies.
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HPV16/18 L1 VLP vaccine induces cross-neutralizing antibodies that may mediate cross-protection.
Vaccine
PUBLISHED: 01-05-2011
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Human papillomavirus (HPV) L1 VLP-based vaccines are protective against HPV vaccine-related types; however, the correlates of protection have not been defined. We observed that vaccination with Cervarix™ induced cross-neutralizing antibodies for HPV types for which evidence of vaccine efficacy has been demonstrated (HPV31/45) but not for other types (HPV52/58). In addition, HPV31/45 cross-neutralizing titers showed a significant increase with number of doses (HPV31, p<0.001; HPV45, p<0.001) and correlated with HPV16/18 neutralizing titers, respectively. These findings raise the possibility that cross-neutralizing antibodies are effectors of cross-protection observed for the HPV16/18 vaccine.
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Chlamydia trachomatis and risk of prevalent and incident cervical premalignancy in a population-based cohort.
J. Natl. Cancer Inst.
PUBLISHED: 11-23-2010
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Cofactors might affect the risk of the rare progression from infection with carcinogenic human papillomavirus (HPV) to cervical premalignancy to invasive cancer. Some studies have observed that Chlamydia trachomatis infection is associated with increased risk for cervical cancer. In a large prospective cohort, we assessed the role of C trachomatis in cervical premalignancy and addressed confounding by HPV.
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Behavioral/lifestyle and immunologic factors associated with HPV infection among women older than 45 years.
Cancer Epidemiol. Biomarkers Prev.
PUBLISHED: 10-15-2010
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Cervical human papilloma virus (HPV) detection increases after menopause, but its determinants need clarification.
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Epidemiological study of anti-HPV16/18 seropositivity and subsequent risk of HPV16 and -18 infections.
J. Natl. Cancer Inst.
PUBLISHED: 10-13-2010
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Infection with human papillomavirus (HPV) 16 or HPV18 elicits an antibody response, but whether the elicited antibodies protect women against subsequent infection by a homologous HPV type compared with seronegative women is unknown.
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[New paradigms and challenges in cervical cancer prevention and control in Latin America].
Salud Publica Mex
PUBLISHED: 09-27-2010
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Cervical cancer continues to be a significant health problem in Latin America. The use of conventional cytology to detect precancerous cervical lesions has had almost no major impact on reducing cervical cancer incidence and mortality rates, which are still high in the region. The availability of new screening tools to detect precancerous lesions provide great opportunities for cervical cancer prevention in the region, as do highly efficacious HPV vaccines able to prevent nearly all lesions associated with HPV-16 and -18 when applied before viral exposure. This paper summarizes the scientific evidence and regional experiences related to: i) the use of HPV testing and visual inspection after the application of acetic acid (VIA) in primary screening and ii) the implementation of adolescent HPV vaccination programs. Finally, we outline a number of recommendations for different resource settings. The feasibility of implementing successful and sustainable national cervical cancer prevention programs in Latin American countries in the region will depend on health priorities and the availability of infrastructure and health personnel--as determined by rigorous local situational analysis.
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Seroprevalence and correlates of human papillomavirus 16/18 seropositivity among young women in Costa Rica.
Sex Transm Dis
PUBLISHED: 07-28-2010
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Serological indicators of human papillomavirus (HPV) infection are being used to differentiate HPV-naïve from previously infected women in vaccine and epidemiologic/clinical studies. We investigated HPV16 and 18 seroepidemiology among young, unvaccinated women aged between 18 and 25.
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Elevated systemic levels of inflammatory cytokines in older women with persistent cervical human papillomavirus infection.
Cancer Epidemiol. Biomarkers Prev.
PUBLISHED: 07-20-2010
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Defects in lymphoproliferative responses to mitogens/antigens in women >45 years old with a persistent type-specific human papillomavirus (HPV) infection have been reported.
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Genetic admixture and population substructure in Guanacaste Costa Rica.
PLoS ONE
PUBLISHED: 06-24-2010
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The population of Costa Rica (CR) represents an admixture of major continental populations. An investigation of the CR population structure would provide an important foundation for mapping genetic variants underlying common diseases and traits. We conducted an analysis of 1,301 women from the Guanacaste region of CR using 27,904 single nucleotide polymorphisms (SNPs) genotyped on a custom Illumina InfiniumII iSelect chip. The program STRUCTURE was used to compare the CR Guanacaste sample with four continental reference samples, including HapMap Europeans (CEU), East Asians (JPT+CHB), West African Yoruba (YRI), as well as Native Americans (NA) from the Illumina iControl database. Our results show that the CR Guanacaste sample comprises a three-way admixture estimated to be 43% European, 38% Native American and 15% West African. An estimated 4% residual Asian ancestry may be within the error range. Results from principal components analysis reveal a correlation between genetic and geographic distance. The magnitude of linkage disequilibrium (LD) measured by the number of tagging SNPs required to cover the same region in the genome in the CR Guanacaste sample appeared to be weaker than that observed in CEU, JPT+CHB and NA reference samples but stronger than that of the HapMap YRI sample. Based on the clustering pattern observed in both STRUCTURE and principal components analysis, two subpopulations were identified that differ by approximately 20% in LD block size averaged over all LD blocks identified by Haploview. We also show in a simulated association study conducted within the two subpopulations, that the failure to account for population stratification (PS) could lead to a noticeable inflation in the false positive rate. However, we further demonstrate that existing PS adjustment approaches can reduce the inflation to an acceptable level for gene discovery.
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Determinants of seropositivity among HPV-16/18 DNA positive young women.
BMC Infect. Dis.
PUBLISHED: 06-02-2010
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Not all women infected with HPV-16/18 have detectable levels of HPV-16/18 antibodies, those who seroconvert develop low antibody levels, and seroconversion occurs typically several months post-infection. We evaluated determinants of seropositivity among 646 women infected with HPV-16 and/or HPV-18.
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Body mass index, cigarette smoking, and alcohol consumption and cancers of the oral cavity, pharynx, and larynx: modeling odds ratios in pooled case-control data.
Am. J. Epidemiol.
PUBLISHED: 05-21-2010
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Odds ratios for head and neck cancer increase with greater cigarette and alcohol use and lower body mass index (BMI; weight (kg)/height(2) (m(2))). Using data from the International Head and Neck Cancer Epidemiology Consortium, the authors conducted a formal analysis of BMI as a modifier of smoking- and alcohol-related effects. Analysis of never and current smokers included 6,333 cases, while analysis of never drinkers and consumers of < or =10 drinks/day included 8,452 cases. There were 8,000 or more controls, depending on the analysis. Odds ratios for all sites increased with lower BMI, greater smoking, and greater drinking. In polytomous regression, odds ratios for BMI (P = 0.65), smoking (P = 0.52), and drinking (P = 0.73) were homogeneous for oral cavity and pharyngeal cancers. Odds ratios for BMI and drinking were greater for oral cavity/pharyngeal cancer (P < 0.01), while smoking odds ratios were greater for laryngeal cancer (P < 0.01). Lower BMI enhanced smoking- and drinking-related odds ratios for oral cavity/pharyngeal cancer (P < 0.01), while BMI did not modify smoking and drinking odds ratios for laryngeal cancer. The increased odds ratios for all sites with low BMI may suggest related carcinogenic mechanisms; however, BMI modification of smoking and drinking odds ratios for cancer of the oral cavity/pharynx but not larynx cancer suggests additional factors specific to oral cavity/pharynx cancer.
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A population-based prospective study of carcinogenic human papillomavirus variant lineages, viral persistence, and cervical neoplasia.
Cancer Res.
PUBLISHED: 03-30-2010
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Human papillomavirus (HPV) types differ profoundly in cervical carcinogenicity. For the most carcinogenic type HPV16, variant lineages representing further evolutionary divergence also differ in cancer risk. Variants of the remaining 10 to 15 carcinogenic HPV types have not been well studied. In the first prospective, population-based study of HPV variants, we explored whether, on average, the oldest evolutionary branches within each carcinogenic type predicted different risks of >2-year viral persistence and/or precancer and cancer [cervical intraepithelial neoplasia grade 3+ (CIN3+)]. We examined the natural history of HPV variants in the 7-year, 10,049-woman Guanacaste Cohort Study, using a nested case-control design. Infections were assigned to a variant lineage determined by phylogenetic parsimony methods based on URR/E6 sequences. We used the Fishers combination test to evaluate significance of the risk associations, cumulating evidence across types. Globally, for HPV types including HPV16, the P value was 0.01 for persistence and 0.07 for CIN3+. Excluding HPV16, the P values were 0.04 and 0.37, respectively. For HPV16, non-European viral variants were significantly more likely than European variants to cause persistence [odds ratio (OR), 2.6; P = 0.01] and CIN3+ (OR, 2.4; P = 0.004). HPV35 and HPV51 variant lineages also predicted CIN3+. HPV variants generally differ in risk of persistence. For some HPV types, especially HPV16, variant lineages differ in risk of CIN3+. The findings indicate that continued evolution of HPV types has led to even finer genetic discrimination linked to HPV natural history and cervical cancer risk. Larger viral genomic studies are warranted, especially to identify the genetic basis for HPV16s unique carcinogenicity.
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Establishment and operation of a biorepository for molecular epidemiologic studies in Costa Rica.
Cancer Epidemiol. Biomarkers Prev.
PUBLISHED: 03-23-2010
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The Proyecto Epidemiológico Guanacaste (PEG) has conducted several large studies related to human papillomavirus (HPV) and cervical cancer in Guanacaste, Costa Rica in a long-standing collaboration with the U.S. National Cancer Institute. To improve molecular epidemiology efforts and save costs, we have gradually transferred technology to Costa Rica, culminating in state-of-the-art laboratories and a biorepository to support a phase III clinical trial investigating the efficacy of HPV 16/18 vaccine.
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Longitudinal study of human papillomavirus persistence and cervical intraepithelial neoplasia grade 2/3: critical role of duration of infection.
J. Natl. Cancer Inst.
PUBLISHED: 02-15-2010
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The natural history of human papillomavirus (HPV) infections in older women is critical for preventive strategies, including vaccination and screening intervals, but is poorly understood. In a 7-year population-based cohort study in Guanacaste, Costa Rica, we examined whether womens age and the duration of carcinogenic HPV infections influenced subsequent persistence of infection and risk of cervical intraepithelial neoplasia grade 2 (CIN 2) or worse disease.
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Concurrent infection with multiple human papillomavirus types: pooled analysis of the IARC HPV Prevalence Surveys.
Cancer Epidemiol. Biomarkers Prev.
PUBLISHED: 02-10-2010
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To understand viral interactions and the cross-reactivity of natural or vaccine-induced responses, we investigated whether multiple human papillomavirus (HPV) infections, particularly certain combinations of types, have the tendency to cluster together. Cervical cell samples were collected from women in the framework of the IARC HPV Prevalence Surveys. Women with a cytology diagnosis of high-grade squamous intraepithelial lesion or worse were excluded, leaving 13,961 women for this analysis. HPV DNA was assessed using a general GP5+/6+ primer-mediated PCR. HPV genotyping was done using enzyme immunoassay or reverse line blot analysis. Logistic regression with type-specific HPV positivity as an outcome was used, adjusted for age, study area, and lifetime number of sexual partners. Woman-level random effects were added to represent unobservable risk factors common to all HPV types. The observed-to-expected ratio was 1.20 (95% credible interval, 1.14-1.26) for infection with two HPV types and 1.02 (95% credible interval, 0.91-1.12) for three for more types, with the best possible adjustment. Among combinations of specific HPV types, the tendency to cluster increased with the genetic similarity of the L1 region. High observed-to-expected ratios were found for closely homologous types, including HPV33/58, 18/45, 33/35, and 31/35. The excess of multiple infections, however, was clearly evident only when enzyme immunoassay, and not reverse line blot, was used as the genotyping method. The different results by genotyping method suggest that the apparent clustering of HPV infections was an artifact of the measurement process. Further investigation is required to evaluate other widely used HPV detection methods.
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Oral human papillomavirus in healthy individuals: a systematic review of the literature.
Sex Transm Dis
PUBLISHED: 01-19-2010
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Human papillomavirus type 16 (HPV16) is a common infection in the anogenital tract. HPV16 DNA detected in oral specimens has recently been identified as a risk factor for some oropharyngeal cancers. The reported prevalence of oral HPV infection from individual studies is highly variable.
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Common genetic variants and risk for HPV persistence and progression to cervical cancer.
PLoS ONE
PUBLISHED: 01-13-2010
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HPV infrequently persists and progresses to cervical cancer. We examined host genetic factors hypothesized to play a role in determining which subset of individuals infected with oncogenic human papillomavirus (HPV) have persistent infection and further develop cervical pre-cancer/cancer compared to the majority of infected individuals who will clear infection.We evaluated 7140 tag single nucleotide polymorphisms (SNPs) from 305 candidate genes hypothesized to be involved in DNA repair, viral infection and cell entry in 416 cervical intraepithelial neoplasia 3 (CIN3)/cancer cases, 356 HPV persistent women (median: 25 months), and 425 random controls (RC) from the 10,049 women Guanacaste Costa Rica Natural History study. We used logistic regression to compute odds ratios and p-trend for CIN3/cancer and HPV persistence in relation to SNP genotypes and haplotypes (adjusted for age). We obtained pathway and gene-level summary of associations by computing the adaptive combination of p-values. Genes/regions statistically significantly associated with CIN3/cancer included the viral infection and cell entry genes 2,5 oligoadenylate synthetase gene 3 (OAS3), sulfatase 1 (SULF1), and interferon gamma (IFNG); the DNA repair genes deoxyuridine triphosphate (DUT), dosage suppressor of mck 1 homolog (DMC1), and general transcription factor IIH, polypeptide 3 (GTF2H4); and the EVER1 and EVER2 genes (p<0.01). From each region, the single most significant SNPs associated with CIN3/cancer were OAS3 rs12302655, SULF1 rs4737999, IFNG rs11177074, DUT rs3784621, DMC1 rs5757133, GTF2H4 rs2894054, EVER1/EVER2 rs9893818 (p-trends
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Lack of heterogeneity of HPV16 E7 sequence compared with HPV31 and HPV73 may be related to its unique carcinogenic properties.
Arch. Virol.
PUBLISHED: 01-06-2010
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To assess the role of human papillomavirus virus (HPV) genetics in cervical lesions, we sequenced the E7 gene of HPV16, 31, or 73 from singly infected women who (1) cleared the infection quickly, (2) had type-specific persistent infection, or (3) progressed to CIN2 or worse lesions. Four of the 296 HPV16 E7 nucleotides were variable, compared with 7 of 296 for HPV31 E7 and 4 of 296 for HPV73 E7. While most of the polymorphisms in HPV31 and -73 resulted in non-synonymous amino acid changes, the polymorphisms in the HPV16 E7 resulted in synonymous changes. The lack of heterogeneity of HPV16 E7 suggests high evolutionary purifying selection that might be related to the unique carcinogenicity of HPV16.
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Determinants and correlation of systemic and cervical concentrations of total IgA and IgG.
Cancer Epidemiol. Biomarkers Prev.
PUBLISHED: 10-10-2009
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We compared systemic and cervical total IgA and IgG during the menstrual cycle among 154 women who attended clinic visits at follicular/early, periovulatory/mid, and luteal/late phases of menstrual cycle. Paired serum and cervical secretions were tested at each visit for total IgA and IgG using ELISA. Geometric mean titers for systemic IgA and IgG were 1.92 and 8.25 mg/mL, respectively. There were no differences in titers by menstrual cycle phase, neither were they correlated to cervical titers (rho = 0.17 and 0.16, respectively). The lack of correlation between systemic and cervical total IgA and IgG suggests that systemic concentrations are not reflective of cervical levels.
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Total exposure and exposure rate effects for alcohol and smoking and risk of head and neck cancer: a pooled analysis of case-control studies.
Am. J. Epidemiol.
PUBLISHED: 09-10-2009
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Although cigarette smoking and alcohol consumption increase risk for head and neck cancers, there have been few attempts to model risks quantitatively and to formally evaluate cancer site-specific risks. The authors pooled data from 15 case-control studies and modeled the excess odds ratio (EOR) to assess risk by total exposure (pack-years and drink-years) and its modification by exposure rate (cigarettes/day and drinks/day). The smoking analysis included 1,761 laryngeal, 2,453 pharyngeal, and 1,990 oral cavity cancers, and the alcohol analysis included 2,551 laryngeal, 3,693 pharyngeal, and 3,116 oval cavity cancers, with over 8,000 controls. Above 15 cigarettes/day, the EOR/pack-year decreased with increasing cigarettes/day, suggesting that greater cigarettes/day for a shorter duration was less deleterious than fewer cigarettes/day for a longer duration. Estimates of EOR/pack-year were homogeneous across sites, while the effects of cigarettes/day varied, indicating that the greater laryngeal cancer risk derived from differential cigarettes/day effects and not pack-years. EOR/drink-year estimates increased through 10 drinks/day, suggesting that greater drinks/day for a shorter duration was more deleterious than fewer drinks/day for a longer duration. Above 10 drinks/day, data were limited. EOR/drink-year estimates varied by site, while drinks/day effects were homogeneous, indicating that the greater pharyngeal/oral cavity cancer risk with alcohol consumption derived from the differential effects of drink-years and not drinks/day.
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JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

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In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.