bluuebunny/crossref_metadata_2025_split huggingface dataset:
O1-S02.05 Population based surveillance for cervical intraepithelial neoplasia grade 3 and adenocarcinoma in situ in three central cancer registries, USA 2009
Authors: Flagg E W , Datta S Deblina , Lyu C , Nagaraja J , Copeland G , Silva W , Peters E , Cole L , Tucker T , Byrne M J , Unger E R , Saraiya M , Weinstock H 
Published: July 2011

BackgroundHuman papillomavirus (HPV) vaccine has been recommended routinely to 11–12-year-old US girls for cervical cancer prevention since 2006, and evaluation of the population impact of HPV vaccine is a critical need. In addition to measuring the impact of HPV vaccines on cervical cancer incidence, surveillance should include endpoints more proximal in time to HPV infection such as cervical intraepithelial neoplasia grade 3 (CIN3) and adenocarcinoma in situ (AIS). These immediate precursors to invasive cervical cancer manifest only 5–10 years after HPV infection. Although CIN3/AIS are detected during cervical cancer screening, these lesions are not routinely reported to US central cancer registries (CCRs). Compared to other precursor lesions, CIN3/AIS show the most consistent inter-pathologist agreement in histopathology interpretation making them the most suitable precursor lesion surveillance endpoints.MethodsThe Centers for Disease Control and Prevention conducted a project in three statewide CCRs to assess the feasibility of collecting data on CIN3/AIS lesions using existing registry infrastructure, a standardised case definition, and well-defined coding rules. State-specific vintage 2009 bridged-race postcensal population estimates were used to calculate incidence rates.ResultsStatewide age-adjusted incidence rates of CIN3/AIS in 2009, using the 2000 US Standard Population, were 76.8 (Kentucky), 57.5 (Michigan), and 54.7 (Louisiana) per 100 000 women. Highest rates were observed in those aged 20 to 29; rates among these women were 272.8 in Kentucky, 196.7 in Louisiana, and 192.6 in Michigan. Race was missing for 16% of records. Among records for which race was reported, incidence rates in Kentucky were highest for whites, while rates in Michigan were highest for blacks; in Louisiana rates did not differ significantly between whites and blacks. In each state, overall rates of CIN3/AIS were over sixfold higher than invasive cervical cancer rates. Only 3.8% of cervical lesions were AIS.ConclusionsThese results are the first reports of statewide population based incidence of CIN3/AIS in the US, and demonstrate that routine collection of CIN3/AIS lesions by cancer registries is feasible and could provide an earlier endpoint than cervical cancer with which to evaluate the impact of HPV vaccination in the US. Sentinel registries should be established to collect ongoing data on CIN3/AIS to monitor the impact of HPV vaccine in the US.
O3-S2.02 Long-term efficacy of human papillomavirus vaccination against CIN3 and invasive carcinoma: registry based follow-up of a phase iii trial (FUTURE II)
Authors: Paavonen J , Rana M , Apter D , Luostarinen T , Pukkala E , Lehtinen M 
Published: July 2011

BackgroundHuman papilloma viruses (HPV) 16/18 are known to cause approximately 70% of cervical cancers. Phase III clinical trials of HPV vaccination have demonstrated >95% efficacy against persistent HPV type 16/18 infections and associated cervical intraepithelial neoplasia (CIN) grade 2+ lesions, and up to 90% efficacy against all CIN3+ lesions. A long-term follow-up is, however, needed to confirm the protective efficacy against cervical carcinoma.MethodsPhase III clinical trial (FUTURE II) consisted of intensive clinical 4-year follow-up including health education and counselling. The intervention potentially affects the incidence of neoplasia also in the placebo group. To increase power of the long-term follow-up and to determine the impact of the clinical intervention as such, a population based reference cohort of similarly aged women not exposed to any intervention was enrolled at the same time from the same communities. The HPV vaccine cohort and placebo vaccine cohort of 16–17-year-old women from the Finnish FUTURE II trial (N=1749) and a reference cohort of 18–19-year-old women (N=15 744) were linked with the Finnish Cancer Registry to determine the incidence of CIN3 and cervical cancer (CIN3+) during the passive follow-up, starting 6 months after the clinical follow-up of the phase III trial was completed.Results & ConclusionsCurrently the incidence of CIN3+ at the age of 20–24 years is 95 per 100 000 person years in Finland (http://www.cancer.fi). The incidence doubles in 5 to 10 years as the cohorts age. Thus, in less than 10 years the cumulative incidence yields 80% power to demonstrate 90% vaccine efficacy against cervical CIN3+. During the first 2 years this passive registry-based follow-up identified no CIN3+ cases in the HPV vaccine cohort, two cases in the placebo vaccine cohort, and 21 cases in the unvaccinated reference cohort suggesting that the vaccine efficacy translates into efficacy against cervical cancer. The passive follow-up continues and new cases emerging in future will be monitored by redoing linkage with the population-based cancer register at specific time intervals in the future, which will effectively add up person years to our follow-up study. In conclusion, valid comparisons between the vaccine and placebo recipients (excluding cross-vaccinated placebo vaccine recipients) and the reference cohort not exposed to intervention are feasible, and will be critical to define more definitively the long-term protection provided by HPV vaccination against the hard endpoints.
O3-S2.06 The effect ofTrichomonas vaginalis(TV) infection on the vaginal microbiome
Authors: Martin D H , Zozaya-Hinchliffe M , Lillis R , Miller J , Ferris M 
Published: July 2011

BackgroundAmong pregnant women the prevalence of TV infection is highest in women who have intermediate Nugent scores (NS) compared to those with low and high scores reflective of normal and bacterial vaginosis (BV) types of vaginal flora. The goals of this study were to determine if this relationship held true for non pregnant women and to determine if TV infection was associated with changes in the vaginal microbiome.MethodsThe study subjects were 394 women enrolled in a cross-sectional study of the aetiology of cervicitis in the New Orleans STD clinic. TV was diagnosed using the InPouch culture method. NS was determined using standard criteria.C trachomatis(CT),N gonorrhoeae(NG), andM genitalium(MG) were diagnosed using NAATs. DNA was extracted from a vaginal swab and stored. Associations between NS and STIs and NS and sexual behaviour were analysed for all 394 women. 454 pyrosequencing analyses were performed on vaginal DNA from 30 TV positive and 30 TV negative samples evenly divided between those with normal, intermediate, and BV flora as determined by NS.Results95% of enrolled women were African American and the mean age of the population was 25.6 years. The prevalence of TV (y axis) by 5 NS categories (x axis) is shown in the Abstract O3-S2.06 figure 1. As opposed to TV, the prevalence rates for CT, GC, and MG were highest among women with NS of 7–10. Also there was no difference in high risk sexual behaviour between those with low and high NS. These data suggested that the striking decrease in TV prevalence observed among women with BV was the result of vaginal environmental factors, not decreased risk for STIs. A heat map based on pyrosequencing data showed that the vaginal flora of 18/30 of the women positive for TV had similar microbiomes which were distinctly different from those of the other 42 women. In the former group,Mycoplasma spp. andUreaplasma spp. were more abundant than in the latter group while the reverse was true ofMegasphaera spp. andGardnerella spp.Abstract O3-S2.06 Figure 1T. vaginalisPrevalence by Nugent Score.ConclusionsThough published research shows that the incidence of TV is highest in women with BV, our data along with those from a previous study in pregnant women clearly establish that TV prevalence is highest in women with intermediate NS. These data in conjunction with our pyrosequencing results suggest that following infection TV modifies the vaginal microbiome by suppressing some of the BV associated organisms and enhancing the abundance of mycoplasmas.
O3-S3.02 Performance of the bio-rad Dx CT/NG/MG assay for simultaneous detection ofChlamydia trachomatis,Neisseria gonorrhoeaeandMycoplasma genitaliumin urogenital samples
Authors: Bébéar C , Le Roy Chloe , Le Hen Isabelle , Clerc M , Arfel V , Normandin F , de Barbeyrac B 
Published: July 2011

ObjectivesTo investigate the performance of the Bio-Rad Dx CT/NG/MG Assay with an internal control for the detection ofChlamydia trachomatis(CT) andMycoplasma genitalium(MG) in urogenital samples in comparison with the Roche Cobas TaqMan CT test and an in-house TaqMan PCR test for MG. ForNeisseria gonorrhoeae(NG), only positive PCR results were controlled by culture.MethodsIn this prospective study, urogenital samples were obtained from symptomatic and asymptomatic patients attending the STI center of Bordeaux, France, from January to April 2010. For symptomatic women and men, two endocervical swabs and two urethral swabs were collected, respectively. All patients and women collected first-catch urines and two vaginal swabs, respectively. Two swabs per site were used, a flocked swab in the universal transport medium and the Bio-Rad flocked swab in its transport medium. For the Bio-Rad CT/NG/MG assay, the DNA was manually extracted and amplified according to the manufacturer's instructions. For the comparator PCR tests, DNA was extracted using the MagNa Pure LC instrument (Roche Diagnostics) and amplified with the Cobas TaqMan CT 48 assay (Roche Diagnostics) and with a MgPa-targeted PCR assay on an ABI Prism 7000 (Applied Biosystems) for MG. The patient was considered as infected if at least two of the 4 or 6 PCR tests performed according to the gender and characteristics of patients, were positive. For asymptomatic men, in case of discrepancy, the urine sample was retested by both methods and the patient was considered infected if at least two of the four PCR results were positive for the considered microorganism.ResultsA total of 658 clinical specimens (259 male and 180 female urines, 191 vaginal, 21 cervix and seven urethral swabs) from 453 patients were analysed. The prevalence of CT and MG infections was 7.7% (20/260) and 1.9% (5/260) in men and 10.3% (20/193) and 2% (4/193) in women, respectively. The Bio-Rad Dx CT/NG/MG test sensitivity was 100% for CT and MG in men and women. In male urines, the specificity was 99.6% for CT and 100% for MG. In women, the specificity was 99.5% for swabs and 100% for urines for CT and MG. All 7 NG-PCR positive samples were positive by culture. Patients were co-infected in 5/56 (9%) with CT/MG in three cases and CT/NG in two cases.ConclusionThe Bio-Rad Dx CT/NG/MG Assay was found to be very effective for the simultaneous detection of CT, MG, and NG infections in urogenital specimens.
O3-S3.05 Chlamydia trachomatisdetection by nucleic acid amplification assay using rectal swabs
Authors: Williams J , Van Der Pol B , Pantone A 
Published: July 2011

BackgroundRectal infection withC trachomatis(CT) is increasing in many settings; however, there are currently no FDA approved NAAT for use with rectal specimens. Access to reliable diagnostics using rectal specimens is critical to both surveillance and disease management and control. This is important as CT culture has been shown to have lower sensitivity, 54.8 %, when compared to NAAT in our patient population. The objective of this study was to evaluate the performance of rectal swabs tested on the Abbott m2000 (m2000) as compared to the GenProbe APTIMA Combo 2 (AC2) for detection of CT.MethodsRectal samples were collected and placed into chlamydia transport medium (CTM) for testing by both m2000 and AC2 for CT. CTM was split as follows; 1 ml into an empty m2000 tube; 100 ul into m2000 multi-collect tube containing buffer; 100 ul into an AC2 swab collection tube. From this point forward, testing was performed according to the package insert for both platforms with two CT negative samples being tested for every positive one. ĸ scores were determined to measure agreement between the m2000 and AC2 collection tubes.ResultsA total of 59 samples were tested for CT by m2000 and AC2. AC2 was considered the reference standard for this study with 20 samples identified as positive and 39 as negative for CT. Neat CTM placed into an empty m2000 tube detected 95% (19/20) and had a single positive that was not detected by AC2 (38/39 agreed). The single neat CTM missed by m2000 was positive in the spiked multi-collect tube. CTM spiked into an m2000 multi-collect tubes also detected all but one of the infections identified by AC2 (19/20) and negatives agreed completely (39/39). The m2000 multi-collect miss was CT positive in the neat sample. Both collection methods on the m2000 generated results that had very good agreement with the reference test: ? scores were 0.924 for empty and 0.962 for multi-collect tubes.ConclusionThe m2000 has excellent performance characteristics compared to AC2 for the detection of CT. NAATs offer an alternative to culture for the detection of CT in rectal samples, and are less susceptible to transport conditions and sterility that are often a concern with culture. The collection of rectal specimens in CTM offers the opportunity for routine testing using multiple collection devices and platforms with the data suggesting that the m2000 assay can be used to meet the revised CDC recommendations for rectal testing for CT.
O1-S02.06 Detection of cervical cancer precursors and associated HPV types in the USA: HPV-IMPACT preliminary results
Authors: Powell S E , Hariri S , Steinau M , Bauer H , Bennett N , Bloch K , Schafer S , Niccolai L , Unger E R , Markowitz L 
Published: July 2011

BackgroundCervical intraepithelial neoplasia (CIN) grade 2 or 3 and adenocarcinoma in situ (AIS) (CIN2+) can be used to monitor HPV vaccine impact. This spectrum of preinvasive cervical lesions are commonly associated with multiple HPV types and detected through screening. This abstract describes baseline CIN2+ data and associated HPV types among defined populations of US females.MethodsAs part of a vaccine impact monitoring project (HPV-IMPACT), CIN2+ cases in females 18–39 years were reported from pathology laboratories in five catchment areas (CA, CT, NY, OR, TN). One diagnostic block was selected and unstained serial sections were prepared for PCR. Extracts from samples with residual lesion on both H&Es were used in Roche Linear array to detect and type HPV. CIN2/3 diagnosis rates were determined in catchment areas (CA, CT and NY) with complete case reporting. HPV typing data were analysed from all five defined catchment areas.ResultsIn 2008, rates per 1000 population in 18–39-year-old females were 2.8 in CA, 5.3 in CT and 4.9 in NY. In all five sites, CIN2 was most common (49%), followed by CIN3 (31%) and AIS (2%). The proportion of lesions not distinguished by grade (CIN2/3) varied across sites (from 12 to 27%). Median diagnosis age was 31 years in CA, 29 in CT, 27 in NY, 29 in OR, 28 in TN. Among 5035 18–39-year-old females, 1413 (28%) specimens were tested; 96% were HPV DNA positive. HPV16 was most prevalent (47%), followed by HPV31 (11%), HPV52 (9%) and HPV51 (8%). HPV18 prevalence was 5.4%. HPV16 prevalence varied by diagnosis: 38% in CIN2, 51% in CIN2/3, and 59% in CIN3.ConclusionsCIN2+ rates varied by catchment area, possibly reflecting differences in screening or case ascertainment. HPV16 or 18 were present in ∼52% of lesions. Type-specific monitoring of CIN2+ can allow evaluation of vaccine impact on cervical disease, and may be useful in determining whether type replacement occurs.
O3-S3.06 Rescreening for chlamydial infection using home-based, self-obtained vaginal swabs: a randomised controlled trial in family planning clinic clients
Authors: Xu F , Stoner B , Taylor S , Mena L , Tian L , Papp J , Hutchins K , Martin D , Markowitz L 
Published: July 2011

BackgroundFamily planning clinics provide contraceptive and preventive services for millions of low-income individuals. Screening and treatment for Chlamydia trachomatis infection in these clinics is a major part of the chlamydia control program in the USA. For women diagnosed with chlamydia, rescreening 3 months after treatment is recommended according to national guidelines. However, rescreening rates are low. The time and effort needed for patients to return to the clinic and the lack of access to follow-up care may contribute to the poor adherence to the rescreening recommendation.MethodsWe conducted a randomised controlled trial in family planning clinics in three cities. After informed consent, women/girls >16 years treated for laboratory-confirmed chlamydial infection were randomly assigned to the Home Group (mailed a vaginal swab kit for self collection at home) or the Clinic Group (made a clinic appointment) for rescreening at 3 months following treatment. Reminder calls were made about 2 weeks before scheduled rescreening. The endpoint was rescreening within a 7 week window, 1 week before to 6 weeks after, the scheduled rescreening date.Results404 women were enrolled and their group assignments were randomised by opening centrally stuffed envelops. Women assigned to the Home Group had higher rescreening rate than those in the Clinic Group: Overall, 40.8% of 196 in the Home Group and 20.7% of 208 in the Clinic Group were rescreened (p<0.001). The rescreening rates were 38.4% (Home) vs 19.8% (Clinic) among those living with parents, and 48.2% (Home) vs 21.2% (Clinic) among those with a history of chlamydia infection prior to the treated episode at enrolment (both p<0.001). Among women reached by a reminder call, rescreening rates were significantly higher in the Home Group (59.2% of 130) than in the Clinic Group (37.8% of 111) (p<0.001). Among 163 women not reached by the reminder call, the rescreening rate were low (<5%) in both groups. In the Home Group, 12 tested positive for chlamydia compared to 8 in the Clinic Group, and the rate of reinfection was 12.9% in the Home Group and 14.6% in the Clinic Group (p=0.8).ConclusionsUse of home-based, self-obtained vaginal swabs resulted in a significant increase in rescreening rates compared to rescreening in the clinic. Our findings indicate a role for home-based specimen collection as an alternative to clinic-based rescreening for chlamydia in women.
O3-S4.02 Is single dose azithromycin adequate for asymptomatic rectal chlamydia?
Authors: Drummond F , Ryder N , Wand H , Guy R , Read P , McNulty A , Wray L , Donovan B 
Published: July 2011

BackgroundAzithromycin is the recommended first-line therapy for asymptomatic rectal chlamydia. However a recent European study reported significant numbers of treatment failures, with higher failure rates in HIV positive men. In 2009, the Sydney Sexual Health Centre instituted a 6 week re-test policy for all cases of asymptomatic rectal chlamydia to assess the extent of azithromycin treatment failures.MethodsWe conducted a retrospective audit of all men who have sex with men (MSM) diagnosed with asymptomatic rectal chlamydia in 2009. MSM with anal symptoms were excluded from this analysis, due to the possibility of lymphogranuloma venereum. We then categorised the infections present at re-testing as probable re-infections (men reported ongoing sexual activity with an untreated partner) or probable treatment failures (men did not have any obvious ongoing exposure, either because they did not report any further anal sex with any existing partners or because condoms were used consistently with all partners).ResultsIn the 12-month period there were 116 asymptomatic MSM treated for rectal chlamydia with 1 gram azithromycin as a single dose. Fourteen (12%) of the men were HIV positive. The median age was 33 years (range 20–64 years). Of the 116 men, 85 (73%) returned at varying times; median time of 10 weeks (78 days, range 21–372 days. Of the 85 men who returned, 11 (13%) were persistently positive and the median time to re-test was 11 weeks (78 days, range 47–209 days). Six of the 11 men were classified as probable re-infection and five as probable treatment failures, equating to an efficacy of 94%. None of the men classified as probable treatment failures were HIV positive.ConclusionsInterpreted conservatively, the azithromycin treatment failure rate could have been as high as 13% in our study. However most of these cases could be explained by re-infection suggesting an actual treatment failure rate of 6%. There was no evidence azithromycin is an ineffective first-line therapy for asymptomatic rectal chlamydia in MSM, but prospective studies would be welcome.
O3-S5.01 Impact of AIC316, a novel antiviral helicase-primase inhibitor, on genital HSV shedding: randomised, double-blind, placebo-controlled trial
Authors: Wald A , Stoelben S , Tyring S , Warren T , Johnston C , Huang M L , Timmler B , Ruebsamen-Schaeff H , Corey L , Birkmann A 
Published: July 2011

BackgroundCurrent treatments for HSV infection are imperfect, do not completely abrogate viral shedding or transmission, and do not interrupt HSV-2—HIV interactions. AIC316 is a helicase-primase inhibitor, a new class of anti-HSV compounds that has a distinct mode of action from currently available nucleoside analogues.MethodsWe investigated the safety and efficacy of AIC316 in patients with genital HSV-2 infection in a Phase 2, randomised, multicenter, parallel, double-blind, placebo-controlled trial of 4 different doses of AIC316 administered orally for 4 weeks. Participants were randomised 1:1:1:1:1 to one of the following dose groups: 5 mg given once daily (qd), 25 mg qd, 75 mg qd, 400 mg given once-a-week, or matching placebo. Participants in the once daily dose groups received a loading dose. During the trial period participants obtained a swab of genital secretions daily and maintained a diary of genital lesions. The primary endpoint was the rate of genital HSV shedding measured by HSV DNA PCR in the AIC316 groups vs placebo.Results156 (105 women and 51 men) healthy, immunocompetent, HSV-2 positive participants with a history of 1–9 recurrences per year prior to trial entry, or previous suppressive therapy, were randomised by seven US sites between May 2010 and October 2010. 147 completed the trial. Overall, about 9000 swabs for HSV PCR were collected and assayed for HSV DNA by a sensitive and accurate assay that can detect >150 copies/ml. The first results of these assessments will be presented.ConclusionThe trial will provide insight into the antiviral activity of the novel agent AIC316 for genital HSV infections. This trial design presents a robust and efficient method for evaluating antiviral activity of candidate agents for mucocutaneous HSV infections. These initial efficacy and safety results will lead to selecting the dose for further trials with AIC316.