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design and methods of a population-based natural history study of cervical neoplasia in a rural province of costa rica: the guanacaste project.this paper reports on the enrollment phase of a population-based natural history study of cervical neoplasia in guanacaste, a rural province of costa rica with consistently high rates of invasive cervical cancer. the main goals of the study are to investigate the role of human papillomavirus (hpv) infection and its co-factors in the etiology of high-grade cervical neoplasia, and to evaluate new cervical cancer screening technologies. to begin, a random sample of censal segments was selected and ...19979180057
epidemiologic determinants of vaginal ph.this study was undertaken to evaluate the relationship between vaginal ph and factors related to cervical cancer.199910329856
population-based study of human papillomavirus infection and cervical neoplasia in rural costa rica.human papillomavirus (hpv) is the main cause of cervical neoplasia. because few population-based studies have investigated the prevalence of type-specific infection in relation to cervical disease, we studied a high-risk population, estimating the prevalence of hpv infection and the risk associated with various hpv types.200010716964
human leukocyte antigen class i and ii alleles and risk of cervical neoplasia: results from a population-based study in costa rica.to examine human leukocyte antigen (hla) involvement in the development of all grades of cervical neoplasia, a nested case-control study of 10,077 women in guanacaste, costa rica, was conducted. participants had invasive cervical cancer, high-grade squamous intraepithelial lesions (hsils; n=166), or low-grade squamous intraepithelial lesions (lsils); were positive for human papillomavirus (hpv) with no evidence of cervical neoplasia (n=320); or were hpv negative with no evidence of cervical neop ...200111679920
seroprevalence of human papillomavirus-16, -18, -31, and -45 in a population-based cohort of 10000 women in costa rica.human papillomavirus (hpv) seroprevalence and determinants of seropositivity were assessed in a 10049-woman population-based cohort in guanacaste, costa rica. serologic responses based on vlp-based elisa were obtained from the plasma collected at study enrollment in 1993/1994 for hpv-16 (n=9949), hpv-18 (n=9928), hpv-31 (n=9932), and hpv-45 (n=3019). seropositivity was defined as five standard deviations above the mean optical density obtained for studied virgins (n=573). hpv-16, -18, -31, and - ...200314520455
immune profiling of plasma and cervical secretions using recycling immunoaffinity chromatography.small volumes of cervical secretions have limited measurements of immunity at the cervix, which may be important to studies of human papillomavirus (hpv). we report the use of recycling immunoaffinity chromatography to efficiently study immune profiles in cervical secretions. frozen pairs of plasma and cervical secretions (collected on ophthalmic sponges) were selected randomly from women with normal cervical cytology (n = 50) participating in a natural history study of hpv in guanacaste, costa ...200314693736
description of a seven-year prospective study of human papillomavirus infection and cervical neoplasia among 10000 women in guanacaste, costa rica,.the guanacaste study ("guanacaste project," or gp), was designed to investigate the role of human papillomavirus (hpv) infection and its cofactors in the development of cervical neoplasia and to evaluate new cervical cancer screening technologies. the follow-up phase of the gp was designed to study why a small proportion of women infected with hpv develop cervical intraepithelial neoplasia grade 2 (cin 2), cin 3, or cancer (these three together are globally referred to as > or = cin 2, that is, ...200415030652
determinants of human papillomavirus 16 serological conversion and persistence in a population-based cohort of 10 000 women in costa rica.determinants of human papillomavirus (hpv)-16 serological conversion and persistence were assessed in a population-based cohort of 10 049 women in guanacaste, costa rica. serologic responses to hpv-16 were measured in 7986 women by vlp-based enzyme-linked immunosorbent assay at both study enrollment (1993/94) and at 5-7 years of follow-up. seropositive women were defined as >/=5 standard deviations above the mean optical density obtained for studied virgins at enrollment (n=573). seroconnversion ...200415292929
validation of p16ink4a as a marker of oncogenic human papillomavirus infection in cervical biopsies from a population-based cohort in costa rica.due to the high prevalence of cancer-associated types of human papillomavirus (hpv) and the poorly reproducible histologic classification of low-grade lesions, identifying infected women at highest risk for cancer prior to neoplastic progression remains a challenge. we therefore explored the utility of p16ink4a immunostaining as a potential diagnostic and prognostic biomarker for cervical neoplasia using paraffin-embedded tissue blocks (punch biopsies and loop electrosurgical excision procedures ...200415298958
epidemiologic profile of type-specific human papillomavirus infection and cervical neoplasia in guanacaste, costa rica.detailed epidemiologic studies of cervical type-specific human papillomavirus (hpv) infection in large populations are scarce.200515871111
a prospective study of age trends in cervical human papillomavirus acquisition and persistence in guanacaste, costa rica.cross-sectional human papillomavirus (hpv) dna prevalence peaks at young ages, reflecting sexual acquisition and typically rapid clearance. in some populations, hpv prevalence demonstrates a second peak in older women. longitudinal data may help to explain this second peak.200515871112
age-related changes of the cervix influence human papillomavirus type distribution.approximately 15 human papillomavirus (hpv) types cause virtually all cervical cancer whereas other hpv types are unrelated to cancer. we were interested in whether some noncarcinogenic types differ from carcinogenic in their affinity for the cervical transformation zone, where nearly all hpv-induced cancers occur. to examine this possibility, we tested cervical specimens from 8,374 women without cervical precancer and cancer participating in a population-based study in guanacaste for >40 hpv ty ...200616424061
the natural history of human papillomavirus infection and cervical intraepithelial neoplasia among young women in the guanacaste cohort shortly after initiation of sexual life.cross-sectional analyses of our 10,000-woman, population-based guanacaste cohort suggest a lag of > or =10 years between the peak of human papillomavirus (hpv) infection and the later peak of cervical intraepithelial neoplasia grade 3 (cin 3). we wanted to explore early hpv natural history and cin 3 prospectively.200717237737
comparison of the spf10-lipa system to the hybrid capture 2 assay for detection of carcinogenic human papillomavirus genotypes among 5,683 young women in guanacaste, costa rica.the objective of this analysis was to compare the performance characteristics of two human papillomavirus (hpv) dna detections assays, the hybrid capture 2 assay (hc2) and the spf(10) assay, for the detection of carcinogenic hpv. data are from the enrollment visits of women who participated in the randomized, double-blind, placebo-controlled phase iii hpv16/18 vaccine trial in guanacaste, costa rica. we compared the results of hc2 and spf(10) testing of cervical specimens. since the line probe a ...200717344361
high load for most high risk human papillomavirus genotypes is associated with prevalent cervical cancer precursors but only hpv16 load predicts the development of incident disease.cervicovaginal human papillomavirus (hpv) viral load has been purported as a potential marker for the detection of high-grade cervical intraepithelial neoplasia or cancer (>/=cin2). to examine disease association with type-specific viral load for the full-range of anogenital hpv infections, we conducted cross-sectional and prospective analyses of approximately 2,000 hpv-infected women from a 10,000-woman population-based study in guanacaste, costa rica with 7 years of follow-up. cervical specime ...200717722112
rapid clearance of human papillomavirus and implications for clinical focus on persistent infections.health professionals and the public need to understand the natural history of human papillomavirus (hpv) infections of the cervix to best use the information provided by new molecular screening tests. we investigated outcomes of 800 carcinogenic hpv infections detected in 599 women at enrollment into a population-based cohort (guanacaste, costa rica). for individual infections, we calculated cumulative proportions of three outcomes (viral clearance, persistence without cervical intraepithelial n ...200818364507
rationale and design of a community-based double-blind randomized clinical trial of an hpv 16 and 18 vaccine in guanacaste, costa rica.we report the rationale, design, methods and details of participation of a community-based, double-blind, randomized clinical trial of an hpv 16 and 18 vaccine conducted in two provinces of costa rica to investigate the efficacy and population impact of the vaccine in the prevention of cervical cancer precursors. more than 24,000 women between 18 and 25 years of age were invited to participate and pre-screened for eligibility, with recruitment of 7466 women (30% of those pre-screened, 59% of tho ...200818640170
common variants in immune and dna repair genes and risk for human papillomavirus persistence and progression to cervical cancer.we examined host genetic factors to identify those more common in individuals whose human papillomavirus (hpv) infections were most likely to persist and progress to cervical intraepithelial neoplasia grade 3 (cin3) and cancer.200919012493
human papillomavirus types by age in cervical cancer precursors: predominance of human papillomavirus 16 in young women.in a population-based study conducted in guanacaste, costa rica, we investigated the human papillomavirus (hpv) types detected in 233 cases of cervical intraepithelial neoplasia (cin) 2/3 and cancer by age. cin2+ and cin3+ in young women were significantly more likely to be associated with hpv 16 than the same lesions in older women (80% of cin3+ were associated with hpv 16 among women ages 18-26 years compared with only 32% among women older than 55 years; ptrend=0.018). there were no differenc ...200919273486
common genetic variation in tp53 and risk of human papillomavirus persistence and progression to cin3/cancer revisited.driven by findings that human papillomavirus (hpv)-induced degradation of p53 differs by a tp53 polymorphism at codon 72 (pro72arg), past studies of tp53 genetic variants and cervical cancer have focused on this nonsynonymous polymorphism, with mixed results. we analyzed common single nucleotide polymorphisms (snp) across the tp53 locus in a population-based nested case-control study in guanacaste, costa rica. we evaluated 11 snps, including pro72arg (rs1042522), among 1,281 women: 465 with cerv ...200919423538
neither one-time negative screening tests nor negative colposcopy provides absolute reassurance against cervical cancer.a population sample of 10,049 women living in guanacaste, costa rica, was recruited into a natural history of human papillomavirus (hpv) and cervical neoplasia study in 1993-1994. at the enrollment visit, we applied multiple state-of-the-art cervical cancer screening methods to detect prevalent cervical cancer and to prevent subsequent cervical cancers by the timely detection and treatment of precancerous lesions. women were screened at enrollment with 3 kinds of cytology (often reviewed by more ...200919569231
short term persistence of human papillomavirus and risk of cervical precancer and cancer: population based cohort study.to evaluate the cumulative incidence of cervical intraepithelial neoplasia ii or worse (grade ii+) or cervical intraepithelial neoplasia grade iii+ after short term persistence of prevalently detected carcinogenic human papillomavirus (hpv).200919638649
longitudinal study of human papillomavirus persistence and cervical intraepithelial neoplasia grade 2/3: critical role of duration of infection.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 women's 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.201020157096
establishment and operation of a biorepository for molecular epidemiologic studies in costa rica.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 vacc ...201020332271
persistence of concurrent infections with multiple human papillomavirus types: a population-based cohort study.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 ...201121257737
long-term persistence of prevalently detected human papillomavirus infections in the absence of detectable cervical precancer and cancer.detailed descriptions of long-term persistence of human papillomavirus (hpv) in the absence of cervical precancer are lacking.201121343148
switch from cytology-based to hpv-based cervical screening: implications for colposcopy.background: hpv testing is more sensitive than cytology; some cervical cancer prevention programs will switch from cytology to carcinogenic hpv test-based screening. objective: to evaluate the clinical implications of a switch to hpv test-based screening on performance and workload of colposcopy. methods: 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 phot ...201121607948
clustering of multiple human papillomavirus infections in women from a population-based study in guanacaste, costa rica.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.201121742837
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.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).201121865087
Longitudinal Analysis of Carcinogenic Human Papillomavirus Infection and Associated Cytologic Abnormalities in the Guanacaste Natural History Study: Looking Ahead to Cotesting.Background. 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.Methods. At each semiannual or annual visit, cervi ...201122147792
prevention of persistent human papillomavirus infection by an hpv16/18 vaccine: a community-based randomized clinical trial in guanacaste, costa rica.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, 82.0-9 ...201122586631
cervical cancer incidence after screening with hpv, cytology, and visual methods: 18-year follow-up of the guanacaste cohort.testing negative for human papillomavirus (hpv) predicts long-term reassurance against invasive cervical cancer (icc). to provide realistic estimates of effectiveness for new screening programs, we studied icc risk after a 7-year repeated multimethod screening effort. in 1993-1994, 10,049 women aged 18-97 years were enrolled into a population-based cohort study of cervical hpv in guanacaste, costa rica. women were screened at different intervals according to enrollment results. each visit (mean ...201728120391
rationale and design of a long term follow-up study of women who did and did not receive hpv 16/18 vaccination in guanacaste, costa rica.the costa rica vaccine trial (cvt) was a randomized clinical trial conducted between 2004 and 2010, which randomized 7466 women aged 18 to 25 to receive the bivalent hpv-16/18 vaccine or control hepatitis-a vaccine. participants were followed for 4 years with cross-over vaccination at the study end. in 2010 the long term follow-up (ltfu) study was initiated to evaluate the 10-year impact of hpv-16/18 vaccination, determinants of the immune response, and hpv natural history in a vaccinated popula ...201525796338
a large, population-based study of age-related associations between vaginal ph and human papillomavirus infection.vaginal ph is related to genital tract inflammation and changes in the bacterial flora, both suggested cofactors for persistence of human papillomavirus (hpv) infection. to evaluate the relationship between vaginal ph and hpv, we analyzed data from our large population-based study in guanacaste, costa rica. we examined vaginal ph and the risk of hpv infection, cytological abnormalities, and c. trachomatis infection.201222316377
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