Rationale and design of a community-based double-blind randomized clinical trial of an HPV 16 and 18 vaccine in Guanacaste, Costa Rica

Herrero, Rolando; Hildesheim, Allan; Rodríguez, Ana Cecilia; Wacholder, Sholom; Bratti, Concepción; Solomon, Diane; González, Paula; Porras, Carolina; Jiménez, Silvia; Guillén, Diego Miguel Gracia; Morales, Jorge; Alfaro, Mario; Cyr, Jean; Morrisey, Kerrygrace; Estrada, Yenory; Cortés, Bernal; Morera, Lidia Ana; Freer, Enrique; Schussler, John; Schiller, John T.; Lowy, Douglas R.; Schiffman, Mark

doi:10.1016/j.vaccine.2008.07.002

Cited by 150 publications

(180 citation statements)

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“…Samples included in this analysis were collected from participants in the Costa Rica Vaccine Trial (CVT), who completed a follow-up screening visit or a colposcopy visit from 24 to 27 November 2009 and from 11 January to 21 May 2010. The methods of the CVT are described in detail elsewhere (12). Briefly, it is a double blind, controlled, randomized, phase III study designed to evaluate the efficacy of the HPV16/18 vaccine (Cervarix; GlaxoSmithKline) for the prevention of HPV16/18 persistent infection and associated cervical lesions (CIN2 ϩ ).…”

Section: Methodsmentioning

confidence: 99%

“…P ersistent infection with one of approximately 13 carcinogenic human papillomaviruses (HPVs) is a necessary cause for the development of cervical cancer (14, 23). Detection of some or all of these HPV types has been shown to be useful for cervical cancer screening (1,15,(26)(27)(28).In clinical trials (including evaluation of current and future HPV vaccines) and epidemiological studies, cervical cells for HPV DNA detection are usually collected and preserved in liquid-based transport medium, which in some cases is used also for cytology slide preparation, allowing the collection of only one sample for both tests (7,12,13,24,25).However, these medium samples can be flammable and require stable transport and storage temperatures, which are difficult and expensive to provide in developing and tropical countries. If samples are tested in a different country, as is usually the case for large research studies conducted in developing countries, the exportation of such samples must fulfill international regulations regarding the transport of hazardous samples (i.e., according to the 53rd edition of IATA's DGR, specimens collected in PreservCyt [Hologic, Inc.] Moreover, these liquid-based samples require expensive and laborious DNA extraction procedures susceptible to cross-contamination, especially when manual extraction of DNA is performed.…”

mentioning

confidence: 99%

“…In clinical trials (including evaluation of current and future HPV vaccines) and epidemiological studies, cervical cells for HPV DNA detection are usually collected and preserved in liquid-based transport medium, which in some cases is used also for cytology slide preparation, allowing the collection of only one sample for both tests (7,12,13,24,25).…”

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confidence: 99%

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Evaluation of the FTA Carrier Device for Human Papillomavirus Testing in Developing Countries

et al. 2012

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e Liquid-based methods for the collection, transportation, and storage of cervical cells are cumbersome and expensive and involve laborious DNA extraction. An FTA cartridge is a solid carrier device, easier to handle and allowing simple DNA elution for human papillomavirus (HPV) testing. HPV-DNA results from cervical specimens collected in PreservCyt medium (Hologic, Inc.) and the indicating FTA elute cartridge were compared in an area where transportation and storage may affect the performance of the test. Cervical cells from 319 young adult women enrolled in the Costa Rica Vaccine Trial were collected by a nurse using a Cervex brush (Roberts), which was placed on the FTA cartridge and subsequently rinsed in 20 ml of PreservCyt medium. Two 0.5-ml PreservCyt aliquots were frozen for HPV-PCR testing; the FTA cartridges were kept at room temperature. HPV-DNA detection and typing was performed using SPF 10 PCR/DEIA (DNA enzyme immunoassay detection of amplimers)/LiPA 25 system. The percent agreement, agreement among positives, and kappas were estimated. Positivity was higher for FTA compared to PreservCyt specimens (54.5% versus 45.8%, P < 0.001). For oncogenic types, the overall agreement was 0.92, the agreement between positives was 0.74, and the kappa was 0.79. For individual HPV types, the overall agreement ranged from 0.97 to 1.00. We did not observe reduced cytology adequacy when specimen collection for cytology was preceded by FTA collection for HPV testing. HPV-DNA detection from FTA cartridges is broadly comparable to detection from PC medium. The higher HPV detection observed for FTA-collected specimens should be explored further. FTA cartridges could provide a simpler and more cost-effective method for cervical cell collection, storage, and transportation for HPV-DNA detection in research settings in developing countries. P ersistent infection with one of approximately 13 carcinogenic human papillomaviruses (HPVs) is a necessary cause for the development of cervical cancer (14, 23). Detection of some or all of these HPV types has been shown to be useful for cervical cancer screening (1,15,(26)(27)(28).In clinical trials (including evaluation of current and future HPV vaccines) and epidemiological studies, cervical cells for HPV DNA detection are usually collected and preserved in liquid-based transport medium, which in some cases is used also for cytology slide preparation, allowing the collection of only one sample for both tests (7,12,13,24,25).However, these medium samples can be flammable and require stable transport and storage temperatures, which are difficult and expensive to provide in developing and tropical countries. If samples are tested in a different country, as is usually the case for large research studies conducted in developing countries, the exportation of such samples must fulfill international regulations regarding the transport of hazardous samples (i.e., according to the 53rd edition of IATA's DGR, specimens collected in PreservCyt [Hologic, Inc.] Moreover, these liquid-based sam...

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Section: Methodsmentioning

confidence: 99%

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confidence: 99%

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Evaluation of the FTA Carrier Device for Human Papillomavirus Testing in Developing Countries

et al. 2012

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“…The trial has been described in detail elsewhere (12). In brief, a total of 7,466 women consented and were enrolled at which time they were randomized to receive either the HPV vaccine or the hepatits A vaccine and were followed for 4 years.…”

Section: Study Populationmentioning

confidence: 99%

Direct Comparison of HPV16 Serological Assays Used to Define HPV-Naïve Women in HPV Vaccine Trials

Safaeian

Ghosh

Porras

et al. 2012

Cancer Epidemiology, Biomarkers &Amp; Prevention

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Background: Two HPV serological assays, the competitive Luminex immunoassay (cLIA), and an enzymelinked immunoassay (ELISA) against HPV16 have been used to define HPV-na€ ve subcohorts within large HPV vaccination trials. Some of the variation in estimated vaccine efficacies may be due to the differences in these assays used to define the HPV-na€ ve subgroups. To guide the interpretation of published results, we compared these assays.Methods: Replicate enrollment sera from a stratified sample of 388 unvaccinated women from the control arm of the Costa Rica HPV 16/18 Vaccine Trial were measured for antibodies against HPV16 using cLIA and ELISA. Agreement between the assays was estimated using standard and alternative assay cutoffs.Results: Using laboratory-determined seropositivity cutoffs, sampling-adjusted HPV16 seropositivity was 24.8% by ELISA and 7.2% by cLIA. Comparing cLIA and ELISA antibody levels based on the standard cutoffs, overall agreement was 53% (positive-agreement ¼ 49%). The poor agreement was mainly driven by the higher sensitivity of the ELISA than cLIA, resulting in 30% of the ELISA-positive sample that were cLIA-negative (none of the ELISA-negatives were cLIA-positive). Increasing ELISA cutoff to 54 ELISA units (EU)/mL (the level which maximized agreement with cLIA; ELISA standard cutoff is 8 EU/mL) resulted in higher agreement (overall agreement ¼ 91%; positive agreement ¼ 78%).Conclusions: ELISA and cLIA are different from each other based on the laboratory-determined cutoff. Increasing ELISA cutoff increased agreement with cLIA, which could facilitate comparisons among studies that use different assays.Impact: Keeping cLIA at the laboratory-determined cutoff but altering ELISA cutoff for seropositivity might facilitate vaccine efficacy comparisons in the na€ ve cohorts defined by cLIA. Cancer Epidemiol Biomarkers Prev; 21(9); 1547-54. Ó2012 AACR.

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“…The study design, procedures, and specimen collection have been described elsewhere (5). In brief, at each visit, blood and cervical specimens (exfoliated cells and secretions) were collected from participants as appropriate.…”

Section: Peg Main Studiesmentioning

confidence: 99%

Establishment and Operation of a Biorepository for Molecular Epidemiologic Studies in Costa Rica

Cortés

Schiffman²,

Herrero³

et al. 2010

Cancer Epidemiology, Biomarkers &Amp; Prevention

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Background: 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.Objective: Here, we describe the rationale and lessons learned in transferring molecular epidemiologic and biorepository technology to a developing country.Results: At the outset of the PEG in the early 1990s, we shipped all specimens to repositories and laboratories in the United States, which created multiple problems. Since then, by intensive personal interactions between experts from the United States and Costa Rica, we have successfully transferred liquid-based cytology, HPV DNA testing and serology, chlamydia and gonorrhea testing, PCR-safe tissue processing, and viable cryopreservation. To accommodate the vaccine trial, a state-of-the-art repository opened in mid-2004. Approximately 15,000 to 50,000 samples are housed in the repository on any given day, and >500,000 specimens have been shipped, many using a custom-made dry shipper that permits exporting >20,000 specimens at a time. Quality control of shipments received by the NCI biorepository has revealed an error rate of <0.2%. Recently, the PEG repository has incorporated other activities; for example, large-scale aliquotting and longterm, cost-efficient storage of frozen specimens returned from the United States. Using Internet-based specimen tracking software has proven to be efficient even across borders.Conclusion: For long-standing collaborations, it makes sense to transfer the molecular epidemiology expertise toward the source of specimens. The successes of the PEG molecular epidemiology laboratories and biorepository prove that the physical and informatics infrastructures of a modern biorepository can be transferred to a resource-limited and weather-challenged region. Technology transfer is an important and feasible goal of international collaborations. Cancer Epidemiol Biomarkers Prev; 19(4); 916-22. ©2010 AACR.

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Rationale and design of a community-based double-blind randomized clinical trial of an HPV 16 and 18 vaccine in Guanacaste, Costa Rica

Cited by 150 publications

References 31 publications

Evaluation of the FTA Carrier Device for Human Papillomavirus Testing in Developing Countries

Evaluation of the FTA Carrier Device for Human Papillomavirus Testing in Developing Countries

Direct Comparison of HPV16 Serological Assays Used to Define HPV-Naïve Women in HPV Vaccine Trials

Establishment and Operation of a Biorepository for Molecular Epidemiologic Studies in Costa Rica

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