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Pectively). doi:10.1371/journal.pone.0056509.tHPV in HIV-Infected Women Paired SamplesFigure 3. Agreement between generic and type-specific detection in cervical and urine samples taken from HIV-positive women. doi:10.1371/journal.pone.0056509.gIn addition, the variations in HPV type-specific distribution profile could have been related to the presence of HIV infection as it has been described that such distribution in immunologicallycompromised women could vary; moreover, it has been described that such incidence is 16 times higher in the immunologicallycompromised group than that found in immunologically-competent women [3]. An additional explanation for the different viral type distribution between samples could be attributable to a varying exfoliation pattern in cells infected with each viral type, however, it has not yet been CPI-455 established whether exfoliated cells in urine are 23727046 influenced by viral infection type or the state of infection [15]. Coinfection was found in both urine and cervical samples in around half the study population; this could have been attributed to the low infection elimination rate allowing different viral types to settle in the cervical epithelium; multiple infection events could have been also due to the reduced systemic and local cell immunity found in HIV-positive women [12]. There was poor agreement between generic and type-specific identification results; this may have been related to the samples’ different nature, as well as HPV tropism for cervical epithelium. A lower number of viral copies in urine are expected regarding cervical samples, as the latter would have been taken from the pathogen’s direct localization site. Interestingly, the test involving self-collected urine samples had greater sensitivity (68.8 in this study vs. 55.3 ) and more specificity (50.0 in this study vs. 44.9 ) for detecting HPV-DNA compared with a previous study using the same identification protocol [19], which could indicate a potential use for the clinicalapplication of this sample purchase CX-4945 source. Nevertheless, additional studies must be carried out in the general population for determining clinical applicability, storage conditions, suitable extraction method, the most appropriate urine fraction to be used in the molecular analysis, and other factors that could affect the diagnostic performance of this sample source. Developing strategies in cervical cancer control and prevention programs will be particularly determinant in contributing towards increasing coverage, sample taking, adherence and follow-up of women, mainly those presenting some type of immunosuppression. According 15900046 to the results obtained here, self-sampling methods, such as urine sampling, could be taken into account as useful tools for preventing this pathology, since they offer good diagnostic performance and greater acceptability among women.AcknowledgmentsWe would like to express our thanks to Camilo Jaimes for technical support and Jason Garry for translating and revising this manuscript. We would also like to extend our thanks to the IDIME laboratory for contributing to sampling logistics. In loving memory of Luis Segundo Fontanilla De La Hoz.Author ContributionsConceived and designed the experiments: MM MC SCSDL RS MEP MAP. Performed the experiments: MM MC SCSDL. Analyzed the data: MM MC SCSDL RS DP ACP OS APP MEP MAP. Contributed reagents/materials/analysis tools: DP ACP OS APP. Wrote the paper: MM MC SCSDL RS APP MEP MAP.
Accurate and non-invasive assessment.Pectively). doi:10.1371/journal.pone.0056509.tHPV in HIV-Infected Women Paired SamplesFigure 3. Agreement between generic and type-specific detection in cervical and urine samples taken from HIV-positive women. doi:10.1371/journal.pone.0056509.gIn addition, the variations in HPV type-specific distribution profile could have been related to the presence of HIV infection as it has been described that such distribution in immunologicallycompromised women could vary; moreover, it has been described that such incidence is 16 times higher in the immunologicallycompromised group than that found in immunologically-competent women [3]. An additional explanation for the different viral type distribution between samples could be attributable to a varying exfoliation pattern in cells infected with each viral type, however, it has not yet been established whether exfoliated cells in urine are 23727046 influenced by viral infection type or the state of infection [15]. Coinfection was found in both urine and cervical samples in around half the study population; this could have been attributed to the low infection elimination rate allowing different viral types to settle in the cervical epithelium; multiple infection events could have been also due to the reduced systemic and local cell immunity found in HIV-positive women [12]. There was poor agreement between generic and type-specific identification results; this may have been related to the samples’ different nature, as well as HPV tropism for cervical epithelium. A lower number of viral copies in urine are expected regarding cervical samples, as the latter would have been taken from the pathogen’s direct localization site. Interestingly, the test involving self-collected urine samples had greater sensitivity (68.8 in this study vs. 55.3 ) and more specificity (50.0 in this study vs. 44.9 ) for detecting HPV-DNA compared with a previous study using the same identification protocol [19], which could indicate a potential use for the clinicalapplication of this sample source. Nevertheless, additional studies must be carried out in the general population for determining clinical applicability, storage conditions, suitable extraction method, the most appropriate urine fraction to be used in the molecular analysis, and other factors that could affect the diagnostic performance of this sample source. Developing strategies in cervical cancer control and prevention programs will be particularly determinant in contributing towards increasing coverage, sample taking, adherence and follow-up of women, mainly those presenting some type of immunosuppression. According 15900046 to the results obtained here, self-sampling methods, such as urine sampling, could be taken into account as useful tools for preventing this pathology, since they offer good diagnostic performance and greater acceptability among women.AcknowledgmentsWe would like to express our thanks to Camilo Jaimes for technical support and Jason Garry for translating and revising this manuscript. We would also like to extend our thanks to the IDIME laboratory for contributing to sampling logistics. In loving memory of Luis Segundo Fontanilla De La Hoz.Author ContributionsConceived and designed the experiments: MM MC SCSDL RS MEP MAP. Performed the experiments: MM MC SCSDL. Analyzed the data: MM MC SCSDL RS DP ACP OS APP MEP MAP. Contributed reagents/materials/analysis tools: DP ACP OS APP. Wrote the paper: MM MC SCSDL RS APP MEP MAP.
Accurate and non-invasive assessment.

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