Urine testing to monitor the impact of HPV vaccination in Bhutan and Rwanda

Franceschi, Silvia; Umulisa, Marie Chantal; Tshomo, Ugyen; Gheit, Tarik; Baussano, Iacopo; Tenet, Vanessa; Tshokey, Tshokey; Gatera, Maurice; Ngabo, Fidèle; Damme, Pierre Van; Snijders, Peter J.F.; Tommasino, Massimo; Vorsters, Alex; Clifford, Gary M.

doi:10.1002/ijc.30092

Cited by 42 publications

(58 citation statements)

References 29 publications

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“…Whether high analytical sensitivity of HPV testing is an advantage or a danger for certain epidemiological study designs, in particular for monitoring of HPV vaccines, remains unclear (8,31). Among the urine samples reported here, estimates of vaccine effectiveness against HPV6/-11/-16/-18 in Rwanda and Bhutan were lower with E7-MPG than with GP5ϩ/6ϩRLB (8), possibly due to increased detection of low-level HPV DNA that may have no clinical significance.…”

Section: Discussionmentioning

confidence: 99%

“…In 2013, 973 high school students self-collected a urine sample using a device designed to collect first-void urine immediately into conservation medium (13). A total of 871 students (90%) reported to be virgins, and 896 (92%) reported having been vaccinated against HPV6/-11/-16/-18 (8). A further 89 urine samples were obtained from Bhutanese women aged 30 years or more in the Bhutan cervical cell survey described above approximately 18 months after an initial diagnosis of GP5ϩ/6ϩRLB-positive normal cytology.…”

Section: Methodsmentioning

confidence: 99%

“…In 2013 to 2014, 912 high school students self-collected a urine sample as described above. A total of 720 students (79%) reported to be virgins, and 393 (43%) reported having been vaccinated against HPV6/-11/-16/-18 (8). All samples were tested with both GP5ϩ/6ϩRLB and E7-MPG.…”

Section: Methodsmentioning

confidence: 99%

“…E7-MPG was neither designed nor validated for cervical cancer screening. However, the balance of analytical sensitivity versus specificity remains an important question for epidemiological studies, most notably those monitoring HPV vaccination efficacy (8,9).…”

mentioning

confidence: 99%

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Comparison of Two Widely Used Human Papillomavirus Detection and Genotyping Methods, GP5+/6+-Based PCR Followed by Reverse Line Blot Hybridization and Multiplex Type-Specific E7-Based PCR

et al. 2016

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f GP5؉/6؉-based PCR followed by reverse line blot hybridization (GP5؉/6؉RLB) and multiplex type-specific PCR (E7-MPG) are two human papillomavirus (HPV) genotyping methodologies widely applied in epidemiological research. We investigated their relative analytical performance in 4,662 samples derived from five studies in Bhutan, Rwanda, and Mongolia coordinated by the International Agency for Research on Cancer (IARC). A total of 630 samples were positive by E7-MPG only (13.5%), 24 were positive by GP5؉/6؉RLB only (0.5%), and 1,014 were positive (21.8%) by both methods. Ratios of HPV type-specific positivity of the two tests (E7-MPG:GP5؉/6؉RLB ratio) were calculated among 1,668 samples that were HPV positive by one or both tests. E7-MPG:GP5؉/6؉RLB ratios were >1 for all types and highly reproducible across populations and sample types. E7-MPG:GP5؉/6؉RLB ratios were highest for HPV53 (7.5) and HPV68 (7.1). HPV16 (1.6) and HPV18 (1.7) had lower than average E7-MPG:GP5؉/6؉RLB ratios. Among E7-MPG positive infections, median mean fluorescence intensity (MFI; a semiquantitative measure of viral load) tended to be higher among samples positive for the same virus type by GP5؉/6؉RLB than for those negative for the same type by GP5؉/6؉RLB. Exceptions, however, included HPV53, -59, and -82, for which the chances of being undetected by GP5؉/6؉RLB appeared to be MFI independent. Furthermore, the probability of detecting an additional type by E7-MPG was higher when another type was already detected by GP5؉/6؉RLB, suggesting the existence of masking effects due to competition for GP5؉/6؉ PCR primers. In conclusion, this analysis is not an evaluation of clinical performance but may inform choices for HPV genotyping methods in epidemiological studies, when the relative merits and dangers of sensitivity versus specificity for individual types should be considered, as well as the potential to unmask nonvaccine types following HPV vaccination. Human papillomavirus (HPV) DNA detection and genotyping are central to molecular epidemiological studies of HPV natural history and carcinogenicity, as well as to evaluations of HPV vaccine efficacy and effectiveness. There are various PCR-based methods for HPV DNA detection and genotyping, of which one of the most commonly used in epidemiological studies is the GP5ϩ/6ϩ primer set targeting conserved sequences within the L1 gene, thus allowing detection of a broad range of mucosal HPV types in a single reaction. The HPV genotype can subsequently be identified by various methods, of which the most commonly used is hybridization with type-specific probes using a reverse line blot hybridization assay (henceforth referred to as GP5ϩ/6ϩRLB) (1). The GP5/6 primers were initially developed to maximize detection of HPV6, and were subsequently elongated at their 3= ends to generate the primers GP5ϩ and GP6ϩ to improve the detection of a broader range of HPV types (3). This methodology has been widely validated against clinical outcomes in large population-based screening programs and shows favorable c...

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

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Comparison of Two Widely Used Human Papillomavirus Detection and Genotyping Methods, GP5+/6+-Based PCR Followed by Reverse Line Blot Hybridization and Multiplex Type-Specific E7-Based PCR

et al. 2016

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“…All material was subsequently transferred to the NucliSENS Lysis Buffer vial, and DNA extraction of the complete content of the vial was performed using the generic easyMAG off-board lysis protocol. DNA was eluted in 55 mL elution buffer (24,26), and the DNA extracts were then shipped to IARC on dry ice.…”

Section: Dna Extraction From Urine Samplesmentioning

confidence: 99%

Comparison between Urine and Cervical Samples for HPV DNA Detection and Typing in Young Women in Colombia

Cómbita

Gheit

González

et al. 2016

Cancer Prevention Research

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Urine sampling for HPV DNA detection has been proposed as an effective method for monitoring the impact of HPV vaccination programs; however, conflicting results have been reported. The goal of this study was to evaluate the performance of optimized urine HPV DNA testing in women aged 19 to 25 years. Optimization process included the use of first void urine, immediate mixing of urine with DNA preservative, and the concentration of all HPV DNA, including cell-free DNA fragments. Urine and cervical samples were collected from 535 young women attending cervical screening at health centers from two Colombian cities. HPV DNA detection and genotyping was performed using an HPV type-specific multiplex genotyping assay, which combines multiplex polymerase chain reaction with bead-based Luminex technology. Concordance between HPV DNA detection in urine and cervical samples was determined using kappa statistics and McNemar tests. The accuracy of HPV DNA testing in urine samples was evaluated measuring sensitivity and specificity using as reference the results obtained from cervical samples. Statistical analysis was performed using STATA11.2 software. The findings revealed an overall HPV prevalence of 60.00% in cervical samples and 64.72% in urine samples, HPV-16 being the most frequent HPV type detected in both specimens. Moreover, our results indicate that detection of HPV DNA in first void urine provides similar results to those obtained with cervical samples and can be used to monitor HPV vaccination trials and programs as evidenced by the substantial concordance found for the detection of the four vaccine types.Cancer Prev Res; 9(9); 766-71. Ó2016 AACR.

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Study to determine efficacy of urinary HPV 16 & HPV 18 detection in predicting premalignant and malignant lesions of uterine cervix

John

Halder

Purwar

et al. 2022

Intl J Gynecology & Obste

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Visual inspection with acetic acid (VIA) and cytology form the core of the screening programs across the globe, which aim at early detection of cervical cancer precursors. 1 Low-and middle-income countries however face operative challenges from the outset, as effectuating mass screening requires the active participation of the clients and a robust healthcare infrastructure that can support population-wide pelvic examination, sample collection, analysis, reporting, and follow up. 2 HPV testing in cervical secretions instead of, or in addition to, cervical cytology has emerged as a better alternative to cytology or VIA in cervical cancer screening because HPV infection contributes to almost 99.7% of all cervical cancers worldwide and testing for HPV provides similar efficacy with an advantage of longer screening interval. 3,4 Keeping pace with the evidence, WHO recommends a rapid transition to HPV DNA testing as

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Urine testing to monitor the impact of HPV vaccination in Bhutan and Rwanda

Cited by 42 publications

References 29 publications

Comparison of Two Widely Used Human Papillomavirus Detection and Genotyping Methods, GP5+/6+-Based PCR Followed by Reverse Line Blot Hybridization and Multiplex Type-Specific E7-Based PCR

Comparison of Two Widely Used Human Papillomavirus Detection and Genotyping Methods, GP5+/6+-Based PCR Followed by Reverse Line Blot Hybridization and Multiplex Type-Specific E7-Based PCR

Comparison between Urine and Cervical Samples for HPV DNA Detection and Typing in Young Women in Colombia

Study to determine efficacy of urinary HPV 16 & HPV 18 detection in predicting premalignant and malignant lesions of uterine cervix

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