Human papillomavirus infection in Bhutan at the moment of implementation of a national HPV vaccination programme

Tshomo, Ugyen; Franceschi, Silvia; Dorji, Dorji; Baussano, Iacopo; Tenet, Vanessa; Snijders, Peter J.F.; Meijer, Chris J.L.M.; Bleeker, Maaike; Gheit, Tarik; Tommasino, Massimo; Clifford, Gary M.

doi:10.1186/1471-2334-14-408

Cited by 27 publications

(38 citation statements)

References 23 publications

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“…This was made possible by testing a large number of clinical samples, a large proportion or which were HPV positive, with the two methods. We confirmed previous smaller studies (7,10) showing that E7-MPG is more analytically sensitive than GP5ϩ/6ϩRLB while rarely not detecting GP5ϩ/ 6ϩRLB-positive women. However, we went on to establish that the relative sensitivity of the two tests is highly HPV type specific and that these type-specific differences are remarkably consistent across studies and populations.…”

Section: Discussionsupporting

confidence: 81%

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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: Discussionsupporting

confidence: 81%

“…During a population-based survey in 2011 to 2012, 2,505 women aged 18 to 69 years were invited for the collection of exfoliated cervical cells in PreservCyt medium for HPV testing with GP5ϩ/6ϩRLB (10). Women aged 18 to 24 years were systematically (884 of 885) tested with E7-MPG.…”

Section: Methodsmentioning

confidence: 99%

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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“…While Australia, Denmark, USA and Canada were the first high-income countries to introduce HPV vaccination in NIPs in 2007, Panama (2008) in Latin America, Bhutan (2009) in Asia and Rwanda (2010) in Africa were the first LMICs that introduced HPV vaccination424344. Currently, eight of 10 girls aged 9-13 yr in the Latin American region have access to HPV vaccination through NIP thanks to the foresight, wisdom and commitment on the part of the national governments and the pooled, bulk, negotiated purchase of the vaccines on behalf of these countries by the revolving fund of the Pan American Health Organization.…”

Section: Countries Implementing Hpv Vaccination As Part Of the Nationmentioning

confidence: 99%

Current global status & impact of human papillomavirus vaccination: Implications for India

Sankaranarayanan¹,

Bhatla²,

Basu³

2016

Indian J Med Res

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This review addresses the effectiveness and safety of human papillomavirus (HPV) vaccines, the current status of its introduction in the National Immunization Programmes (NIPs) and its relevance to India, which contributes a fifth of the global burden of cervical cancer. The vast literature on efficacy, acceptability and safety of HPV vaccination and its impact after population level introduction was reviewed and discussed. The efficacy of HPV vaccines in preventing high-grade precancerous lesions caused by vaccine-targeted HPV infections was 90 per cent or higher in HPV naïve women in randomized clinical trials. Two doses at 6 or 12 months apart are recommended for 9-14 yr old girls and three doses over six months to one year period for those aged above 15 yr. More than 80 countries or territories have introduced HPV vaccination in their NIPs, of which 33 are low- and middle-income countries (LMICs); in addition, 25 LMICs have introduced pilot programmes before a phased national expansion. Significant reductions in the frequency of HPV 16 and 18 infections, genital warts and cervical premalignant lesions in vaccinated cohorts and herd immunity in general populations have been reported from countries that introduced vaccination in NIPs as early as 2007. More than 280 million doses of HPV vaccines have been administered worldwide with the excellent safety profile with no serious adverse events linked to it. The high burden of cervical cancer and the high efficacy and safety of HPV vaccination justify its introduction in the Indian NIP at the earliest possibility to substantially reduce the cervical cancer burden in future.

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“…Second, our data might provide some useful information for clinical implication. HPV vaccination is currently approved for prevention of HPV infection, cervical dysplasia as well as cervical cancer [48]. If our observed association could be confirmed by larger prospective cohort studies, this might suggest a potential role of HPV vaccination for reducing the risk of certain obstetrical complications.…”

Section: Discussionmentioning

confidence: 52%

Can HPV vaccine have other health benefits more than cancer prevention? A systematic review of association between cervical HPV infection and preterm birth

Huang

Zhong

Gao

et al. 2014

Journal of Clinical Virology

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Human papillomavirus infection in Bhutan at the moment of implementation of a national HPV vaccination programme

Cited by 27 publications

References 23 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

Current global status & impact of human papillomavirus vaccination: Implications for India

Can HPV vaccine have other health benefits more than cancer prevention? A systematic review of association between cervical HPV infection and preterm birth

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