The impact of HPV vaccination on future cervical screening: a simulation study of two birth cohorts in Denmark

Hestbech, Mie Sara; Lynge, Elsebeth; Kragstrup, Jakob; Siersma, Volkert; Baillet, Miguel Vazquez Prada; Brodersen, John

doi:10.1136/bmjopen-2015-007921

Cited by 18 publications

(15 citation statements)

References 27 publications

(33 reference statements)

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“…Finally, from a screening laboratory operational perspective, HPV assays with extended genotyping for cervical cancer screening are already available, and these assays have the capacity for returning detailed genotype results on an HPV‐positive sample without further analysis required. On the other hand, assays with limited genotyping reporting HPV16 and 18 individually combined with bulk detection of the remaining hrHPV genotypes will have limited value in such strategy as well as in screening populations with increasing proportions of HPV16/18 vaccinated women reducing the assay to a simple hrHPV “yes/no” assay …”

Section: Discussionmentioning

confidence: 99%

“…On the other hand, assays with limited genotyping reporting HPV16 and 18 individually combined with bulk detection of the remaining hrHPV genotypes will have limited value in such strategy as well as in screening populations with increasing proportions of HPV16/18 vaccinated women reducing the assay to a simple hrHPV "yes/no" assay. [44][45][46][47][48]…”

Section: Discussionmentioning

confidence: 99%

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Bayesian analysis of baseline risk of CIN2 and ≥CIN3 by HPV genotype in a European referral cohort

Bonde

Bottari

Parvu

et al. 2019

Intl Journal of Cancer

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Whereas HPV16 and HPV18 have been the focus in current risk‐based cervical cancer screening algorithms using HPV genotype information, mounting evidence suggests that oncogenic HPV types such as HPV31, 33, 52 and 58 pose a ≥CIN3 risk equivalent to or greater than that of HPV18, and the combined risk of HPV31 and HPV33 rivals even HPV16 in women above 30 years of age. Here, we evaluate the baseline risk of CIN2 and CIN3 by genotype in a colposcopy referral population from Denmark and Italy. In total, 655 women were enrolled upon a referral to colposcopy after a positive screening sample. All samples were HPV analyzed using Onclarity HPV assay with extended genotyping and combined with the histology outcomes, a Bayesian probability modeling was used to determine the risk per genotype assessed. The combined data for this referral population showed that the ≥CIN2 risk of HPV16 was 69.1%, HPV31 at 63.3%, HPV33/58 at 52.7%, HPV18 at 46.6% and HPV52 at 40.8%. For ≥CIN3, the risks were 44.3%, 38.5%, 36.8%, 30.9% and 16.8% for HPV16, HPV31, HPV18, HPV33/58 and HPV52, respectively, indicating that the baseline risk of disease arising from HPV16 is, not surprisingly, the highest among the oncogenic HPV genotypes. We find that the HPV genotype‐specific ≥CIN2 and ≥CIN3 risk‐patterns are so distinct that, for example, 35/39/68 and 56/59/66 should be considered only for low intensive follow‐up, thereby proposing active use of this information in triage strategies for screening HPV‐positive women.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Bayesian analysis of baseline risk of CIN2 and ≥CIN3 by HPV genotype in a European referral cohort

Bonde

Bottari

Parvu

et al. 2019

Intl Journal of Cancer

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“…The vaccines have been licensed and introduced to the market in 2006 and 2007, respectively, and ever since, millions of doses have been administered to young female adolescents or adults. Countries with vaccination programs against HPV such as Australia and the United Kingdom achieved high vaccine coverage and meanwhile reported reduction in low-grade lesions and genital warts (12). Recently, an expandedspectrum vaccine, comprised of a mixture of virus-like particles (VLPs) from 7 oncogenic HPVs plus VLPs from HPV6 and -11 has been licensed to a number of countries (13).…”

Section: Importancementioning

confidence: 99%

Minor Capsid Protein L2 Polytope Induces Broad Protection against Oncogenic and Mucosal Human Papillomaviruses

Pouyanfard

Spagnoli

Bulli

et al. 2018

J Virol

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The amino terminus of the human papillomavirus (HPV) minor capsid protein L2 contains a major cross-neutralization epitope which provides the basis for the development of a broadly protecting HPV vaccine. A wide range of protection against different HPV types would eliminate one of the major drawbacks of the commercial, L1-based prophylactic vaccines. Previously, we have reported that insertion of the L2 epitope into a scaffold composed of bacterial thioredoxin protein generates a potent antigen inducing comprehensive protection against different animal and human papillomaviruses. We also reported, however, that although protection is broad, some oncogenic HPV types escape the neutralizing antibody response, if L2 epitopes from single HPV types are used as immunogen. We were able to compensate for this by applying a mix of thioredoxin proteins carrying L2 epitopes from HPV16, -31, and -51. As the development of a cost-efficient HPV prophylactic vaccines is one of our objectives, this approach is not feasible as it requires the development of multiple good manufacturing production processes in combination with a complex vaccine formulation. Here, we report the development of a thermostable thioredoxin-based single-peptide vaccine carrying an L2 polytope of up to 11 different HPV types. The L2 polytope antigens have excellent abilities in respect to broadness of protection and robustness of induced immune responses. To further increase immunogenicity, we fused the thioredoxin L2 polytope antigen with a heptamerization domain. In the final vaccine design, we achieve protective responses against all 14 oncogenic HPV types that we have analyzed plus the low-risk HPVs 6 and 11 and a number of cutaneous HPVs. Infections by a large number of human papillomaviruses lead to malignant and nonmalignant disease. Current commercial vaccines based on virus-like particles (VLPs) effectively protect against some HPV types but fail to do so for most others. Further, only about a third of all countries have access to the VLP vaccines. The minor capsid protein L2 has been shown to contain so-called neutralization epitopes within its N terminus. We designed polytopes comprising the L2 epitope amino acids 20 to 38 of up to 11 different mucosal HPV types and inserted them into the scaffold of thioredoxin derived from a thermophile archaebacterium. The antigen induced neutralizing antibody responses in mice and guinea pigs against 26 mucosal and cutaneous HPV types. Further, addition of a heptamerization domain significantly increased the immunogenicity. The final vaccine design comprising a heptamerized L2 8-mer thioredoxin single-peptide antigen with excellent thermal stability might overcome some of the limitations of the current VLP vaccines.

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“…Tem sido demonstrada uma diminuição da incidência de lesões do colo do útero em áreas geográficas onde foi introduzida a vacina contra o HPV. 39 A vacinação foi introduzida em Portugal há uma década, 29 pelo que se aguardam estudos para perceber o seu efeito a longo prazo na mortalidade por CCU no nosso país. Entretanto, deve haver incentivos à participação em rastreios na população portuguesa, aconselhando e promovendo a adesão aos rastreios de toda a população feminina.…”

Section: Discussionunclassified

Evolução Temporal da Mortalidade por Cancro do Colo do Útero em Portugal

Teixeira¹,

Pereira²,

Anes³

et al. 2019

Acta Med Port

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Introduction: The mortality rate due to cervical cancer is higher in Portugal compared to other European countries. This study aimed to evaluate the time-trends in cervical cancer mortality rates observed in Portugal over the last six decades.Material and Methods: Age-standardized cervical cancer mortality rates reported in Portugal between 1955 and 2014, were collected from the International Agency for Research on Cancer (IARC). Joinpoint regression analysis was used to identify significant changes in mortality rates by assessing the percentage of annual variation (%AV) of the rate and respective 95% confidence interval (95%CI) according to the age groups.Results: Among women with 30–39 years, cervical cancer mortality decreased 1.9% per year (95%CI: –2.3; –1.4) throughout the time-period, reaching 0.5/100 000 in 2014. Among women aged 40–49 years, CC mortality decreased between 1971 and 1981 (%AV = –11.6; IC 95%: –14.6; –8.6). Rates then increased by 2.4% per year (95%CI: 1.0; 3.8) until 2001 and such trend reverted from 2001 onwards (%AV = –5.2; IC 95%: –7.7; –2.6), reaching 3.0/100 000 in 2014. In women aged 50–64, 65–74 and 75 years or older, cervical cancer mortality rates decreased from 29.2 to 6.7/100 000, from 34.3 to 7.7/100 000 and from 24.7 to 9.2/100 000. The decline in mortality rates in these three age groups occurred mainly between 1970 and 1980, and there have been no significant changes in the last three decades.Discussion: In Portugal, the most impressive decline in cervical cancer mortality rates occurred in the 1970s concurrently with changes in the National Healthcare System. The most important changes were the increased access to early diagnosis and the improvement in therapeutic approaches. The plateau that we observed among older women over the last three decades can be partially explained by factors with negative impact on adherence to cervical screening.Conclusion: There was a marked decrease in mortality due to CC among all age groups. However, we observed a plateau of this indicator in more advanced age groups over the last three decades. These findings suggest the need of promoting adherence to cervical screening in Portugal.

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The impact of HPV vaccination on future cervical screening: a simulation study of two birth cohorts in Denmark

Cited by 18 publications

References 27 publications

Bayesian analysis of baseline risk of CIN2 and ≥CIN3 by HPV genotype in a European referral cohort

Bayesian analysis of baseline risk of CIN2 and ≥CIN3 by HPV genotype in a European referral cohort

Minor Capsid Protein L2 Polytope Induces Broad Protection against Oncogenic and Mucosal Human Papillomaviruses

Evolução Temporal da Mortalidade por Cancro do Colo do Útero em Portugal

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