• Health and Economic Impact of a Tender-Based, Sex-Neutral Human Papillomavirus 16/18 Vaccination Program in the Netherlands.

      Qendri, Venetia; Bogaards, Johannes A; Berkhof, Johannes (2017-07-15)
      Uptake of human papillomavirus (HPV) vaccine among girls in the Dutch immunization program has plateaued at around 60%. Vaccinating boys may be an appealing complementary strategy for the prevention of HPV-related diseases, especially since tender negotiations and reduced dosing schemes have driven down the cost of vaccination.
    • Immune Responses After 2 Versus 3 Doses of HPV Vaccination up to 4½ Years After Vaccination: An Observational Study Among Dutch Routinely Vaccinated Girls.

      Donken, Robine; Schurink-Van't Klooster, Tessa M; Schepp, Rutger M; van der Klis, Fiona R M; Knol, Mirjam J; Meijer, Chris J L M; de Melker, Hester E (2017-02-01)
      In 2014 the Netherlands switched from 3 to 2 doses for routine vaccination with the prophylactic bivalent human papillomavirus (HPV) vaccine. The current study explored whether antibody responses are noninferior after 2 versus 3 doses in girls.
    • Population-level impact, herd immunity, and elimination after human papillomavirus vaccination: a systematic review and meta-analysis of predictions from transmission-dynamic models.

      Brisson, Marc; Bénard, Élodie; Drolet, Mélanie; Bogaards, Johannes A; Baussano, Iacopo; Vänskä, Simopekka; Jit, Mark; Boily, Marie-Claude; Smith, Megan A; Berkhof, Johannes; Canfell, Karen; Chesson, Harrell W; Burger, Emily A; Choi, Yoon H; De Blasio, Birgitte Freiesleben; De Vlas, Sake J; Guzzetta, Giorgio; Hontelez, Jan A C; Horn, Johannes; Jepsen, Martin R; Kim, Jane J; Lazzarato, Fulvio; Matthijsse, Suzette M; Mikolajczyk, Rafael; Pavelyev, Andrew; Pillsbury, Matthew; Shafer, Leigh Anne; Tully, Stephen P; Turner, Hugo C; Usher, Cara; Walsh, Cathal (2016-11)
      Modelling studies have been widely used to inform human papillomavirus (HPV) vaccination policy decisions; however, many models exist and it is not known whether they produce consistent predictions of population-level effectiveness and herd effects. We did a systematic review and meta-analysis of model predictions of the long-term population-level effectiveness of vaccination against HPV 16, 18, 6, and 11 infection in women and men, to examine the variability in predicted herd effects, incremental benefit of vaccinating boys, and potential for HPV-vaccine-type elimination.
    • Whole-Genome Sequencing and Variant Analysis of Human Papillomavirus 16 Infections.

      van der Weele, Pascal; Meijer, Chris J L M; King, Audrey J (2017-10-01)
      Human papillomavirus (HPV) is a strongly conserved DNA virus, high-risk types of which can cause cervical cancer in persistent infections. The most common type found in HPV-attributable cancer is HPV16, which can be subdivided into four lineages (A to D) with different carcinogenic properties. Studies have shown HPV16 sequence diversity in different geographical areas, but only limited information is available regarding HPV16 diversity within a population, especially at the whole-genome level. We analyzed HPV16 major variant diversity and conservation in persistent infections and performed a single nucleotide polymorphism (SNP) comparison between persistent and clearing infections. Materials were obtained in the Netherlands from a cohort study with longitudinal follow-up for up to 3 years. Our analysis shows a remarkably large variant diversity in the population. Whole-genome sequences were obtained for 57 persistent and 59 clearing HPV16 infections, resulting in 109 unique variants. Interestingly, persistent infections were completely conserved through time. One reinfection event was identified where the initial and follow-up samples clustered differently. Non-A1/A2 variants seemed to clear preferentially (P = 0.02). Our analysis shows that population-wide HPV16 sequence diversity is very large. In persistent infections, the HPV16 sequence was fully conserved. Sequencing can identify HPV16 reinfections, although occurrence is rare. SNP comparison identified no strongly acting effect of the viral genome affecting HPV16 infection clearance or persistence in up to 3 years of follow-up. These findings suggest the progression of an early HPV16 infection could be host related.IMPORTANCE Human papillomavirus 16 (HPV16) is the predominant type found in cervical cancer. Progression of initial infection to cervical cancer has been linked to sequence properties; however, knowledge of variants circulating in European populations, especially with longitudinal follow-up, is limited. By sequencing a number of infections with known follow-up for up to 3 years, we gained initial insights into the genetic diversity of HPV16 and the effects of the viral genome on the persistence of infections. A SNP comparison between sequences obtained from clearing and persistent infections did not identify strongly acting DNA variations responsible for these infection outcomes. In addition, we identified an HPV16 reinfection event where sequencing of initial and follow-up samples showed different HPV16 variants. Based on conventional genotyping, this infection would incorrectly be considered a persistent HPV16 infection. In the context of vaccine efficacy and monitoring studies, such infections could potentially cause reduced reported efficacy or efficiency.