Aim: This study aimed to follow the impact of human papillomavirus (HPV) catch-up and vaccination on the very high cervical HPV-prevalence in women at a youth clinic in central Stockholm during the period 2008–2018.Background: 2008–2010, cervical HPV-prevalence (69.5%) and HPV16 prevalence (34.7%) were high in non-vaccinated women at a youth clinic in Stockholm. 2013–2015, after the introduction of the quadrivalent-Gardasil® HPV-vaccine, HPV16 and HPV6 prevalence had decreased. Here, cervical HPV-prevalence was investigated 10 years after primary sampling.Material and Methods: 2017–2018, 178 cervical swabs, from women aged 15–23 years old, were tested for 27 HPV types by a bead-based multiplex method. HPV-prevalence data were then related to vaccination status and age and compared to HPV-prevalence in 615 samples from 2008 to 2010 and 338 samples from 2013 to 2015 from the same clinic, and to HPV types in 143 cervical cancer cases during 2003–2008 in Stockholm.Results: The proportion of vaccinated women increased from 10.7% (2008–2010) to 82.1% (2017–2018). The prevalence of all 27 HPVs, all high-risk HPVs (HR-HPVs) and the combined presence of the quadrivalent-Gardasil® types HPV16, 18, 6, and 11, was lower in vaccinated compared to unvaccinated women (67.4 vs. 93.3%, p = 0.0031, 60.1 vs. 86.7%, p = 0.0057 and 5.8 vs. 26.7%, p = 0.002, respectively). Furthermore, HPV16 prevalence in non-vaccinated women 2017–2018 was lower than that in 2008–2010 (16.7 and 34.7%, respectively, p = 0.0471) and similar trends were observed for HPV18 and 11. In both vaccinated and non-vaccinated women, the most common non-quadrivalent-Gardasil® vaccine HR-HPV types were HPV39, 51, 52, 56, and 59. Together they accounted for around 9.8% of cervical cancer cases in Stockholm during 2003–2008, and their prevalence tended to have increased during 2017–2018 compared to 2008–2010.Conclusion: Quadrivalent-Gardasil® vaccination has decreased HPV-vaccine type prevalence significantly. However, non-vaccine HR-HPV types remain high in potentially high-risk women at a youth clinic in Stockholm.
Background/Aim: Medulloblastoma (MB) accounts for ~20% of pediatric malignant central nervous system tumors. Treatment strategies, including surgery, radiation therapy and/or chemotherapy, are effective, but recurrence and metastasis frequently occur. Therefore, novel therapies are required. Herein, the effects of fibroblast growth factor receptor (FGFR) and phosphoinositide 3kinase (PI3K) inhibitors on MB cells lines were evaluated. Materials and Methods: ΜΒ cell lines (UW228-3, DAOY, Med8a, D425, D283) were tested for sensitivity to FGFR (AZD4547) and PI3K (BEZ235 and BYL719) inhibitors by viability, cytotoxicity, apoptosis, and proliferation assays. Results: Single treatments with FGFR and PI3K inhibitors decreased viability and proliferation in a dose-dependent pattern in most cell lines. Combinination of the two type of drugs, increased sensitivity, especially of the most resistant cell line UW228-3. Conclusion: Combination treatments with FGFR and PI3K inhibitors were superior to single treatments with FGFR and PI3K inhibitors, especially with BEZ235, for MB cell lines.Cancer is a leading cause of death for children and adolescents around the world and approximately 300,000 children aged 0 to 19 years old are diagnosed with cancer each year (1). Although leukaemia is the most common cancer in childhood (30% of paediatric malignancies), brain and central nervous system (CNS) tumors are the most frequent among the solid tumors (20% of childhood cancers) (2). Medulloblastomas (MBs), which are the main focus of the current study, are among the most common malignant brain tumors, accounting for 16-25% of all CNS tumors in children, and usually arise in the cerebellum (3-6). According to recent advances in genomics, gene expression profiling, and epigenomics, MBs are divided into at least four subgroups: Wingles/Integrated (WNT), Sonic Hedgehog (SHH), Group 3 and Group 4 (7-9). The largest subgroups are: Group 4 and SHH-activated MB, which account for 35% and 30% of tumors respectively, and they both have intermediate prognosis. Group 3 tumors are found in 25% cases and have the worst prognosis, while WNT comprises 10% of MB tumors and has the best prognosis (7,10,11).The current treatment of MBs consists of removal of the tumor by surgery, radiation therapy (X-rays or protons) and chemotherapy (12). Despite this multipronged approach to therapy, approximately 30% of patients still die from the disease, and survivors suffer from severe long-term side effects, including neurological deficits, endocrine disorders, and secondary cancers (13). Therefore, novel combination therapies, ideally with fewer side effects, are needed. In this context, the present study focuses on the fibroblast growth factor receptor (FGFR) and its downstream phosphatidylinositol 3-kinase (PI3K) pathways, which both could be potential targets for future treatment strategies for MB.FGFRs are a family of receptor tyrosine kinases expressed on the cell membrane, and are crucial during development, as well as in adult cells. Their dysregulation ...
In patients with HPVTSCC/BOTSCC and wild-type FGFR3, overexpression of FGFR3 was correlated with better DFS.
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