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Worldwide, the COVID-19 pandemic disrupted healthcare services, including cervical cancer management, and an increased burden for this condition is expected. This systematic review synthetizes the available evidence on the impact of the pandemic on prevention, diagnosis and treatment of cervical cancer. Searches were performed on PubMed, Embase, and Scopus for relevant studies on these topics with the purpose of comparing service access and care delivery before and during COVID-19 pandemic. Due to the methodological heterogeneity among the studies, findings were narratively discussed. Of the 715 screened titles and abstracts, 33 articles were included, corresponding to 42 reports that covered the outcomes of interest: vaccination against human papillomavirus (HPV) (6 reports), cancer screening (19), diagnosis (8), and treatment (8). Seven studies observed reductions in HPV vaccination uptake and coverage during COVID-19. Reports on cervical screening and cancer diagnosis activities showed a substantial impact of the pandemic on access to screening services and diagnostic procedures. All but one study that investigated cervical cancer treatment reported changes in the number of women with cervical lesions who received treatments, as well as treatment delay and interruption. With a major impact during the first wave in 2020, COVID-19 and restriction measures resulted in a substantial disruption in cervical cancer prevention and management, with declines in screening and delays in treatment. Taken together, findings from this systematic review calls for urgent policy interventions for recovering cervical cancer prevention and care.

Human transferrin receptor-2 (TFR-2) is a protein highly homologous to TFR-1/CD71 and is endowed with the ability to bind transferrin (TF) with low affinity. High levels of TFR-2 mRNA were found in the liver and in erythroid precursors. Mutations affecting the TFR-2gene led to hemochromatosis type 3, a form of inherited iron overload. Several issues on distribution and function of the receptor were answered by raising a panel of 9 monoclonal antibodies specific for TFR-2 by immunizing mice with murine fibroblasts transfected with the human TFR-2 cDNA. A polyclonal antiserum was also produced in mice immunized with 3 peptides derived from the TFR-2 sequence, exploiting an innovative technique. The specificity of all the reagents produced was confirmed by reactivity with TFR-2+ target cells and simultaneous negativity with TFR-1+ cells. Western blot analyses showed a dominant chain of approximately 90 kDa in TFR-2 transfectants and HepG2 cell line. Analysis of distribution in normal tissues and in representative cell lines revealed that TFR-2 displays a restricted expression pattern—it is present at high levels in hepatocytes and in the epithelial cells of the small intestine, including the duodenal crypts. Exposure of human TFR-2+cells to TF-bound iron is followed by a significant up-regulation and relocalization of membrane TFR-2. The tissue distribution pattern, the behavior following exposure to iron-loaded TF, and the features of the disease resulting from TFR-2 inactivation support the hypothesis that TFR-2 contributes to body iron sensing.

Hemochromatosis type 2 (HFE2) or juvenile hemochromatosis (JH) is a rare recessive disorder that causes iron overload, characterized by early onset and severe clinical course. The JH locus maps to chromosome 1q, in a 4-cM region encompassing markers D1S442 and D1S2347. Recently a gene named ZIRTL has been characterized and mapped to 1q21. This gene belongs to a family of divalent metal ion-transporting genes that encode for proteins involved in transport of different metals, including iron. Thus, the ZIRTL gene represents a positional and functional candidate for JH. Here we further restrict the candidate region through segregation analysis of two new polymorphic markers and haplotype analysis in JH families. Furthermore, we exclude ZIRTL as a JH candidate gene showing that it maps outside the critical interval and that its genomic sequence is normal in three patients.

Mutations in exon 12 of the nucleophosmin (NPM1) gene occur in about 60% of adult AML with normal karyotype. By exploiting a specific feature of NPM1 mutants, that is insertion at residue 956 or deletion/insertion at residue 960, we developed highly sensitive, real-time quantitative (RQ) polymerase chain reaction (PCR) assays, either in DNA or RNA, that are specific for various NPM1 mutations. In all 13 AML patients carrying NPM1 mutations at diagnosis, cDNA RQ-PCR showed > 30000 copies of NPM1-mutated transcript. A small or no decrease in copies was observed in three patients showing partial or no response to induction therapy. The number of NPM1-mutated copies was markedly reduced in 10 patients achieving complete hematological remission (five cases:< 100 copies; five cases: 580-5046 copies). In four patients studied at different time intervals, the number of NPM1 copies closely correlated with clinical status and predicted impending hematological relapse in two. Thus, reliable, sensitive RQ-PCR assays for NPM1 mutations can now monitor and quantify MRD in AML patients with normal karyotype and NPM1 gene mutations.

Animal models indicate that the antimicrobial peptide hepcidin (HAMP; OMIM 606464) is probably a key regulator of iron absorption in mammals. Here we report the identification of two mutations (93delG and 166C--T) in HAMP on 19q13 in two families with a new type of juvenile hemochromatosis.