We previously developed a multivariate model based on the RNA expression of 6 genes (LMO2, BCL6, FN1, CCND2, SCYA3, and BCL2) that predicts survival in diffuse large B-cell lymphoma (DLBCL) patients. Since LMO2 emerged as the strongest predictor of superior outcome, we generated a monoclonal anti-LMO2 antibody in order to study its tissue expression pattern. Immunohistologic analysis of over 1200 normal and neoplastic tissue and cell lines showed that LMO2 protein is expressed as a nuclear marker in normal germinal-center (GC) B cells and GC-derived B-cell lines and in a subset of GC-derived B-cell lymphomas. LMO2 was also expressed in erythroid and myeloid precursors and in megakaryocytes and also in lymphoblastic and acute myeloid leukemias. It was rarely expressed in mature T, natural killer (NK), and plasma cell neoplasms and was absent from nonhematolymphoid tissues except for endothelial cells. Hierarchical cluster analysis of immunohistologic data in DLBCL demonstrated that the expression profile of the LMO2 protein was similar to that of other GC-associated proteins (HGAL, BCL6, and CD10) but different from that of non-GC proteins (MUM1/IRF4 and BCL2). Our results warrant inclusion of LMO2 in multivariate analyses to construct a clinically applicable immunohistologic algorithm for predicting survival in patients with DLBCL.

Background: HPV testing is replacing cytology for cervical cancer screening because of greater sensitivity and superior reassurance following negative tests for the dozen HPV genotypes that cause cervical cancer. Management of women testing positive is unresolved. The need for identification of individual HPV genotypes for clinical use is debated. Also, it is unclear how long to observe persistent infections when precancer is not initially found. Methods: In the longitudinal NCI-Kaiser Permanente Northern California Persistence and Progression (PaP) Study, we observed the clinical outcomes (clearance, progression to CIN3+, or persistence without progression) of 11,573 HPV-positive women aged 30À65 yielding 14,158 type-specific infections. Findings: Risks of CIN3+ progression differed substantially by type, with HPV16 conveying uniquely elevated risk (26% of infections with seven-year CIN3+ risk of 22%). The other carcinogenic HPV types fell into 3 distinct seven-year CIN3+ risk groups: HPV18, 45 (13% of infections, risks >5%, with known elevated cancer risk); HPV31, 33, 35, 52, 58 (39%, risks >5%); and HPV39, 51, 56, 59, 68 (23%, risks <5%). In the absence of progression, HPV clearance rates were similar by type, with 80% of infections no longer detected within three years; persistence to seven years without progression was uncommon. The predictive value of abnormal cytology was most evident for prevalent CIN3+, but less evident in follow-up. A woman's age did not modify risk; rather it was the duration of persistence that was important.

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Angiogenesis is known to play a major role in neoplasia, including hematolymphoid neoplasia. We assessed the relationships among angiogenesis and expression of vascular endothelial growth factor and its receptors in the context of clinically and biologically relevant subtypes of diffuse large B-cell lymphoma using immunohistochemical evaluation of tissue microarrays. We found that diffuse large B-cell lymphoma specimens showing higher local vascular endothelial growth factor expression showed correspondingly higher microvessel density, implying that lymphoma cells induce local tumor angiogenesis. In addition, local vascular endothelial growth factor expression was higher in those specimens showing higher expression of the receptors of the growth factor, suggesting an autocrine growth-promoting feedback loop. The germinal center-like and nongerminal center-like subtypes of diffuse large Bcell lymphoma were biologically and prognostically distinct. Interestingly, only in the more clinically aggressive nongerminal center-like subtype were microvessel densities significantly higher in specimens showing higher vascular endothelial growth factor expression; the same was true for the finding of higher vascular endothelial growth factor receptor-1 expression in conjunction with higher vascular endothelial growth factor expression. These differences may have important implications for the responsiveness of the two diffuse large B-cell lymphoma subtypes to anti-vascular endothelial growth factor and anti-an- Angiogenesis and the proangiogenic growth factor vascular endothelial growth factor (VEGF; also known as vascular permeability factor) have a known role in solid neoplasia, and there is increasing evidence that they also play a role in hematolymphoid neoplasia. Increased microvessel density has been noted in a range of hematolymphoid disorders, including multiple myeloma, nonHodgkin lymphoma, acute and chronic leukemias of myeloid and lymphoid lineages, and myelodysplastic disorders.

The prevalence of HPV16/18 in cervical cancer has been reported to decline with age in some papers. However, whether this decline in proportion of cancers positive for HPV16/18 is consistently observed across studies remains to be elucidated. Thus, the aim of this study was to identify papers reporting data on age-specific prevalence of HPV16/18 in cervical cancer and to summarize the results. We employed MEDLINE and Embase for a systematic literature search and thereby identified a total of 644 papers published in the period 1999-2015, of which 15 papers, reporting cross-sectional data, were included for review (11,526 cervical cancers). The prevalence of HPV16/18 in cervical cancer declined significantly with age (q 5 20.83, p 5 0.04) from 74.8% (95% CI 67.6-80.8) in women aged 30-39 years to 56.8% (95% CI 43.9-68.8) in women aged 70 years. As the HPV16/18 positive cancers are prevented in fully vaccinated cohorts, the age-specific epidemiology of cervical cancer is anticipated to change, with a shift in peak incidence rate to older ages. It will be important for integrated vaccination and screening strategies to consider predicted change in the age-specific epidemiology of cervical cancer.High-risk human papillomavirus (HPV) has been established as a necessary, though not a sufficient, cause of cervical cancer.1 The five most common high-risk HPV types in cervical cancer are, in descending order, HPV16,18, 45,31,and 33,2 with HPV16 and 18 as the most common causes, accounting for 39-78% of all cervical cancer cases 2,3 depending on geographical region, histological type, and age. This knowledge has led to the development of the bivalent, the quadrivalent, and the nonavalent HPV vaccines that offer protection against HPV16 and 18 induced cervical lesions, and for the quadrivalent and the nonavalent vaccine, protection against low-risk HPV6 and 11 as well. The quadrivalent vaccine has been highly effective in reducing the prevalence of condylomas, 4,5 and the quadrivalent and the bivalent vaccines show high efficacy in preventing HPV16 and 18 caused dysplasia. [6][7][8][9] The HPV vaccine has therefore been implemented in vaccination programs in several countries worldwide. Owing to the high efficacy of the HPV vaccines, a recent study has suggested that initiation of cervical cancer screening could be postponed in HPV-vaccinated women. 10 Interestingly, some studies have indicated that the prevalence of HPV16 and 18 in cervical lesions and cervical cancers declines with increasing age, and that the prevalence of other HPV types seems to increase. [10][11][12][13] In this article, we aimed to review and summarize the existing literature on age-specific prevalence of HPV16/18 in cervical cancers to determine whether the decline in proportion of cancers positive for HPV16/18 is consistently observed across multiple populations. Methods SourcesWe performed a systematic literature search through May 6, 2015. We searched MEDLINE (Pubmed) using a combination of the MESH terms "humans," "papillomaviridae,"Key words: c...

In this study, we aimed to provide molecular evidence of HPV latency in humans and discuss potential challenges of conducting studies on latency. We analyzed the entire cervix of two women who underwent hysterectomy unrelated to cervical abnormality. The cervices were sectioned into 242 and 186 sets respectively, and each set was tested separately for HPV using the SPF10-PCR-DEIA-LiPA25 system. To identify whether there was any evidence of transforming or productive infection, we used the biomarkers E4 and P16 INK4a to stain slides immediately adjacent to HPV-positive sections. HPV was detected in both cervices. In patient 1, 1/242 sets was positive for HPV31. In patient 2, 13/186 sets were positive for HPV18 and 1/186 was positive for HPV53. The infection was very focal in both patients, and there was no sign of a transforming or productive infection, as evaluated by the markers E4 and P16 INK4a . Had we only analyzed one set from each block, the probability of detecting the infection would have been 32.3% and 2%, respectively.Our findings support the idea that HPV may be able to establish latency in the human cervix; however, the risk associated with a latent HPV infection remains unclear.

Background: State Trait Anxiety Inventory (STAI) scale was developed in the 1980's and has been widely used both in clinical settings and in research. However the Danish version of STAI has not been validated. The aim of this study was to assess the validity and reliability of STAI-state anxiety scale in Danish women aged 45 years and older with abnormal cervical cancer screening results. Methods: Women ≥45 years referred with an abnormal cervical cytology and healthy volunteers (n = 12) underwent cognitive interview after completing STAI. Further, STAI was sent out in an electronic questionnaire to women (n = 109) seen at the gynecological department with abnormal cervical cancer screening test during 2018. Validity and reliability of STAI was evaluated according to the Consensus-based Standards for the selection of health Measurement Instruments (COSMIN) checklist by examining internal consistency, test-retest reliability, measurement error, floor and ceiling, construct validity and content validity. Results: In the cognitive interviews the content validity was evaluated to be very good. The internal consistency of the scale was excellent with Cronbach's α = 0.93. Test-retest reliability was good with an intra-class correlation coefficient of 0.80 and the systematic difference between test-retest results was negligible. The construct validity was good. Conclusion: To our best knowledge, this is the first validation study of the Danish translation of STAI-state anxiety scale. This version of STAI demonstrates an acceptable reliability and validity when used in a gynecological setting.