Awareness and knowledge of Human Papillomavirus (HPV) among ethnically diverse women varying in generation status

Although Human papillomavirus (HPV) is a common sexually transmitted infection, there is limited knowledge of HPV with ethnic/racial minorities experiencing the greatest disparities. This cross-sectional study used the most recent available data from the California Health Interview Survey to assess disparities in awareness and knowledge of HPV among ethnically/racially diverse women varying in generation status (N = 19,928). Generation status emerged as a significant predictor of HPV awareness across ethnic/racial groups, with 1st generation Asian-Americans and 1st and 2nd generation Latinas reporting the least awareness when compared to same-generation White counterparts. Also, generation status was a significant predictor of HPV knowledge, but only for Asian-Americans. Regardless of ethnicity/race, 1st generation women reported lowest HPV knowledge when compared to 2nd and 3rd generation women. These findings underscore the importance of looking at differences within and across ethnic/racial groups to identify subgroups at greatest risk for poor health outcomes. In particular, we found generation status to be an important yet often overlooked factor in the identification of health disparities.

The effect of HLA-DR on susceptibility to rheumatoid arthritis is influenced by the associated lymphotoxin α-tumor necrosis factor haplotype

Objective. HLA-DRB1, a major genetic determinant of susceptibility to rheumatoid arthritis (RA), is located within 1,000 kb of the gene encoding tumor necrosis factor (TNF). Because certain HLA-DRB1*04 subtypes increase susceptibility to RA, investigation of the role of the TNF gene is complicated by linkage disequilibrium (LD) between TNF and DRB1 alleles. By adequately controlling for this LD, we aimed to investigate the presence of additional major histocompatibility complex (MHC) susceptibility genes. Methods. We identified 274 HLA-DRB1*04-positive cases of RA and 271 HLA-DRB1*04-positive population controls. Each subject was typed for 6 single-nucleotide polymorphisms within a 4.5-kb region encompassing TNF and lymphotoxin a (LTA). LTA-TNF haplotypes in these unrelated individuals were determined using a combination of family data and the PHASE software program. Results. Significant differences in LTA-TNF haplotype frequencies were observed between different subtypes of HLA-DRB1*04. The LTA-TNF haplotypes observed were very restricted, with only 4 haplotypes constituting 81% of all haplotypes present. Among individuals carrying DRB1*0401, the LTA-TNF 2 haplotype was significantly underrepresented in cases compared with controls (odds ratio 0.5 [95% confidence interval 0.3-0.8], P = 0.007), while in those with DRB1*0404, the opposite effect was observed (P = 0.007). Conclusion. These findings suggest that the MHC contains genetic elements outside the LTA-TNF region that modify the effect of HLA-DRB1 on susceptibility to RA.

Prevalence and risk factors for oral HPV infection in young Australians

The prevalence of human papillomavirus (HPV)–associated head and neck cancers is increasing, but the prevalence of oral HPV infection in the wider community remains unknown. We sought to determine the prevalence of, and identify risk factors for, oral HPV infection in a sample of young, healthy Australians. For this study, we recruited 307 Australian university students (18–35 years). Participants reported anonymously about basic characteristics, sexual behaviour, and alcohol, tobacco and illicit drugs use. We collected oral rinse samples from all participants for HPV testing and typing. Seven of 307 (2.3%) students tested positive for oral HPV infection (3 HPV-18, one each of HPV-16, -67, -69, -90), and six of them were males (p = 0.008). Compared to HPV negative students, those with oral HPV infection were more likely to have received oral sex from more partners in their lifetime (p = 0.0004) and in the last year (p = 0.008). We found no statistically significant associations with alcohol consumption, smoking or numbers of partners for passionate kissing or sexual intercourse. In conclusion, oral HPV infection was associated with male gender and receiving oral sex in our sample of young Australians.

Tumor-associated mutations inO6-methylguanine DNA-methyltransferase (MGMT) reduce DNA repair functionality

MGMT is the primary vehicle for cellular removal of alkyl lesions from the O-6 position of guanine and the O-4 position of thymine. While key to the maintenance of genomic integrity, MGMT also removes damage induced by alkylating chemotherapies, inhibiting the efficacy of cancer treatment. Germline variants of human MGMT are well-characterized, but somatic variants found in tumors were, prior to this work, uncharacterized. We found that MGMT G132R, from a human esophageal tumor, and MGMT G156C, from a human colorectal cancer cell line, are unable to rescue methyltransferase-deficient Escherichia coli as well as wild type (WT) human MGMT after treatment with a methylating agent. Using pre-steady state kinetics, we biochemically characterized these variants as having a reduced rate constant. G132R binds DNA containing an O6-methylguanine lesion half as tightly as WT MGMT, while G156C has a 40-fold decrease in binding affinity for the same damaged DNA versus WT. Mammalian cells expressing either G132R or G156C are more sensitive to methylating agents than mammalian cells expressing WT MGMT. G132R is slightly resistant to O6-benzylguanine, an inhibitor of MGMT in clinical trials, while G156C is almost completely resistant to this inhibitor. The impared functionality of expressed variants G132R and G156C suggests that the presence of somatic variants of MGMT in a tumor could impact chemotherapeutic outcomes.

Heterogeneity of miR-10b expression in circulating tumor cells

Circulating tumor cells (CTCs) in the blood of cancer patients are recognized as important potential targets for future anticancer therapies. As mediators of metastatic spread, CTCs are also promising to be used as € liquid biopsyto aid clinical decision-making. Recent work has revealed potentially important genotypic and phenotypic heterogeneity within CTC populations, even within the same patient. MicroRNAs (miRNAs) are key regulators of gene expression and have emerged as potentially important diagnostic markers and targets for anti-cancer therapy. Here, we describe a robust in situ hybridization (ISH) protocol, incorporating the CellSearch ® CTC detection system, enabling clinical investigation of important miRNAs, such as miR-10b on a cell by cell basis. We also use this method to demonstrate heterogeneity of such as miR-10b on a cell-by-cell basis. We also use this method to demonstrate heterogeneity of miR-10b in individual CTCs from breast, prostate and colorectal cancer patients.

Circulating tumor cell detection in high-risk non-metastatic prostate cancer

Purpose The detection of circulating tumor cells (CTCs) provides important prognostic information in men with metastatic prostate cancer. We aim to determine the rate of detection of CTCs in patients with high-risk non-metastatic prostate cancer using the CellSearch® method. Method Samples of peripheral blood (7.5 mL) were drawn from 36 men with newly diagnosed high-risk non-metastatic prostate cancer, prior to any initiation of therapy and analyzed for CTCs using the CellSearch® method. Results The median age was 70 years, median PSA was 14.1, and the median Gleason score was 9. The median 5-year risk of progression of disease using a validated nomogram was 39 %. Five out of 36 patients (14 %, 95 % CI 5–30 %) had CTCs detected in their circulation. Four patients had only 1 CTC per 7.5 mL of blood detected. One patient had 3 CTCs per 7.5 mL of blood detected, which included a circulating tumor microemboli. Both on univariate analysis and multivariate analysis, there were no correlations found between CTC positivity and the classic prognostic factors including PSA, Gleason score, T-stage and age. Conclusion This study demonstrates that patients with high-risk, non-metastatic prostate cancer present infrequently with small number of CTCs in peripheral blood. This finding is consistent with the limited literature available in this setting. Other CTC isolation and detection technologies with improved sensitivity and specificity may enable detection of CTCs with mesenchymal phenotypes, although none as yet have been validated for clinical use. Newer assays are emerging for detection of new putative biomarkers for prostate cancer. Correlation of disease control outcomes with CTC detection will be important.

A liquid biopsy for head and neck cancers

Head and neck cancer patients often present with advanced metastatic disease resulting in a poor 5-year survival. Therefore, there is a need for non-invasive diagnostic tools that could complement conventional imaging to inform clinicians of patient outcomes and treatment responses. A liquid biopsy addresses this unmet clinical need; a simple peripheral blood draw could provide information about the disseminated disease in terms of circulating tumor cells and circulating tumor DNA. Moreover, detectable tumor DNA in the saliva of head and neck cancer patients could signify the early signs of the disease and present an opportunity for clinical intervention. This review provides an overview of the current literature with regard to the feasibility of such a test in the head and neck cancer field and highlights the need for such a test.

Primary brain tumor patients’ supportive care needs and multidisciplinary rehabilitation, community and psychosocial support services: Awareness, referral and utilization

Primary brain tumors are associated with significant physical, cognitive and psychosocial changes. Although treatment guidelines recommend offering multidisciplinary rehabilitation and support services to address patients’ residual deficits, the extent to which patients access such services is unclear. This study aimed to assess patients’ supportive care needs early after diagnosis, and quantify service awareness, referral and utilization. A population-based sample of 40 adults recently diagnosed with primary brain tumors was recruited through the Queensland Cancer Registry, representing 18.9% of the eligible population of 203 patients. Patients or carer proxies completed surveys of supportive care needs at baseline (approximately three months after diagnosis) and three months later. Descriptive statistics summarized needs and service utilization, and linear regression identified predictors of service use. Unmet supportive care needs were highest at baseline for all domains, and highest for the physical and psychological needs domains at each time point. At follow-up, participants reported awareness of, referral to, and use of 32 informational, support, health professional or practical services. All or almost all participants were aware of at least one informational (100%), health professional (100%), support (97%) or practical service (94%). Participants were most commonly aware of speech therapists (97%), physiotherapists (94%) and diagnostic information from the internet (88%). Clinician referrals were most commonly made to physiotherapists (53%), speech therapists (50%) and diagnostic information booklets (44%), and accordingly, participants most commonly used physiotherapists (56%), diagnostic information booklets (47%), diagnostic information from the internet (47%), and speech therapists (43%). Comparatively low referral to and use of psychosocial services may limit patients’ abilities to cope with their condition and the changes they experience.

Human papillomavirus infection and vaccination: Awareness and knowledge of HPV and acceptability of HPV vaccine among mothers of teenage daughters in Weihai, Shandong, China

In preparation for the introduction of human papillomavirus (HPV) vaccine, we investigated awareness and knowledge of HPV/HPV vaccine and potential acceptability to HPV vaccine among mothers with a teenage daughter in Weihai, Shandong, China. A cross-sectional survey was conducted in 2013 with a sample of 1850 mothers who had a daughter (aged 9–17 years) attending primary, junior and senior high schools. In the final sample (N = 1578, response rate 85.30%), awareness of HPV was reported by 305 (19.32%) mothers. Awareness varied significantly by daughter’s age (P<0.01), mother’s education level (P<0.01), mother’s occupation (P<0.01), household income (P<0.01) and residence type (P<0.01). Knowledge about HPV/HPV vaccine was poor with a mean total score of 3.56 (SD = 2.40) out of a possible score of 13. Mothers with a higher education level reported higher levels of knowledge (P = 0.02). Slightly more than one-fourth (26.49%) of mothers expressed their potential acceptability of HPV vaccine for their daughters. Acceptability increased along with increased daughters’ age (P<0.01), household income (P<0.01) and knowledge level (P<0.01). House wives and unemployed mothers had the highest acceptability (P<0.01). The most common reasons for not accepting HPV vaccination were “My daughter is too young to have risk of cervical cancer (30.95%)”, “The vaccine has not been widely used, and the decision will be made after it is widely used (24.91%)”, “Worry about the safety of the vaccine (22.85%)”. Awareness and knowledge of HPV/HPV vaccines are poor and HPV vaccine acceptability is low among these Chinese mothers. These results may help inform appropriate health education programs in this population.

Circulating tumor cells: Isolation, expansion, characterization and translation to clinic

Circulating tumor cells (CTCs) are the seeds for cancer metastases development, which is responsible for >90% of cancer-related deaths. Accurate quantification of CTCs in human fluids could be an invaluable tool for understanding cancer prognosis, delivering personalized medicine to prevent metastasis and finding cancer therapy effectiveness. Although CTCs were first discovered more than 200 years ago, until now it has been a nightmare for clinical practitioners to capture and diagnose CTCs in clinical settings. Our society needs rapid, sensitive, and reliable assays to identify the CTCs from blood in order to help save millions of lives. Due to the phenotypic EMT transition, CTCs are undetected for more than one-third of metastatic breast cancer patients in clinics. To tackle the above challenges, the first volume in “Circulating Tumor Cells (CTCs): Detection Methods, Health Impact and Emerging Clinical Challenges discusses recent developments of different technologies, which have the capability to target and elucidate the phenotype heterogenity of CTCS. It contains seven chapters written by world leaders in this area, covering basic science to possible device design which can have beneficial applications in society. This book is unique in its design and content, providing an in-depth analysis to elucidate biological mechanisms of cancer disease progression, CTC detection challenges, possible health effects and the latest research on evolving technologies which have the capability to tackle the above challenges. It describes the broad range of coverage on understanding CTCs biology from early predictors of the metastatic spread of cancer, new promising technology for CTC separation and detection in clinical environment and monitoring therapy efficacy via finding the heterogeneous nature of CTCs. (Imprint: Nova Biomedical)

Distinct subpopulations of gamma delta T cells are present in normal and tumor-bearing human liver

Gamma delta T cells are thought to mediate immune responses at epithelial surfaces. We have quantified and characterized hepatic and peripheral blood gamma delta T cells from 11 normal and 13 unresolved tumor-bearing human liver specimens. gamma delta T cells are enriched in normal liver (6.6% of T cells) relative to matched blood (0.9%; P = 0.008). The majority express CD4(-)CD8(-) phenotypes and many express CD56 and/or CD161. In vitro, hepatic gamma delta T cells can be induced to kill tumor cell lines and release interferon-gamma, tumor necrosis factor-alpha, interleukin-2 and interleukin-4. Analysis of V gamma and V delta chain usage indicated that V delta 3(+) cells are expanded in normal livers (21.2% of gamma delta T cells) compared to blood (0.5%; P = 0.001). Tumor-bearing livers had significant expansions and depletions of gamma delta T cell subsets but normal cytolytic activity. This study identifies novel populations of liver T cells that may play a role in immunity against tumors.

NKT cells from normal and tumor-bearing human livers are phenotypically and functionally distinct from murine NKT cells

A major group of murine NK T (NKT) cells express an invariant Vα14Jα18 TCR α-chain specific for glycolipid Ags presented by CD1d. Murine Vα14Jα18+ account for 30–50% of hepatic T cells and have potent antitumor activities. We have enumerated and characterized their human counterparts, Vα24Vβ11+ NKT cells, freshly isolated from histologically normal and tumor-bearing livers. In contrast to mice, human NKT cells are found in small numbers in healthy liver (0.5% of CD3+ cells) and blood (0.02%). In contrast to those in blood, most hepatic Vα24+ NKT cells express the Vβ11 chain. They include CD4+, CD8+, and CD4−CD8− cells, and many express the NK cell markers CD56, CD161, and/or CD69. Importantly, human hepatic Vα24+ T cells are potent producers of IFN-γ and TNF-α, but not IL-2 or IL-4, when stimulated pharmacologically or with the NKT cell ligand, α-galactosylceramide. Vα24+Vβ11+ cell numbers are reduced in tumor-bearing compared with healthy liver (0.1 vs 0.5%; p < 0.04). However, hepatic cells from cancer patients and healthy donors release similar amounts of IFN-γ in response to α-galactosylceramide. These data indicate that hepatic NKT cell repertoires are phenotypically and functionally distinct in humans and mice. Depletions of hepatic NKT cell subpopulations may underlie the susceptibility to metastatic liver disease.

Chemotherapy pretreatment sensitizes solid tumor-derived cell lines to Vα24+ NKT cell-mediated cytotoxicity

There is an increasing awareness of the therapeutic potential for combining immune-based therapies with chemotherapy in the treatment of malignant diseases, but few published studies evaluate possible cytotoxic synergies between chemotherapy and cytotoxic immune cells. Human Vα24 +/Vβ11+ NKT cells are being evaluated for use in cell-based immunotherapy of malignancy because of their immune regulatory functions and potent cytotoxic potential. In this study, we evaluated the cytotoxicity of combinations of chemotherapy and NKT cells to determine whether there is a potential to combine these treatment modalities for human cancer therapy. The cytotoxicity of NKT cells was tested against solid-tumor derived cell lines NCI-H358, DLD-1, HT-29, DU-145, TSU-Pr1 and MDA-MB231, with or without prior treatment of these target cells, with a range of chemotherapy agents. Low concentrations of chemotherapeutic agents led to sensitization of cell lines to NKT-mediated cytotoxicity, with the greatest effect being observed for prostate cancer cells. Synergistic cytotoxicity occurred in an NKT cell in a dose-dependent manner. Chemotherapy agents induced upregulation of cell surface TRAIL-R2 (DR5) and Fas (CD95) expression, increasing the capacity for NKT cells to recognize and kill via TRAIL- and FasL-mediated pathways. We conclude that administration of cytotoxic immune cells after chemotherapy may increase antitumor activities in comparison with the use of either treatment alone.

Improving diagnosis of tumor-induced osteomalacia with gallium-68 DOTATATE PET/CT

Context: Tumor-induced osteomalacia (TIO) is a rarely diagnosed disorder presenting with bone pain, fractures, muscle weakness, and moderate-to-severe hypophosphatemia resulting from fibroblast growth factor 23-mediated renal phosphate wasting. Tumors secreting fibroblast growth factor 23 are often small and difficult to find with conventional imaging. Objective: We studied the utility of 68Ga-DOTA-octreotate (DOTATATE) somatostatin receptor positron emission tomography (PET)/computed tomography (CT) imaging in the diagnosis of TIO. Design and Setting: A multicenter case series was conducted at tertiary referral hospitals. Patients and Methods: Six patients with TIO diagnosed between 2003 and 2012 in Australia were referred for DOTATATE PET imaging. We reviewed the clinical history, biochemistry, imaging characteristics, histopathology, and clinical outcome of each patient. Results: Each case demonstrated delayed diagnosis despite severe symptoms. DOTATATE PET/CT imaging demonstrated high uptake and localized the tumor with confidence in each case. After surgical excision, there was resolution of clinical symptoms and serum phosphate, except in one patient who demonstrated residual disease on PET/CT. All tumors demonstrated high somatostatin receptor subtype 2 cell surface receptor expression using immunohistochemistry. Conclusions: In patients with TIO, DOTATATE PET/CT can successfully localize phosphaturic mesenchymal tumors and may be a practical first step in functional imaging for this disorder. Serum phosphate should be measured routinely in patients with unexplained muscle weakness, bone pain, or stress fractures to allow earlier diagnosis of TIO. - See more at: http://press.endocrine.org/doi/abs/10.1210/jc.2012-3642#sthash.eXD0CopL.dpuf