HPV genotypes and cervical intraepithelial neoplasia in a multiethnic cohort in the southeastern USA

Purpose

For poorly understood reasons, invasive cervical cancer (ICC) incidence and mortality rates are higher in women of African descent. Oncogenic human papillomavirus (HPV) genotypes distribution may vary between European American (EA) and African-American (AA) women and may contribute to differences in ICC incidence. The current study aimed at disentangling differences in HPV distribution among AA and EA women.

Methods

Five-hundred and seventy-two women were enrolled at the time of colposcopic evaluation following an abnormal liquid-based cytology screen. HPV infections were detected using HPV linear array, and chi-squared tests and linear regression models were used to compare HPV genotypes across racial/ethnic groups by CIN status.

Results

Of the 572 participants, 494 (86 %) had detectable HPV; 245 (43 %) had no CIN lesion, 239 (42 %) had CIN1, and 88 (15 %) had CIN2/3. Seventy-three percent of all women were infected with multiple HPV genotypes. After adjusting for race, age, parity, income, oral contraception use, and current smoking, AAs were two times less likely to harbor HPV 16/18 (OR 0.48, 95 % CI 0.21–0.94, p = 0.03) when all women were considered. This association remained unchanged when only women with CIN2/3 lesions were examined (OR 0.22, 95 % CI 0.05–0.95, p = 0.04). The most frequent high-risk HPV genotypes detected among EAs were 16, 18, 56, 39, and 66, while HPV genotypes 33, 35, 45, 58, and 68 were the most frequent ones detected in AAs.

Conclusions

Our data suggest that while HPV 16/18 are the most common genotypes among EA women with CIN, AAs may harbor different genotypes.     

Multiple experimental designs to evaluate the role of T-cell-mediated immunity against experimental vaginal Candida albicans infection.

Studies to date suggest a limited protective role for Candida-specific Th1-type cell-mediated immunity (CMI) against Candida albicans vaginitis, despite protection against other mucosal Candida infections. Recent evidence suggests this may be due to immunoregulatory mechanisms that inhibit a more profound CMI response against C. albicans vaginal infections. The present study was designed to conduct an evaluation of the protective role of CMI against experimental C. albicans vaginitis using multiple approaches, including the use of T-cell-immunodeficient (SCID, Nude) and knockout (CD4) mice and several immunization designs in immunocompetent mice. Results showed, with few exceptions, that most T-cell-immunodeficient or knockout mice had a vaginal fungal burden similar to that of wild-type strains throughout the observation period. In addition, no correlation was observed between vaginal T-helper and proinflammatory cytokines and fungal burden, suggesting a generalized state of immunoregulation. Evaluation of the effects of various immunization designs that included different Candida antigens, routes of delivery and strains of mice yielded no protection against vaginal candidiasis. These studies provide further evidence of a lack of a protective role of T cells against C. albicans vaginitis, and continue to support the concept of immunoregulation against vaginal CMI responses.     

Cytokine and Chemokine Production by Human Oral and Vaginal Epithelial Cells in Response to Candida albicans

Oropharyngeal and vaginal candidiases are the most common forms of mucosal fungal infections and are primarily caused by Candida albicans, a dimorphic fungal commensal organism of the gastrointestinal and lower female reproductive tracts. Clinical and experimental observations suggest that local immunity is important in host defense against candidiasis. Accordingly, cytokines and chemokines are present at the oral and vaginal mucosa during C. albicans infections. Since mucosal epithelial cells produce a variety of cytokines and chemokines in response to microorganisms and since C. albicans is closely associated with mucosal epithelial cells as a commensal, we sought to identify cytokines and/or chemokines produced by primary oral and vaginal epithelial cells and cell lines in response to C. albicans. The results showed that proinflammatory cytokines were produced by oral and/or vaginal epithelial cells at various levels constitutively with considerable interleukin-1alpha (IL-1alpha) and tumor necrosis factor alpha, but not IL-6, produced in response to C. albicans. In contrast, Th1-type (IL-12 and gamma interferon) and Th2-type-immunoregulatory (IL-10 and transforming growth factor beta) cytokines and the chemokines monocyte chemoattractant protein 1 and IL-8 were produced in low to undetectable concentrations with little additional production in response to C. albicans. Taken together, these results indicate that cytokines and chemokines are variably produced by oral and vaginal epithelial cells constitutively, as well as in response to C. albicans, and are predominated by proinflammatory cytokines.     

Circulating CD4 and CD8 T cells have little impact on host defense against experimental vaginal candidiasis.

The etiology of recurrent vulvovaginal candidiasis in otherwise healthy women of child-bearing age remains an enigma. To date, results from both clinical studies and a murine model of vaginal candidiasis indicate that Candida vaginitis can occur in the presence of Candida-specific Th1-type cell-mediated immunity expressed in the peripheral circulation. The present study was designed to determine the role of circulating CD4 and CD8 cells in primary and secondary vaginal infections with Candida albicans. Vaginal fungal burden, Candida-specific delayed-type hypersensitivity (DTH), and lymph node cell Th1/Th2 cytokine production were monitored in CD4 and/or CD8 cell-depleted mice during persistent primary vaginal infections and secondary vaginal infections against which partial protection was observed. Treatment of mice with anti-CD4 or anti-CD8 antibodies resulted in 90% or greater depletion of the respective cell populations. Mice depleted of CD4 cells had significantly reduced Candida-specific DTH and lymph node cell Th1-type cytokine production during a primary vaginal infection, as well as reduced anamnestic DTH during a secondary vaginal infection. In contrast, mice depleted of CD8 cells showed only reduced gamma interferon production during a primary infection; no alterations in DTH were observed. Despite reductions in DTH and cytokine production, however, CD4 and/or CD8 cell depletion had no effect on vaginal C. albicans burden in mice after a primary or secondary vaginal inoculation. Taken together, these results suggest that while circulating CD4 and CD8 cells contribute to systemic Candida-specific cell-mediated immunity in vaginally infected mice, neither CD4 nor CD8 circulating T cells appear to provide significant host defenses against C. albicans at the vaginal mucosa.     

Health-Related Quality of Life in Spanish Women with Eating Disorders

People with eating disorders show impaired health-related quality of life (HRQoL). We aimed to investigate the relative role of physical and mental factors and stage of change as possible predictors of HRQoL in a group of Spanish women (n = 124) with eating disorders. For this purpose, initial and follow-up data were obtained after 6 months from patients attending an outpatient treatment unit for eating disorders. The determinants of the physical and mental domains of the Medical Outcomes Survey Short-form Health Survey (SF-36) questionnaire were investigated in the total sample and separately based on the eating disorder diagnosis by multiple linear regression. Lower scores in the physical component of the SF-36 questionnaire were associated with the presence of a higher body mass index (BMI) at follow-up as well as a higher score in the “action” component of the Attitudes towards Change in Eating Disorders Questionnaire (ACTA). Conversely, a higher index in the EuroQoL-5D overall quality of life questionnaire (EQ-5D) and the presence of obsessive compulsive disorder were associated with a higher score in the physical dimension. The instrument used demonstrated the ability to assess changes associated with the physical component of these patients over the period studied, and the analysis provided more information and specific data on different aspects of HRQoL, thus allowing a more detailed analysis of the information.     

Effect of the Intake of a Traditional Mexican Beverage Fermented with Lactic Acid Bacteria on Academic Stress in Medical Students

Dysbiosis of the gut microbiota has been associated with different illnesses and emotional disorders such as stress. Traditional fermented foods that are rich in probiotics suggest modulation of dysbiosis, which protects against stress-induced disorders. The academic stress was evaluated in medical students using the SISCO Inventory of Academic Stress before and after ingestion of an aguamiel-based beverage fermented with Lactobacillus plantarum, Lactobacillus paracasei and Lactobacillus brevis (n = 27) and a control group (n = 18). In addition, microbial phyla in feces were quantified by qPCR. The results showed that the consumption of 100 mL of a beverage fermented with lactic acid bacteria (3 × 10⁸ cfu/mL) for 8 weeks significantly reduced academic stress (p = 0.001), while the control group (placebo intervention) had no significant changes in the perception of academic stress (p = 0.607). Significant change (p = 0.001) was shown in the scores for environmental demands, and physical and psychological factors. Consumption of the fermented beverage significantly increased the phyla Firmicutes and Bacteroidetes but not Gammaproteobacteria. No significant changes were found in the control group, except for a slight increase in the phylum Firmicutes. The intake of this fermented beverage suggest a modulation of gut microbiota and possible reduction in stress-related symptoms in university students, without changing their lifestyle or diet.     

A situational analysis of breast cancer early detection services in Trinidad and Tobago

Purpose

A situational analysis of breast cancer (BC) early detection services was carried out to investigate whether Trinidad and Tobago (T&T) has the framework for successful organized national screening.

Methods

An online survey was designed to assess the availability, accessibility, quality control and assurance (QC&A), and monitoring and evaluation (M&E) mechanisms for public and private BC early detection. A focus group with local radiologists (n = 3) was held to identify unaddressed challenges and make recommendations for improvement.

Results

Major public hospitals offer free detection services with wait times of 1–6 months for an appointment. Private institutions offer mammograms for TTD$240 (USD$37) at minimum with same day service. Both sectors report a lack of trained staff. Using 1.2 mammograms per 10,000 women ≥40 years as sufficient, the public sector’s rate of 0.19 mammograms per 10,000 women ≥40 years for screening and diagnosis is inadequate. Program M&E mechanisms, QC&A guidelines for machinery use, delays in receipt of pathology reports, and unreliable drug access are further unaddressed challenges.

Conclusion

T&T must first strengthen its human and physical resources, implement M&E and QC&A measures, strengthen cancer care, and address other impediments to BC early detection before investing in nationally organized BC screening.

     

DNA methylation of imprinted gene control regions in the regression of low‐grade cervical lesions

The role of host epigenetic mechanisms in the natural history of low‐grade cervical intraepithelial neoplasia (CIN1) is not well characterized. We explored differential methylation of imprinted gene regulatory regions as predictors of the risk of CIN1 regression. A total of 164 patients with CIN1 were recruited from 10 Duke University clinics for the CIN Cohort Study. Participants had colposcopies at enrollment and up to five follow‐up visits over 3 years. DNA was extracted from exfoliated cervical cells for methylation quantitation at CpG (cytosine‐phosphate‐guanine) sites and human papillomavirus (HPV) genotyping. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated using Cox regression to quantify the effect of methylation on CIN1 regression over two consecutive visits, compared to non‐regression (persistent CIN1; progression to CIN2+; or CIN1 regression at a single time‐point), adjusting for age, race, high‐risk HPV (hrHPV), parity, oral contraceptive and smoking status. Median participant age was 26.6 years (range: 21.0–64.4 years), 39% were African‐American, and 11% were current smokers. Most participants were hrHPV‐positive at enrollment (80.5%). Over one‐third of cases regressed (n = 53, 35.1%). Median time‐to‐regression was 12.6 months (range: 4.5–24.0 months). Probability of CIN1 regression was negatively correlated with methylation at IGF2AS CpG 5 (HR = 0.41; 95% CI = 0.23–0.77) and PEG10 DMR (HR = 0.80; 95% CI = 0.65–0.98). Altered methylation of imprinted IGF2AS and PEG10 DMRs may play a role in the natural history of CIN1. If confirmed in larger studies, further research on imprinted gene DMR methylation is warranted to determine its efficacy as a biomarker for cervical cancer screening.     

Sex Work Regulation and Sexually Transmitted Infections in Tijuana,Mexico

While reducing the transmission of sexually transmitted infections is a common argument for regulating sex work, relatively little empirical evidence is available regarding the effectiveness of these policies. We investigate the effects of highly publicized sex work regulations introduced in 2005 in Tijuana, Mexico on the incidence of trichomoniasis. State‐level, annual data for the 1995–2012 period are employed that include the incidence rates of trichomoniasis by age group and predictor variables. We find that the regulations led to a decrease in the incidence rate of trichomoniasis. Specifically, while our estimates are somewhat noisy, the all‐ages incidence rate in the 2005–2012 period is roughly 37% lower than what is predicted by our synthetic control estimates and corresponds to approximately 800 fewer reported cases of trichomoniasis per year. We find that the decreases are especially pronounced for 15–24 and 25–44 age cohorts. Copyright © 2016 John Wiley & Sons, Ltd.     

Functional interaction between mutations in the granulocyte colony-stimulating factor receptor in severe congenital neutropenia

Most severe congenital neutropenia (SCN) cases possess constitutive neutrophil elastase mutations; a smaller cohort has acquired mutations truncating the granulocyte colony-stimulating factor receptor (G-CSF-R). We have described a case with constitutive extracellular G-CSF-R mutation hyporesponsive to ligand. Here we report two independent acquired G-CSF-R truncation mutations and a novel constitutive neutrophil elastase mutation in this patient. Co-expression of a truncated receptor chain restored STAT5 signalling responses of the extracellular G-CSF-R mutant, while constitutively-active STAT5 enhanced its proliferative capacity. These data add to our knowledge of SCN and further highlight the importance of STAT5 in mediating proliferative responses to G-CSF.