Distribution of human papillomaviruses and bacterial vaginosis in HIV positive women with abnormal cytology in Mombasa, Kenya

Background: HPV is the major etiological factor in the causal pathway for cervical cancer, which is the leading cancer among women in sub-Saharan Africa. HIV is associated with a higher prevalence and a broader range of high-risk HPV genotypes. Studies have shown a positive association between Bacterial vaginosis (BV) and HPV and HIV. Also, in African women, BV was found to be significantly associated with vaginal inflammation. The high prevalence of BV, HIV and HPV infections in the African continent makes elucidation of the interactions with one another of utmost public health interest. The aims of the current study are to examine the frequency of HPV genotypes and BV as well as their respective risk factors within an HIV infected population with abnormal cytology in the resource-constrained setting of Mombasa, Kenya and, secondly, highlight issues to consider for triple co-infection clinical management. Method: Cross-sectional analysis with a sample drawn from an ongoing cohort study. All consenting, non-pregnant HIV infected women, between 18 and 50 years of age, without a history of cervical cancer or hysterectomy, between November 2005 and April 2006 were screened for HR HPV DNA in Mombasa, Kenya. 1 out of 4 HIV positive women fulfilled the criteria by having SIL (24.9 %). 600 HIV infected women were tested to reach a cohort of 74 HIV women with abnormal cytology. To assess which factors were associated with HR HPV, crude statistical analysis was performed through logistic regression. Results: Bacterial vaginosis (BV) was found in 46 women out of 74 (62.2 %). Cervicitis was diagnosed in 15 % of women (n = 11), of which 8 had BV. The most prevalent HPV genotypes were HPV 16 (33.8), HPV 53 (24.3) and HPV 18 (17.6 %), while 65 % of the participants had multiple genotype infection. Statistically significant associations between CD4 counts = 350 mu l and HPV 16 adjusted for age (OR = 2.9; 95 % CI: 1.0-8.3; p = 0.05). A borderline statistically significant association was observed between BV and HPV58 (crude OR = 4.1, 95 % CI: 0.8-21.0; p = 0.07). Conclusion: The most prevalent HPV genotypes observed were HPV 16, HPV 53, and HPV 18, which have a combined prevalence of 76 %. Our results show that a triage based on CD4 count should start at CD4 count >= 350 mu l as our study suggests that HPV 16 are more prevalent when women are moderately immunosuppressed. Given the high prevalence of HPV 53 in a HIV infected population with abnormal cytology, its cervical carcinoma genesis potential as a stand-alone genotype and as well as its synergism with multiple infections should be investigated. The new WHO guideline in resource-poor settings to rescreen women for HPV within ten years may be more effective if BV and cervicitis management become a major component for HIV-HPV management

Knowledge, attitude and practice about cancer of the uterine cervix among women living in Kinshasa, the Democratic Republic of Congo

Background: Cervical cancer is the most frequent cancer of women in the Democratic Republic of Congo (DRC). Nevertheless, the level of women's awareness about cervical cancer is unknown. Knowledge, attitude and practice (KAP) are important elements for designing and monitoring screening programs. The study purpose was to estimate KAP on cervical cancer and to identify associated factors. Methods: A cross-sectional study was conducted in Kinshasa, DRC, including 524 women aged 16-78 years (median age 28; interquartile range 22-35). The women were interviewed at home by trained field workers using a standardized questionnaire. The women's score on knowledge, attitude and practice were dichotomized as sufficient or insufficient. We used binary and multiple logistic regression to assess associations between obtaining sufficient scores and a series of socio-demographic factors: age, residence, marital status, education, occupation, religion, and parity. Results: The women's score on knowledge was not significantly correlated with their score on practice (Spearman's rho = 0.08; P > 0.05). Obtaining a sufficient score on knowledge was positively associated with higher education (adjusted odds ratio (OR) 7.65; 95% confidence interval (95% CI) 3.31-17.66) and formal employment (adjusted OR 3.35; 95% CI 1.85-6.09); it was negatively associated with being single (adjusted OR 0.44; 95% CI 0.24-0.81) and living in the eastern, western and northern zone of Kinshasa compared to the city centre. The attitude score was associated with place of residence (adjusted OR for east Kinshasa: 0.49; 95% CI 0.27-0.86 and for south Kinshasa: 0.48; 95% CI 0.27-0.85) and with religion (adjusted OR 0.55; 95% CI 0.35-0.86 for women with a religion other than Catholicism or Protestantism compared to Catholics). Regarding practice, there were negative associations between a sufficient score on practice and being single (adjusted OR 0.24; 95% CI 0.13-0.41) and living in the eastern zone of the city (adjusted OR 0.39; 95% CI 0.22-0.70). Although 84% of women had heard about cervical cancer, only 9% had ever had a Papanicolaou (Pap) smear test. Conclusions: This study shows a low level of knowledge, attitude and practice on cervical cancer among women in Kinshasa. Increasing women's awareness would be a first step in the long chain of conditions to attain a lower incidence and mortality

Distinct role of clathrin-mediated endocytosis in the functional uptake of cholera toxin

The involvement of the clathrin-mediated endocytic internalization route in the uptake of cholera toxin (CT) was investigated using different cell lines, including the human intestinal Caco-2 and T84 cell lines, green monkey Vero cells, SH-SY5Y neuroblastoma cells and Madin-Darby canine kidney cells. Suppression of the clathrin-mediated endocytic pathway by classical biochemical procedures, like intracellular acidification and potassium depletion, inhibited cholera toxin uptake by up to about 50% as well as its ability to raise intracellular levels of cAMP. Also prior exposure of these cell types to the cationic amphiphilic drug chlorpromazine reduced the functional uptake of cholera toxin, even to a greater extent. These effects were dose- and cell type-dependent, suggesting an involvement of clathrin-mediated endocytosis in the functional uptake of cholera toxin. For a more straightforward approach to study the role of the clathrin-mediated uptake in the internalization of cholera toxin, a Caco-2(eps-) cell line was exploited. These Caco2(eps-) cells constitutively suppress the expression of epsin, an essential accessory protein of clathrin-mediated endocytosis, thereby selectively blocking this internalization route. CT uptake was found to be reduced by over 60% in Caco-2(eps-) paralleled by a diminished ability of CT to raise the level of cAMP. The data presented suggest that the clathrin-mediated uptake route fulfils an important role in the functional internalization of cholera toxin in several cell types

Association between bacterial vaginosis and cervical intraepithelial neoplasia: systematic review and meta-analysis

Objective: Bacterial vaginosis (BV), the most common vaginal disorder among women of reproductive age, has been suggested as co-factor in the development of cervical cancer. Previous studies examining the relationship between BV and cervical intra-epithelial neoplasia (CIN) provided inconsistent and conflicting results. The aim of this study is to clarify the association between these two conditions. Methods: A systematic review and meta-analysis were conducted to summarize published literature on the association between BV and cervical pre-cancerous lesions. An extensive search of electronic databases Medline (Pubmed) and Web of Science was performed. The key words 'bacterial vaginosis' and 'bacterial infections and vaginitis' were used in combination with 'cervical intraepithelial neoplasia', 'squamous intraepithelial lesions', 'cervical lesions', 'cervical dysplasia', and 'cervical screening'. Eligible studies required a clear description of diagnostic methods used for detecting both BV and cervical precancerous lesions. Publications were included if they either reported odds ratios (OR) and corresponding 95% confidence intervals (CI) representing the magnitude of association between these two conditions, or presented data that allowed calculation of the OR. Results: Out of 329 articles, 17 cross-sectional and 2 incidence studies were selected. In addition, two studies conducted in The Netherlands, using the national KOPAC system, were retained. After testing for heterogeneity and publication bias, meta-analysis and meta-regression were performed, using a random effects model. Although heterogeneity among studies was high (chi(2) = 164.7, p < 0.01, I-2 = 88.5), a positive association between BV and cervical pre-cancerous lesions was found, with an overall estimated odds ratio of 1.51 (95% CI, 1.24-1.83). Meta-regression analysis could not detect a significant difference between studies based on BV diagnosis, CIN diagnosis or study population. Conclusions: Although most studies were cross-sectional and heterogeneity was high, this meta-analysis confirms a connection between BV and CIN

Using the VALGENT-3 framework to assess the clinical and analytical performance of the RIATOL qPCR HPV genotyping assay

Background and objective: The VALGENT framework is developed to assess the clinical performance of HPV tests that offer genotyping capability. Samples from the VALGENT-3 panel are used to identify an optimal viral concentration threshold for the RIATOL qPCR HPV genotyping assay (RIATOL qPCR) to assure non-inferior accuracy to detect high-grade cervical intraepithelial neoplasia (CIN), compared to Qiagen Hybrid Capture 2 (HC2), a standard comparator test validated for cervical cancer screening. Study design: The VALGENT-3 panel comprised 1300 samples from women participating in the Slovenian cervical cancer screening programme, enriched with 300 samples from women with abnormal cytology. In follow-up, 126 women were diagnosed with CIN2+ (defined as diseased) and 1167 women had two consecutive negative Pap smears (defined as non-diseased). All 1600 samples were analyzed with the RIATOL qPCR. Viral concentration was expressed as viral log10 of the number of copies/ml. A zone of viral concentration cut-offs was defined by relative ROC analysis where the sensitivity and specificity were not inferior to HC2. Results: The RIATOL qPCR had a sensitivity and specificity for CIN2+ of 97.6% (CI: 93.2-99.5%) and 85.1% (CI: 82.9-87.1%), respectively, when the analytical cut off was used. At a cut off of 6.5, RIATOL qPCR had a sensitivity of 96.0% (CI: 91.0-98.7%) and a specificity of 89.5% (87.6-91.2%). At optimized cut off, accuracy of the qPCR was non-inferior to the HC2 with a relative sensitivity of 1.00 [CI: 0.95-1.05 (p= 0.006)] and relative specificity of 1.00 [CI: 0.98-1.01 (p= 0.0069)]. Conclusions: The RIATOL qPCR has a high sensitivity and specificity for the detection of CIN2+. By using a fixed cut-off based on viral concentration, the test is non-inferior to HC2. HPV tests that provide viral concentration measurements or other quantifiable signals allow flexibility to optimize accuracy required for cervical cancer screening