Davy Vanden Broeck

Bacterial vaginosis is associated with uterine cervical human papillomavirus infection: a meta-analysis

BackgroundBacterial vaginosis (BV), an alteration of vaginal flora involving a decrease in Lactobacilli and predominance of anaerobic bacteria, is among the most common cause of vaginal complaints for women of childbearing age. It is well known that BV has an influence in acquisition of certain genital infections. However, association between BV and cervical human papillomavirus (HPV) infection has been inconsistent among studies. The objective of this meta-analysis of published studies is to clarify and summarize published literature on the extent to which BV is associated with cervical HPV infection.MethodsMedline and Web of Science were systematically searched for eligible publications until December 2009. Articles were selected based on inclusion and exclusion criteria. After testing heterogeneity of studies, meta-analysis was performed using random effect model.ResultsTwelve eligible studies were selected to review the association between BV and HPV, including a total of 6,372 women. The pooled prevalence of BV was 32%. The overall estimated odds ratio (OR) showed a positive association between BV and cervical HPV infection (OR, 1.43; 95% confidence interval, 1.11-1.84).ConclusionThis meta-analysis of available literature resulted in a positive association between BV and uterine cervical HPV infection.

Association of HIV infection with distribution and viral load of HPV types in Kenya: a survey with 820 female sex workers.

BackgroundHuman papillomavirus (HPV) and HIV are each responsible for a considerable burden of disease. Interactions between these infections pose substantial public health challenges, especially where HIV prevalence is high and HPV vaccine coverage low.MethodsBetween July 2005 and January 2006, a cross-sectional community-based survey in Mombasa, Kenya, enrolled female sex workers using snowball sampling. After interview and a gynaecological examination, blood and cervical cytology samples were taken. Quantitative real-time PCR detected HPV types and viral load measures. Prevalence of high-risk HPV was compared between HIV-infected and -uninfected women, and in women with abnormal cervical cytology, measured using conventional Pap smears.ResultsMedian age of the 820 participants was 28 years (inter-quartile range [IQR] = 24-36 years). One third of women were HIV infected (283/803; 35.2%) and these women were y more likely to have abnormal cervical cytology than HIV-negative women (27%, 73/269, versus 8%, 42/503; P < 0.001). Of HIV-infected women, 73.3% had high-risk HPV (200/273) and 35.5% had HPV 16 and/or 18 (97/273). Corresponding figures for HIV-negative women were 45.5% (229/503) and 15.7% (79/503). After adjusting for age, number of children and condom use, high-risk HPV was 3.6 fold more common in HIV-infected women (95%CI = 2.6-5.1). Prevalence of all 15 of the high-risk HPV types measured was higher among HIV-infected women, between 1.4 and 5.5 fold. Median total HPV viral load was 881 copies/cell in HIV-infected women (IQR = 33-12,110 copies/cell) and 48 copies/cell in HIV-uninfected women (IQR = 6-756 copies/cell; P < 0.001). HPV 16 and/or HPV 18 were identified in 42.7% of LSIL (32/75) and 42.3% of HSIL (11/26) lesions (P= 0.98). High-risk HPV types other than 16 and 18 were common in LSIL (74.7%; 56/75) and HSIL (84.6%; 22/26); even higher among HIV-infected women.ConclusionsHIV-infected sex workers had almost four-fold higher prevalence of high-risk HPV, raised viral load and more precancerous lesions. HPV 16 and HPV 18, preventable with current vaccines, were associated with cervical disease, though other high-risk types were commoner. HIV-infected sex workers likely contribute disproportionately to HPV transmission dynamics in the general population. Current efforts to prevent HIV and HPV are inadequate. New interventions are required and improved implementation of existing strategies.

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 pre-cancerous 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 (χ2 = 164.7, p<0.01, I2 = 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.

Prior knowledge of HPV status improves detection of CIN2+ by cytology screening

OBJECTIVE The objective of the study was to investigate whether knowledge of human papillomavirus (HPV) deoxyribonucleic acid test results increases sensitivity of guided cytology screening for the detection of cervical intraepithelial neoplasia (CIN)-2 or higher-grade cervical lesions. STUDY DESIGN This was a prospective colposcopy-controlled study of 2905 BD SurePath samples to identify cases with CIN2+ within a 24 month follow-up period. Sensitivity and specificity to detect CIN2+ was evaluated, comparing guided cytology screening with and without prior knowledge of HPV status. RESULTS Prior knowledge of HPV status resulted in significantly higher detection rate of CIN2+ compared with screening blinded to HPV status (P = .005) with limited loss of specificity (P = .026). Gain in sensitivity is higher in older women (43.8%, P = .008) vs in younger women (10.2%, P = .317), whereas loss of specificity is more pronounced in younger women (P < .001) vs older women (P = .729). CONCLUSION Guided cytological screening performed with prior knowledge of HPV status results in an improved detection of CIN2 or higher-grade lesions.

Selective blocking of clathrin-mediated endocytosis by RNA interference: epsin as target protein

Epsin is an essential accessory protein exclusively implicated in clathrin-mediated endocytosis and therefore an ideal target to study involvement of this entry route in the uptake of bioligands. T...

Performance of a Cartridge-Based Assay for Detection of Clinically Significant Human Papillomavirus (HPV) Infection: Lessons from VALGENT (Validation of HPV Genotyping Tests)

ABSTRACT The Validation of Human Papillomavirus (HPV) Genotyping Tests (VALGENT) studies offer an opportunity to clinically validate HPV assays for use in primary screening for cervical cancer and also provide a framework for the comparison of analytical and type-specific performance. Through VALGENT, we assessed the performance of the cartridge-based Xpert HPV assay (Xpert HPV), which detects 14 high-risk (HR) types and resolves HPV16 and HPV18/45. Samples from women attending the United Kingdom cervical screening program enriched with cytologically abnormal samples were collated. All had been previously tested by a clinically validated standard comparator test (SCT), the GP5+/6+ enzyme immunoassay (EIA). The clinical sensitivity and specificity of the Xpert HPV for the detection of cervical intraepithelial neoplasia grade 2 or higher (CIN2+) and CIN3+ relative to those of the SCT were assessed as were the inter- and intralaboratory reproducibilities according to international criteria for test validation. Type concordance for HPV16 and HPV18/45 between the Xpert HPV and the SCT was also analyzed. The Xpert HPV detected 94% of CIN2+ and 98% of CIN3+ lesions among all screened women and 90% of CIN2+ and 96% of CIN3+ lesions in women 30 years and older. The specificity for CIN1 or less (≤CIN1) was 83% (95% confidence interval [CI], 80 to 85%) in all women and 88% (95% CI, 86 to 91%) in women 30 years and older. Inter- and intralaboratory agreements for the Xpert HPV were 98% and 97%, respectively. The kappa agreements for HPV16 and HPV18/45 between the clinically validated reference test (GP5+/6+ LMNX) and the Xpert HPV were 0.92 and 0.91, respectively. The clinical performance and reproducibility of the Xpert HPV are comparable to those of well-established HPV assays and fulfill the criteria for use in primary cervical cancer screening.

Determinants of Acceptance and Subsequent Uptake of the HPV Vaccine in a Cohort in Eldoret, Kenya

The development of Human Papillomavirus (HPV) vaccines provides new opportunities in the fight against cervical cancer. Many acceptability studies have revealed high interest in these vaccines, but acceptance is only a precursor of behavior, and many factors, at personal, community and provider level, may inhibit the translation of willingness to vaccinate into actual uptake. Through a longitudinal study in Eldoret, Kenya, HPV vaccine acceptability was measured before a vaccination program (n = 287) and vaccine uptake, as reported by mothers, once the program was finished (n = 256). In between baseline and follow-up, a pilot HPV vaccination program was implemented via the GARDASIL Access Program, in which parents could have their daughter vaccinated for free at the referral hospital. The program was promoted at schools: Health staff informed teachers who were then asked to inform students and parents. Even though baseline acceptance was very high (88.1%), only 31.1% of the women reported at follow-up that their daughter had been vaccinated. The vaccine was declined by 17.7%, while another 51.2% had wanted the vaccination but were obstructed by practical barriers. Being well-informed about the program and baseline awareness of cervical cancer were independently associated with vaccine uptake, while baseline acceptance was correlated in bivariate analysis. Side effects were of great concern, even among those whose daughter was vaccinated. Possible partner disapproval lowered acceptance at baseline, and women indeed reported at follow-up that they had encountered his opposition. In Kenya, women prove to be very willing to have their daughter vaccinated against cervical cancer. However, in this study, uptake was more determined by program awareness than by HPV vaccine acceptance. School-based vaccination might improve coverage since it reduces operational problems for parents. In addition, future HPV vaccination campaigns should address concerns about side effects, targeting men and women, given both their involvement in HPV vaccination decision-making.

Transmission of carcinogenic human papillomavirus types from mother to child: a meta-analysis of published studies

Currently, human papillomavirus (HPV) research focuses on HPV infection in adults and sexual transmission. Data on HPV infection in children are slowly becoming available. It is a matter of debate whether mother-to-child transmission of HPV is an important infection route and whether children born to HPV-positive mothers are at a higher risk of HPV infection compared with children born to HPV-negative mothers. The objective of this meta-analysis is to summarize the published literature on the extent to which genital HPV infection is vertically transmitted from mother to child. Medline, Web of Science, and CINAHL were searched for eligible reports published before January 2011. Differences in the risk of HPV infection between newborns from HPV-positive and HPV-negative mothers were pooled using a random-effects model. Twenty eligible studies, including 3128 women/children pairs, fulfilled the selection criteria. High heterogeneity could be found (I2=96%). The overall estimated risk difference was 33% (95% confidence interval: 22–44%). On restricting to high-risk HPV-positive mothers only (n=4; women=231), the difference in risk was 45% (95% confidence interval: 33–56%). The heterogeneity was found to be low (I2=15%). This meta-analysis indicates a significantly higher risk for children born to HPV-positive mothers to become HPV positive themselves. Plausible explanations include vertical transmission of HPV during pregnancy and/or birth or a higher infection rate during early nursing from mother to child. More research is required to gain an insight into the precise mode of transmission and the clinical effects of infection on the child.

HIV Testing and Sexually Transmitted Infection Care among Sexually Active Youth in the Balkans

In light of the imminent threat of a growing HIV epidemic in east and southeast Europe, optimal accessibility of primary and secondary HIV preventative interventions, including HIV testing and sexually transmitted infection (STI) care, are fast becoming public health priorities. We surveyed 2150 high school students in Bosnia and Herzegovina, FYR of Macedonia, Serbia, and Montenegro to examine the uptake of HIV testing and associated predictors. Among sexually active youth (n = 651), 5.9% had already been tested for HIV. In marginal logistic regression, country of origin, type of high school, knowing a friend or relative with HIV, poor self-assessed health status, suspicion of having had an STI, and not having used a condom at first sex were independently associated with HIV testing. Fear of the diagnosis, fear of violation of confidentiality, and not knowing where to go for HIV testing were reported as barriers to HIV testing. Of sexually active adolescents who thought they might have contracted an STI, only 42% had subsequently visited a doctor or health facility. The main reasons for not doing so were spontaneous disappearance of the complaints, fear of the diagnosis and being ashamed of discussing the problem. In conclusion, the uptake of HIV testing among this population of sexually active, urban high school students was found to be low, although a higher prevalence of HIV testing history was observed among students showing evidence of risky sexual behavior. Practical and psychological factors seem to challenge the accessibility of facilities for HIV testing and STI care.

Surveillance of effects of HPV vaccination in Belgium

BACKGROUND Early effects of HPV (human papillomavirus) vaccination are reflected by changes observable in young women attending cervical cancer screening. SUBJECT AND METHODS The SEHIB study included HPV geno-typing of ∼6000 continuous and 650 pathological cervical cell specimen as well as biopsies, collected from women in Belgium in 2010-2014. Data were linked to vaccination status. RESULTS HPV vaccination offered protection among women aged <30years against infection with HPV16 (vaccine effectiveness [VE]=67%, 95% CI: 48-79%), HPV18 (VE=93%, 95% CI: 52-99%), and high-risk HPV (VE=16%, 95% CI: 2-29%). Vaccination protected also against cytological lesions. Vaccination protected against histologically confirmed lesions: significantly lower absolute risks of CIN1+ (risk difference [RD]=-1.6%, 95% CI: -2.6% to -0.7%) and CIN3+ associated with HPV16/18 (RD=-0.3%, 95% CI -0.6% to -0.1%). Vaccine effectiveness decreased with age. Protection against HPV16 and 18 infection was significant in all age groups, however no protection was observed against cytological lesions associated with these types in age-group 25-29. CONCLUSION The SEHIB study demonstrates the effectiveness of HPV vaccination in Belgian young women in particular in age group 18-19. Declining effectiveness with increasing age may be explained by higher tendency of women already exposed to infection to get the vaccine.