Evaluation of the clinical significance of human papillomavirus (HPV) 53.

OBJECTIVE: Human papillomaviruses (HPV) are classified according to their potential for the development of cervical neoplasia. However, the carcinogenicity of HPV types forms an evolving continuum based on the newly available data especially regarding the role of probable and possible high-risk HPV types (pHR-HPV). The objective of the present work was to evaluate clinical significance of the pHR-HPV53. STUDY DESIGN: An observational cohort study of potential aetiological association between infection with HPV53 and development of high-grade cervical cytology was performed. The study was conducted in two geographically remoted hospitals, in Belgium and Democratic Republic of Congo, as an attempt to collect data from regions with different geographical distribution of HPV genotypes. The samples were taken during routine gynaecological visit in outpatient clinics of both participating hospitals. RESULTS: A total of 2283 liquid-Pap samples were taken from 1465 women at Ghent University Hospital, Belgium, and from 660 women at General Hospital and Ngaliema Hospital of Kinshasa, DRC. "HPV53-only"-pattern as evaluated by full HPV genotyping was found in samples from only 34 (1.6%) samples. The initial cytology represented next to non-dysplastic, undetermined and low-grade lesions also high-grade lesions (12%). For 26 (76.5%) from the 34 women presented with "HPV53-only"-pattern follow-up results were available showing no progression to malignancy. CONCLUSION: Our findings support very low to lacking carcinogenic potential of HPV53. Recognising extreme rarity in cervical cancer next to high prevalence in general population of HPV53, further studies investigating progression to high-grade lesions are needed to elucidate the oncogenic potential of pHR-HPV53.

Comparative analysis of cervical cytology and human papillomavirus genotyping by three different methods in a routine diagnostic setting.

Application of Bethesda guidelines on cervical cytology involves human papillomavirus (HPV) determinations on all ASC-US and ASC-H results. We compared HPV DNA results in view of the eventual development of a cervical intraepithelial neoplasia lesion determined either on cytology or histology. A total of 214 liquid-based cytology samples were analysed. Three different HPV DNA methods were applied: the Abbott RealTime High Risk HPV test, INNO-Lipa HPV Genotyping Extra and Full Spectrum PCR HPV Amplification and Detection/Genotyping System by Lab2Lab Diagnostic Service. A comparison of these three methods showed full concordance only for 49 samples (23%), and 27 (13%) of the samples were discordant in indicating the presence of the high-risk HPV type. Out of 214 patients, 88 were selected who presented with a cervical intraepithelial neoplasia or a VAIN lesion at follow-up cytology or histology. In this group, full concordance with HPV genotyping was present only in 19 (22%) follow-up samples. Nine (10%) follow-up samples showed discordant results for the presence of a high-risk genotype between the three genotyping methods tested either by negativity for high-risk HPV by one of the methods (n=6) or by failure to genotype HPV (n=2), or by a combination of both (n=1). Moreover, discordance for the detection of HPV16 or HPV18 was observed between the three HPV DNA genotyping methods used in 9 (10%) follow-up samples. In addition, the performance of genotyping methods on 20 external quality samples was assessed, showing discordant results for HPV16 and HPV18. Major differences were found in the genotyping results according to the HPV DNA method. Our findings highlight the importance of careful interpretation of data from studies using different HPV genotyping methods and underline the need for standardization by method validation in clinical laboratories, especially in the setting of primary HPV screening.

Prospective evaluation of E6/E7 mRNA detection by the NucliSENS Easy Q HPV assay in a stepwise protocol.

The objective of the study was to evaluate prospectively the added value of E6/E7 mRNA detection in a stepwise protocol. A total of 1,422 samples were collected over a period of 17 months. The samples were referred for human papillomavirus (HPV) genotyping if they showed cytological evidence of atypical squamous cells of undetermined significance, low- or high-grade squamous intraepithelial lesion. If one or more of HPV types 16, 18, 31, 33, or 45 were present, mRNA was analyzed by the NucliSENS EasyQ HPV assay. The genotypical distribution of high-risk HPV was very heterogeneous; HPV 16, 18, 31, 33, and 45 represented 20.2%, 3.4%, 10.8%, 3.4%, and 3.8% of HPV-positive samples, respectively. Follow-up data were available for 35 patients. Although over the half (51.4%) of follow-up samples showing HPV DNA/mRNA consensus evolved to cervical intraepithelial neoplastic lesions, 25.7% showed no progression to neoplasia despite mRNA positivity. However, the major concern was the group (14.3%) that showed progression to cervical intraepithelial neoplasia despite mRNA negativity: all but one of these cases had a high-risk HPV genotype other than the five included in the NucliSENS EasyQ HPV assay. Markedly, 66.7% of the discordant samples between colposcopy and histology that underestimated the degree of cervical dysplasia were found in this group. Close monitoring of high-risk HPV DNA-positive/mRNA-negative cases remains necessary, which leads to questions about the added value of the evaluated protocol.

Comparison of four serological assays for the diagnosis of Chlamydia trachomatis in subfertile women.

INTRODUCTION: Chlamydia antibody testing (CAT) in serum has been introduced as a screening method in the infertility workup. We evaluated the test characteristics of two ELISA tests compared to micro-immunofluorescence tests (MIFs). MIFs are considered the gold standard in the C. trachomatis IgG antibodies detection. We also compared the accuracy of all CAT tests in predicting tubal subfertility, using laparoscopy as a reference. METHODOLOGY: Four commercial serological methods were used to analyse 101 serum samples for the presence of C. trachomatis IgG antibodies from patients at the Infertility Clinic of Ghent University Hospital. The diagnostic utility for prediction of tubal infertility of serological methods was evaluated based on patients' medical records. RESULTS: A comparison of the serological assays showed  little difference  in the major performance characteristics: the sensitivities of all MIFs and ELISAs were 100% for all assays (except the ELISA Vircell, with a sensitivity of 90%), and the specificities ranged from 92% for MIF Ani Labsystems to 98% for the MIF Focus and ELISA Vircell. As compared to laparoscopy data, CAT positivity in subfertile women with tubal damage (n=40) did not significantly differ from that of subfertile women without tubal damage (n=61): Positive predictive values (PPV) of CAT ranged from 53% to 60% and negative predictive values (NPV) ranged from 62% to 64%.  CONCLUSION: evaluated ELISAs are comparable to MIFs in the detection of C. trachomatis IgG antibodies and should be preferred for large serological studies, especially in resource poor settings.

Associations between dimensions of job stress and biomarkers of inflammation and infection.

OBJECTIVE: The objective of this study was to examine associations between dimensions of job stress and indicators of chronic inflammation and infection. METHODS: Within a subsample from the BELSTRESS study of 892 male subjects free of cardiovascular disease, dimensions of job stress from the job demand-control-support model were related to biomarkers of inflammation (plasma fibrinogen concentrations, high-sensitivity C-reactive protein, and serum amyloid A) and infection (titers against Chlamydia pneumoniae, cytomegalovirus, and Helicobacter pylori). RESULTS: A negative association was found between job control and plasma fibrinogen concentration, independent from age, education, occupation, body mass index, smoking, alcohol consumption, and use of lipid-lowering and antihypertensive medication. Higher social support at work was independently related to an increased risk of positive titers against cytomegalovirus. CONCLUSIONS: Results confirm previous findings regarding elevated plasma fibrinogen and low job control.

Distribution of human papillomavirus in a family planning population in nairobi, kenya.

BACKGROUND: In sub-Saharan Africa, cervical cancer is the leading cancer among women. The causative role of different human papillomavirus (HPV) types in cervical cancer is established, but the distribution of HPV types within this region is largely unknown. GOAL: The goal was to study the distribution of HPV among family planning clinic attendees in Nairobi, Kenya. STUDY DESIGN: This was a cross-sectional study of persons attending a family planning center in Nairobi, Kenya. RESULTS: HPV data of 429 women were analyzed; 7.0% had low-grade intraepithelial lesions, 6.8% had high-grade intraepithelial lesions, and 0.23% had invasive cancer. One hundred ninety samples (44.3%) were HPV-positive (28.4% were positive for multiple types). The most common HPV types were HPV 52 (17.9% of positive samples), HPV 16 (14.7%), HPV 35 (11.6%), and HPV 66 (9.0%). The risk of high-grade squamous intraepithelial lesions (HSIL) was 88.5 times higher (95% CI, 8.5-1.4 x 10 ) in HPV 16-positive women than in HPV-negative women. Relative risks were 54.3 (95% CI, 4.0-1.4 x 10 ) for HPV 35, 49.2 (95% CI, 3.6-9.5 x 10 ) for HPV 52, and 21.7 (95% CI, 0.0-1.9 x 10 ) for HPV 18. The prevalence of HSIL was not increased in association with HIV-positivity, yet HIV-1 was significantly associated with high-risk HPV types ( P< 0.00001). CONCLUSION: The pattern of HPV distribution in this population was different from that in other regions in the world, which has important consequences for HPV vaccine development.

Discriminative value of serum amyloid A and other acute-phase proteins for coronary heart disease.

We studied the value of serum amyloid A (SAA), a first-class acute-phase protein, as a marker for coronary heart disease (CHD) in a middle-aged male population. In a working population of 16307 men (age, 35-59 years), 446 cases had a history of CHD or prominent Q:QS waves on electrocardiogram. For each case, two matched controls were investigated. SAA, measured by immunonephelometry, was correlated with other acute-phase proteins, cardiovascular risk factors, and infectious serology markers. SAA concentrations were significantly higher in the cases than in controls (P<0.05) and correlated with serum C-reactive protein (CRP) (r=0.61), plasma fibrinogen (r=0.39), serum haptoglobin (r=0.26), and body mass index (r=0.13) (P<0.001). Serum CRP is a better marker for CHD than SAA, which showed discriminative power only in a univariate model comparing highest versus lowest tertile (odds ratio, 1.39; 95% confidence interval, 1.03-1.87). Neither SAA nor other acute-phase proteins correlated with Chlamydia pneumoniae immunoglobulin (Ig)G, Helicobacter pylori IgG and IgA, and cytomegalovirus IgG. In conclusion, although SAA has a discriminative value for CHD, serum CRP is to be preferred as a first-class acute-phase reactant for detection of the disease.