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To assess the concordance and performance of 2 different assays in detection of human papillomavirus (HPV) genotypes among women with abnormal Pap smear.A series of 575 women referred for colposcopy due to an abnormal Pap smear were analyzed with the Linear Array HPV Genotyping test detecting 37 HPV types and compared with Hybrid Capture II (HCII) assay for detection of carcinogenic HPV. Histologic outcomes of cervical intraepithelial neoplasia grade 2 (CIN2) or worse (CIN2+) and CIN3+ were the primary endpoints. Clinical performance, including receiver operating characteristics, was determined for both tests.HCII and linear array (LA) were concordant in 88.1% (433/491; 95% CI 85.3%-91.0%), having a substantial agreement with regular kappa (kappa = 0.70, 95% CI 0.62-0.77) and almost perfect agreement with weighted kappa (ICC = 0.82, 95% CI 0.7-0.85). In detecting CIN2+ and CIN3+, LA is 5% and 6% more sensitive but 9.5% and 8.7% less specific than HCII (area under ROC curve; P = 0.317 and P = 0.875, respectively).Performance of HCII and LA does not significantly differ in detecting CIN2+ or CIN3+.

Objectives. To assess the performance of a novel PCR-based assay (Roche AMPLICOR® HPV test) in detection of cervical pathology as a part of management for abnormal PAP smear (MAPS) and in women participating in cervical cancer screening. Study design. Altogether, 504 women comprising 270 patients referred for colposcopy due to an abnormal Pap smear and another 234 women participating in cervical cancer screening (tested for comparison) were analyzed for oncogenic (HR) Human papillomavirus (HPV) types 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, and 68 using the Roche AMPLICOR® HPV test in cervical samples collected in PreservCyt® liquid media. Colposcopic biopsy and/or LEEP cone biopsy was used as the gold standard in the triage group, while liquid-based cytology (LBC) was the reference test in the screening group. Results. The prevalence of HPV was significantly higher in the MAPS group (65.9%) than in the screening group (31.2%) ( P = 0.0001). There was a poor concordance between the referral PAP and the current LBC, being only moderate in the screening series, ICC (weighted kappa) = 0.291 (95%CI 0.070–0.459) ( P = 0.007), and almost poor in the MAPS Series, with ICC = 0.217 (95%CI 0.04–0.384) ( P = 0.023). AMPLICOR® HPV positivity increased linearly with the increasing grade of cervical lesions. In detecting high-grade (CIN2–3), colposcopy was the most sensitive test (96.5%), very similar to AMPLICOR (95.2%) ( P = 0.731), while LBC with HSIL cutoff was by far the most specific test (99.5%) and showed the highest PPV (96.1%). NPV of colposcopy (97.2%) and AMPLICOR (96.7%) were similar ( P = 0.839). Together with abnormal colposcopy and HSIL cytology, the AMPLICOR® HPV test is a powerful independent predictor of high-grade CIN2–3, and as such suitable to replace cervical cytology in management of women with abnormal PAP test (MAPS). Conclusions. The Roche AMPLICOR® HPV test is comparable to other HPV tests (HCII, PCR) in detecting CIN in MAPS. However, more data are clearly needed on the performance of AMPLICOR test in management of abnormal PAP and particularly as a screening tool.

Sexually transmitted infections are a major public health problem in France and other European countries. Particularly, surveillance data about Neisseria gonorrhoeae infections have clearly indicated an increase in the incidence of gonorrhoea in France in 2006. The French laboratories participated on voluntary basis in the RENAGO (Réseau National du Gonocoque) network and sent all of their collected strains to the National Reference Center for Neisseria gonorrhoeae . In this first French molecular epidemiological study, 93 isolates collected in 2006 and representative of the French gonorrhoea epidemiology were selected. Antibiotic susceptibility to six antibiotics was determined, and serotyping and N. gonorrhoeae multiantigen sequence typing (NG-MAST) were performed. NG-MAST identified 53 sequence types (STs), of which 13 STs contained 2 to 16 isolates. The major STs identified in France were previously described elsewhere. However, two newly described STs, ST1479 and ST1987, had only been found in France until now. ST1479 was characterized by a multiple-resistance phenotype, whereas ST1987 presented a susceptibility phenotype. Moreover, among the predominant French STs, ST225, which had already been described in many countries, comprised isolates (14/16) resistant to ciprofloxacin and with reduced susceptibility to ceftriaxone. Thus, the surveillance of resistance to antibiotics is a priority in order to adapt treatment and decrease the transmission of resistant strains. Of note, no predominant ST was identified among rectal isolates from men who have sex with men.

Summary: The main objective of this study was to assess the feasibility of human papillomavirus (HPV) genotyping in women referred for colposcopy due to abnormal Papanicolaou (Pap) smear. A series of 248 women referred for colposcopy due to an abnormal Pap smear were analysed with the Roche Linear Array HPV genotyping test detecting 37 most frequent HPV types, and compared with hybrid capture II (HCII) assay for oncogenic (high-risk [HR] HPV) types as well as for p16INK4a expression using immunocytochemistry. All tests were performed in cervical samples collected in PreservCyt® liquid media for liquid-based cytology (ThinPrep), and colposcopic biopsy and/or loop electro excision procedure cone biopsy was used as the gold standard. HPV16 was the single most frequent genotype (29/258; 11.7%), followed by HPV51 (4.4%), HPV66 (3.6%), HPV42, 52 and 56 (3.2% for all). Linear array genotyping test significantly predicts both abnormal colposcopy (odds ratio [OR] = 9.0; 3.12-25.93), high-grade squamous intraepithelial lesions (OR = 9.6; 1.26-74.17) and cervical intraepithelial neoplasia (CIN) 3+ (OR = 29.3; 3.95-218.06). In detecting CIN3, linear array was equivalent (97.6%) to colposcopy in sensitivity (SE), both being superior to HCII (92.7%). Concordance between linear array and HCII was moderate (Cohen's kappa κ = 0.547; 95% confidence interval [CI]: 0.435-659). Specificity (SP) and positive predictive value (PPV) of linear array were significantly improved, if only HPV16 genotype was considered. Performance in the best balance is obtained, when linear array and colposcopy are combined, giving 82.9% SE, 93.9% SP, 73.9% PPV and 96.3% negative predictive value (NPV) as predictor of CIN3+ (OR 74.5; 95% CI: 27.36-202.72). In conclusion, linear array for HR-HPV is a highly sensitive test (97.6%) with high NPV (98.9%) in detecting CIN3+ lesions. HPV16 genotyping alone significantly improves SP and PPV of this test in management of women with abnormal cytology.

To test whether p1l6(INK4a) immunocytochemistry (ICC) in liquid-based cytology (LBC) is useful with colposcopy in abnormal Pap smears.A series of 248 women with abnormal Pap smear were analyzed for oncogenic (HR) human papillomavirus (HPV) types using the Hybrid Capture II assay and for p16(INK4a) expression using ICC on cervical samples in PreservCyt liquid media. Colposcopic and loop electrosurgical excision procedure (LEEP) cone biopsy were the gold standard.p16(INK4a) ICC did best as predictor of high-grade squamous intraepithelial lesion, with OR 12.18 (2.72-54.57) (p = 0.0001), showing 88.2% sensitivity (SE), 61.9% specificity (SP), 14.6% positive predictive value (PPV) and 98.6% negative predictive value (NPV). In sorting discrepant cases, p16(INK4a) ICC results in 100% SE and 100% NPV in detecting cervical intraepithelial neoplasia (CIN) 2 lesions among Pap+/biopsy- women. In atypical squamous cells undetermined significance (ASCUS) cytology, adding p16(INK4a) ICC improves specificity of colposcopy from 27.3% to 81.8% and PPV from 42.8% to 71.4%. Best performance is obtained with p16(INK4a) ICC and colposcopy: 83.3% SE, 81.8% SP, 71.4% PPV and 90.0% NPV. CONCLUSION p16(INK4a) is useful in sorting clinically relevant discrepant cases, and p16(INK4a) ICC significantly improves SP and PPV of colposcopy in management of ASCUS cytology.

Objective To evaluate high-dose intravenous methotrexate in primary central nervous system (CNS) lymphoma in HIV-infected patients. Design An uncontrolled pilot trial. Setting An infectious diseases department in Paris, France. Patients All consecutive AIDS patients with primary CNS lymphoma attending the same unit from August 1994 to March 1996. Interventions Methotrexate was intravenously administered at a dose of 3 g/m2 every 14 days with leucovorin rescue. A maximum of six cycles was planned. Steroids were given to all patients and haematological growth factors were administered as required. Main outcome measures Rate of response, time to response and survival. Results Fifteen patients (10 with histological documentation) were recruited. The median time since clinical onset was 27 days (range, 7-69 days), median Karnofsky score was 51 (range, 30-70), and mean CD4+ cell count was 30 +/- 19 x 10(6)/l (range, 7-69 x 10(6)/l). Complete responses, defined as clinical improvement and disappearance of contrast-enhancing brain abnormalities on computed tomography or magnetic resonance imaging, were obtained in seven out of 15 patients (three out of 10 patients with histological diagnosis and four out of five patients without histological confirmation). The Karnofsky score of these seven patients improved to 80 +/- 10 (range, 70-100). The mean time taken to respond was 62 +/- 20 days (range, 45-90 days). One patient relapsed at 6 months. Six patients failed to respond, and two died of severe sepsis on days 15 and 45. The median survival time was 290 days (range, 11-570 days): 73 days (range, 11-570 days) in the 10 patients with histological diagnosis, and 347 days (range, 286-409 days) in the five patients without histological confirmation. Side-effects occurred in 10 patients, with gastrointestinal disorders in five, mucositis and skin rash in two, and fever in three patients; however, these events were mild and did not require cycle postponement or dose changes. No cognitive dysfunction occurred. Conclusion Methotrexate appears to be an attractive alternative to radiation therapy for primary CNS lymphoma and is associated with a far greater improvement in quality of life relative to historical series of radiation therapy.

The definition and routine diagnosis of cytomegalovirus (CMV) colitis in patients infected by human immunodeficiency virus (HIV) are controversial. In 100 consecutive HIV-infected patients who underwent colonoscopy for the investigation of diarrhea, we compared the yields of routine diagnostic tools for CMV infection and assessed the risk of further CMV organ disease in subgroups of patients with the following features: full evidence of CMV colitis (group 1), colonic CMV infection but no endoscopic lesions (group 2), and no evidence of colonic CMV infection (group 3). All biopsies taken during colonoscopy were examined immediately by routine hematoxylin and eosin (H&E) staining and viral culture and then pooled for second-line H&E staining and immunohistology. Among the 15 diagnoses of CMV colitis (group 1), two were missed during initial H&E examination, and both patients developed further CMV organ disease during follow-up. Of the 12 group 2 patients 11 were not receiving anti-CMV drugs at the time of initial colonoscopy. CMV organ disease was not significantly more common in these patients than in group 3 during follow-up. We conclude that routine H&E staining of colonic biopsy specimens for CMV inclusions is not 100% sensitive for CMV colitis. The favorable outcome of colonic CMV infection without endoscopic lesions suggests that only patients with full evidence of CMV colitis warrant specific antiviral therapy.