XRCC2 R188H (rs3218536), XRCC3 T241M (rs861539) and R243H (rs77381814) single nucleotide polymorphisms in cervical cancer risk

Human Papillomavirus (HPV) is the main cause of cervical cancer and its precursor lesions. Transformation may be induced by several mechanisms, including oncogene activation and genome instability. Individual differences in DNA damage recognition and repair have been hypothesized to influence cervical cancer risk. The aim of this study was to evaluate whether the double strand break gene polymorphisms XRCC2 R188H G>A (rs3218536), XRCC3 T241M C>T (rs861539) and R243H G>A (rs77381814) are associated to cervical cancer in Argentine women. A case control study consisting of 322 samples (205 cases and 117 controls) was carried out. HPV DNA detection was performed by PCR and genotyping of positive samples by EIA (enzyme immunoassay). XRCC2 and 3 polymorphisms were determined by pyrosequencing. The HPV-adjusted odds ratio (OR) of XRCC2 188 GG/AG genotypes was OR = 2.4 (CI = 1.1-4.9, p = 0.02) for cervical cancer. In contrast, there was no increased risk for cervical cancer with XRCC3 241 TT/CC genotypes (OR = 0.48; CI = 0.2-1; p = 0.1) or XRCC3 241 CT/CC (OR = 0.87; CI = 0.52-1.4; p = 0.6). Regarding XRCC3 R243H, the G allele was almost fixed in the population studied. In conclusion, although the sample size was modest, the present data indicate a statistical association between cervical cancer and XRCC2 R188H polymorphism. Future studies are needed to confirm these findings.Fil: Perez, Luis Orlando. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico CONICET- La Plata. Instituto de Genética Veterinaria "Ing. Fernando Noel Dulout". Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias. Instituto de Genética Veterinaria; ArgentinaFil: Crivaro, Andrea Natalia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico CONICET- La Plata. Instituto de Genética Veterinaria "Ing. Fernando Noel Dulout". Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias. Instituto de Genética Veterinaria; ArgentinaFil: Barbisan, Gisela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico CONICET- La Plata. Instituto de Genética Veterinaria "Ing. Fernando Noel Dulout". Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias. Instituto de Genética Veterinaria; ArgentinaFil: Poleri, Lucía Belén. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico CONICET- La Plata. Instituto de Genética Veterinaria "Ing. Fernando Noel Dulout". Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias. Instituto de Genética Veterinaria; ArgentinaFil: Golijow, Carlos Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico CONICET- La Plata. Instituto de Genética Veterinaria "Ing. Fernando Noel Dulout". Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias. Instituto de Genética Veterinaria; Argentin

Population-level effects of human papillomavirus vaccination programs on infections with nonvaccine genotypes

We analyzed human papillomavirus (HPV) prevalences during prevaccination and postvaccination periods to consider possible changes in nonvaccine HPV genotypes after introduction of vaccines that confer protection against 2 high-risk types, HPV16 and HPV18. Our meta-analysis included 9 studies with data for 13,886 girls and women ≤19 years of age and 23,340 women 20–24 years of age. We found evidence of cross-protection for HPV31 among the younger age group after vaccine introduction but little evidence for reductions of HPV33 and HPV45. For the group this same age group, we also found slight increases in 2 nonvaccine high-risk HPV types (HPV39 and HPV52) and in 2 possible high-risk types (HPV53 and HPV73). However, results between age groups and vaccines used were inconsistent, and the increases had possible alternative explanations; consequently, these data provided no clear evidence for type replacement. Continued monitoring of these HPV genotypes is important

A European multicentre evaluation of detection and typing methods for human enteroviruses and parechoviruses using RNA transcripts

Polymerase chain reaction (PCR) detection has become the gold standard for diagnosis and typing of enterovirus (EV) and human parechovirus (HPeV) infections. Its effectiveness depends critically on using the appropriate sample types and high assay sensitivity as viral loads in cerebrospinal fluid samples from meningitis and sepsis clinical presentation can be extremely low. This study evaluated the sensitivity and specificity of currently used commercial and in-house diagnostic and typing assays. Accurately quantified RNA transcript controls were distributed to 27 diagnostic and 12 reference laboratories in 17 European countries for blinded testing. Transcripts represented the four human EV species (EV-A71, echovirus 30, coxsackie A virus 21, and EV-D68), HPeV3, and specificity controls. Reported results from 48 in-house and 15 commercial assays showed 98% detection frequencies of high copy (1000 RNA copies/5 mu L) transcripts. In-house assays showed significantly greater detection frequencies of the low copy (10 copies/5 mu L) EV and HPeV transcripts (81% and 86%, respectively) compared with commercial assays (56%, 50%; P = 7 x 10(-5)). EV-specific PCRs showed low cross-reactivity with human rhinovirus C (3 of 42 tests) and infrequent positivity in the negative control (2 of 63 tests). Most or all high copy EV and HPeV controls were successfully typed (88%, 100%) by reference laboratories, but showed reduced effectiveness for low copy controls (41%, 67%). Stabilized RNA transcripts provide an effective, logistically simple and inexpensive reagent for evaluation of diagnostic assay performance. The study provides reassurance of the performance of the many in-house assay formats used across Europe. However, it identified often substantially reduced sensitivities of commercial assays often used as point-of-care tests.Peer reviewe

Risk of environmental transmission of norovirus infection from prior room occupants

BACKGROUND: Environmental contamination of norovirus (NoV) is believed to be a significant source for further transmission in hospitals.AIM: To investigate the risk of acquiring NoV in a cleaned room previously occupied by a patient with NoV infection. The risk of having a roommate with recent NoV infection was also assessed.METHODS: In a retrospective cohort, comprising 33,788 room stays at five infectious Disease wards in southern Sweden from 2013 to 2018, the risk of acquiring NoV infection after admission to an exposed or non-exposed room was analysed with uni- and multivariable statistical analysis, controlling for age, colonization pressure and any roommate. RNA sequencing of the NoV strains involved in suspected room transmission was also performed.RESULTS: Five of the 1106 patients exposed to a room with a prior occupant with NoV infection and 49 in the non-exposed group acquired NoV infection. An association between NoV acquisition was found in the univariable analysis (odds ratio (OR) 3.3, P=0.01), but not when adjusting for potential confounders (OR 1.9, P=0.2). Sequencing of the NoV samples showed that only two of the five exposed patients with acquired NoV infection were infected by identical strains to the prior room occupant, inferring a room transmission risk of 0.2% (95% confidence interval 0.05-0.78%). None of the 52 patients who shared room with a roommate with NoV symptoms resolved for ≥48 h acquired NoV infection.CONCLUSIONS: In absolute terms, the risk of room transmission of NoV is low. Discontinuation of isolation ≥48 h after resolution of symptoms seems adequate

Risk factors for hospital norovirus outbreaks : impact of vomiting, genotype, and multi-occupancy rooms

Background: Norovirus is frequently introduced to the hospital and is a frequent cause of hospital outbreaks. Recognition of the factors that facilitate or impede norovirus transmission is an important step to effectively prevent hospital outbreaks. Aim: To investigate risk factors for norovirus outbreaks in hospital settings. Methods: Clinical data, ward setting, and norovirus genotype were collected from all 65 norovirus-positive index cases in outbreaks and all 186 sporadic norovirus cases at 192 wards in southern Sweden during 2010–2012 in a nested case–control study. Uni- and multivariate statistical analyses were conducted. Findings: Outbreak was independently associated with the number of patients sharing a room with the norovirus case (odds ratio (OR): 1.9 per additional patient in the room; P 80 years (OR: 3.2; P < 0.01), comorbidity (OR: 2.3; P = 0.05), and onset of symptoms after admission to the ward (OR: 3.5; P < 0.01) in the multivariate analysis. Infection with genotype GII.4 was found to be strongly associated with outbreak in the univariate analysis (OR: 5.7; P < 0.01). Moreover, associations between GII.4 and vomiting (OR: 2.5; P = 0.01) and old age (OR: 4.3: P < 0.01) were found. Conclusion: This is the first study to investigate clinical, ward and genotype risk factors for norovirus hospital outbreaks. Recognition of these factors may help direct and prioritize infection control actions based on the outbreak risk. The results also suggest that the outbreak association with GII.4 partly may be explained by an enhanced ability to induce vomiting

Cervical cytology biobanks as a resource for molecular epidemiology

&lt;p&gt;A cervical cytology biobank (CCB) is an extension of current cytopathology laboratory practice consisting in the systematic storage of Pap smears or liquid-based cytology samples from women participating in cervical cancer screening with the explicit purpose of facilitating future scientific research and quality audit of preventive services. A CCB should use an internationally agreed uniform cytology terminology, be integrated in a national or regional screening registry, and linked to other registries (histology, cancer, and vaccination). Legal and ethical principles concerning personal integrity and data safety must be respected strictly. Biobank-based studies require approval from ethical review boards. A CCB constitutes a nearly inexhaustible resource to perform fundamental and applied biologic research. In particular, it can contribute in answering questions on the natural history of HPV infection and HPV-induced lesions and cancers, screening effectiveness, exploration of new biomarkers, and surveillance of short- and long-term effects of the introduction of HPV vaccination. To understand the limitations of CCB, more studies are needed on quality of samples in relation to sample type, storage procedures, and duration of storage.&lt;/p&gt;</p