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Study objectiveEvidence suggests that vaccine-type human papillomavirus (HPV) prevalence may decrease in unvaccinated women after HPV vaccine introduction, indicating herd protection. The aim of this study was to determine factors associated with vaccine-type HPV (i.e. absence of herd protection) after vaccine introduction.DesignWe conducted three cross-sectional studies from 2006-2014 (n = 1180): wave 1 (2006-2007), wave 2 (2009-2010), and wave 3 (2013-2014).SettingParticipants were recruited from a hospital-based teen health center and a community health department.ParticipantsWe recruited 13-26 year-old young women; those included in this analysis had not received an HPV vaccine.Interventions and main outcome measuresThe outcome measure was infection with at least one vaccine-type HPV (HPV6, 11, 16, 18).ResultsMultivariable logistic regression demonstrated that in wave 1 (before vaccine introduction), history of anal intercourse (OR = 1.8, 95% CI = 1.1-3.0), age 18-21 vs 13-17 years (OR = 2.1, CI = 1.2-3.6), and Black/multiracial vs White race (OR = 1.8, CI = 1.1-3.0) were associated with vaccine-type HPV in unvaccinated women. In wave 2, no variables were associated with HPV. In wave 3, sexually transmitted infection history (OR = 3.6, CI = 1.3-9.7) was associated with HPV.ConclusionWe did not identify a consistent set of modifiable risk factors associated with vaccine-type HPV after vaccine introduction across the three study waves, underscoring the urgency of vaccination for primary HPV prevention and the limitations of relying on herd protection.

PURPOSENowadays, websites, online journals, and social media give access to an extraordinary amount of medical information. Misleading news are often disseminated generating false expectations, exaggerated anxiety, and confusion; in oncology setting, disinformation is perhaps more deleterious than in other fields, with a considerable impact on single patients as well as on families and, more in general, on Public Health. We aimed to promote a better interaction between the health care and the world of communication.MATERIALS AND METHODSA regional technical table was established with the aim of drafting a shared document through the consensus conference method in the RAND/University of California Los Angeles variant, identifying strategies to overcome barriers between communication and health care as well as to propose common criteria for an effective dissemination of medical information.RESULTSSixteen articles met the inclusion criteria, from which 72 recommendations were drawn to the communication and health field (40 related to specific issues and 32 transversal to all the specific topics). Following an evaluation of relevance by the panel of experts, it was found that 57 recommendations scored more than 7, 13 between 4 and 6.9, and 2 below 4.CONCLUSIONThis consensus and the drawn up document represent a concrete attempt to find a renewed and strategic alliance between key figures in health care and communication operators. As the American Declaration of Independence, our Declaration of Good Communication has identified high-impact recommendations for the best management of patients, providing simple but fundamental concepts and recommendations about effectiveness especially in oncology setting.

Introducción El objetivo del presente estudio fue determinar la frecuencia y factores relacionados a enterobiasis en la población de 5 a 11 años de los colegios del distrito de Quisqui-Huánuco durante el periodo de junio a setiembre del 2014. Métodos: Se llevó a cabo un estudio de prevalencia en 430 niños, tomados aleatoriamente de 880 niños de entre 5 y 11 años (IC: 95%). Todos los datos fueron recolectados a partir de fuentes primarias: entrevista e informe de resultados del test de Graham. La recolección de las muestras para el diagnóstico de Enterobiasis fue seriada, por la técnica de Graham, durante 3 días consecutivos, que luego fueron analizadas por microscopía directa. Resultados: Se encontró una prevalencia general de Enterobiasis del 60%. Las diferencias entre las frecuencias de infección según edades y sexo no fueron significativas. Se evidenció un mayor porcentaje de infección en el sexo femenino que en el masculino (63.5% vs 56.8%), y en el rango etario >8 años. En el análisis bivariado se encontró asociación significativa (P

Epidemiologists are well aware of the negative consequences of measurement error in exposure and outcome variables to their ability to detect putative causal associations. However, empirical proof that remedying the misclassification problem improves estimates of epidemiologic effect is seldom examined in detail. Of all areas in cancer epidemiology, perhaps the best example of the consequences of misclassification and of the steps taken to circumvent them was the pursuit, beginning in the mid-1980s, of the human papillomavirus (HPV) infection-cervical cancer association. The stakes were high: Had the wrong conclusions been reached epidemiologists would have been led astray in the search for competing hypotheses for the sexually transmissible agent causing cervical cancer or in ascribing to HPV infection a mere ancillary role among many lifestyle, hormonal, and environmental factors. The article by Castle et al. in this issue of the Journal (Am J Epidemiol. 2010;171(2):155-163) provides a detailed account of the joint influences of improved HPV and cervical precancer measurements in gradually unveiling the strong magnitude of the underlying association between viral exposure and cervical lesion risk. In this commentary, the authors extend the findings of Castle et al. by providing additional empirical evidence in support of their arguments. [ABSTRACT FROM AUTHOR]

Educating concerned patients that getting HPV is less about promiscuity and more about having sex with a new male partner can soften the stigma. Here's expert advice for reassuring those who test HPV-positive that they most likely don't have cancer, their husbands aren't necessarily cheating, that it's just as easy to get rid of HPV as to get it--and more. [ABSTRACT FROM AUTHOR]

Objective: Cohort studies of the natural history of human papillomavirus (HPV) infection and cervical squamous intraepithelial lesions with repeated screening allow the comparison of different macroscopic and microscopic diagnostic methods. Materials and Methods: Concurrent visual inspection using cervicography and conventional Pap cytology tests were performed during multiple visits in a cohort of women attending a maternal and child health clinic in São Paulo, Brazil. HPV infection status at the same visits was determined by polymerase chain reaction followed by typing with specific oligonucleotide probing and viral load quantification. Information on reproductive health and hygiene habits was also collected at each visit. Results: Overall agreement between cervicography and cytology was low (kappa = 0.046), which increased only slightly when high oncogenic-risk HPV types (kappa = 0.120) or high viral burden (>100 copies/cell) (kappa = 0.170) was present. Analysis of reproductive health and hygiene habits revealed somewhat different risk factors for cervical lesions detected by these tests. However, presence of oncogenic HPV DNA (odds ratio = 36.0, 95% CI = 16.6-77.8) and high viral burden (odds ratio = 67.34; 95% CI = 27.1-167.0) were strongly associated with lesions detected by cytology but not by cervicography. Conclusions: Although changes in the cervix (because of age, gravidity, or hormonal effects) may influence the performance of morphology-based screening tests, the lack of agreement and the different degrees of association with HPV infection measures indicate that a visual inspection method such as cervicography may detect different cervical abnormalities relative to cytology. [ABSTRACT FROM AUTHOR]

Background: Sex-specific issues have not been extensively addressed in studies of HIV prevalence, despite the strong implications of differences between men and women in the risk of HIV transmission. The objective of this study was to examine sex-specific behaviours associated with HIV infection among injection drug users in Montreal.Methods: A total of 2741 active drug users (2209 [80.6%] men) were recruited between 1988 and 1998. Information was sought on sociodemographic characteristics, drug-related behaviour and sexual behaviour, and participants were tested for HIV antibodies. Sex-specific independent predictors of HIV prevalence were assessed by stepwise logistic regression.Results: The overall prevalence of HIV among study subjects was 11.1%; the prevalence was 12.0% among men and 7.5% among women. In multivariate models, a history of sharing syringes with a known seropositive partner (odds ratio [OR] for men 2.44, 95% confidence interval [CI] 1.72-3.46; OR for women 3.03, 95% CI 1.29-7.13) and of sharing syringes in the past 6 months (OR for men 0.61, 95% CI 0.44-0.85; OR for women 0.32, 95% CI 0.14-0.73) were independently associated with HIV infection. Other variables associated with HIV infection were homosexual or bisexual orientation, cocaine rather than heroin as drug of choice, frequency of injection drug use, and obtaining needles at a pharmacy or through needle exchange programs (for men only) and obtaining needles at shooting galleries and being out of treatment (for women only).Interpretation: These results support the hypothesis that risk factors for HIV seropositivity differ between men and women. These sex-related differences should be taken into account in the development of preventive and clinical interventions. [ABSTRACT FROM AUTHOR]

Background: Incidence rates for cancers of the upper aero-digestive tract in Southern Brazil are among the highest in the world. A case-control study was designed to identify the main risk factors for carcinomas of mouth, pharynx, and larynx in the region. We tested the hypothesis of whether use of wood stoves is associated with these cancers.Methods: Information on known and potential risk factors was obtained from interviews with 784 cases and 1568 non-cancer controls. We estimated the effect of use of wood stove by conditional logistic regression, with adjustment for smoking, alcohol consumption and for other sociodemographic and dietary variables chosen as empirical confounders based on a change-in-estimate criterion.Results: After extensive adjustment for all the empirical confounders the odds ratio (OR) for all upper aero-digestive tract cancers was 2.68 (95% confidence interval [CI] : 2.2-3.3). Increased risks were also seen in site-specific analyses for mouth (OR = 2.73; 95% CI: 1.8-4.2), pharyngeal (OR = 3.82; 95% CI: 2.0-7.4), and laryngeal carcinomas (OR = 2.34; 95% CI: 1.2-4.7). Significant risk elevations remained for each of the three anatomic sites and for all sites combined even after we purposefully biased the analyses towards the null hypothesis by adjusting the effect of wood stove use only for positive empirical confounders.Conclusions: The association of use of wood stoves with cancers of the upper aero-digestive tract is genuine and unlikely to result from insufficient control of confounding. Due to its high prevalence, use of wood stoves may be linked to as many as 30% of all cancers occurring in the region. [ABSTRACT FROM AUTHOR]

Natural Killer (NK) cells play a major role in the T-cell depleted haploidentical haematopoietic stem cell transplantation (haplo-HSCT) to cure high-risk leukemias. NK cells belong to the expanding family of innate lymphoid cells (ILC). At variance with NK cells, the other ILC populations (ILC1/2/3) are non-cytolytic, while they secrete different patterns of cytokines. ILC provide host defences against viruses, bacteria and parasites, drive lymphoid organogenesis, and contribute to tissue remodelling. In haplo-HSCT patients, the extensive T-cell depletion is required to prevent graft-versus-host disease (GvHD) but increases risks of developing a wide range of life-threatening infections. However, these patients may rely on innate defences that are reconstituted more rapidly than the adaptive ones. In this context, ILC may represent important players in the early phases following transplantation. They may contribute to tissue homeostasis/remodelling and lymphoid tissue reconstitution. While the reconstitution of NK cell repertoire and its role in haplo-HSCT have been largely investigated, little information is available on ILC. Of note, CD34+ cells isolated from different sources of HSC, may differentiate in vitro towards various ILC subsets. Moreover, cytokines released from leukemia blasts (e.g. IL-1β) may alter the proportions of NK cells and ILC3, suggesting the possibility that leukemia may skew the ILC repertoire. Further studies are required to define the timing of ILC development and their potential protective role after HSCT.

The Long QT Syndrome (LQTS), classified as congenital or acquired, is a multi-factorial disorder of myocardial repolarization predisposing to life-threatening ventricular arrhythmias, particularly torsades de pointes. In the latest years inflammation and immunity have been increasingly recognized as novel factors crucially involved in modulating ventricular repolarization. In the present paper we critically review the available information on this topic, also analyzing putative mechanisms and potential interplays with the other etiologic factors, either acquired and inherited.Accumulating data indicate inflammatory activation as a potential cause of acquired LQTS. The putative underlying mechanisms are complex but essentially cytokine-mediated, including both direct actions on cardiomyocyte ion channels expression and function, and indirect effects resulting from an increased central nervous system sympathetic drive on the heart. Autoimmunity represents another recently arising cause of acquired LQTS. Indeed, increasing evidence demonstrates that autoantibodies may affect myocardial electric properties by directly cross-reacting with the cardiomyocyte and interfering with specific ion currents as a result of molecular mimicry mechanisms. Intriguingly, recent data suggest that inflammation and immunity may be also involved in modulating the clinical expression of congenital forms of LQTS, possibly triggering or enhancing electrical instability in patients who already are genetically predisposed to arrhythmias. In this view, targeting immuno-inflammatory pathways may in the future represent an attractive therapeutic approach in a number of LQTS patients, thus opening new exciting avenues in antiarrhythmic therapy.

Children aged 0–2 years (i.e. infants) with acute myeloid leukemia (AML) are a peculiar subgroup of patients in the childhood AML scenario. They present with distinctive biological and clinical characteristics, including a high prevalence of prognostically unfavorable risk factors and an increased susceptibility to therapy-related toxicity. Remarkable improvements have been achieved over the last 2 decades in the treatment of these patients and their outcome is becoming superimposable to that of the older age groups. In this review, we will focus on peculiarities of this young subgroup of children with AML, describing their clinical presentation, the biology of disease and factors influencing outcome. Treatment results and toxicity data reported by major collaborative groups are also summarized and compared.

Plasticity in the human and animal brain is the rule, the base for development, and the way to deal effectively with the environment for making the most efficient use of all the senses. When the brain is deprived of one sensory modality, plasticity becomes compensatory: the exception that invalidates the general loss hypothesis giving the opportunity of effective change. Sensory deprivation comes with massive alterations in brain structure and function, behavioural outcomes, and neural interactions. Blind individuals do as good as the sighted and even more, show superior abilities in auditory, tactile and olfactory processing. This behavioural enhancement is accompanied with changes in occipital cortex function, where visual areas at different levels become responsive to non-visual information. The intact senses are in general used more efficiently in the blind but are also used more exclusively. New findings are disentangling these two aspects of compensatory plasticity. What is due to visual deprivation and what is dependent on the extended use of spared modalities? The latter seems to contribute highly to compensatory changes in the congenitally blind. Short term deprivation through the use of blindfolds shows that cortical excitability of the visual cortex is likely to show rapid modulatory changes after few minutes of light deprivation and therefore changes are possible in adulthood. However, reorganization remains more pronounced in the congenitally blind. Cortico-cortical pathways between visual areas and the areas of preserved sensory modalities are inhibited in the presence of vision, but are unmasked after loss of vision or blindfolding as a mechanism likely to drive cross-modal information to the deafferented visual cortex. Plasticity in the blind is also accompanied with neurochemical and morphological changes; both intrinsic connectivity and functional coupling at rest are altered but are likewise dependent on different sensory experience and training.

Emotional visual perception deficits constitute a major problem in alcohol-dependence. Indeed, the ability to assess the affective content of external cues is a key adaptive function, as it allows on the one hand the processing of potentially threatening or advantageous stimuli, and on the other hand the establishment of appropriate social interactions (by enabling rapid decoding of the affective state of others from their facial expressions). While such deficits have been classically considered as reflecting a genuine emotion decoding impairment in alcohol-dependence, converging evidence suggests that underlying visual deficits might play a role in emotional alterations. This hypothesis appears to be relevant especially as data from healthy populations indicate that a coarse but fast analysis of visual inputs would allow emotional processing to arise from early stages of perception. After reviewing those findings and the associated models, the present paper underlines data showing that rapid interactions between emotion and vision could be impaired in alcohol-dependence and provides new research avenues that may ultimately offer a better understanding of the roots of emotional deficits in this pathological state.

The global level of hierarchical stimuli (Navon’s stimuli) is typically processed quicker and better than the local level; further differential hemispheric dominance is described for local (left hemisphere, LH) and global (right hemisphere, RH) processing. However, neuroimaging and behavioural data indicate that stimulus category (letter or object) could modulate the hemispheric asymmetry for the local level processing. Besides, when the targets are unpredictably displayed at the global or local level, the participant has to switch between levels, and the magnitude of the switch cost increases with the number of repeated-level trials preceding the switch. The hemispheric asymmetries associated with level switching is an unresolved issue. LH areas may be involved in carrying over the target level information in case of level repetition. These areas may also largely participate in the processing of level-changed trials. Here we hypothesized that RH areas underly the inhibitory mechanism performed on the irrelevant level, as one of the components of the level switching process. In an experiment using a within-subject design, hierarchical stimuli were briefly presented either to the right or to the left visual field. Thirty-two adults were instructed to identify the target at the global or local level. We assessed a possible RH dominance for the non-target level inhibition by varying the attentional demands through the manipulation of level repetitions (2 or 4 repeated-level trials before the switch). The behavioural data confirmed a LH specialization only for the local level processing of letter-based stimuli, and detrimental effect of increased level repetitions before a switch. Further, data provides evidence for a RH advantage in inhibiting the non-target level. Taken together, the data supports the notion of the existence of multiple mechanisms underlying level-switch effects.

Natural Killer (NK) cells are major effector cells of the innate immunity. The discovery, over two decades ago, of MHC-class I specific NK receptors and subsequently of activating receptors, recognizing ligands expressed by tumor or virus-infected cells, paved the way to our understanding of the mechanisms of selective recognition and killing of tumor cells. Although NK cells can efficiently kill tumor cells of different histotypes in vitro, their activity may be limited in vivo by their inefficient trafficking to tumor lesions and by the inhibition of their function induced by tumor cells themselves and by the tumor microenvironment. On the other hand, the important role of NK cells has been clearly demonstrated in the therapy of high risk leukemias in the haploidentical hematopoietic cell (HSC) transplantation setting. NK cells derived from donor HSC kill leukemic cells residual after the conditioning regimen, thus preventing leukemia relapses. In addition, they also kill residual dendritic cells and T lymphocytes, thus preventing both GvHD and graft rejection.

Neuroblastoma (NB) is the most common extra-cranial solid tumor of childhood and arises from developing sympathetic nervous system. Most primary tumors localize in the abdomen, the adrenal gland or lumbar sympathetic ganglia. Amplification in tumor cells of MYCN, the major oncogenic driver, patients’ age over 18 months and the presence at diagnosis of a metastatic disease (stage IV, M) identify NB at high risk of treatment failure. Conventional therapies did not significantly improve the overall survival of these patients. Moreover, the limited landscape of somatic mutations detected in NB is hampering the development of novel pharmacological approaches. Major efforts aim to identify novel NB-associated surface molecules that activate immune responses and/or direct drugs to tumor cells and tumor-associated vessels. PVR (Poliovirus Receptor) and B7-H3 are promising targets, since they are expressed by most high-risk NB, are upregulated in tumor vasculature and are essential for tumor survival/invasiveness. PVR is a ligand of DNAM-1 activating receptor that triggers the cytolytic activity of Natural Killer (NK) cells against NB. In animal models targeting of PVR with an attenuated oncolytic poliovirus induced tumor regression and elimination. Also B7-H3 was successfully targeted in preclinical studies and is now being tested in phase I/II clinical trials. B7-H3 down-regulates NK cytotoxicity, providing NB with a mechanism of escape from immune response. The immunosuppressive potential of NB can be enhanced by the release of soluble factors that impair NK cell function and/or recruitment. Among these, TGF-β1 modulates the cytotoxicity receptors and the chemokine receptor repertoire of NK cells.Here, we summarize the current knowledge on the main cell surface molecules and soluble mediators that modulate the function of NK cells in NB, considering the pros and cons that must be taken into account in the design of novel NK cell-based immunotherapeutic approaches.

Natural Killer (NK) cell function is regulated by an array of inhibitory and activating surface receptors that during NK cell differentiation, at variance with T and B cells, do not require genetic rearrangement. Importantly, NK cells are the first lymphocyte population recovering after hematopoietic stem cell transplantation (HSCT). Thus, their role in early immunity after HSCT is considered crucial, as they can importantly contribute to protect the host from tumor recurrence and viral infections before T-cell immunity is fully recovered.In order to acquire effector functions and regulatory receptors, NK cell precursors undergo a maturation process that can be analysed during immune reconstitution after HSCT. In this context, the occurrence of human cytomegalovirus (HCMV) infection/reactivation was shown to accelerate NK cell maturation by promoting the differentiation of high frequencies of NK cells characterized by a KIR+NKG2A− and NKG2C+ mature phenotype. Thus, it appears that the development of NK cells and the distribution of NK cell receptors can be deeply influenced by HCMV infection. Moreover, in HCMV-infected subjects the emergence of so called memory-like or long-lived NK cells has been documented. These cells could play an important role in protecting from infections and maybe from relapse in patients transplanted for leukemia.All the aspects regarding the influence of HCMV infection on NK cell development will be discussed.

Use of alternative donors/sources of hematopoietic stem cells (HSC), such as cord blood (CB) or HLA-haploidentical (Haplo) related donors, is associated with a significant delay in immune reconstitution after transplantation. Long-term T-cell immune reconstitution largely relies on the generation of new T cells in the recipient thymus, which can be evaluated through signal joint (sj) and beta T-cell-Receptor Excision Circles (TREC) quantification. We studied two groups of 33 and 24 children receiving, respectively, HSC Transplantation (HSCT) from an HLA-haploidentical family donor or an unrelated CB donor, for both malignant (46) and non-malignant disorders (11). Relative and absolute sj and beta-TREC values indicated comparable thymic function reconstitution at 3 and 6 months after the allograft in both groups. Compared to children with non-malignant disorders, those with hematological malignancies had significantly lower pre-transplantation TREC counts. Patients who relapsed after HSCT had a significantly less efficient thymic function both before and 6 months after HSCT with especially low beta-TREC values, this finding suggesting an impact of early intra-thymic T-cell differentiation on the occurrence of leukemia relapse.

Natural Killer (NK) cells are involved in innate immune responses and play a major role in tumor surveillance and in defence against viruses. Human NK cells recognize HLA-class I molecules via surface receptors (KIR and NKG2A) delivering signals that inhibit NK cell function and kill HLA-class I-deficient target cells, a frequent event in tumors or virus-infected cells. NK cell triggering is mediated by activating receptors that recognize ligands expressed primarily on tumors or virus-infected cells. NK cells play also a key role in the cure of high-risk leukemias. Thus, donor-derived alloreactive NK cells are fundamental effectors in adult acute myeloid leukemia (AML) and in pediatric acute lymphoblastic leukemia (ALL) patients undergoing haploidentical hematopoietic stem cell transplantation (HSCT). Alloreactive NK cells mediate killing of leukemia cells and patient’s DC, thus preventing respectively leukemic relapses and graft-versus-host responses. FACS analysis of KIRs expressed by NK cells allows to define the size of the alloreactive NK subset and the selection of the best potential donor. Recently, it has been shown that also the expression of activating KIRs, in particular the (C2-specific) KIR2DS1, may contribute to donor NK alloreactivity. It has also been established a correlation between the size of the alloreactive NK cell population and the clinical outcome. Notably, the alloreactive NK cells derived from donor’s HSC are generated and persist in patients over time. The high survival rates of patients undergoing haploidentical HSCT highlight an important new reality in the setting of allograft performed to cure otherwise fatal leukemias. Novel approaches are in progress to further improve the clinical outcome based on the infusion of donor alloreactive NK cells either as a component of the transplanted cell population or as in vitro expanded NK cells.

Higher order sensory processing follows a general subdivision into a ventral and a dorsal stream for visual, auditory, and tactile information. Object identification is processed in temporal structures (ventral stream), whereas object localization leads to activation of parietal structures (dorsal stream). To examine whether the chemical senses demonstrate a similar dissociation, we investigated odor identification and odor localization in 16 healthy young subjects using functional MRI. We used two odors (1. eucalyptol; 2. a mixture of phenylethanol and carbon dioxide) which were delivered to only one nostril. During odor identification subjects had to recognize the odor; during odor localisation they had to detect the stimulated nostril.We used General Linear Model (GLM) as a classical method as well as Independent Component Analysis (ICA) in order to investigate a possible neuroanatomical dissociation between both tasks. Both methods showed differences between tasks - confirming a dual processing stream in the chemical senses - but revealed complementary results. Specifically, GLM identified the left intraparietal sulcus and the right superior frontal sulcus to be more activated when subjects were localising the odorants. For the same task, ICA identified a significant cluster in the left parietal lobe (paracentral lobule) but also in the right hippocampus. While GLM did not find significant activations for odor identification, ICA revealed two clusters (in the left central fissure and the left superior frontal gyrus) for this task. These data demonstrate that higher order chemosensory processing shares the general subdivision into a ventral and a dorsal processing stream with other sensory systems and suggest that this is a global principle, independent of sensory channels.

Previous studies have shown that complex visual stimuli, such as emotional facial expressions, can influence brain activity independently of the observers’ awareness. Little is known yet, however, about the informational correlates of consciousness—i.e., which low-level information correlates with brain activation during conscious vs. non-conscious perception. Here, we investigated this question in the spatial frequency (SF) domain. We examined which SFs in disgusted and fearful facial expressions modulate activation in the insula and amygdala over time and as a function of awareness, using a combination of intracranial event-related potentials (ERPs), SF Bubbles (Willenbockel et al., 2010a), and Continuous Flash Suppression (CFS; Tsuchiya and Koch, 2005). Patients implanted with electrodes for epilepsy monitoring viewed face photographs (13° x 7°) that were randomly SF filtered trial-by-trial. In the conscious condition, the faces were visible; in the non-conscious condition, they were rendered invisible using CFS. Data were analyzed by performing multiple linear regressions on the SF filters from each trial and the transformed ERP amplitudes across time. The resulting classification images suggest that many SFs are involved in the conscious and non-conscious perception of emotional expressions, with those between 6 and 10 cycles per face width being particularly important early on. The results also revealed qualitative differences between the awareness conditions for both regions. Non-conscious processing relied on low SFs more and was faster than conscious processing. Overall, our findings are consistent with the idea that different pathways are employed for the processing of emotional stimuli under different degrees of awareness. The present study represents a first step to mapping with a high temporal resolution how SF information flows through the emotion-processing network and to shedding light on the informational correlates of consciousness in general.

We have previously shown that some blind individuals can localize sounds more accurately than their sighted counterparts when one ear is obstructed, and that this ability is strongly associated with occipital cortex activity. Given that spectral cues are important for monaural localizing sounds when one ear is obstructed, and that blind individuals are more sensitive to small spectral differences, we hypothesized that enhanced use of spectral cues via occipital cortex mechanisms could explain the better performance of blind individuals in monaural localization. Using PET, we scanned blind and sighted persons as they discriminated between sounds originating from a single spatial position, but with different spectral profiles that simulated different spatial positions based on head-related transfer functions. We show here that a sub-group of early-blind individuals showing superior monaural sound localization abilities performed significantly better than any other group on this spectral discrimination task. For all groups, performance was best for stimuli simulating peripheral positions, consistent with the notion that spectral cues are more helpful for discriminating peripheral sources. PET results showed that all blind groups showed cerebral blood flow increases in the occipital cortex; but this was also the case in the sighted group. A voxel-wise covariation analysis showed that more occipital recruitment was associated with better performance across all blind subjects but not the sighted. Inter-regional covariation analysis showed that the occipital activity in the blind covaried with that of several frontal and parietal regions known for their role in auditory spatial processing. Overall, these results support the notion that the superior ability of a sub-group of early blind individuals to localize sounds is mediated by their superior ability to use spectral cues, and that this ability is subserved by cortical processing in the occipital cortex.

Abstract Background The purpose of this work was to explore the knowledge and acceptance of Varicella Zoster Virus (VZV)-Herpes Zoster (HZ) vaccination in the general Italian population, where the HZ vaccine has not yet been distributed, using a prevalence study of subjects from two regions in Italy. Methods A group of 3,173 individuals were interviewed using a questionnaire. The youngest age group (≤ 20 year) was composed of students interviewed at university. The middle age group (21-40 years) and the older age group (≥ 41 years) were interviewed by general practitioners in their office. Results In both regions, the majority of subjects had been infected with varicella, and only 165 (5.2%) subjects reported receiving the VZV vaccination. Regarding HZ, 2,749 (86.6%) individuals stated that they knew of the virus and 2,233 (70%) were willing to be vaccinated against HZ. The majority of people willing to be vaccinated were in the middle and older age groups (36.6% and 44.7%, respectively). Conclusion Compliance versus vaccination results were satisfactory and probably, with the upcoming availability of the HZ vaccine in Italy, adults will be favourably disposed towards vaccination.

Background: Persistent infection with oncogenic types of human papillomavirus (HPV) is the major risk factor for invasive cervical cancer (ICC), and non-European variants of HPV-16 are associated with an increased risk of persistence and ICC. HLA class II polymorphisms are also associated with genetic susceptibility to ICC. Our aim is to verify if these associations are influenced by HPV-16 variability.Methods: We characterized HPV-16 variants by PCR in 107 ICC cases, which were typed for HLA-DQA1, DRB1 and DQB1 genes and compared to 257 controls. We measured the magnitude of associations by logistic regression analysis.Results: European (E), Asian-American (AA) and African (Af) variants were identified. Here we show that inverse association between DQB1*05 (adjusted odds ratio [OR] = 0.66; 95% confidence interval [CI]: 0.39-1.12]) and HPV-16 positive ICC in our previous report was mostly attributable to AA variant carriers (OR = 0.27; 95%CI: 0.10-0.75). We observed similar proportions of HLA DRB1*1302 carriers in E-P positive cases and controls, but interestingly, this allele was not found in AA cases (p = 0.03, Fisher exact test). A positive association with DRB1*15 was observed in both groups of women harboring either E (OR = 2.99; 95% CI: 1.13-7.86) or AA variants (OR = 2.34; 95% CI: 1.00-5.46). There was an inverse association between DRB1*04 and ICC among women with HPV-16 carrying the 350T [83L] single nucleotide polymorphism in the E6 gene (OR = 0.27; 95% CI: 0.08-0.96). An inverse association between DQB1*05 and cases carrying 350G (83V) variants was also found (OR = 0.37; 95% CI: 0.15-0.89).Conclusion: Our results suggest that the association between HLA polymorphism and risk of ICC might be influenced by the distribution of HPV-16 variants. [ABSTRACT FROM AUTHOR]

Of the 190,000 deaths from cervical cancer that occur annually worldwide, the majority take place in developing countries. Recent advances in our understanding of the causes and natural history of cervical neoplasia and, in particular, the establishment of the central role of human papilloma virus (HPV) infection have created opportunities for the primary and secondary prevention of cervical cancer. In the future, prevention efforts will include the incorporation of HPV testing as an adjunct to or replacement for cytology-based screening programs and the use of recombinant DNA technologies for the development of prophylactic vaccines. [ABSTRACT FROM AUTHOR]

Background: Carrageenan-containing gels researched for the prevention of sexually transmitted infections (STIs) have shown promising results for human papillomavirus prevention in women, but not in men. We conducted a narrative review to assess the safety of these gels for genital use., Methods: We searched PubMed using MeSH terms and keywords on 5 November 2023. Title/abstract of articles were screened to identify relevant ones. Full-text screening determined eligibility: empirical study evaluating safety of carrageenan-containing gel(s) for genital use., Results: Of the 125 identified records, 15 were eligible, comprising 14 (10 randomised controlled trials and 4 cohorts) unique study populations. Studies included women only (n=11), men only (n=1) or both (n=3); number of participants ranged from 4 to 6202. Safety was assessed for vaginal (n=13), penile (n=3) and anal use (n=2). Most studies assessed safety of Carraguard (53%), followed by Divine9 (14%), and one each of iota-carrageenan gel, lambda-carrageenan gel, Carvir, PC-6500 (griffithsin and carrageenan) and PC-1005 (MIV-150/zinc acetate/carrageenan). Safety assessment relied on self-report (80.0%), testing for STIs (53.3%), investigator-identified genital findings (93.3%) and/or testing for changes in genital flora (60.0%). Adverse events (AEs) were described by investigators as mostly mild, (mostly) comparable between groups, not observed and/or not significant for vaginal and penile use. Only one study, assessing anal use of carrageenan, reported a significantly higher proportion of AEs in the carrageenan compared with placebo group., Conclusions: Carrageenan-based gels are generally well tolerated for vaginal and penile, but not anal use. Studies on carrageenan gel's safety for anal use are scarce., Competing Interests: Competing interests: ELF reports grants and personal fees from Merck, grants, personal fees and non-financial support from Roche, and personal fees from GSK, outside the submitted work. ELF and ME hold a patent related to the discovery ‘DNA methylation markers for early detection of cervical cancer’, registered at the Office of Innovation and Partnerships, McGill University, Montreal, Quebec, Canada (October 2018). CL has no conflicts of interest to declare., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Cervical cancer is the first cancer deemed amenable to elimination through prevention, and thus lessons from the epidemiology and prevention of this cancer type can provide information on strategies to manage other cancers. Infection with the human papillomavirus (HPV) causes virtually all cervical cancers, and an important proportion of oropharyngeal, anal and genital cancers. Whereas 20th century prevention efforts were dominated by cytology-based screening, the present and future of HPV-associated cancer prevention relies mostly on HPV vaccination and molecular screening tests. In this Review, we provide an overview of the epidemiology of HPV-associated cancers, their disease burden, how past and contemporary preventive interventions have shaped their incidence and mortality, and the potential for elimination. We particularly focus on the cofactors that could have the greatest effect on prevention efforts, such as parity and human immunodeficiency virus infection, as well as on social determinants of health. Given that the incidence of and mortality from HPV-associated cancers remain strongly associated with the socioeconomic status of individuals and the human development index of countries, elimination efforts are unlikely to succeed unless prevention efforts focus on health equity, with a commitment to both primary and secondary prevention., (© 2024. Springer Nature Limited.)

Background: The growing use of primary human papillomavirus (HPV) cervical cancer screening requires determining appropriate screening intervals to avoid overtreatment of transient disease. This study examined the long-term risk of cervical precancer after HPV screening to inform screening interval recommendations., Methods: This longitudinal cohort study (British Columbia, Canada, 2008 to 2022) recruited women and individuals with a cervix who received 1 to 2 negative HPV screens (HPV1 cohort, N = 5,546; HPV2 cohort, N = 6,624) during a randomized trial and women and individuals with a cervix with 1 to 2 normal cytology results (BCS1 cohort, N = 782,297; BCS2 cohort, N = 673,778) extracted from the provincial screening registry. All participants were followed through the registry for 14 years. Long-term risk of cervical precancer or worse [cervical intraepithelial neoplasia grade 2 or worse (CIN2+)] was compared between HPV and cytology cohorts., Results: Cumulative risks of CIN2+ were 3.2/1,000 [95% confidence interval (CI), 1.6-4.7] in HPV1 and 2.7/1,000 (95% CI, 1.2-4.2) in HPV2 after 8 years. This was comparable with the risk in the cytology cohorts after 3 years [BCS1: 3.3/1,000 (95% CI, 3.1-3.4); BCS2: 2.5/1,000 (95% CI, 2.4-2.6)]. The cumulative risk of CIN2+ after 10 years was low in the HPV cohorts [HPV1: 4.7/1,000 (95% CI, 2.6-6.7); HPV2: 3.9 (95% CI, 1.1-6.6)]., Conclusions: Risk of CIN2+ 8 years after a negative screen in the HPV cohorts was comparable with risk after 3 years in the cytology cohorts (the benchmark for acceptable risk)., Impact: These findings suggest that primary HPV screening intervals could be extended beyond the current 5-year recommendation, potentially reducing barriers to screening., (©2024 American Association for Cancer Research.)

We assessed whether contemporary immunosuppression agents were associated with cancer among kidney transplant recipients (KTR), and if this association varied by age and sex. We studied a retrospective province-wide cohort of primary KTR (1997-2016). Employing multivariable Cox models, we estimated associations of cumulative doses of prednisone, mycophenolate and tacrolimus administered over the past 10 years, lagged by 2 years, with the incidence of primary malignant neoplasms (PMN). We assessed interactions with age and sex. To assess the impact of exposure recency, we used weighted cumulative exposure (WCE) modeling. Among 1064 KTR, 108 (10.2%) developed PMN over median follow-up of 73 months (interquartile range: 32-120). Adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) of 0.96 (0.64-1.43), 1.34 (0.96-1.86), and 1.06 (0.88-1.29) were estimated for cumulative daily doses of prednisone (5 mg), mycophenolate (1000 mg), and tacrolimus (2 mg) administered continuously over the past 10 years, respectively. PMN risk associated with cumulative tacrolimus exposure was modified by age (interaction p = .035) and was more pronounced in 15-year and 30-year-old KTR (aHRs of 1.57 [1.08-2.28] and 1.31 [1.03-1.66], respectively) in comparison to older KTR. PMN risk increase associated with higher cumulative mycophenolate dose was more pronounced in females (aHR = 1.86 [1.15-3.00]) than in males (aHR = 1.16 [0.74-1.81]; interaction p = .131). WCE analyses suggested increased PMN risk the higher the mycophenolate doses taken 5-10 years ago. A trend toward increased PMN risk with long-term mycophenolate exposure, particularly in females, and more pronounced risk with long-term tacrolimus exposure in younger KTR, identify opportunities for tailored immunosuppression to mitigate cancer risk., (© 2024 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)

Given low seroconversion rates following human papillomavirus (HPV) infection, fixed external cutoffs may lead to errors in estimating HPV seroprevalence. We evaluated finite mixture modeling (FMM) and group-based trajectory modeling (GBTM) among unvaccinated, sexually active, HPV-exposed women to determine study-specific HPV16 and HPV18 seropositivity thresholds. We included 399 women (aged 18-24 years) enrolled in the HPV Infection and Transmission Among Couples Through Heterosexual Activity (HITCH) cohort study between 2005 and 2011 in Montreal, Canada. Participants' blood samples from up to six visits spanning 2 years were tested by multiplex serology for antibodies [median fluorescence intensity (MFI)] specific to bacterially expressed HPV16 and HPV18 L1 glutathione S-transferase fusion proteins. We applied FMM and GBTM to baseline and longitudinal antibody titer measurements, respectively, to define HPV type-specific seronegative and seropositive distributions. Study-specific thresholds were generated as five standard deviations above the mean seronegative antibody titers, mimicking cutoffs (HPV16: 422 MFI; HPV18: 394 MFI) derived from an external population of sexually inactive, HPV DNA-negative Korean women (aged 15-29 years). Agreement (kappa) of study-specific thresholds was evaluated against external cutoffs. Seroprevalence estimates using FMM (HPV16: 27.5%-43.2%; HPV18: 21.7%-49.5%) and GBTM (HPV16: 11.8%-11.8%; HPV18: 9.9%-13.4%) thresholds exceeded those of external cutoffs (HPV: 10.2%; HPV18: 9.7%). FMM thresholds showed slight-to-moderate agreement with external cutoffs (HPV16: 0.26%-0.46%; HPV18: 0.20%-0.56%), while GBTM thresholds exhibited high agreement (HPV16: 0.92%-0.92%; HPV18: 0.82%-0.99%). Kappa values suggest that GBTM, used for longitudinal serological data, and otherwise FMM, for cross-sectional data, are robust methods for determining the HPV serostatus without prior classification rules.IMPORTANCEWhile human papillomavirus (HPV) seropositivity has been employed as an epidemiologic determinant of the natural history of genital HPV infections, only a fraction of women incidentally infected with HPV respond by developing significant antibody levels. HPV seropositivity is often determined by a dichotomous fixed cutoff based on the seroreactivity of an external population of women presumed as seronegative, given the lack of evidence of HPV exposure. However, considering the variable nature of seroreactivity upon HPV infection, which arguably varies across populations, such externally defined cutoffs may lack specificity to the population of interest, causing inappropriate assessment of HPV seroprevalence and related epidemiologic uses of that information. This study demonstrates that finite mixture modeling (FMM) and group-based trajectory modeling (GBTM) can be used to independently estimate seroprevalence or serve as the basis for defining study-specific seropositivity thresholds without requiring prior subjective assumptions, consequently providing a more apt internally valid discrimination of seropositive from seronegative individuals., Competing Interests: E.L.F. has served as an occasional advisor to companies involved with human papillomavirus (HPV) diagnostics (Roche, BD, Qiagen, and Gen-Probe) and HPV vaccines (Merck and GSK). His institution has received unconditional grants from Merck in aid of investigator-initiated studies. M.Z. and E.L.F. hold a patent related to the discovery "DNA methylation markers for early detection of cervical cancer", registered at the Office of Innovation and Partnerships, McGill University, Montreal, Quebec, Canada (October 2018). F.C. has received grants or free reagents through his institution from Merck Sharp and Dohme, Becton Dickinson and Roche, as well as honoraria from Merck and Roche for lectures on HPV. T.W. serves on advisory boards for MSD (Merck) Sharp & Dohme. All other authors report no potential conflicts of interest. None of the work presented in this manuscript was paid for or influenced by any of the aforementioned companies.

The cervicovaginal microbiome may contribute to human papillomavirus (HPV)-associated cervical carcinogenesis, but studies have been limited by low-resolution analysis methods. Using a high-resolution bioinformatics pipeline, we evaluated the relationship of the cervicovaginal microbiome with HPV and cervical intraepithelial neoplasia (CIN). The cervicovaginal microbiome of 186 women was characterized by sequencing 16S rRNA regions (V3-V4 and V5-V6) and annotated with the high-resolution ANCHOR pipeline. Samples were genotyped for HPV using the Roche-Cobas 4800 assay. We fitted logistic regression models using stepwise forward selection to select species (presence/absence) as correlates of CIN1+ and constructed a linear microbiome-based score using the regression coefficients. An HPV-based score was calculated from a separate logistic regression model to detect CIN1+ . Receiver operating characteristic curve analyses were performed; the area under the curve (AUC) and 95% confidence intervals (CI) were compared between scores. Overall, 66.7% of participants were HPV-positive. 77 unique species were identified: 8 using V3-V4, 48 using V5-V6, and 21 shared. Twelve species were retained via stepwise selection. The AUCs for the microbiome-, and HPV-based scores were 0.7656 (95% CI 0.6885-0.8426), and 0.7529 (95% CI 0.6855-0.8204), respectively. Bacterial species may be involved in cervical carcinogenesis as the microbiome- and HPV-based scores performed similarly for CIN1+ detection., (© 2024 The Author(s). Journal of Medical Virology published by Wiley Periodicals LLC.)

At the 2023 EUROGIN workshop scientific basis for strategies to accelerate the elimination of cervical cancer and its causative agent, human papillomavirus (HPV) were reviewed. Although some countries have reached key performance indicators toward elimination (>90% of girls HPV vaccinated and >70% of women HPV screened), most are yet to reach these targets, implying a need for improved strategies. Gender-neutral vaccination, even with moderate vaccination coverage was highlighted as a strategy to achieve elimination more rapidly. It is more resilient against major disturbances in vaccination delivery, such as what happened during the coronavirus pandemic. Further, an analysis of ethical/legal issues indicated that female-restricted vaccination is problematic. Extended catch-up of vaccination with concomitant screening, and outreach to vulnerable groups were highlighted. Although birth cohorts with high coverage of HPV vaccination at school are protected against HPV, and HPVs have a very low reproductive rate in women above age 35, adult women below age 30 have inadequate direct protection. In addition to herd protection from gender-neutral vaccination, this group can be protected by offering concomitant catch-up HPV vaccination and HPV screening. Furthermore, hepatitis B vaccination experiences indicate that elimination cannot be achieved without prioritizing vulnerable/migrant populations. The long-lasting durability of vaccination-induced antibody responses suggests prolonged protection with HPV vaccines when adequately administrated. Finally, cost-effectiveness modelling suggests that high-coverage HPV vaccination in multiple population segments will be resource-saving due to reduced need for screening. In summary, the workshop found that strategically optimal deployment of vaccination will accelerate elimination of HPV and cervical cancer., (© 2024 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)

Previous research has shown that women's use of a carrageenan gel reduces the risk of acquiring genital human papillomavirus (HPV) infections but does not help to clear existing ones. Although gel use may not result in complete clearance, it may decrease the viral load of HPV infections. We tested this hypothesis in the Carrageenan-gel Against Transmission of Cervical Human papillomavirus (CATCH) randomized controlled trial. Participants of the CATCH study were selected for viral load testing if they had completed the first four study visits and tested positive for HPV42 or HPV51 in at least one of these visits. HPV42 and HPV51 were chosen as they were among the most abundant low- and high-risk types, respectively, in the study sample. We measured viral load with a type-specific real-time polymerase chain reaction. Results were displayed using summary statistics. Of 461 enrolled participants, 39 were included in the HPV42 analysis set and 56 in the HPV51 analysis set. The median time between visits 1 and 4 was 3.7 months. The viral load (copies/cell) of HPV42 ranged from <0.001 to 13 434.1, and that of HPV51 from <0.001 to 967.1. The net median change in HPV42 viral load over all four visits was -1.04 copies/cell in the carrageenan and -147 copies/cell in the placebo arm (Wilcoxon rank sum test, p = 0.26). There was no net median change in HPV51 viral load over all four visits in either arm (p = 0.45). The use of a carrageenan-based gel is unlikely to reduce the viral load of HPVs 42 or 51., (© 2024 The Authors. Journal of Medical Virology published by Wiley Periodicals LLC.)

Little is known about the protection conferred by antibodies from natural human papillomavirus (HPV) infection. Our objective was to evaluate the association between HPV16 seroreactivity and HPV16 redetection, newly detected HPV infections, and loss of HPV DNA detection during follow-up. We analyzed data from 2462 unvaccinated Brazilian women. HPV16 IgG and neutralizing antibodies at baseline were assessed by enzyme-linked immunosorbent assay (n = 1975) and by the pseudovirus-based papillomavirus neutralization assay (n = 487). HPV detection, genotyping, and viral load were assessed by PCR-based methods. The associations were analyzed by Cox proportional hazards models. We observed a positive association between HPV16 IgG seroreactivity and redetection of HPV16 infections. Age-adjusted hazard ratios (HR) with 95% confidence intervals (CI) ranged from 2.45 (1.04-5.74) to 5.10 (1.37-19.00). Positive associations were also observed between HPV16 IgG antibodies and (1) newly detected HPV infections by genotypes unrelated to HPV16 (age-adjusted HR [95% CI] = 1.32 [1.08-1.2]) and (2) loss of detection of HPV infections by genotypes unrelated to HPV16 (age-adjusted HR [95% CI] = 1.24 [1.03-1.50]). Naturally developed HPV16 antibodies do not prevent recurrent HPV infections. Overall HPV16 IgG and neutralizing antibodies seem to be serological markers for latent or past infections., (© 2024 Wiley Periodicals LLC.)