SARS-CoV-2-reactive antibody waning, booster effect and breakthrough SARS-CoV-2 infection in hematopoietic stem cell transplant and cell therapy recipients at one year after vaccination.

The kinetics of SARS-CoV-2 reactive IgG antibodies after full vaccination and booster in allogeneic and autologous stem cell transplantation (allo-HSCT, ASCT) and chimeric antigen receptor T-cell therapy (CAR-T) are of utmost importance for estimating risk of infection. A prospective multicenter registry-based cohort study, conducted from December 2020 to July 2022 was used to analyze antibody waning over time, booster effect and the relationship of antibody response and breakthrough infection in 572 recipients (429 allo-HSCT, 121 ASCT and 22 CAR-T cell therapy). A significant decline in antibody titers was observed at 3 and 6 months after full vaccination in recipients without pre-vaccine SARS-CoV-2 infection, whereas recipients infected prior to vaccination showed higher and stable antibody titers over time. In poor responders, a booster dose was able to increase antibody titers in 83% of allo-HSCT and 58% of ASCT recipients but not in CART-T cell recipients [0%] (p < 0.01). One-year cumulative incidence of breakthrough infection was 15%, similar among cell therapy procedures. Immunosuppressive drugs at the time of vaccination [hazard ratio (HR) 1.81, p = 0.0028] and reduced intensity conditioning (HR 0.49, p = 0.011) were identified as the only conditions associated with different risk of breakthrough infection in allo-HSCT recipients. Antibody titers were associated with breakthrough infection and disease severity. No death was observed among the 72 breakthrough infections. Antibody level decay after the first two vaccine doses was common except in recipients with pre-vaccination SARS-CoV-2 infection. Poorly responding allo-HSCT recipients showed a response advantage with the booster as compared to ASCT and, especially, the null response found in CAR-T cell recipients. Antibody titers were positively correlated with the risk of breakthrough SARS-CoV-2 infection which was mainly driven by the immunosuppression status.

One-year breakthrough SARS-CoV-2 infection and correlates of protection in fully vaccinated hematological patients.

The long-term clinical efficacy of SARS-CoV-2 vaccines according to antibody response in immunosuppressed patients such as hematological patients has been little explored. A prospective multicenter registry-based cohort study conducted from December 2020 to July 2022 by the Spanish Transplant and Cell Therapy group, was used to analyze the relationship of antibody response over time after full vaccination (at 3-6 weeks, 3, 6 and 12 months) (2 doses) and of booster doses with breakthrough SARS-CoV-2 infection in 1551 patients with hematological disorders. At a median follow-up of 388 days after complete immunization, 266 out of 1551 (17%) developed breakthrough SARS-CoV-2 infection at median of 86 days (range 7-391) after full vaccination. The cumulative incidence was 18% [95% confidence interval (C.I.), 16-20%]. Multivariate analysis identified higher incidence in chronic lymphocytic leukemia patients (29%) and with the use of corticosteroids (24.5%), whereas female sex (15.5%) and more than 1 year after last therapy (14%) were associated with a lower incidence (p < 0.05 for all comparisons). Median antibody titers at different time points were significantly lower in breakthrough cases than in non-cases. A serological titer cut-off of 250 BAU/mL was predictive of breakthrough infection and its severity. SARS-CoV-2 infection-related mortality was encouragingly low (1.9%) in our series. Our study describes the incidence of and risk factors for COVID-19 breakthrough infections during the initial vaccination and booster doses in the 2021 to mid-2022 period. The level of antibody titers at any time after 2-dose vaccination is strongly linked with protection against both breakthrough infection and severe disease, even with the Omicron SARS-CoV-2 variant.

Detecting anal human papillomavirus infection in men who have sex with men living with HIV: implications of assay variability.

BACKGROUND: Incidence of anal cancer (AC) caused by persistent human papillomavirus (HPV) infection has risen in the last years in men who have sex with men (MSM) living with HIV. There is consensus that this population should be screened for anal precancerous lesions, but the role of HPV DNA testing in AC screening programmes is still under debate. OBJECTIVES: This study employed two molecular test to detect anal HPV DNA and compared assay performance and prognostic value for the diagnosis of histology proven high-grade intraepithelial anal lesions. METHODS: MSM living with HIV attended their regular check-up visits consisting of detection of anal HPV infection, anal cytology, digital anorectal examination and high resolution anoscopy. HPV DNA was detected using Hybrid Capture 2 High-Risk test (HC2, total assay) and LINEAR ARRAY HPV Genotyping Test (LA, type-specific assay) RESULTS: Among 274 participant, prevalence of HPV DNA was 48.5% by HC2 and 89.4% by LA. HPV16 (30.6%) and HPV6 (19.6%) were the most common genotypes identified. Prevalence of multiple HPV infections was 56.2%. Agreement between HPV DNA assays was 75.2% (κ=0.51; 95% CI 0.42 to 0.60). Total HPV detection demonstrated high sensitivity (90%; 95% CI 68.3 to 98.8) and moderate specificity (58.4%; 95% CI 50.2 to 66.3), while type-specific HPV16/18 genotyping provided an increase in specificity and showed the highest area under the curve (0.81; 95% CI 0.74 to 0.89) and Youden's index (0.63). CONCLUSIONS: Both methodologies identified a high prevalence of anal HPV infection and multiple HPV infections in MSM living with HIV, showing a moderate overall agreement between them. Either total HPV detection or type-specific HPV16/18 detection together with a threshold ≥atypical squamous cells of undetermined significance for abnormal cytology showed an acceptable diagnostic accuracy.

Applicability of probabilistic graphical models for early detection of SARS-CoV-2 reactive antibodies after SARS-CoV-2 vaccination in hematological patients.

Prior studies of antibody response after full SARS-CoV-2 vaccination in hematological patients have confirmed lower antibody levels compared to the general population. Serological response in hematological patients varies widely according to the disease type and its status, and the treatment given and its timing with respect to vaccination. Through probabilistic machine learning graphical models, we estimated the conditional probabilities of having detectable anti-SARS-CoV-2 antibodies at 3-6 weeks after SARS-CoV-2 vaccination in a large cohort of patients with several hematological diseases (n= 1166). Most patients received mRNA-based vaccines (97%), mainly Moderna® mRNA-1273 (74%) followed by Pfizer-BioNTech® BNT162b2 (23%). The overall antibody detection rate at 3 to 6 weeks after full vaccination for the entire cohort was 79%. Variables such as type of disease, timing of anti-CD20 monoclonal antibody therapy, age, corticosteroids therapy, vaccine type, disease status, or prior infection with SARS-CoV-2 are among the most relevant conditions influencing SARS-CoV-2-IgG-reactive antibody detection. A lower probability of having detectable antibodies was observed in patients with B-cell non-Hodgkin's lymphoma treated with anti-CD20 monoclonal antibodies within 6 months before vaccination (29.32%), whereas the highest probability was observed in younger patients with chronic myeloproliferative neoplasms (99.53%). The Moderna® mRNA-1273 compound provided higher probabilities of antibody detection in all scenarios. This study depicts conditional probabilities of having detectable antibodies in the whole cohort and in specific scenarios such as B cell NHL, CLL, MM, and cMPN that may impact humoral responses. These results could be useful to focus on additional preventive and/or monitoring interventions in these highly immunosuppressed hematological patients.

SARS-CoV-2-reactive antibody detection after SARS-CoV-2 vaccination in hematopoietic stem cell transplant recipients: Prospective survey from the Spanish Hematopoietic Stem Cell Transplantation and Cell Therapy Group.

This is a multicenter prospective observational study that included a large cohort (n = 397) of allogeneic (allo-HSCT; (n = 311) and autologous (ASCT) hematopoietic stem cell transplant (n = 86) recipients who were monitored for antibody detection within 3-6 weeks after complete severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination from February 1, 2021, to July 20, 2021. Most patients (n = 387, 97.4%) received mRNA-based vaccines. Most of the recipients (93%) were vaccinated more than 1 year after transplant. Detectable SARS-CoV-2-reactive antibodies were observed in 242 (78%) of allo-HSCT and in 73 (85%) of ASCT recipients. Multivariate analysis in allo-HSCT recipients identified lymphopenia < 1 × 109 /ml (odds ratio [OR] 0.33, 95% confidence interval [95% CI] 0.16-0.69, p = .003), active graft versus host disease (GvHD; OR 0.51, 95% CI 0.27-0.98, p = .04) and vaccination within the first year of transplant (OR 0.3, 95% CI 0.15-0.9, p = .04) associated with lower antibody detection whereas. In ASCT, non-Hodgkin's lymphoma (NHL; OR 0.09, 95% CI 0.02-0.44, p = .003) and active corticosteroid therapy (OR 0.2, 95% CI 0.02-0.87, p = .03) were associated with lower detection rate. We report an encouraging rate of SARS-CoV-2-reactive antibodies detection in these severe immunocompromised patients. Lymphopenia, GvHD, the timing of vaccine, and NHL and corticosteroids therapy should be considered in allo-HSCT and ASCT, respectively, to identify candidates for SARS-CoV-2 antibodies monitoring.

Short- and long-term mortality in patients with left-sided infective endocarditis not undergoing surgery despite indication.

INTRODUCTION AND OBJECTIVES: In infective endocarditis (IE), decisions on surgical interventions are challenging and a high percentage of patients with surgical indication do not undergo these procedures. This study aimed to evaluate the short- and long-term prognosis of patients with surgical indication, comparing those who underwent surgery with those who did not. METHODS: We included 271 patients with left-sided IE treated at our institution from 2003 to 2018 and with an indication for surgery. There were 83 (31%) surgery-indicated not undergoing surgery patients with left-sided infective endocarditis (SINUS-LSIE). The primary outcome was all-cause death by day 60 and the secondary outcome was all-cause death from day 61 to 3 years of follow-up. Multivariable Cox regression and propensity score matching were used for the analysis. RESULTS: At the 60-day follow-up, 40 (21.3%) surgically-treated patients and 53 (63.9%) SINUS-LSIE patients died (P <.001). Risk of 60-day mortality was higher in SINUS-LSIE patients (HR, 3.59; 95%CI, 2.16-5.96; P <.001). Other independent predictors of the primary endpoint were unknown etiology, heart failure, atrioventricular block, and shock. From day 61 to the 3-year follow-up, there were no significant differences in the risk of death between surgically-treated and SINUS-LSIE patients (HR, 1.89; 95%CI, 0.68-5.19; P=.220). Results were consistent after propensity score matching. Independent variables associated with the secondary endpoint were previous IE, diabetes mellitus, and Charlson index. CONCLUSIONS: Two-thirds of SINUS-LSIE patients died within 60 days. Among survivors, the long-term mortality depends more on host conditions than on the treatment received during admission.

Evolutive echocardiographic changes in cardiac amyloidosis: Look at the whole picture.

Doppler echocardiogram provides not only structural information about heart chambers, valves and pericardium but also contributes to functional assessment. A unique feature of this assessment is its variability, not only due to heart disease course but also related to extracardiac conditions. We present a case of primary amyloidosis with two atypical characteristics: left ventricular outflow obstruction and low-grade diastolic dysfunction. Nevertheless, a more typical picture of cardiac amyloidosis was observed in the evolution of the disease coinciding with a second cardiac stressor, emphasizing the necessity of not focusing our attention exclusively to the heart.

Risk factors for diabetic retinopathy in people with Type 2 diabetes: A case-control study in a UK primary care setting.

AIM: To identify risk factors of diabetic retinopathy (DR) among people with Type 2 diabetes mellitus in UK primary care. METHODS: A case-control study nested in a cohort of incident Type 2 diabetes identified in The Health Improvement Network database from 2000 to 2007. Cases were people with DR (N=7735) and controls were a DR-free sample (N=9395). No age restrictions were applied. Adjusted odds ratios and 95% CIs were estimated. RESULTS: 21% of DR cases were identified during the first semester after Type 2 diabetes diagnosis. After controlling for delay on the Type 2 diabetes diagnosis, the DR risk increased with the duration of diabetes. DR increased with a mean systolic BP ≥150mmHg (1.18; 1.10-1.27), high alcohol consumption (1.34; 1.11-1.61), glycated haemoglobin (≥75 to <86: 1.14; 1.00-1.31; ≥86 to <97mmol/mol: 1.25; 1.07-1.45; ≥97mmol/mol: 1.21; 1.07-1.37), microalbuminuria (1.16; 1.06-1.27), and retinal vein occlusion (2.47; 1.67-3.66). Glaucoma and retinal arterial occlusion showed an OR of 0.71 (0.60-0.84) and 0.63 (0.40-1.01), respectively. HDL ≥1.55mmol/l (0.88; 0.80-0.98), high triglycerides (2.3-5.6mmol/l: 0.90; 0.82-0.99; >5.6mmol/l: 0.85; 0.64-1.13) or smoking (0.89; 0.81-0.97) had a slightly reduced DR risk. Users of hypoglycaemic agents had an increased DR risk. CONCLUSION: Some DR cases were identified near the diabetes diagnosis date suggesting that a delayed diabetes diagnosis is still common. Glaucoma, retinal arterial occlusion and high HDL levels were inversely associated with DR, while retinal vein occlusion, alcohol and other well-known risk factors were positively associated.

Randomized trial of a multidisciplinary lifestyle intervention in HIV-infected patients with moderate-high cardiovascular risk.

OBJECTIVE: To assess the impact of a multidisciplinary lifestyle intervention on cardiovascular risk and carotid intima-media thickness (c-IMT) in HIV-infected patients with Framingham scores (FS) > 10%. DESIGN: Randomized pilot study; follow-up 36 months. METHODS: Virologically suppressed adult HIV-1-infected patients with FS >10% were randomized 1:1 to the intervention group (multidisciplinary lifestyle intervention) or control group (routine care). At baseline and months 12, 24 and 36, lipid parameters were analyzed and carotid ultrasound was performed to determine c-IMT and presence of plaques. Biomarkers were measured at baseline and month 36. The primary endpoints were lipid and FS changes at 36 months. RESULTS: Fifty-four patients were included, 27 in each arm. Median age was 50.5 years, all patients but one were men, and FS was 16.5%. Relative to controls, total and LDL cholesterol had significantly decreased in the intervention group at 24 months (p = 0.039, p = 0.011, respectively). However, no differences between groups were found at month 36 in lipid variables, neither in FS. Tobacco use decreased in the intervention group (p = 0.031). At baseline, 74.5% of patients had subclinical atherosclerosis, and at month 36, we observed a progression in c-IMT that was greater in the intervention group (p = 0.030). D-dimer increased (p = 0.027) and soluble intercellular adhesion molecule-1 decreased (p = 0.018) at 36 months. CONCLUSIONS: In this cohort of HIV-infected patients with FS>10% and a high percentage of subclinical atherosclerosis, a multidisciplinary lifestyle intervention resulted in a slight improvement in some cardiovascular risk factors and the FS during the first 2 years, but did not prevent c-IMT progression.

Comparative effectiveness of immediate antiretroviral therapy versus CD4-based initiation in HIV-positive individuals in high-income countries: observational cohort study.

BACKGROUND: Recommendations have differed nationally and internationally with respect to the best time to start antiretroviral therapy (ART). We compared effectiveness of three strategies for initiation of ART in high-income countries for HIV-positive individuals who do not have AIDS: immediate initiation, initiation at a CD4 count less than 500 cells per µL, and initiation at a CD4 count less than 350 cells per µL. METHODS: We used data from the HIV-CAUSAL Collaboration of cohort studies in Europe and the USA. We included 55,826 individuals aged 18 years or older who were diagnosed with HIV-1 infection between January, 2000, and September, 2013, had not started ART, did not have AIDS, and had CD4 count and HIV-RNA viral load measurements within 6 months of HIV diagnosis. We estimated relative risks of death and of death or AIDS-defining illness, mean survival time, the proportion of individuals in need of ART, and the proportion of individuals with HIV-RNA viral load less than 50 copies per mL, as would have been recorded under each ART initiation strategy after 7 years of HIV diagnosis. We used the parametric g-formula to adjust for baseline and time-varying confounders. FINDINGS: Median CD4 count at diagnosis of HIV infection was 376 cells per µL (IQR 222-551). Compared with immediate initiation, the estimated relative risk of death was 1·02 (95% CI 1·01-1·02) when ART was started at a CD4 count less than 500 cells per µL, and 1·06 (1·04-1·08) with initiation at a CD4 count less than 350 cells per µL. Corresponding estimates for death or AIDS-defining illness were 1·06 (1·06-1·07) and 1·20 (1·17-1·23), respectively. Compared with immediate initiation, the mean survival time at 7 years with a strategy of initiation at a CD4 count less than 500 cells per µL was 2 days shorter (95% CI 1-2) and at a CD4 count less than 350 cells per µL was 5 days shorter (4-6). 7 years after diagnosis of HIV, 100%, 98·7% (95% CI 98·6-98·7), and 92·6% (92·2-92·9) of individuals would have been in need of ART with immediate initiation, initiation at a CD4 count less than 500 cells per µL, and initiation at a CD4 count less than 350 cells per µL, respectively. Corresponding proportions of individuals with HIV-RNA viral load less than 50 copies per mL at 7 years were 87·3% (87·3-88·6), 87·4% (87·4-88·6), and 83·8% (83·6-84·9). INTERPRETATION: The benefits of immediate initiation of ART, such as prolonged survival and AIDS-free survival and increased virological suppression, were small in this high-income setting with relatively low CD4 count at HIV diagnosis. The estimated beneficial effect on AIDS is less than in recently reported randomised trials. Increasing rates of HIV testing might be as important as a policy of early initiation of ART. FUNDING: National Institutes of Health.

[Mitral valve repair in the course of active infectious endocarditis. Study of four patients]. / Reparación valvular mitral en el curso de una endocarditis infecciosa activa. Estudio de cuatro pacientes.

BACKGROUND AND OBJECTIVE: Mitral valve (MV) repair is the preferred surgical treatment for degenerative mitral regurgitation (MR). However, questions remain about the efficacy of MV repair when performed for MR caused by infective endocarditis (IE), particularly during its active phase. Although several observational studies have suggested the superiority of MV repair over replacement in patients undergoing surgery for IE, many centres are still opting for valve replacement because of its technical feasibility and reproducibility. In the following document we expose the experience of our hospital. PATIENTS AND METHOD: We present a series of 4 patients who recently underwent surgery for IE during its active phase. Epidemiological and clinical characteristics are discussed. RESULTS: All patients underwent different MV repair techniques. No relapse or reinfection has been reported. All patients present MR grades 0 or iI/ivIV at follow up. CONCLUSIONS: Even during the active phase of IE, MV repair is a feasible technique with good postoperatory results.

Human papillomavirus infection in HIV-1 infected women in Catalonia (Spain): implications for prevention of cervical cancer.

BACKGROUND: High-risk human Papillomavirus infection is a necessary factor for cervical squamous intraepithelial lesions and invasive cervical cancer. In HIV-1-infected women, HPV infection is more prevalent and a higher risk of cervical cancer has been identified. We aimed to calculate the prevalence of infection by HR-HPV, determine the factors associated with this infection and abnormal cytology findings and to describe the history of cervical cancer screening in HIV-1-infected women. METHODS: We enrolled 479 HIV-1-infected women from the PISCIS cohort. Each patient underwent a gynecological check-up, PAP smear, HPV AND Hybrid capture, HPV genotyping, and colposcopy and biopsy, if necessary. We applied questionnaires to obtain information on sociodemographic, behavioral, clinical, and cervical screening variables. We present a cross-sectional analysis. RESULTS: Median age was 42 years. The prevalence of HR-HPV infection was 33.2% and that of high-grade squamous intraepithelial lesions (HSIL) was 3.8%. The most common genotypes were 16(23%), 53(20.3%), and 52(16.2%). The factor associated with HR-HPV infection was age <30 years (odds ratio[OR],2.5; 95%confidence interval[CI],1.1-5.6). The factors associated with the presence of HSIL or low-grade squamous intraepithelial lesions (LSIL) were CD4T-lymphocyte count <200 cells/mm(3) versus >500 cells/mm(3) (OR,8.4; 95%CI,3.7-19.2), HIV-1 viral load >10,000 copies/mL versus <400 copies/mL (OR,2.1; 95%CI,1.0-4.4), and use of oral contraceptives (OR,2.0; 95%CI,1.0-3.9). Sixty percent of HIV-1-infected women had had one Pap smear within the last 2 years. CONCLUSIONS: The high prevalence of HPV infection and cervical lesions in the HIV-1-infected population in Catalonia, as well as the low coverage and frequency of screening in this group, means that better preventive efforts are necessary and should include vaccination against HPV, better accessibility to screening programs, training of health care professionals, and specific health education for HIV-1-infected women.

Cervical human papillomavirus prevalence in 5 continents: meta-analysis of 1 million women with normal cytological findings.

BACKGROUND: Baseline information on human papillomavirus (HPV) prevalence and type distribution is highly desirable to evaluate the impact of prophylactic HPV vaccines in the near future. METHODS: A meta-analysis was performed of studies published between 1995 and 2009 that used polymerase chain reaction or Hybrid Capture 2 for HPV detection in women with normal cytological findings. RESULTS: The analysis included 194 studies comprising 1,016,719 women with normal cytological findings. The estimated global HPV prevalence was 11.7% (95% confidence interval, 11.6%-11.7%). Sub-Saharan Africa (24.0%), Eastern Europe (21.4%), and Latin America (16.1%) showed the highest prevalences. Age-specific HPV distribution presented with a first peak at younger ages (<25 years) and, in the Americas and Africa, a rebound at older ages (≥45 years). Among the women with type-specific HPV data (n = 215,568), the 5 most common types worldwide were HPV-16 (3.2%), HPV-18 (1.4%), HPV-52 (0.9%), HPV-31 (0.8%), and HPV-58 (0.7%). CONCLUSIONS: Although the prevalence of HPV in women with normal cytological findings is high and variable across world regions, HPV types 16, 18, 31, 52, and 58 are consistently found among the 10 most common types in all of them. These results represent the most comprehensive assessment of HPV burden among women with normal cytological findings in the pre-HPV vaccination era worldwide.

Critical stenosis of pulmonary homograft induced by Surgicel in Ross procedure.

Surgicel is bio-absorbable cellulose used to control bleeding. A 52-year-old woman with severe aortic valve regurgitation and aortic dilatation underwent the Ross procedure and ascending aortic replacement. After 48 h, she suffered severe hypotension and hypoxemia. Arteriography revealed stenosis of the pulmonary homograft, which required urgent re-intervention. Extrinsic compression of the posterior wall of the homograft due to Surgicel was found.

Immunization with a DNA vaccine candidate in chronic hepatitis C patients is safe, well tolerated and does not impair immune response induction after anti-hepatitis B vaccination.

BACKGROUND: In the present study, we evaluated the safety of CIGB-230, a novel vaccine candidate based on the mixture of a plasmid for DNA immunization, expressing hepatitis C virus (HCV) structural antigens, with a recombinant HCV Core protein. METHODS: Fifteen HCV chronically-infected volunteers with detectable levels of HCV RNA genotype 1b, who were nonresponders to previous treatment with interferon plus ribavirin, were intramuscularly injected with CIGB-230 on weeks 0, 4, 8, 12, 16 and 20. Individuals were also immunized at weeks 28, 32 and 36 with a recombinant vaccine against hepatitis B. Adverse events were recorded and analyzed. Blood samples were taken every 4 weeks up to month 12 for hematological, biochemical, virological and immunological analysis. RESULTS: All patients completed the treatment with CIGB-230. Adverse events were only slight (83.6%) or moderate (16.4%). No significant differences in hematological and biochemical parameters, including serum aminotransferases, were detected between the baseline and post-treatment state. Induction of a CD4+ T lymphocyte response against a particular region in HCV E1, spanning amino acids 230-312 in HCV polyprotein, was detected in 42.8% of patients during treatment with CIGB-230. The ability of T cells to proliferate in response to mitogenic stimulation was not weakened. Most individuals (78.6%) were seroprotected after anti-hepatitis B vaccination and 42.8% were hyper-responders (antibody titers > 100 UI/ml). No anti-mitochondrial, anti-nuclear and anti-extractable nuclear antigen antibodies were generated during immunization with CIGB-230. CONCLUSIONS: Vaccination with CIGB-230 in HCV chronically-infected individuals was safe, well tolerated and did not impair the ability to respond to non-HCV antigens.

Left atrial intramural haematoma associated with mitral annular calcification.

Left atrial wall haematoma is a very uncommon entity, associated mainly to cardiac surgery, interventional procedures, or trauma. Spontaneous cases are supposed to be associated with left atrial wall pathology. We present a case of a 53-year-old male who was admitted for prolonged chest pain, with transthoracic and transesophagic echocardiography documentation of a left atrial mass in close proximity to a mitral annular calcification. Tissue characterization with cardiac magnetic resonance suggested the aetiology of the mass, which was confirmed histologically.

Cervical cancer screening programs in Latin America and the Caribbean.

Latin America and the Caribbean (LAC) have a significant burden of cervical cancer. Prophylactic human papillomavirus (HPV) vaccines are an opportunity for primary prevention and new screening methods, such as new HPV DNA testing, are promising alternatives to cytology screening that should be analyzed in the context of regional preventive programs. Cytology-based screening programs have not fulfilled their expectations and coverage does not sufficiently explain the lack of impact on screening in LAC. While improved evaluation of screening programs is necessary to increase the impact of screening on the reduction of incidence and mortality, other programmatic aspects will need to be addressed such as follow-up of positive tests and quality control. The implementation of new technologies might enhance screening performance and reduce mortality in the region. The characteristics, performance and impact of cervical cancer screening programs in LAC are reviewed in this article.

Epidemiology of human papillomavirus infection in men, cancers other than cervical and benign conditions.

Human papillomavirus (HPV) infection is commonly found in the genital tract of men and women with or without any clinical lesion. The association of HPV DNA with several different ano-genital cancers other than cervical has been reported for the vulva, vagina, anus and penis. HPV DNA has also been identified in head and neck cancers in the oral cavity, the oropharynx and the larynx in both sexes. In men, 80-85% of anal cancers and close to 50% of penile cancers are associated with HPV infection. In women, HPV DNA is prevalent in 36-40% vulvar cancer cases and close to 90% of vaginal cancers. There is limited data available on the natural history and HPV-related diseases in the genital tract in men, although studies are ongoing. Efficacy of HPV vaccines in the prevention of HPV infection and disease among men also remains unknown. Among HPV DNA positive ano-genital cancer cases, HPV-16 is the most frequently found followed distantly by HPV-18. In benign HPV-related diseases such as genital warts or recurrent respiratory papillomatosis HPV-6 and 11, the two most frequent non-oncogenic types, are the predominant types detected. Oncogenic types are rarely detected. In this article we summarize and review studies describing the natural history of HPV infections among men and its impact on HPV related disease in women. We summarize the evidence linking HPV in the epidemiology and etiology of cancers of the vulva, vagina, anus and oropharynx and present recent estimates of the burden of and HPV type distribution in genital warts and in cases of HPV infection of the airways.