Low-risk Genotypes Research Articles

HPV and Covid-19 Era: effects of nonpharmaceutical interventions on HPV transmission

ABSTRACT Human papillomavirus (HPV) is considered the commonest viral cause of sexually transmitted infections. The impact of social distance measures due to Covid-19 pandemic on HPV spread is unknown. Therefore, this study has analyzed the seven-year trend of HPV prevalence in all patients tested for HPV DNA at the Microbiology and Virology Unit at Bari Policlinico. Moreover, the HPV prevalence in 2020 has been compared with the previous year ones in order to evaluate the consequences of lockdown and social distancing measures on transmission risks. From 2013 to 2020, we retrospectively analyzed 64 anal swabs, 418 biopsies, 5925 cervical-vaginal swabs, 512 cervical swabs, 104 gland swabs, 154 oral swabs, 21 seminal fluids and 503 urethral swabs. HPV DNA detection was initially performed using nested-polymerase chain reaction (PCR) and subsequently multiplex real-time PCR assay. All statistical tests were carried out by the open-source environment R 4.0.3 (R Core Team). The data were analyzed according to yearly positivity rates, temporal trend and prevalence of HPV genotypes (HPV-6, HPV-11, HPV-16, HPV-18, high risk and low risk) by age category and sex. The number of patients increased steadily from 2016 to 2019 and then decreased in 2020. There were significant differences in prevalence between females and males for HPV-6 (6.16% in females Vs 30.80% in males), HPV-11 (0.82% Vs 7.16%) and HPV-16 (7.77% Vs 5.01%). The prevalence of HPV-6 and HPV-11 significantly increased in 2020 compared to 2013–2019 (15.72% Vs 8.52 and 3.18% Vs 1.44%). On the contrary, the overall prevalence of HPV DNA remained constant in 2020 (52.84% Vs 48.44%). Over time, the prevalence of HPV DNA (Coefficient=-0.020, p-value = 0.036) and particularly high-risk genotypes (Coefficient=-0.030, p-value = 0.005) decreased in females, while low-risk genotypes (Coefficient = 0.141, p-value= < 0.001) and the prevalence of HPV DNA increased in males (Coefficient = 0.068, p-value = 0.008). During the pandemic, the number of screened patients declined, although HPV prevalence compared to 2013–2019 remained constant or increased as in the case of low-risk genotypes. It can be assumed that the reduction of the screening coverage favored the emerging of the more symptomatic low-risk infections. In conclusion, nonpharmaceutical interventions due to Covid-19 pandemic did not reduce the risk of HPV infection but it likely caused a decrease in access to health services resulting in an increased risk of undiagnosed HPV.

Does infection of multiple HPV high-risk genotypes carry a higher malignant potential than a single genotype in uterine cervix? A retrospective study.

86 Background: The high-risk genotype of human papilloma virus (HPV) has been known as the most important carcinogen in uterine cervical carcinoma. It remains unclear that the infection with multiple high-risk genotypes carry a higher malignant potential risk compared with a single genotype in uterine cervix. Methods: This is a retrospective study of 695 patients underwent conization at Kyungpook National University Hospital in South Korea from 2012 to 2023. Participants were required to have undergone an HPV test by cervical swab within 12 months prior to the surgery. Patients with a negative result or a previous history of cancer were excluded. Additionally, patients older than 50 years were excluded to reduce bias. We included patients with the most common genotype in the cohort with only one high-risk genotype, and patients with multiple high-risk genotypes including the most common genotype. We categorized them based on pathologic results. Patients with HSIL, carcinoma in situ (CIS), invasive carcinoma were classified as ≥HSIL, while those with CIS, invasive carcinoma were classified as ≥CIS. The HPV test was performed using DNA microarray or real-time polymerase chain reaction, can detect 18 high-risk genotypes and 14 low-risk genotypes. The infection status of low-risk HPV and the vaccination for HPV were not considered in this study. The statistical analysis was conducted using SPSS (version 26). Results: A total of 146 patients younger than 50 years found to be infected with HPV high-risk genotype 16 or 16 with other high-risk genotypes. The HPV 16 single infection and multiple infection were found in 79 (54.1%), 67 (45.9%), respectively. Among patients with HPV 16 single infection, 61 (77.2%) were diagnosed with ≥HSIL and 45 (57.0%) were ≥CIS. In the HPV 16 multiple infection group, 56 (83.6%) were diagnosed with ≥HSIL and 34 (50.7%) were ≥CIS. There was no statistically significant correlation based on the HPV 16 single or multiple infection status for either ≥HSIL (HPV 16 single infection vs. multiple infection, odds ratio (OR)=0.666 [95% CI=0.289-1.531], p=0.407) or ≥CIS (HPV 16 single infection vs. multiple infection, OR=1.285 [95% CI=0.668-2.471], p=0.507). Conclusions: Among young women with only a single HPV high-risk genotype, the genotype 16 was the most common. Compared to the infection group with a single HPV high-risk 16 genotype, the malignant potential was not found to be significantly increased in the infection group with multiple HPV high-risk genotypes, including HPV genotype 16. [Table: see text]

Influence of sexually transmitted infections on the cervical cytological abnormalities among Iranian women: A cross-sectional study.

Sexually transmitted infections (STIs) are one of the world's most severe health challenges. The existence of STIs such as human papillomavirus (HPV) might cause cervical cell changes leading to cervical cancer. This study aims to assess the association of STIs with cervical cytological abnormalities and genital warts among women in northeastern Iran. This cross-sectional study was carried out on 190 women referred to the central laboratory of Academic Center for Education, Culture, and Research, Mashhad, Iran from March to July 2022. The presence of genital infections caused by Chlamydia trachomatis, Neisseria gonorrhoeae, Mycoplasma genitalium, and Herpes simplex viruses (1 and 2) were assessed using the real-time polymerase chain reaction method. HPV genital infection was detected based on the principles of reverse hybridization, and cellular changes in the cervix were examined by the liquid-based cytology technique. The mean age of participants was 35.33 8.9 yr. 34 different HPV genotypes were detected in all HPV-positive cases, and the most common genotype was low-risk HPV6. No significant association was found between STIs and cervical cytology abnormalities. The prevalence rates of sexually transmitted pathogens among HPV-positive and HPV-negative individuals were 10.9 and 1.6%, respectively. The frequency of genital warts was significantly higher in cases with multiple infections of high- and low-risk HPV genotypes. High percentages of the participants with non-HPV STIs and HPV infection had normal cervical cytology. It is advised to use STIs and HPV diagnostic tests along with cytology examinations for cervical cancer screening.

Evaluation of the Roche MagNA Pure 96 nucleic acid extraction platform for the SPF10 line probe assay system.

To evaluate the MagNA Pure 96 (MP96) nucleic acid extraction system as an alternative for cervical specimen processing for human papillomavirus (HPV) genotyping detection by reverse hybridization line probe assay (LiPA-25), compared to the well-established extraction system MagNA Pure LC 2.0 (MPLC). A total of 200 cervical samples preserved in ThinPrepCyt® solution were extracted by MP96 and MPLC, respectively, and then purified nucleic acids were amplified using the SPF10 PCR primer set. Amplification products were subjected to SPF10-DNA enzyme immunoassay (DEIA) and LiPA-25. The concordance between different extraction methods in this study was reflected in the comparison of the results of the DEIA and LiPA-25. Agreement of HPV-positive results (DEIA) was 97.5% (Kappa=0.932). Pair-wise analyses of either HPV grouping (any HPV genotypes, any high-risk HPV genotypes, any low-risk HPV genotypes, any nonavalent vaccine-targeted HPV, and any non-vaccine-targeted oncogenic HPV genotypes) identified >95% agreement (all Kappa>0.900). For the two extraction methods, there was no statistical difference (chi-square test: P=0.690) for single versus multiple genotypes, and concordant, compatible, and discordant genotypes were observed in 87.0%, 9.5%, and 3.5% of 200 samples, respectively. HPV genotyping results of the MPLC system and the MP96 system showed a high degree of concordance. Combined with the advantages of high-throughput and anti-contamination of MP96, the MP96 extraction system could be more suitable for the testing of samples in future studies.

An Alarming Evidence Of Increased HPV Infection In Cervical Smear In Iraqi Patients

Background: Cervical cancer is one of the common cancers among women worldwide, with increasing incidence. This study was designed to assess the role of cervical cytology in detecting the various cervical lesions predisposed to cervical cancer with the special emphasis on squamous intraepithelial lesions (SIL) and to predict the prevalence of these lesions and their association with Human papilloma virus (HPV). Patients and methods: This study enrolled 3500 women aged 17 years and above, presented with cervical lesions and attended for cytological evaluation of cervical smears. The data was retrieved from the archives of these patients for the period from January 2017 to December 2021. All results were classified according to Bethesda system (2014) and statistically analyzed. Results: the cytological examinations revealed that 91.7% of the submitted cases were negative for intraepithelial lesion or malignancy (NILM). Abnormal cellular changes were reported in 8.3% of the cases; Low-grade squamous intraepithelial lesion was the most common abnormality representing 4.7%, while High-grade squamous intraepithelial lesion constituted 0.5% of the total cases. A HPV-DNA test was done to 220 cases; 52 cases (23.6%) were positive, most of them (73%) were of low-risk genotypes while high risk genotypes were reported in 27% of the cases. Conclusion: the cervical squamous abnormality has formed a low prevalence rate while HPV-DNA test has been detected in a considerable proportion of Iraqi patients. This fact discloses alarming evidence of a growing problem in the population that needs to introduce a screening program for early diagnosis of precancerous cervical lesions.

#3155 APOL1 GENOTYPE IS A MAJOR DETERMINANT OF LUPUS NEPHRITIS SEVERITY IN PATIENTS OF AFRICAN ANCESTRY

Abstract Background and Aims Two polymorphisms of APOL1 gene, G1 and G2, exclusively found among patients of African ancestry, have been associated with chronic kidney disease (CKD) and end-stage kidney disease (ESKD)1. These high-risk polymorphisms have also been associated with collapsing glomerulopathy in various diseases. We aimed to evaluate the impact of APOL1 G1 and G2 polymorphisms on the clinical and pathological course LN which is already known to be more severe among patients of African ancestry2. Method We included patients from 6 hospitals in Paris and Marseille in France, between January 2017 and March 2020, with biopsy-proven LN, African ancestry and age &amp;gt;18 years at the time of inclusion. We excluded those with HIV infection. The data were retrospectively collected at LN diagnosis, 1 year after diagnosis and at last follow-up. APOL1 genotyping was performed and we divided patients in 2 groups: the high-risk genotype (HRG) group with 2 risk alleles and the low risk genotype (LRG) group with 1 or 0 risk allele. All patients signed a consent form for the genetic analysis and protocol approval was obtained from the ethic committee CERAPHP (Comité d'Ethique de la Recherche AP-HP Centre), registration number 00011928. Results Ninety-nine patients were included in the study, 13 in the HRG group and 86 in the LRG group. The median duration between LN diagnosis and inclusion in the study was 9.6 years [4.9-16.9]. At LN diagnosis, clinical and biological characteristics were similar except for kidney function that was lower in the HRG group compared to the LRG group with a median serum creatinine of 131μmol/L [69-687] versus 66μmol/L [52-133] (p = 0.0085). Patients in the HRG group were more likely to have a serum creatinine above 200 μmol/L compared to the LRG group (45.5% versus 10.5%, p = 0.0096, OR 7.1[1.8-28.6]), and required acute haemodialysis more frequently (30.8% versus 1.3% respectively, p = 0.0012, OR 34.7[3.5-345.1]). Collapsing glomerulopathy was more frequent in the HRG group (45.5% of patients, versus 4.5%, OR 17.5[3.3-91.9], p = 0.001). No significant difference was observed in the proportion of kidney response at 12 months, however, patients in the HRG group were more likely to develop CKD (33.3% versus 4.9%, OR 9.6[2.0-46.1]). Median follow-up from LN diagnosis to the end of study, ESKD or last follow-up was 7.9 years [3.4-13.3] and was similar between the 2 groups. At last follow-up, median eGFR was 22mL/min/1.73m2 [10-98] vs 99mL/min/1.73m2 [55-118] respectively, p = 0.0189. Survival without ESKD was poorer in the HRG group than in the LRG group with a hazard ratio (HR) of 5.0[1.6-15.8], p = 0.006, even after adjusting with the kidney response at 12 months (adjusted HR 6.24[1.8-21.6], p = 0.004) (Figure 1). Conclusion APOL1 genotype affects LN prognosis, resulting in a worse kidney function at diagnosis, development of collapsing glomerulopathy and higher risk of subsequent ESKD. Kidney survival remained significantly lower in the HRG group, after adjustment for kidney response at 12 months, suggesting that the prognosis of LN is heavily driven by APOL1 genotype regardless of the kidney response. APOL1 inhibitors are currently being developed, and could be used in the next future, for HRG patients with primary or secondary forms of collapsing glomerulopathy.

#4385 RELEVANCE OF REPEATED ALBUMINURIA AND GLOMERULAR FILTRATION RATE IN A LARGE COHORT OF SICKLE CELL ANEMIA CHILDREN LIVING IN A RESOURCE-LIMITED AREA

Abstract Background and Aims Chronic kidney disease (CKD) is associated with significant morbidity and mortality among patients with sickle cell anemia (SCA). Glomerular hyperfiltration (GHF) and albuminuria are known as early manifestations of kidney disease occurring in early childhood and can predict the progression to CKD in these patients. Studies reported the prevalence of these kidney abnormalities in SCA children using a single measure and their association with genetic risk factors, especially the co-inheritance of APOL1 risk variants (RVs). However, data on the prevalence of persistent kidney abnormalities (based on the KDIGO CKD definition) and their association with APOL1 RVs are limited in SCA children, particularly those living in sub-Saharan Africa. This study aimed: (i) to determine the prevalence of persistent kidney abnormalities (albuminuria and/or GHF) in SCA children living in the Democratic Republic of Congo (DRC); and (ii) to assess the association between persistent kidney abnormalities with clinical and genetic risk factors. Method From March 2021 to December 2022, we prospectively enrolled 585 steady state SCA children aged 2 to 18 years (male gender 278/585; 47.5%). The SCA status was confirmed through the molecular sequencing of beta-globin gene. Clinical and biological parameters were obtained. All participants were genotyped for apolipoprotein-L1 (APOL1) G1 (rs73885319, rs60910145) and G2 (rs71785313) variants. APOL1 high-risk genotype (HRG) was defined by the presence of 2 risk variants (G1/G1, G2/G2, and G1/G2), and low-risk genotype (LRG) by the presence of 0 or 1 risk variant. Albuminuria was defined as urinary albumin-to-creatinine ratio (ACR) ≥ 30mg/g. The estimated glomerular filtration rate (eGFRcr) was calculated using the original Schwartz formula and GHF was defined as eGFRcr ≥ 180 ml/min/1.73 m2 for children between 2-10 years of age and &amp;gt; 140 ml/min/1.73 m2 for children more than 10 years of age. All measurements were repeated at least three months later in participants who presented with kidney abnormalities at the first screening. The main outcome parameter was persistent albuminuria or persistent GHF for more than three months. Results At enrollment, 234/585 (40.0%) participants presented with kidney abnormalities, among which 80/585 (13.7%) with albuminuria and 171/585 (29.2%) with hyperfiltration. From participants found with kidney abnormalities at the first screening, 176/234 (75.2%) were available for repeated screening: 56/176 (31.8%) presented with persistent kidney abnormalities and 120/176 (68.2%) had a regression of kidney abnormalities without any treatment. Out of 176 participants who benefited from repeated screening, 57 had baseline albuminuria and 130 had baseline GHF. Persistent albuminuria and persistent GHF were found in 38.6% (22/57) and 28.5% (37/130), respectively. Multivariate logistic regression revealed that APOL1 HRG was significantly associated with persistent albuminuria (OR 3.4, 95CI 1.1-10.7, p = 0.037), while male gender was significantly associated with persistent GHF (OR 2.1, 95CI 1.0-4.2, p = 0.042). Conclusion A significant proportion (almost 70.0%) of SCA children who had kidney abnormalities at the first measure, presented regression of these abnormalities without any reno-protective drugs. This result emphasizes the importance of repeating screening at least three months later to confirm CKD, as recommended by the KDIGO Guidelines. This strategy will reduce the need for unnecessary treatment, which represents a high financial burden in a resource-limited area.

Pattern of infection and genotypes of human papillomavirus in Zhengzhou City based on a four–year (2015-2018) epidemiological study

ABSTRACT Persistent human papillomavirus (HPV) infection has been associated with the development of cervical cancer. To reduce the incidence of cervical cancer and promote awareness of HPV, a government-sponsored epidemiological study was conducted from 2015 to 2018 in Zhengzhou City. A total of 184,092 women aged 25–64 years were included, of which 19,579 were infected with HPV, reflecting a prevalence of 10.64 percent (19,579/184,092). The HPV genotypes found were classified as high-risk (13 genotypes) and low-risk (8 genotypes). Single and multiple infections were detected in 13,787 (70.42 percent) and 5,792 (29.58 percent) women, respectively. The five most common high-risk genotypes detected, listed in descending order, were HPV52 (2.14 percent; 3,931/184,092), HPV16 (2.04 percent; 3,756/184,092), HPV58 (1.42 percent; 2,607/184,092), HPV56 (1.01 percent; 1,858/184,092), and HPV39 (0.81 percent; 1,491/184,092). Meanwhile, the most common low-risk genotype was HPV53 (0.88 percent; 1,625/184,092). The prevalence of HPV gradually increased with age, with the highest occurring in women aged 55–64 years. The prevalence of single-type HPV infection decreased with age, whereas that of multiple-type HPV infection increased with age. This study indicates a high burden of HPV infection in women in Zhengzhou City.

The Burden of HPV-Related Hospitalizations: Analysis of Hospital Discharge Records from the Years 2015-2021 from a Southern Italian Region.

(1) Background: The human papillomavirus (HPV) is the most common agent related to sexually transmitted infections in the general population. Its genotypes are classified into two main classes, high-risk genotypes and low-risk genotypes, according to their capacity to induce cancers. The low-risk class (types 6 and 11) is associated with anogenital and genital lesions. The high-risk class is responsible for up to 4.5% of all new cancer cases yearly. The aim of this study was to evaluate the incidence of HPV-related hospitalizations and its trend in a southern Italian region for the years 2015-2021. (2) Methods: This was a retrospective study performed in the Abruzzo region, Italy. All admissions for the period 2015-2021 were extracted from the hospital discharge record (HDR). (3) Results: During the study period (2015-2021), a total of 5492 hospitalizations attributable to HPV infection occurred in the Abruzzo region, Italy. A significant number of admissions were related to cervical cancer (3386 cases) and genital warts (638 cases). The trend declined for all diagnoses except for penile cancer admissions. Considering the first year of the pandemic (year 2020), a decrease in the standardized incidence of the majority of the diseases considered was reported, particularly among cases of cervical cancer. (4) Conclusions: HPV-related hospitalizations decreased in Abruzzo during study period. These results could be useful to LHAs and policy-makers in improving vaccination coverage and screening adherence.

The impact of cryopreservation on both sperm HPV-negative and positive subtypes

It is well known that various human papillomavirus (HPV) genotypes are present in semen specimens. Also, it has been demonstrated that sperm parameters are negatively affected when HPV infection is present in the sperm sample. Besides all these, the effect of cryopreservation on HPV sensitivity and resistance is not known. The aim of the present study is to evaluate first the prevalence of HPV and secondly to elucidate whether cryopreservation of sperm HPV-positive samples has any effect on the viability of HPV. For this purpose, a cohort of 78 sperm specimens was used from a respective number of patients. After giving informed consent, semen analysis was performed. Each sperm sample was divided into four equal aliquots. The first one (fresh) was evaluated for the prevalence of HPV, while the other three aliquots were cryopreserved by adding an equal quantity of cryoprotectant and plunged into the LN. Each of the three aliquots was thawed 3, 6, and 12 months later, respectively, so as to evaluate whether there is a time-resistance period of HPV prevalence. HPV infection was found to be in eleven sperm samples, demonstrating a 14.1% (11/78) HPV prevalence. Among the HPV-positive samples, six of them were high-risk and the remaining were low-risk genotypes. Moreover, the high-risk fresh samples demonstrated higher motility values than the low-risk samples (60% ± 2.7 vs 45.6% ± 3.7, p < .05), while semen volume in the high-risk samples was significantly lower than the respective volume in the low-risk samples (2.26 ± 0.2ml vs 3.5 ± 0.6ml, p < .05). Interestingly, cryopreservation of the HPV-positive samples resulted in the sustainability and time-resistance of HPV in all high-risk HPV-positive samples, something that was not the case with the low-risk HPV-positive samples. Conclusively, sperm samples infected with high-risk HPV, demonstrate lower sperm parameters and time-resistance activity during cryopreservation.

APOL1 and the risk of adverse renal outcomes in patients of African ancestry with systemic lupus erythematosus

Systemic lupus erythematosus (SLE) disproportionately affects individuals of African ancestry (AA) compared to European ancestry (EA). In the general population, high risk (HR) variants in the apolipoprotein L1 (APOL1) gene increase the risk of renal and hypertensive disorders in individuals of AA. Since SLE is characterized by an interferon signature and APOL1 expression is driven by interferon, we examined the hypothesis that APOL1 HR genotypes predominantly drive higher rates of renal and hypertensive-related comorbidities observed in SLE patients of AA versus those of EA. We performed a retrospective cohort study in patients with SLE of EA and AA using a genetic biobank linked to de-identified electronic health records. APOL1 HR genotypes were defined as G1/G1, G2/G2, or G1/G2 and low risk (LR) genotypes as 1 or 0 copies of the G1 and G2 alleles. To identify renal and hypertensive-related disorders that differed in prevalence by ancestry, we used a phenome-wide association approach. We then used logistic regression to compare the prevalence of renal and hypertensive-related disorders in EA and AA patients, both including and excluding patients with the APOL1 HR genotype. In a sensitivity analysis, we examined the association of end stage renal disease secondary to lupus nephritis (LN-related ESRD) with ancestry and the APOL1 genotype. We studied 784 patients with SLE; 195 (24.9%) were of AA, of whom 27 (13.8%) had APOL1 HR genotypes. Eighteen renal and hypertensive-related phenotypes were more common in AA than EA patients (p-value ≤ 1.4E-4). All phenotypes remained significantly different after exclusion of patients with APOL1 HR genotypes, and most point odds ratios (ORs) decreased only slightly. Even among ORs with the greatest decrease, risk for AA patients without the APOL1 HR genotype remained significantly elevated compared to EA patients. In the sensitivity analysis, LN-related ESRD was more prevalent in SLE patients of AA versus EA and AA patients with the APOL1 HR genotype versus LR (p-value < .05 for both). The higher prevalence of renal and hypertensive disorders in SLE patients of AA compared to those of EA is not fully explained by the presence of APOL1 high risk variants.

Characterization of early psychosis patients carrying a genetic vulnerability to redox dysregulation: a computational analysis of mechanism-based gene expression profile in fibroblasts

In view of its heterogeneity, schizophrenia needs new diagnostic tools based on mechanistic biomarkers that would allow early detection. Complex interaction between genetic and environmental risk factors may lead to NMDAR hypofunction, inflammation and redox dysregulation, all converging on oxidative stress. Using computational analysis, the expression of 76 genes linked to these systems, known to be abnormally regulated in schizophrenia, was studied in skin-fibroblasts from early psychosis patients and age-matched controls (N = 30), under additional pro-oxidant challenge to mimic environmental stress. To evaluate the contribution of a genetic risk related to redox dysregulation, we investigated the GAG trinucleotide polymorphism in the key glutathione (GSH) synthesizing enzyme, glutamate-cysteine-ligase-catalytic-subunit (gclc) gene, known to be associated with the disease. Patients and controls showed different gene expression profiles that were modulated by GAG-gclc genotypes in combination with oxidative challenge. In GAG-gclc low-risk genotype patients, a global gene expression dysregulation was observed, especially in the antioxidant system, potentially induced by other risks. Both controls and patients with GAG-gclc high-risk genotype (gclcGAG-HR) showed similar gene expression profiles. However, under oxidative challenge, a boosting of other antioxidant defense, including the master regulator Nrf2 and TRX systems was observed only in gclcGAG-HR controls, suggesting a protective compensation against the genetic GSH dysregulation. Moreover, RAGE (redox/inflammation interaction) and AGMAT (arginine pathway) were increased in the gclcGAG-HR patients, suggesting some additional risk factors interacting with this genotype. Finally, the use of a machine-learning approach allowed discriminating patients and controls with an accuracy up to 100%, paving the way towards early detection of schizophrenia.

Role of Low-Risk HPV PCR Monoinfection in Screening for HSIL and Anal Cancer in Men Who Have Sex with Men Living with HIV.

To determine the value of low-risk human papillomavirus (HPV) PCR to screen for "high-grade anal squamous intraepithelial lesion and anal cancer" (HSIL-plus), rate of patients with low-grade anal squamous intraepithelial lesion (LSIL) progressing to HSIL-plus, and progression-related factors. Prospective, longitudinal study of consecutive MSM-LHIV attended between May 2010 and December 2021 and followed for 43 months (IQR: 12-76). HIV-related variables were gathered at baseline, performing anal cytology for HPV detection/genotyping, thin-layer cytological study, and high-resolution anoscopy (HRA). Follow-up was annual when HRA was normal or LSIL, and post-treatment in cases of HSIL-plus, re-evaluating sexual behavior, viral-immunological status, and HPV infection of anal mucosa. The 493 participants had mean age of 36 years: CD4 nadir < 200 cells/uL in 23.1%, virological failure in 4.1%, and tetravalent HPV vaccine > 5 years earlier in 15%. HSIL-plus was ruled out in patients with monoinfection by low-risk HPV genotype and normal cytology (100% sensitivity, 91.9% specificity, PPV 2.9%, and NPV 100%). Progression from LISL to HSIL-plus occurred in 4.27% of patients within 12 months (IQR: 12-12): risk factors were acquisition of high-risk (HR: 4.15; 95% CI: 1.14-15.03) and low-risk (HR: 3.68 95% CI: 1.04-12.94) HPV genotypes, specifically genotype 6 (HR: 4.47, 95% CI: 1.34-14.91), and history of AIDS (HR: 5.81 95% CI: 1.78-18.92). Monoinfection by LR-HPV genotypes in patients with normal cytology is not associated with anal cancer or precursor lesions. Progression from LSIL to HSIL-plus, observed in <5% of patients, was related to acquisition of HR and LR HPV genotypes, especially 6, and a history of AIDS.

Dietary Patterns, Apolipoprotein L1 Risk Genotypes, and CKD Outcomes Among Black Adults in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) Cohort Study

Dietary factors may impact inflammation and interferon production, which could influence phenotypic expression of Apolipoprotein1 (APOL1) genotypes. We investigated whether associations of dietary patterns with kidney outcomes differed by APOL1 genotypes. Prospective cohort. 5,640 Black participants in the Reasons for Geographic and Racial Differences in Stroke (REGARDS). Five dietary patterns derived from food frequency questionnaires: Convenience foods, Southern, Sweets and Fats, Plant-based, and Alcohol/Salads. Incident chronic kidney disease (CKD), CKD progression, and kidney failure. Incident CKD was defined as a change in estimated glomerular filtration rate (eGFR) to<60mL/min/1.73m2 accompanied by a≥25% decline from baseline eGFR or development of kidney failure among those with baseline eGFR≥60mL/1.73m2 body surface area. CKD progression was defined as a composite of 40% reduction in eGFR from baseline or development of kidney failure in the subset of participants who had serum creatinine levels at baseline and completed a second in-home visit/follow-up visit. We examined associations of dietary pattern quartiles with incident CKD (n=4,188), CKD progression (n=5,640), and kidney failure (n=5,640). We tested for statistical interaction between dietary patterns and APOL1 genotypes for CKD outcomes and explored stratified analyses by APOL1 genotypes. Among 5,640 Black REGARDS participants, mean age was 64 years (standard deviation=9), 35% were male, and 682 (12.1%) had high-risk APOL1 genotypes. Highest versus lowest quartiles (Q4 vs Q1) of Southern dietary pattern were associated with higher adjusted odds of CKD progression (OR, 1.28; 95% CI, 1.01-1.63) but not incident CKD (OR, 0.92; 95% CI, 0.74-1.14) or kidney failure (HR, 1.48; 95% CI, 0.90-2.44). No other dietary patterns showed significant associations with CKD. There were no statistically significant interactions between APOL1 genotypes and dietary patterns. Stratified analysis showed no consistent associations across genotypes, although Q3 and Q4 versus Q1 of Plant-based and Southern patterns were associated with lower odds of CKD progression among APOL1 high- but not low-risk genotypes. Included overlapping dietary patterns based on a single time point and multiple testing. In Black REGARDS participants, Southern dietary pattern was associated with increased risk of CKD progression. Analyses stratified by APOL1 genotypes suggest associations may differ by genetic background, but these findings require confirmation in other cohorts.

Alterations of Vaginal Microbiota and Chlamydia trachomatis as Crucial Co-Causative Factors in Cervical Cancer Genesis Procured by HPV

Chlamydia trachomatis and human papillomavirus (HPV) are the most common pathogens found in sexually transmitted infections (STIs), and both are known to increase the risk of cervical cancer (CC) and infertility. HPV is extremely common worldwide, and scientists use it to distinguish between low-risk and high-risk genotypes. In addition, HPV transmission can occur via simple contact in the genital area. From 50 to 80% of sexually active individuals become infected with both C. trachomatis and HPV viruses during their lifetime, and up to 50% become infected with an HPV oncogenic genotype. The natural history of this coinfection is strongly conditioned by the balance between the host microbiome and immune condition and the infecting agent. Though the infection often regresses, it tends to persist throughout adult life asymptomatically and silently. The partnership between HPV and C. trachomatis is basically due to their similarities: common transmission routes, reciprocal advantages, and the same risk factors. C. trachomatis is a Gram-negative bacteria, similar to HPV, and an intracellular bacterium, which shows a unique biphasic development that helps the latter continue its steady progression into the host throughout the entire life. Indeed, depending on the individual's immune condition, the C. trachomatis infection tends to migrate toward the upper genital tract and spread to the uterus, and the fallopian tubes open up a pathway to HPV invasion. In addition, most HPV and C. trachomatis infections related to the female genital tract are facilitated by the decay of the first line of defense in the vaginal environment, which is constituted by a healthy vaginal microbiome that is characterized by a net equilibrium of all its components. Thus, the aim of this paper was to highlight the complexity and fragility of the vaginal microenvironment and accentuate the fundamental role of all elements and systems involved, including the Lactobacillus strains (Lactobacillus gasseri, Lactobacillus jensenii, Lactobacillus crispatus) and the immune-endocrine system, in preserving it from oncogenic mutation. Therefore, age, diet, and genetic predisposition together with an unspecific, persistent low-grade inflammatory state were found to be implicated in a high frequency and severity grade of disease, potentially resulting in pre-cancerous and cancerous cervical lesions.

Clinical and Genetic Characteristics of CKD Patients with High-Risk APOL1 Genotypes.

APOL1 high-risk genotypes confer a significant risk of kidney disease, but variability in patient outcomes suggests the presence of modifiers of the APOL1 effect. We show that a diverse population of CKD patients with high-risk APOL1 genotypes have an increased lifetime risk of kidney failure and higher eGFR decline rates, with a graded risk among specific high-risk genotypes. CKD patients with high-risk APOL1 genotypes have a lower diagnostic yield for monogenic kidney disease. Exome sequencing revealed enrichment of rare missense variants within the inflammasome pathway modifying the effect of APOL1 risk genotypes, which may explain some clinical heterogeneity. APOL1 genotype has significant effects on kidney disease development and progression that vary among specific causes of kidney disease, suggesting the presence of effect modifiers. We assessed the risk of kidney failure and the eGFR decline rate in patients with CKD carrying high-risk ( N =239) and genetically matched low-risk ( N =1187) APOL1 genotypes. Exome sequencing revealed monogenic kidney diseases. Exome-wide association studies and gene-based and gene set-based collapsing analyses evaluated genetic modifiers of the effect of APOL1 genotype on CKD. Compared with genetic ancestry-matched patients with CKD with low-risk APOL1 genotypes, those with high-risk APOL1 genotypes had a higher risk of kidney failure (Hazard Ratio [HR]=1.58), a higher decline in eGFR (6.55 versus 3.63 ml/min/1.73 m 2 /yr), and were younger at time of kidney failure (45.1 versus 53.6 years), with the G1/G1 genotype demonstrating the highest risk. The rate for monogenic kidney disorders was lower among patients with CKD with high-risk APOL1 genotypes (2.5%) compared with those with low-risk genotypes (6.7%). Gene set analysis identified an enrichment of rare missense variants in the inflammasome pathway in individuals with high-risk APOL1 genotypes and CKD (odds ratio=1.90). In this genetically matched cohort, high-risk APOL1 genotypes were associated with an increased risk of kidney failure and eGFR decline rate, with a graded risk between specific high-risk genotypes and a lower rate of monogenic kidney disease. Rare missense variants in the inflammasome pathway may act as genetic modifiers of APOL1 effect on kidney disease.

Kidney Disease Progression in Membranous Nephropathy among Black Participants with High-Risk APOL1 Genotype.

Disparity in CKD progression among Black individuals persists in glomerular diseases. Genetic variants in the apolipoprotein L1 ( APOL1 ) gene in the Black population contribute to kidney disease, but the influence in membranous nephropathy remains unknown. Longitudinally followed participants enrolled in the Glomerular Disease Collaborative Network or Cure Glomerulonephropathy Network were included if they had DNA or genotyping available for APOL1 (Black participants with membranous nephropathy) or had membranous nephropathy but were not Black. eGFR slopes were estimated using linear mixed-effects models with random effects and adjusting for covariates and interaction terms of covariates. Fisher exact test, Kruskal-Wallis test, and Kaplan-Meier curves with log-rank tests were used to compare groups. Among 118 Black membranous nephropathy participants, 16 (14%) had high-risk APOL1 genotype (two risk alleles) and 102 (86%) had low-risk APOL1 genotype (zero or one risk alleles, n =53 and n =49, respectively). High-risk APOL1 membranous nephropathy participants were notably younger at disease onset than low-risk APOL1 and membranous nephropathy participants that were not Black ( n =572). eGFR at disease onset was not different between groups, although eGFR decline (slope) was steeper in participants with high-risk APOL1 genotype (-16±2 [±SE] ml/min per 1.73 m 2 per year) compared with low-risk APOL1 genotype (-4±0.8 ml/min per 1.73 m 2 per year) or membranous nephropathy participants that did not identify themselves as Black (-2.0±0.4 ml/min per 1.73 m 2 per year) ( P <0.0001). Time to kidney failure was faster in the high-risk APOL1 genotype than low-risk APOL1 genotype or membranous nephropathy participants that were not Black. The prevalence of high-risk APOL1 variant among Black membranous nephropathy participants is comparable with the general Black population (10%-15%), yet the high-risk genotype was associated with worse eGFR decline and faster time to kidney failure compared with low-risk genotype and participants that were not Black.

Brain-derived neurotrophic factor (BDNF) variants and promoter I methylation are associated with prolonged nocturnal awakenings in older adults.

Brain-derived neurotrophic factor (BDNF) is important for sleep physiology. This study investigates whether BDNF variants and promoter I methylation may be implicated in sleep disturbances in older adults. Genotyping was performed for seven BDNF single nucleotide polymorphisms (SNPs) in 355 community-dwelling older adults (aged ≥65 years) and BDNF exon 1 promoter methylation was measured in blood samples at baseline (n=153). Self-reported daytime sleepiness and insomnia, ambulatory polysomnography measures of sleep continuity and architecture, and psychotropic drug intake were assayed during follow-up. Logistic regression adjusted for age, sex, comorbidities, body mass index, and psychotropic drug intake. Associations were found specifically between wake time after sleep onset (WASO) and four SNPs in the participants not taking psychotropic drugs, whereas in those taking drugs, the associations were either not significant (rs6265 and rs7103411) or in the reverse direction (rs11030101 and rs28722151). Higher BDNF methylation levels were found at most CpG units in those with long WASO and this varied according to psychotropic drug use. The reference group with short WASO not taking drugs showed the lowest methylation levels and the group with long WASO taking treatment, the highest levels. Some SNPs also modified the associations, the participants carrying the low-risk genotype having the lower methylation levels. This genetic and epigenetic study demonstrated blood BDNF promoter methylation to be a potential biomarker of prolonged nocturnal awakenings in older people. Our results suggest the modifying effect of psychotropic drugs and BDNF genetic variants in the associations between methylation and WASO.

HPV Type Distribution in Benign, High-Grade Squamous Intraepithelial Lesions and Squamous Cell Cancers of the Anus by HIV Status.

The incidence of anal cancer is increasing, especially in high-risk groups, such as PLWH. HPV 16, a high-risk (HR) HPV genotype, is the most common genotype in anal high-grade squamous intraepithelial lesions (HSIL) and squamous cell carcinoma (SCC) in the general population. However, few studies have described the distribution of HR HPV genotypes other than HPV 16 in the anus of PLWH. HPV genotyping was performed by DNA amplification followed by dot-blot hybridization to identify the HR and low-risk (LR) genotypes in benign anal lesions (n = 34), HSIL (n = 30), and SCC (n = 51) of PLWH and HIV-negative individuals. HPV 16 was the most prominent HR HPV identified, but it was less common in HSIL and SCC from PLWH compared with HIV-negative individuals, and other non-HPV 16 HR HPV (non-16 HR HPV) types were more prevalent in samples from PLWH. A higher proportion of clinically normal tissues from PLWH were positive for one or more HPV genotypes. Multiple HPV infection was a hallmark feature for all tissues (benign, HSIL, SCC) of PLWH. These results indicate that the development of anal screening approaches based on HPV DNA testing need to include non-16 HR HPVs along with HPV 16, especially for PLWH. Along with anal cytology, these updated screening approaches may help to identify and prevent anal disease progression in PLWH.

Correlation of High-Risk Human Papilloma Virus with Deep Endometriosis: A Cross-Sectional Study.

Recently, it has been suggested that microbial infections play a role in the pathogenesis of endometriosis. One of the most commonly suggested infections associated with the pathogenesis of endometriosis is human papillomavirus (HPV) infection. The present study is aimed at evaluating the prevalence, types, and risk factors for HPV infection in women with endometriosis and at investigating the association of upper and lower genital tract involvement with HPV and the severity of endometriosis. This cross-sectional study was conducted on 81 patients with endometriosis, referred to Rasool Akram Medical Complex in Tehran, Iran, for laparoscopic surgery. The patients' demographic, clinical, and anthropometric data were extracted from their medical records, as well as interviews. The stage of disease was scored based on the revised American Society for Reproductive Medicine (rASRM) classification. The HPV-positive and HPV-negative cases were compared using the chi-square test for categorical variables and Student t-test for continuous variables. Twenty (24.69%) out of 81 women with endometriosis were infected with HPV (nine cases of pelvic HPV, nine cases of vaginal HPV, and two cases of both pelvic and vaginal HPV). The HPV-infected women had a significantly lower infertility rate (15% vs. 45.9%; P = 0.014). The VAS scores for dysmenorrhea and dyspareunia were relatively the same in the two groups (P > 0.05). HPV 6 and HPV 11 were the most common types of HPV, reported in 35% and 30% of endometriosis cases, respectively. The prevalence of HPV was 24.69%, and low-risk genotypes were dominant. No significant association was found between HPV and the severity of endometriosis.