Oxidative stress is essential in developing multiple bone metabolism diseases, including osteoporosis. Single-nucleotide variants (SNVs) have been associated with oxidative stress, promoting an ...imbalance between the production of reactive oxygen species and the ability to neutralize them, and it has been reported that antioxidant nutrient intake can influence bone mineral density (BMD). This work reports the association between oxidative stress-related SNVs (
-rs1050450, rs17650792,
-rs4880, and
-rs769217), BMD, and antioxidant nutrient intake. The study included 1269 Mexican women from the Health Workers Cohort Study. Genotyping was performed using predesigned TaqMan assays. Dietary data were collected using a 116-item semi-quantitative food frequency questionnaire. A dietary antioxidant quality score (DAQS) was used to estimate antioxidant-nutrient intake. Association analysis was estimated via linear, logistic, or quantile regression models. The results showed an association of the rs1050450-A and rs17650792-A alleles with femoral neck BMD (
= 0.038 and
= 0.017, respectively) and the SNV rs4880-A allele with total hip BMD (
= 0.026) in respondents aged 45 years or older. In addition, antioxidant-nutrient intake was associated with the rs4880-GG genotype, being significant for fiber (
= 0.007), riboflavin (
= 0.005), vitamin B6 (
= 0.034), and vitamin D (
= 0.002). The study showed an association between oxidative stress-related SNVs, BMD, and antioxidant-nutrient intake in Mexican women. Therefore, treatments for low BMD could be developed based on antioxidant supplementation.
Background. We examined risk of newly detected human papillomavirus (HPV) infection and cervical abnormalities in relation to HPV type 16/18 antibody levels at enrollment in PATRICIA (Papilloma Trial ...Against Cancer in Young Adults; NCT00122681). Methods. Using Poisson regression, we compared risk of newly detected infection and cervical abnormalities associated with HPV-16/18 between seronegative vs seropositive women (15-25 years) in the control arm (DNA negative at baseline for the corresponding HPV type HPV-16: n = 8193; HPV-18: n = 8463). Results. High titers of naturally acquired HPV-16 antibodies and/or linear trend for increasing antibody levels were significantly associated with lower risk of incident and persistent infection, atypical squamous cells of undetermined significance or greater (ASCUS+), and cervical intraepithelial neoplasia grades 1/2 or greater (CIN1+, CIN2+). For HPV-18, although seropositivity was associated with lower risk of ASCUS+ and CIN1+, no association between naturally acquired antibodies and infection was demonstrated. Naturally acquired HPV-16 antibody levels of 371 (95% confidence interval CI, 242-794), 204 (95% CI, 129-480), and 480 (95% CI, 250-5756) EU/mL were associated with 90% reduction of incident infection, 6-month persistent infection, and ASCUS+, respectively. Conclusions. Naturally acquired antibodies to HPV-16, and to a lesser extent HPV-18, are associated with some reduced risk of subsequent infection and cervical abnormalities associated with the same HPV type.
Evidence suggests low-grade inflammation as the cause of metabolic syndrome and suggests diet as a promoter of chronic inflammation.
We evaluated the association between inflammatory diets and the ...development of metabolic syndrome in Mexican adults.
A total of 399 participants of the Health Workers Cohort Study were included in this study. The follow-up period was 13 y. Metabolic syndrome definition was the presence of ≥3 of the following components: waist circumference ≥102 cm for males or ≥88 cm for females, blood pressure ≥130 mmHg for systolic or ≥85 mmHg for diastolic, HDL cholesterol <40 mg/dL for males and <50 mg/dL for females; triglycerides ≥150 mg/dL, and glucose ≥100 mg/dL. To evaluate the inflammatory potential of the diet we used the Dietary Inflammatory Index (DII), which was divided into quartiles. To assess the risk of metabolic syndrome we estimated HRs and 95% CIs using Cox proportional hazards models.
After adjustment for potential confounders, we found a positive association between participants in the highest quartile (Q) of DII and the incidence of metabolic syndrome (HRQ4vsQ1= 1.99; 95% CI: 1.03, 3.85; P-trend = 0.04) over a period of 13 y. When we divided the metabolic syndrome by its components, we found that participants in the highest quartile of DII were associated with hypertriglyceridemia (HRQ4vsQ1= 2.28; 95% CI: 1.13, 4.57; P-trend = 0.01), hypertension (HRQ4vsQ1= 2.22; 95% CI: 1.03, 4.77; P-trend = 0.032), and abdominal obesity (HRQ4vsQ1= 2.68; 95% CI: 1.06, 6.79; P-trend = 0.02).
A highly inflammatory diet is associated with metabolic syndrome, hypertension, abdominal obesity, and hypertriglyceridemia. Further studies are needed to corroborate the role of inflammation and diet in the development of metabolic syndrome; yet, a reduction in dietary components that have been linked to inflammation is desirable.
Background: While receptive anal sex is an established risk factor for anal human papillomavirus (HPV) infection and squamous cell carcinoma of the anus (SCCA), people with anal HPV infection and ...SCCA commonly report no lifetime receptive anal sex suggesting other factors may also increase risk for anal HPV infection and persistence. Given potential associations between obesity and conditions that may cause perianal or anal canal lesions, we hypothesized that body mass index (BMI) was associated with HPV infection.
Methods: Genotyping for 36 HPV types was conducted on anal canal specimens from men, ages 18-70, from Brazil, Mexico, and the USA. Eligibility included no history of genital warts or HIV. Evaluable specimens were collected from 328 men having sex with men (MSM) and 1348 men having sex with women (MSW) who reported no lifetime receptive anal sex. Prevalence of anal HPV infection and six-month persistence by BMI were estimated in addition to adjusted prevalence ratios for the association between BMI and HPV infection.
Results: Among MSW, obese men had a higher prevalence of HPV-16 in the anal canal (3.1%), compared to normal weight men (1.3%) although 95% CI overlapped. Among MSM, prevalence of HPV decreased with increasing BMI. A similar pattern was observed for persistence. After adjustment for confounders, obese MSW had 2.4 times higher odds of HPV-16 compared to normal weight men.
Conclusions: BMI may be positively associated with anal HPV (especially HPV-16) among MSW and negatively associated with anal HPV among MSM which supports continued universal HPV vaccination programs.
Background. Data on the natural history of human papillomavirus (HPV)-related genital warts (GWs) in men are sparse. We described the distribution of HPV types in incident GWs and estimated GW ...incidence and time from type-specific incident HPV infections to GW detection in a multinational cohort of men aged 18-70 years. Methods. Participants included 2487 men examined for GWs and tested for HPV every 6 months and followed up for a median of 17.9 months. Samples were taken from 112 men with incident GWs to test for HPV DNA by polymerase chain reaction. Results. Incidence of GWs was 2.35 cases per 1000 person-years, with highest incidence among men aged 18-30 years (3.43 cases per 1000 person-years). HPV 6 (43.8%), HPV 11 (10.7%), and HPV 16 (9.8%) were the genotypes most commonly detected in GWs. The 24-month cumulative incidence of GWs among men with incident HPV 6/11 infections was 14.6% (95% confidence interval CI, 7.5%–21.1%). Median time to GW detection was 17.1 months (95% CI, 12.4-19.3 months), with shortest time to detection among men with incident infections with HPV 6/11 only (6.2 months; 95% CI, 5.6-24.2 months). Conclusions. HPV 6/11 plays an important role in GW development, with the highest incidence and shortest time to detection among men with incident HPV 6/11 infection.
Describe the natural history of anal HPV among men.
Prospective study among men 18-70 years (n=665), from Cuernavaca, Mexico who completed questionnaires and provided specimens (HPV genotyped) at ...enrollment and 1+ follow-up visit. HPV prevalence and incidence were estimated. Prevalence ratios were calculated with Poisson regression using robust variance estimation. Person-time for incident HPV infection was estimated using number of events modeled as Poisson variable for total person-months.
Anal infection prevalence: any HPV type=15%, high-risk=8.4%, HPV16=1.4%, tetravalent vaccine types (4vHPV)=4.4%, nonavalent vaccine types (9vHPV)=6.3%. Factors associated with prevalence: 50+ lifetime female sex partners (adjusted prevalence ratio, a PR=3.25, 95% CI:1.12- 9.47), 10+ lifetime male sex partners (aPR=3.06, 95%CI:1.4- 6.68), and 1+ recent male anal sex partners (aPR=2.28, 95%CI:1.15-4.5). Anal incidence rate: high-risk HPV=7.8/1000 person-months (95%CI:6.0-10.1), HPV16=1.8/1000 personmonths (95%CI:1.1-2.9),4vHPV=3.4/1000 person-months (95%CI:2.3-4.9) and 9vHPV=5.5/1000 person-months (95%CI:4.1-7.5).
Implementation of universal HPV vaccination programs, including men, is a public health priority.
IMPORTANCE: Triage tests enhance the efficiency cervical cancer screening based on human papillomavirus (HPV), but the best approach for maximizing programmatic effectiveness is still uncertain, ...particularly in a real-world scenario. OBJECTIVE: To compare the clinical performance of 6 triage strategies based on liquid-based cytology (LBC) and HPV-16 and HPV-18 genotyping individually or in combination as sequential triage tests to detect cervical intraepithelial neoplasia (CIN) grade 2 or higher among women with high-risk HPV. DESIGN, SETTING, AND PARTICIPANTS: This diagnostic study of routine cervical cancer screening was conducted at 100 primary health centers in Tlaxcala, Mexico. Women aged 30 to 64 years were recruited from August 1, 2013, to February 24, 2016, as part of the Forwarding Research for Improved Detection and Access for Cervical Cancer Screening and Triage study. Six triage scenarios for referral to colposcopy were examined: (1) LBC testing that found atypical squamous cells of undetermined significance (ASC-US) or worse, (2) positive results in HPV-16 genotyping, (3) positive results in HPV-18 genotyping, (4) positive results in HPV-16/HPV-18 genotyping, (5) positive results in HPV-16 genotyping or, if genotyping results were negative, reflex LBC testing that found ASC-US or worse, and (6) positive results in HPV-16/HPV-18 genotyping or, if genotyping results were negative, reflex LBC testing that found ASC-US or worse. Data were analyzed from October 2017 to August 2018. EXPOSURES: Liquid-based cytological testing with simultaneous HPV-16 and HPV-18 genotyping. Women whose HPV genotyping results were positive for HPV-16 or HPV-18 or whose LBC results found ASC-US or worse and a random set of negative and normal results were referred to colposcopy with histologic analysis used for disease confirmation. MAIN OUTCOMES AND MEASURES: Clinical performance of each test strategy for detection of CIN grade 2 or higher. Secondary outcomes included resource utilization of each triage scenario, measured by the number of tests performed, the referral rate for colposcopy, and the numbers of colposcopies per CIN grade 2 or higher detected. RESULTS: A total of 36 212 women (median interquartile range age, 40 35-47 years) were screened, and 4051 women (11.2%) had high-risk HPV. Of these women, 1109 (24.6%) were found to have HPV-16, HPV-18, or ASC-US or worse. Further histologic testing detected CIN grade 2 or higher in 110 of 788 women (14.0%) who underwent follow-up colposcopy. Sensitivity and specificity for 3 main triage strategies were 42.9% and 74.0% for LBC; 58.3% and 54.4% for HPV-16/HPV-18 genotyping; and 86.6% and 34.0% for HPV-16/HPV-18 genotyping with reflex LBC. The referral rate to colposcopy was 29% for HPV-16/HPV-18 with reflex LBC, which was 2-fold higher than the referral rate of 12% for LBC. CONCLUSIONS AND RELEVANCE: Triage of women with high-risk HPV with HPV-16/HPV-18 genotyping with reflex LBC was significantly associated with improvement in detection of CIN grade 2 or higher compared with LBC alone. The benefit of disease prevented may outweigh the cost of increasing requirements for colposcopy services in settings with limited adherence to follow-up after a positive screening result.
Abstract Objective We evaluated baseline data from the PApilloma TRIal against Cancer In young Adults (PATRICIA; NCT00122681) on the association between behavioral risk factors and HPV infection and ...cervical abnormalities. Methods Women completed behavioral questionnaires at baseline. Prevalence of HPV infection and cervical abnormalities (detected by cytological or histological procedures) and association with behavioral risk factors were analyzed by univariate and stepwise multivariable logistic regressions. Results 16782 women completed questionnaires. Among 16748 women with data for HPV infection, 4059 (24.2%) were infected with any HPV type. Among 16757 women with data for cytological abnormalities, 1626 (9.7%) had a cytological abnormality, of whom 1170 (72.0%) were infected with at least one oncogenic HPV type including HPV-16 (22.7%) and HPV-18 (9.3%). Multivariable analysis (adjusted for age and region, N = 14404) showed a significant association between infection with any HPV type and not living with a partner, smoking, age < 15 years at first sexual intercourse, higher number of sexual partners during the past 12 months, longer duration of hormonal contraception and history of sexually transmitted infection (STI). For cervical abnormalities, only history of STI (excluding Chlamydia trachomatis) remained significant in the multivariable analysis after adjusting for HPV infection. Conclusions Women reporting 3 + sexual partners in the past 12 months had the highest risk of HPV infection at baseline. HPV infection was the main risk factor for cervical abnormalities, and history of STIs excluding Chlamydia trachomatis increased risk to a lesser extent. Although behavioral factors can influence risk, all sexually active women are susceptible to HPV infection.
Vigilant management of women with high-risk human papillomavirus (hrHPV) is necessary in cancer screening programs. To this end, we evaluated the performance of S5 (targeting DNA methylation in ...HPV16, HPV18, HPV31, HPV33, and human gene EPB41L3) to predict cervical intraepithelial neoplasia grade 2 or higher (CIN2+) in a sample of hrHPV-infected women referred to colposcopy in the FRIDA Study, a large screening trial in Mexico. A nested case-control sample with women referred to colposcopy either by atypical squamous cells of undetermined significance or higher (ASCUS+) in cytology and/or positive for HPV types 16 or 18 was tested by S5. Seventy-nine cases of CIN2+ were age-matched to 237 controls without a diagnosis of CIN2+ (<CIN2). DNA from exfoliated cervical cells was bisulfite converted and PCR amplified for S5 targets, and methylation was quantified at specific cytosines by pyrosequencing.
The S5 classifier separated women with CIN2+ from <CIN2 with a highly significant area under the curve (AUC) of 0.75 (95% CI 0.69-0.82), while AUC for CIN3+ was 0.81 (95% CI 0.74-0.89). To optimize sensitivity and specificity for Mexico, an alternative S5 cutoff of 3.7 was implemented to account for overall higher methylation seen in our already triaged women. All three invasive cancers were detected by methylation or HPV16/18 but none by cytology. Sensitivity of S5 for CIN2+ was 62% (95% CI 50.4-72.7%), specificity was 73% (95% CI 66.9-78.5%), and adjusted PPV was 15.1% (95% CI 12.0-18.3%). In contrast, the crude sensitivity of HPV16/18 detection and cytology were 63.3% (95% CI 51.7-73.9%) and 57.0% (95% CI 45.3-68.1%) respectively; specificity was 29.1% (95% CI 23.4-35.3%) and 62.4% (95% CI 55.9-68.6%) respectively, while adjusted PPV was 6.4% (95% CI 4.9-8.1%) and 10.5% (95% CI 8.0-13.1%), respectively. Methylation testing could reduce colposcopy referrals by 30 to 50% with virtually no loss of sensitivity for CIN2+ and CIN3+.
S5 testing on hrHPV-positive women significantly increased diagnostic information compared to triage by HPV16/18 plus cytology and appears to have clinical utility as an additional test to substantially lessen burdens on colposcopy.
The FRIDA Study is registered in ClinicalTrials.gov , number NCT02510027.
The Mexican population has one of the highest prevalences of metabolic syndrome (MetS) worldwide. The aim of this study was to investigate the association of single-nucleotide polymorphisms (SNPs) ...with MetS and its components. First, we performed a pilot Genome-wide association study (GWAS) scan on a sub-sample derived from the Health Workers Cohort Study (HWCS) (n = 411). Based on GWAS results, we selected the rs1784042 and rs17120425 SNPs in the SIDT1 transmembrane family member 2 (SIDT2) gene for replication in the entire cohort (n = 1963), using predesigned TaqMan assays. We observed a prevalence of MetS in the HWCS of 52.6%. The minor allele frequency for the variant rs17120425 was 10% and 29% for the rs1784042. The SNP rs1784042 showed an overall association with MetS (OR = 0.82, p = 0.01) and with low levels of high-density lipoprotein (HDL-c) (odds ratio (OR) = 0.77, p = 0.001). The SNP rs17120425 had a significant association with type 2 diabetes (T2D) risk in the overall population (OR = 1.39, p = 0.033). Our results suggest an association of the rs1784042 and rs17120425 variants with MetS, through different mechanisms in the Mexican population. Further studies in larger samples and other populations are required to validate these findings and the relevance of these SNPs in MetS.
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