Our study can offer new insights into disease mechanisms and prevention through the analysis of risk factor information in a large sample of Mexicans.

Background 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. Results 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+. Conclusions 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. Trial registration The FRIDA Study is registered in ClinicalTrials.gov, number NCT02510027.

This diagnostic study compares the efficiency and effectiveness of 6 triage testing scenarios for screening women with high-risk human papillomavirus (HPV) for referral for colposcopy.

Introduction Urine self-sampling for human papillomavirus (HPV)-based cervical cancer screening is a non-invasive method that offers several logistical advantages and high acceptability, reducing barriers related to low screening coverage. This study developed and evaluated the performance of a low-cost urine self-sampling method for HPV-testing and explored the acceptability and feasibility of potential implementation of this alternative in routine screening. Methods A series of sequential laboratory assays examined the impact of several pre-analytical conditions for obtaining DNA from urine and subsequent HPV detection. Initially, we assessed the effect of ethylaminediaminetetraacetic acid (EDTA) as a DNA preservative examining several variables including EDTA concentration, specimen storage temperature, time between urine collection and DNA extraction, and first-morning micturition versus convenience sample collection. We further evaluated the agreement of HPV-testing between urine and clinician-collected cervical samples among 95 women. Finally, we explored the costs of self-sampling supplies as well as the acceptability and feasibility of urine self-sampling among women and healthcare workers. Results Our results revealed higher DNA concentrations were obtained when using a 40mM EDTA solution, storing specimens at 25°C and extracting DNA within 72 hrs. of urine collection, regardless of using first-morning micturition or a convenience sampling. We observed good agreement (Kappa = 0.72) between urine and clinician-collected cervical samples for HPV detection. Furthermore, urine self-sampling was an affordable method (USD 1.10), well accepted among cervical cancer screening users, healthcare workers, and decision-makers. Conclusion These results suggest urine self-sampling is feasible and appropriate alternative for HPV-testing in HPV-based screening programs in lower-resource contexts.

ABSTRACT Background The elevated consumption of sugar-sweetened beverages (SSBs) in Mexico is an important public health concern. However, the association between SSB consumption and hyperuricemia has been scarcely studied and not well documented. Objectives To prospectively evaluate the association between SSB consumption and risk of hyperuricemia in Mexican adults. Methods A longitudinal analysis was conducted using data from the Health Workers Cohort Study. Participants were followed from 2004 to 2018, with measurements every 6 y. The analysis sample consisted of 1300 adults, aged 18 to 85 y. SSB consumption during the previous year was evaluated through a semiquantitative FFQ. Hyperuricemia was defined as a concentration of uric acid ≥7.0 mg/dL in men and ≥5.7 mg/dL in women. We evaluated the association of interest using 2 methodologies: fixed-effects logistic regression and generalized estimating equations (GEEs). Potential confounders were included in both approaches. Results At baseline, median intake of SSBs was 472.1 mL/wk (IQR: 198.8–1416.4 mL/wk), and 233 participants had hyperuricemia. Uric acid was higher in participants with an SSB intake ≥7 servings/wk, compared with those with an intake &lt;1 serving/wk (P  &lt; 0.001). Participants who changed from the lowest to the highest category of servings consumption experienced 2.6 increased odds of hyperuricemia (95% CI: 1.27, 5.26). Results from the GEE model indicated the odds of hyperuricemia increased by 44% (OR=1.44; 95% CI: 1.13, 1.84) in the 2–6 servings/wk group, and by 89% (OR=1.89; 95% CI: 1.39, 2.57) in the ≥7 servings/wk categories, compared with the &lt;1 serving/wk category. Diet soft drinks were not associated with hyperuricemia. Conclusions Our results suggest that the consumption of SSBs is associated with an increased risk of hyperuricemia in Mexican adults, but diet soft drink consumption is not, which supports the need to strengthen existing recommendations to reduce the intake of SSBs. The Health Workers Cohort Study (HWCS) has been approved by the Institutional Review Board of the Mexican Social Security Institute (12CEI 09 006 14), and the National Institute of Public Health of Mexico (13CEI 17 007 36).