Performance of urine samples compared to cervical samples for detection of precancer lesions among HPV-positive women attending colposcopy clinic in Mexico City.

BACKGROUND: High-risk human papillomavirus (hrHPV) detection in self-collected urine samples (SeCUS) may be a promising alternative for cervical cancer screening because of its greater acceptability, as long as it can offer comparable sensitivity to clinician-collected cervical samples (CCoS) for detecting precancer lesions. OBJECTIVE: To evaluate the performance of the SeCUS compared to that of the CCoS for cervical intraepithelial neoplasia grade 3 (CIN3) detection among hrHPV-positive women receiving colposcopy in Mexico City using different specific extended HPV typing procedures: HPV16/18, HPV16/18/35/39/68 or HPV16/18/35/39/68/31. METHODS: From March 2017 to August 2018, 4,158 female users of the cervical cancer screening program at Tlalpan Sanitary Jurisdiction in Mexico City were invited to participate in the FRIDA-Tlalpan study. All participants provided ≥ 30 mL of SeCUS, and then a CCoS was obtained with Cervex-Brush®, which was used for hrHPV typing. Participants who tested positive for hrHPV in CCoS were referred for colposcopy for diagnostic confirmation, and all SeCUS of these women were also tested for hrHPV typing. RESULTS: In total, 561 hrHPV-positive women were identified by CCoS via colposcopy, and 82.2% of the SeCUS of these women were also hrHPV positive. From both CCoS and SeCUS, 7 cases of CIN3 were detected. Considering HPV16/18 typing, CCoS and SeCUS detected 4 cases of CIN3, but after HPV16/18/35/39/68/31 extension typing, both CCoS and SeCUS detected all 7 of the CIN3 cases among the hrHPV-positive women. CONCLUSIONS: Using extended hrHPV typing based on HPV16/18/35/39/68/31, our results suggest that the performance of SeCUS may be equivalent to that of CCoS for detecting CIN3 lesions. Although our results are inconclusive, they support the hypothesis that SeCUS may be an attractive alternative worthy of further research.

The Cervical Cancer Treatment Gap in Mexico Under Seguro Popular, 2006-2016.

From 2005 to 2019, the Mexican government financed cervical cancer treatment for individuals without social security insurance through Seguro Popular's Fund for Protection against Catastrophic Health Expenses. To better understand the impact of this program on access to treatment, we estimated the cervical cancer treatment gap (the proportion of patients with cervical cancer in this population who did not receive treatment). To calculate the expected number of incident cervical cancer cases we used national surveys with information on insurance affiliation and incidence estimates from the Global Burden of Disease study. We used a national claims database to determine the number of cases whose treatment was financed by Seguro Popular. From 2006 to 2016, the national cervical cancer treatment gap changed from 0.61 (95% CI 0.59 to 0.62) to 0.45 (95% CI 0.43 to 0.48), with an average yearly reduction of -0.012 (95% CI -0.024 to -0.001). The gap was greater in states with higher levels of marginalization and in the youngest and oldest age groups. Although the cervical cancer treatment gap among individuals eligible for Seguro Popular decreased after the introduction of public financing for treatment, it remained high. Seguro Popular was eliminated in 2019; however, individuals without social security have continued to receive cancer care financed by the government in the same healthcare facilities. These results suggest that barriers to care persisted after the introduction of public financing for treatment. These barriers must be reduced to improve cervical cancer care in Mexico, particularly in states with high levels of marginalization.

Prevalence of Chlamydia trachomatis and Neisseria gonorrhoeae infections in Tlaxcala, Mexico.

Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) are widely recognised as two prevalent sexually transmitted infections that can have detrimental effects on women's reproductive health. Previous research has concentrated on studying high-risk populations, resulting in limited epidemiological data regarding the general population. Therefore, the objective of this study was to estimate the prevalence of CT and NG among women attending public primary health care in Tlaxcala, Mexico. The study sample included 2,396 women already participating in the cervical cancer screening programme, from July to November 2014. After obtaining informed consent, the CT and NG tests were conducted on cervical samples, using a nucleic acid amplification test. We estimate the prevalence with 95% confidence intervals (CIs). Women who tested positive were promptly notified and provided with appropriate treatment. In our study population, CT and NG prevalences were 3.2 (95% CI: 2.6-4.0) and 0.01 (95% CI: 0.01-0.03), respectively. CT prevalence was higher in younger women (age < 40), although the results indicate a low prevalence; due to the potentially significant impact of CT and NG on women's health, we require adequate surveillance, and guaranteeing rapid referral to the correct treatment is a priority for the control of these diseases.

Clinical Performance of hrHPV Primary Screening Using Vaginal versus Cervical Samples to Detect High-grade Intraepithelial Lesions.

High-risk human papillomavirus (hrHPV) testing is now the most recommended primary method for cervical cancer screening worldwide. Clinician-collected cervical sampling continues to be the main sampling method, but hrHPV vaginal self-sampling is an appealing alternative because of its greater acceptability and potentially higher cost-effectiveness. This study aimed to determine whether hrHPV vaginal self-sampling is comparable with clinician-collected cervical sampling for detecting histologically confirmed high-grade cervical intraepithelial neoplasia (CIN2/3) as part of a cervical cancer screening program in Mexico. We analyzed data from 5,856 women screened during a hrHPV-based screening study. Clinical performance and diagnostic efficiency metrics were estimated for the two sampling methods for the CIN3 and CIN2+ endpoints, using three triage strategies: HPV16/18 genotyping, HPV16/18/33/58 extended genotyping, and HPV16/18/31/33/58 extended genotyping. hrHPV-positivity was found in 801 (13.7%) cervical and 897 (15.3%) vaginal samples. All women with hrHPV-positive samples were referred to colposcopy, which detected 17 total CIN3 cases before considering retrospective triage strategies. Using the HPV16/18/31/33/58 extended genotyping strategy, 245 women had hrHPV-positive cervical samples and 269 had hrHPV-positive vaginal samples. Ten CIN3 cases were detected each among women with hrHPV-positive cervical samples and among those with hrHPV-positive vaginal samples when using this strategy, with no significant differences in sensitivity and specificity observed. We observe that self- and clinician-collected sampling methods are comparable for detecting CIN3 and CIN2+ regardless of the triage strategy used. These findings can help public health officials to develop more cost-effective cervical cancer screening programs that maximize participation. PREVENTION RELEVANCE: We found that hrHPV vaginal self-sampling is comparable with hrHPV clinician cervical sampling when using any triage strategy to refer women to colposcopy, so self-sampling is a viable cervical screening method. Therefore, policymakers should consider incorporating self-sampling into cervical screening programs to increase screening coverage and reduce cervical cancer burden. See related Spotlight, p. 649.

Factors associated with receiving results and attending colposcopy in patients with positive HPV screens in Mexico City.

We identified patient and healthcare system factors related to receipt of screening results and attendance to colposcopy among patients with positive screening results in a cervical cancer screening program in Mexico City, Mexico. We analyzed data from 1,351 patients with high-risk human papillomavirus (HPV)-positive results from two screening demonstration studies conducted between 2017 and 2018. Factors associated with receipt of screening results and with adherence to a colposcopy appointment were identified using multivariable logistic regression. Participants had a median age of 40 years (IQR = 32-48), 60% had less than high school education, and 74% had a previous Pap screening in the last 5 years. Fifty-five percent of participants retrieved their screening results at the healthcare facility (HCF) without any reminder. Providing an email address for contact information, attending a HCF with family medicine, and receiving care from experienced nurses were associated with greater adherence to obtaining screening test results. Fifty-seven percent of participants attended their first scheduled colposcopy appointment. Providing a phone number improved adherence to colposcopy, whereas longer travel times between the HCF and the colposcopy clinic was associated with a decrease in colposcopy adherence. Having a Pap test in the last 5 years was positively associated with better compliance with both outcomes. Securing contact information may help to overcome barriers to future follow-up. Additional research is necessary on strategies for obtaining screening test results and scheduling appointments, which may help address barriers to access, such as limited staff availability, distance from the clinic, and travel costs.

Incremental levels of diagnostic information incentivize health-seeking in non-alcoholic fatty liver: a randomized clinical trial.

Patients with chronic disorders like non-alcoholic fatty liver disease (NAFLD) face important challenges adhering to diagnostic and treatment tracks. As NAFLD increases, the need to incentivize health-seeking behaviors grows. No evidence-based interventions to address this gap exist. The aim of the study was to estimate the effect of providing increasing levels of diagnostic information on medical care-seeking in adults newly diagnosed with NAFLD. We randomly assigned adults with a sonographic diagnosis of NAFLD at a check-up unit in Mexico to one of five groups. All groups received medical consultation. A: no further interventions; B: received multimedia educational material (MEM); C: MEM + NAFLD-fibrosis-score (NFS); D: MEM + transient elastography (TE); E: MEM + NFS + TE. 1209 participants were randomized, follow-up rate 91%; 82% male, BMI 30.5 ± 4 kg/m2. There were no differences in the proportion of patients undergoing further diagnostic evaluation of liver fibrosis (A 0.4%, E 0.4%, P-for-trend = 0.269). Groups who received more information sought specialized medical care more frequently: A 22%, E 30% (P-for-trend = 0.047). A trend to receive treatment was also observed at higher levels of information: A 26.7%, E 36.3% (P-for-trend = 0.134). Increasing the amount of diagnostic information seemed to increase patient's health-seeking. Tailoring the communication of information obtained for diagnosis could help to increase health-seeking in chronic disease patients.Trial registration: NCT01874249 (full date of first registration 11-06-2013).

Performance of an affordable urine self-sampling method for human papillomavirus detection in Mexican women.

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.

Reduction of HPV16/18 prevalence in young women after eight years of three- and two-dose vaccination schemes.

BACKGROUND: Recommendations for human papillomavirus vaccination have relied on immunogenicity studies and efficacy results derived from adult women. Insufficient information exists regarding HPV effectiveness in vaccinated girls as they become sexually active, regardless of dose scheme. We aimed to compare the prevalence of high-risk HPV between unvaccinated and vaccinated young women eight years after immunization. METHODS: After eight years, we recontacted women who received two-dose of bivalent or three-dose-either bivalent or quadrivalent-, HPV vaccine when aged 9-10 years-old as part of a clinical trial. Additionally, we recruited a contemporaneous unvaccinated woman group for comparison. Only those sexually active were included. High-risk HPV DNA was determined in urine samples and compared across groups. RESULTS: The prevalence of HPV16/18 types was 6.8% (95 %CI 3.2-14.1%) in the unvaccinated (n = 6/88), 1.1% (95 %CI 0.2-5.8%) in the three-dose (n = 1/93), and 0.0% (95 %CI 0.0-7.0%) in the two-dose group (n = 0/51). CONCLUSION: HPV vaccination, with two-dose of bivalent or three-dose schemes-either with the bivalent or quadrivalent vaccine-, was associated with a lower prevalence of HPV16/18 types eight years after primary immunization.

Revisión rápida de la transmisión del SARS-CoV-2 por contacto con objetos y superficies / Rapid review of transmission of SARS-CoV-2 by contact with objects and surfaces

Resumen: Objetivo: Identificar evidencia científica sobre la transmisión indirecta del SARS-CoV-2 en espacios extrahospitalarios y medidas poblacionales para su prevención. Material y métodos: Una revisión rápida de lo publicado en PubMed y MedRxiv entre 01/12/2019 y 24/04/2020 sobre los temas 1) la contaminación y viabilidad del SARS-CoV-2 en distintas superficies inanimadas; 2) la efectividad desinfectante ante SARS-CoV-2 de productos accesibles a nivel domiciliario; 3) los casos y brotes de contagio de SARS-CoV-2 por medio de superficies. Resultados: Una alta proporción de los objetos de personas infectadas con SARS-CoV-2 (inodoro, ollas y tabletas electrónicas) se encuentran contaminados. Este virus permanece viable desde horas hasta días en papel, cartón, tela, vidrio, madera, plástico, acero y cubrebocas. El etanol, 2-propanol, cloro y jabón son efectivos para desactivarlo. Existe poca evidencia sobre casos y brotes por contagio indirecto. Conclusiones: Se requieren estudios que determinen la dosis mínima infectante por autoinoculación. Apelando al principio precautorio, se incluyeron recomendaciones para reducir el riesgo de contagio indirecto.

Abstract: Objective: To identify scientific evidence on the indirect transmission of SARS-CoV-2 in out-of-hospital spaces and population measures for its prevention. Materials and methods: A rapid review of what has been published in PubMed and MedRxiv between 12/01/2019 and 04/24/2020, on the topics: 1) the contamination and viability of SARS-CoV-2 in different inanimate surfaces; 2) products accessible at home level with disinfectant efficacy against SARS-CoV-2; 3) the cases and outbreaks of SARS-CoV-2 transmitted through surfaces. Results: A high proportion of the objects people infected with SARS-CoV-2 use (toilet, pots and electronic tablets) are contaminated. This virus remains viable from hours to days in paper, cardboard, cloth, glass, wood, plastic, steel and face masks. Ethanol, 2-propanol, chlorine, and soap are effective in deactivating it. There is little evidence on cases and outbreaks by indirect contact. Conclusions: Studies are required to determine the minimum infectious dose by autoinoculation. Appealing to the precautionary principle, we include recommendations to reduce the risk of indirect contagion.

Adjunctive testing by cytology, p16/Ki-67 dual-stained cytology or HPV16/18 E6 oncoprotein for the management of HPV16/18 screen-positive women.

High-risk human papillomavirus type 16/18 (HPV16/18) genotyping is unable to accurately discriminate nonprogressive infections from those that will progress to cervical cancer. Our study aimed to assesses if additional testing either with liquid-based cytology (LBC) or the putative progression markers p16/Ki-67 and HPV16/18 E6 oncoprotein (E6) can improve the efficiency of HPV16/18 genotyping for triaging high-risk HPV (hrHPV)-positive women through better cancer risk stratification. Women attending colposcopy after positive HPV16/18 genotyping results within the Forwarding Research for Improved Detection and Access for Cervical Cancer Screening and Triage (FRIDA) hrHPV-based screening study in Tlaxcala, Mexico, underwent further testing with LBC, p16/Ki-67 dual-stained (DS) cytology and E6. We calculated measures of test performance for detecting histologically confirmed cervical intraepithelial neoplasia grade 2 or higher (CIN2+) and grade 3 or higher (CIN3+). A number of 475 (64.3%) of 739 HPV16/18-positive women had complete results for all tests. Triage positivity rates were 14.1%, 18.5% and 24.4%, for LBC, E6 and DS, respectively. Compared with LBC, DS had higher sensitivity (24.4% vs 60.0%) although lower specificity (87.0% vs 79.3%) for CIN3+ (P < .001), whereas E6 had a sensitivity of 37.8% and a specificity of 83.5%. No invasive cancer was missed by DS or E6, but 75% were in normal cytology. DS test was associated with nearly 75% reduction of colposcopy referrals compared with the direct referral of all HPV16/18-positive women, giving the least number of colposcopies (n = 4.3) per CIN3+ detected. We show that adjunctive testing of HPV16/18-positive women with DS may greatly reduce unnecessary colposcopy referrals within HPV-based screening employing HPV16/18 genotyping while retaining acceptable sensitivity for CIN2+ and CIN3+.

Benefit of double-reading cytology smears as a triage strategy among high-risk human papillomavirus-positive women in Mexico.

BACKGROUND: The goal of this study was to determine whether the detection of histologically confirmed cases of cervical high-grade squamous intraepithelial lesions or worse (HSIL+) can be increased by having each liquid-based cytology (LBC) slide read by 2 cytotechnologists as part of routine screening. METHODS: Over 36,212 women aged 30 to 64 years participated in the Forwarding Research for Improved Detection and Access for Cervical Cancer Screening and Triage (FRIDA) Study in Mexico between 2013 and 2016. For each participant, 2 cervical samples were collected at the same clinic visit, one to test for high-risk human papillomavirus (hrHPV) and the other for LBC, which was used to triage those with a hrHPV positive result. LBC slides were evaluated by 7 cytotechnologists, with each slide read independently by 2 blinded cytotechnologists. All women with atypical cells of undetermined significance or a worse result were referred to colposcopy for further evaluation and diagnosis. Three pathologists evaluated the biopsy specimens to confirm the final HSIL+ diagnosis. The HSIL+ detection rates for the single versus double reading were estimated and compared. RESULTS: A total of 3,914 women with a positive hrHPV result were triaged with LBC. The first and second cytology readings resulted in 43 HSIL+ cases detected; the double-reading strategy detected 9 additional HSIL+ cases, resulting in a total of 52 HSIL+ cases. The HSIL+ detection rate increased from 10.99/1000 with a single reading to 13.29/1000 with the double-reading strategy (P = .004). CONCLUSION: A 20.9% increase in HSIL+ cases detected was achieved with a double reading of the LBC slides in this sample of hrHPV-positive women.

Soft drink intake is associated with weight gain, regardless of physical activity levels: the health workers cohort study.

BACKGROUND: While soft drink intake is positively associated with weight gain, no previous study has investigated whether leisure-time physical activity modifies this association. We estimated the association between soft drink intake and body weight, and explored if this association differed by levels of leisure-time physical activity. METHODS: We used data from the health workers cohort study, a prospective study of Mexican adults (20 to 85y old), including 1268 health workers and their families, who were assessed at baseline (2004-2006) and follow-up (2010-2012). We assessed soft drink intake (cola and flavored soda) using a validated food frequency questionnaire. We measured leisure-time physical activity using a self-report questionnaire, and categorized according to the 2010 World Health Organization (WHO) recommendations. Body weight was measured by trained personnel. The association between changes in soft drink intake and weight change, and if such association varied by levels of physical activity was estimated through fixed-effect models. RESULTS: An increase in one serving per day of soft drink was associated with 0.10 kg (95% CI 0.00, 0.19) increase in weight per year. This association was not modified by leisure-time physical activity, as demonstrated by the magnitude of the coefficient of the interaction between soft drink, leisure-time physical activity, and time (- 0.03 kg, 95% CI - 0.27 to 0.21); people who complied with the WHO physical activity recommendations gained 0.36 kg/year per serving of soft drink, compared to 0.48 kg/year for people without sufficient physical activity. CONCLUSIONS: Soft drink intake was associated with weight gain. Leisure-time physical activity did not modify the association between soft drink intake and weight gain. This finding challenges the idea that leisure-time physical activity is sufficient to counterbalance weight gain associated to soft drink intake.

Comparison of HPV-16 and HPV-18 Genotyping and Cytological Testing as Triage Testing Within Human Papillomavirus-Based Screening in Mexico.

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.

Methylation estimates the risk of precancer in HPV-infected women with discrepant results between cytology and HPV16/18 genotyping.

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+ (

Persistence of Immunity When Using Different Human Papillomavirus Vaccination Schedules and Booster-Dose Effects 5 Years After Primary Vaccination.

Background: There are limited data regarding the duration of immunity induced by different human papillomavirus (HPV) vaccination schedules and the immunogenicity of a booster dose of both bivalent HPV vaccine (bHPV) or quadrivalent HPV vaccine (qHPV). Methods: Follow-up of a nonrandomized clinical trial to evaluate the 5-year antibody persistence of the bHPV in girls (age, 9-10 years) and women (age, 18-24 years). Noninferiority of the 2-dose versus 3-dose schedule among girls was evaluated at months 54 (n = 639) and 64 (n = 990). Girls vaccinated with a 2-dose schedule of bHPV or qHPV received a booster dose of either vaccine at month 61. Immunogenicity was measured using a virus-like particle-based enzyme-linked immunosorbent assay. Geometric mean titers (GMTs) for HPV16/18 were estimated after stratification by vaccination schedule and age group. Results: At months 54 and 64, the 2-dose schedule remained noninferior to the 3-dose schedule. GMTs remained above natural infection levels across all age groups up to 64 months. After the booster, anti-HPV16/18 GMTs increased exponentially with the same pattern, regardless of vaccine administered. No safety concerns were identified with the booster dose. Conclusions: A 2-dose schedule is highly immunogenic in girls, suggesting a high immune memory. Thus, a booster dose is likely to be unprofitable, considering the low global immunization coverage. Clinical Trials Registration: NCT01717118.

HPV vaccine acceptance is high among adults in Mexico, particularly in people living with HIV / Aceptación de la vacuna contra VPH es alta entre adultos en México, especialmente en personas con VIH

Abstract: Objective. To measure HPV vaccine acceptance in diverse Mexican adult popula­tions, taking into account HIV status. Materials and methods: A total of 1 329 men and women, with and without HIV, participated in one of three intervention studies, offering HPV vaccination, carried out in the states of Morelos, Tlaxcala and Mexico City; either the bivalent (Morelos n=103, Tlaxcala n=127) or quadrivalent HPV-vaccine (Mexico City n=1 099) was offered. Results: HPV vaccine was accepted by 80.3% of participants; acceptance was higher in people living with HIV than those without (84.4 vs. 78%, p=0.004). Women had greater HPV infection knowledge (p<0.0001) than men and slightly higher (p=0.4) vaccine acceptance. The main reason for vaccine non-acceptance among HIV-positive participants was their doctor recommended they not get vaccinated. Conclusion: Acceptance of HPV-vaccine was high in men and women regardless of HIV status. Even higher rates of acceptability may be achieved by educating healthcare providers to recommend HPV vaccine to their patients.

Resumen: Objetivo. Medir la aceptación de la vacuna de VPH en una muestra diversa de población adulta mexicana, teniendo en cuenta su estado de VIH. Material y métodos: 1 329 hombres y mujeres con y sin VIH participaron en tres estudios de intervención, realizados en los estados de Morelos, Tlaxcala y Ciudad de México. Se ofreció la vacuna bivalente (Morelos n=103, Tlaxcala n=127) o la cuadrivalente (Ciudad de México n=1 099) contra VPH. Resultados: La vacuna fue aceptada por 80.3% de los participantes; la aceptación fue mayor en personas que viven con VIH que en aquéllas que no (84.4 vs. 78%, p=0.004). Las mujeres (p<0.0001) tenían mayor conocimientos sobre VPH que los hombres y una aceptación de la vacuna ligeramente mayor (p=0.4). El motivo principal de la no aceptación de la vacuna entre personas con VIH fue que su médico recomendó que no se vacunaran. Conclusión: La aceptación de la vacuna contra el VPH fue alta en hombres y mujeres, independientemente del estado de VIH. Se pueden lograr mayores tasas de aceptabilidad educando a los proveedores de atención médica para que recomienden la vacuna contra el VPH a sus pacientes.

The effect of a booster dose of HPV tetravalent vaccine after 51 months: implications for extended vaccination schedules / El efecto de un refuerzo de la vacuna tetravalente de VPH después de 51 meses: implicaciones para un esquema de vacunación extendido

Abstract: Objective: To asses the non-inferiority between two different vaccination schedules one month after the administration of the third dose. Materials and methods: We evaluated the anti-HPV 16/18 antibody titers induced by quadrivalent HPV vaccine administered using two different schedules in girls 9 to 10-year-old girls: a traditional (0-2-6) and an alternative (0-6-50). Blood samples were collected at month 7, 21 and 51. Results: The antibody geometric mean titer ratios one month after the application of the third dose -month 51 for the alternative and month 7 for the traditional- were 1.55 for HPV16 (95%CI, 1.15-2.08) and 1.53 for HPV18 (95%CI, 1.12-2.09). The seropositive rate was above 99% in both groups. Conclusions: The application of an alternative 3-dose schedule in 9 to 10-year-old girls induces a non-inferior immune response compared to the standard one month after the last dose. Further research is needed to understand the minimal number of doses and their timing to provide the best coverage for HPV infection.

Resumen: Objetivo: Evaluar la no inferioridad entre dos diferentes esquemas de vacunación un mes después de la administración de la tercera dosis. Material y métodos: Se evaluaron los títulos de anticuerpos anti-VPH 16/18 inducidos por la vacuna contra VPH tetravalente administrada en niñas de 9 a 10 años utilizando dos esquemas diferentes: tradicional (0-2-6) y alternativo (0-6-50). Se recolectaron muestras en los meses 7, 21 y 51. Resultados: La media geométrica de títulos de anticuerpos un mes después de la aplicación de la tercera dosis -mes 51 para la alternativa y mes 7 para el tradicional- fueron 1.55 para HPV16 (95% IC 1.15-2.08) y 1.53 para HPV18 (95% IC 1.12-2.09). La tasa de seropositividad fue superior a 99% en ambos grupos. Conclusiones: la aplicación de un esquema alternativo de tres dosis (0-6-50 meses) en niñas parece inducir una respuesta inmune no inferior al esquema tradicional un mes después de la última dosis. Se necesitan más estudios para determinar las dosis mínimas e intervalos óptimos para obtener la mejor cobertura para la infección por VPH.

HPV vaccine acceptance is high among adults in Mexico, particularly in people living with HIV.

OBJECTIVE: To measure HPV vaccine acceptance in diverse Mexican adult popula-tions, taking into account HIV status. MATERIALS AND METHODS: A total of 1 329 men and women, with and without HIV, participated in one of three intervention studies, offering HPV vaccination, carried out in the states of Morelos, Tlaxcala and Mexico City; either the bivalent (Morelos n=103, Tlaxcala n=127) or quadrivalent HPV-vaccine (Mexico City n=1 099) was offered. RESULTS: HPV vaccine was accepted by 80.3% of participants; acceptance was higher in people living with HIV than those without (84.4 vs. 78%, p=0.004). Women had greater HPV infection knowledge (p<0.0001) than men and slightly higher (p=0.4) vaccine acceptance. The main reason for vaccine non-acceptance among HIV-positive participants was their doctor recommended they not get vaccinated. CONCLUSIONS: Acceptance of HPV-vaccine was high in men and women regardless of HIV status. Even higher rates of acceptability may be achieved by educating healthcare providers to recommend HPV vaccine to their patients.

OBJETIVO: Medir la aceptación de la vacuna de VPH en una muestra diversa de población adulta mexicana, teniendo en cuenta su estado de VIH. MATERIAL Y MÉTODOS: 1 329 hombres y mujeres con y sin VIH participaron en tres estudios de intervención, realizados en los estados de Morelos, Tlaxcala y Ciudad de México. Se ofreció la vacuna bivalente (Morelos n=103, Tlaxcala n=127) o la cuadrivalente (Ciudad de México n=1 099) contra VPH. RESULTADOS: La vacuna fue aceptada por 80.3% de los participantes; la aceptación fue mayor en personas que viven con VIH que en aquéllas que no (84.4 vs. 78%, p=0.004). Las mujeres (p<0.0001) tenían mayor conocimientos sobre VPH que los hombres y una aceptación de la vacuna ligeramente mayor (p=0.4). El motivo principal de la no aceptación de la vacuna entre personas con VIH fue que su médico recomendó que no se vacunaran. CONCLUSIONES: La aceptación de la vacuna contra el VPH fue alta en hombres y mujeres,independientemente del estado de VIH. Se pueden lograr mayores tasas de aceptabilidad educando a los proveedores de atención médica para que recomienden la vacuna contra el VPH a sus pacientes.

The effect of a booster dose of HPV tetravalent vaccine after 51 months: implications for extended vaccination schedules.

OBJECTIVE: To asses the non-inferiority between two differ- ent vaccination schedules one month after the administration of the third dose. MATERIALS AND METHODS: We evaluated the anti-HPV 16/18 antibody titers induced by quadrivalent HPV vaccine administered using two different schedules in girls 9 to 10-year-old girls: a traditional (0-2-6) and an alterna- tive (0-6-50). Blood samples were collected at month 7, 21 and 51. RESULTS: The antibody geometric mean titer ratios one month after the application of the third dose -month 51 for the alternative and month 7 for the traditional- were 1.55 for HPV16 (95%CI, 1.15-2.08) and 1.53 for HPV18 (95%CI, 1.12-2.09). The seropositive rate was above 99% in both groups. CONCLUSIONS: The application of an alternative 3-dose schedule in 9 to 10-year-old girls induces a non-inferior immune response compared to the standard one month after the last dose. Further research is needed to understand the minimal number of doses and their timing to provide the best coverage for HPV infection.

OBJETIVO: Evaluar la no inferioridad entre dos diferentes esquemas de vacunación un mes después de la administración de la tercera dosis. MATERIAL Y MÉTODOS: Se evaluaron los títulos de anticuerpos anti-VPH 16/18 inducidos por la vacuna contra VPH tetravalente administrada en niñas de 9 a 10 años utilizando dos esquemas diferentes: tradicional (0-2-6) y alternativo (0-6-50). Se recolectaron muestras en los meses 7, 21 y 51. RESULTADOS: La media geométrica de títulos de anticuerpos un mes después de la aplicación de la tercera dosis ­mes 51 para la alternativa y mes 7 para el tradicional­ fueron 1.55 para HPV16 (95% IC 1.15-2.08) y 1.53 para HPV18 (95% IC 1.12-2.09). La tasa de seropositividad fue superior a 99% en ambos grupos. CONCLUSIONES: la aplicación de un esquema alternativo de tres dosis (0-6-50 meses) en niñas parece inducir una respuesta inmune no inferior al esquema tradicional un mes después de la última dosis. Se necesitan más estudios para determinar las dosis mínimas e intervalos óptimos para obtener la mejor cobertura para la infección por VPH.

Health workers cohort study: methods and study design / Cohorte de trabajadores de la salud: métodos y diseño del estudio

Abstract: Objective: To examine different health outcomes that are associated with specific lifestyle and genetic factors. Materials and methods: From March 2004 to April 2006, a sample of employees from three different health and academic institutions, as well as their family members, were enrolled in the study after providing informed consent. At baseline and follow-up (2010-2013), participants completed a self-administered questionnaire, a physical examination, and provided blood samples. Results: A total of 10 729 participants aged 6 to 94 years were recruited at baseline. Of these, 70% were females, and 50% were from the Mexican Social Security Institute. Nearly 42% of the adults in the sample were overweight, while 20% were obese. Conclusion: Our study can offer new insights into disease mechanisms and prevention through the analysis of risk factor information in a large sample of Mexicans.

Resumen: Objetivo: Examinar diferentes desenlaces en salud y su asociación con factores genéticos y del estilo de vida. Material y métodos: De marzo de 2004 a abril de 2006, una muestra de empleados de tres diferentes instituciones de salud y académicas, así como miembros de sus familias, fueron enrolados en el estudio, previa firma de consentimiento informado. Durante la medición basal y el seguimiento (2010-2013) los participantes completaron un cuestionario autoaplicado, exámenes físicos y proporcionaron muestras sanguíneas. Resultados: Fueron incluidos participantes (10 729) de entre 6 y 94 años en la medición basal. De estos, 70% fueron mujeres y 50% del Instituto Mexicano del Seguro Social. Aproximadamente 42% de los adultos tuvieron sobrepeso y 20% obesidad. Conclusión: Este estudio puede ofrecer conocimientos sobre los mecanismos de la enfermedad a través del análisis de factores de riesgo en una muestra de mexicanos.