Eduardo Lazcano

Incidence and clearance of genital human papillomavirus infection in men (HIM): a cohort study

BACKGROUND Human papillomaviruses (HPVs) cause genital warts and cancers in men. The natural history of HPV infection in men is largely unknown, and that information is needed to inform prevention strategies. The goal in this study was to estimate incidence and clearance of type-specific genital HPV infection in men, and to assess the associated factors. METHODS Men (aged 18-70 years), residing in Brazil, Mexico, and the USA, who were HIV negative and reported no history of cancer were recruited from the general population, universities, and organised health-care systems. They were assessed every 6 months for a median follow-up of 27·5 months (18·0-31·2). Specimens from the coronal sulcus, glans penis, shaft, and scrotum were obtained for the assessment of the status of HPV genotypes. FINDINGS In 1159 men, the incidence of a new genital HPV infection was 38·4 per 1000 person months (95% CI 34·3-43·0). Oncogenic HPV infection was significantly associated with having a high number of lifetime female sexual partners (hazard ratio 2·40, 1·38-4·18, for at least 50 partners vs not more than one partner), and number of male anal-sexual partners (2·57, 1·46-4·49, for at least three male partners vs no recent partners). Median duration of HPV infection was 7·52 months (6·80-8·61) for any HPV and 12·19 months (7·16-18·17) for HPV 16. Clearance of oncogenic HPV infection decreased in men with a high number of lifetime female partners (0·49, 0·31-0·76, for at least 50 female partners vs not more than one partner), and in men in Brazil (0·71, 0·56-0·91) and Mexico (0·73, 0·57-0·94) compared with the USA. Clearance of oncogenic HPV was more rapid with increasing age (1·02, 1·01-1·03). INTERPRETATION The data from this study are useful for the development of realistic cost-effectiveness models for male HPV vaccination internationally. FUNDING National Cancer Institute.

Circumcision and sexual behavior: factors independently associated with human papillomavirus detection among men in the HIM study.

There is growing interest in understanding human papillomavirus (HPV) infection and related disease among men. To date there have been numerous studies reporting HPV DNA prevalence among men from several different countries, however, few have incorporated multivariable analyses to determine factors independently associated with male HPV detection. The purpose of this study was to assess the factors independently associated with HPV detection in men ages 18–70 years residing in Brazil (n = 343), Mexico (n = 312), and the United States (US) (n = 333). In samples combined from the coronal sulcus, glans penis, shaft, and scrotum, we evaluated factors associated with any, oncogenic, and nononcogenic HPV infections. In multivariable analyses, detection of any HPV infection was significantly associated with reported race of Asian/Pacific Islander, lifetime and recent number of sexual partners, and having sex in the past 3 months. Oncogenic HPV detection was independently associated with lifetime and recent number of sexual partners, and having sex in the past 3 months. NonOncogenic HPV infection was independently associated with lifetime number of sexual partners. Circumcision, assessed by clinical examination, was associated with reduced risk of HPV detection across all categories of HPV evaluated. HPV detection in men in the current study was strongly related to sexual behavior and circumcision status. Interventions such as circumcision may provide a low‐cost method to reduce HPV infection.

TLR4 single-nucleotide polymorphisms alter mucosal cytokine and chemokine patterns in Mexican patients with Helicobacter pylori-associated gastroduodenal diseases.

Helicobacter pylori is associated with peptic ulcer and gastric adenocarcinoma. Toll-like receptors (TLRs) participate in H. pylori recognition, and single-nucleotide polymorphisms (SNPs) in TLRs are associated with impaired immune response. We aimed to evaluate the association of TLR2/R753Q and TLR4/D299G/T399I SNPs with gastroduodenal diseases; and study the effect of SNPs on cytokine and chemokine expression in the gastric mucosa. Study included 450 Mexican patients with gastroduodenal diseases. SNPs in TLRs 2 and 4 genes were analyzed by allele-specific PCR. Cytokines and chemokines were assessed by qRT-PCR and immunoassay. TLR4/D299G/T399I polymorphisms were more frequent in duodenal ulcer and showed a trend in gastric cancer, when compared with non-atrophic gastritis. Patients with TLR4 polymorphisms expressed significantly lower levels of IL-1beta, IL-6, IL-8 and GRO-alpha; and higher levels of TNF-alpha, IL-10, MCP-1 and MIP-1alpha . SNPs in TLR4 gene had an association with severe H. pylori-associated disease and with modified pattern of inflammatory cytokines and chemokines in the gastric mucosa. These results suggest that TLR4 SNPs contributes importantly to the clinical outcome of H. pylori infection.

Polymorphisms in TNF and HSP-70 show a significant association with gastric cancer and duodenal ulcer.

Tumour Necrosis Factor (TNF) and Heat Shock Protein 70 (HSP70) are important molecules in inflammatory, infectious and tumoral processes. The genes codifying these molecules are polymorphic and certain alleles have been associated with susceptibility to disease. Gastric cancer is associated with an Helicobacter pylori‐induced chronic inflammatory response. The aim of this work was to analyze whether polymorphisms in inflammation‐related genes are associated with the development of gastric cancer. We studied 447 Mexican adult patients including 228 with non‐atrophic gastritis, 98 with intestinal metaplasia, 63 with gastric cancer and 58 with duodenal ulcer, and 132 asymptomatic individuals as well. DNA from peripheral white blood cells was typed for the Single Nucleotide Polymorphisms (SNPs) −308 of TNF‐α, +252 of TNF‐β, +190 of HSP70‐1, +1267 of HSP70‐2 and +2437 of HSP70‐HOM. Compared with the asymptomatic group, we found a significant association of TNF‐β*A and HSP70‐1*C alleles with gastric cancer (OR 5.69 and 3.76, respectively) and HSP70‐1*C with duodenal ulcer (OR 3.08). Genotype TNF‐β G/G showed a significant gene‐dose effect with gastric cancer (OR 0.09); whereas HSP70‐1 C/G showed significant association with both, gastric cancer (OR 13.31) and duodenal ulcer (OR 16.19). Polymorphisms in TNF and HSP70 showed a significant severity‐dose‐response as risk markers from preneoplastic lesions to gastric cancer in Mexican population, probably because of their association with an intense and sustained inflammatory response.

Improving cervical cancer screening in Mexico: results from the Morelos HPV Study

OBJECTIVE The purpose of this paper is to describe some of the results of the Morelos HPV Study. The main objective of the Morelos HPV Study is to evaluate the use of human papillomavirus (HPV) DNA testing, as compared to the Papanicolaou (Pap) test, for cervical cancer (CC) screening. MATERIAL AND METHODS The Morelos HPV Study is currently being conducted in Mexico, to examine the possibility of using HPV testing for CC screening. The HPV testing of self-collected vaginal and clinician-collected cervical specimens was evaluated as part of this study. The acceptability of the HPV testing of self-collected specimens was compared to that of the Pap test. A cost-effectiveness analysis (CEA) and cost-benefit analysis (CBA) was also performed. RESULTS The Morelos HPV Study results indicate that HPV testing has a greater sensitivity to detect cervical intraepithelial neoplasia (CIN) 2/3 and CC than the Pap test. Our results also indicate an over-all lower acceptability of the Pap test as compared to the self-collected procedure. The results of the CEA and CBA indicate that screening women between the ages of 20-80 for CC using some type of HPV testing is always more cost-effective than screening for CC using the Pap test. CONCLUSIONS Our results suggest that self- and clinician-collected HPV testing could be used in CC prevention programs, as an effective complement or substitute for the Pap test. This paper is available too at: http://www.insp.mx/salud.index.html.

High-Risk Human Papillomavirus Detection and Related Risk Factors Among Pregnant and Nonpregnant Women in Mexico

Background: Significant differences in human papillomavirus (HPV) prevalence between pregnant and nonpregnant women have been reported. Some studies suggest that physiological processes during pregnancy modify the host–immune response, increasing detectability of high-risk HPV infection as a result of viral reactivation. It remains uncertain, however, whether pregnancy has an effect on HPV DNA positivity as a result of a general lack of data and based on contradictory results found in previous epidemiologic studies. We conducted an epidemiologic study to identify differences in the prevalence of HPV infection between pregnant and nonpregnant women in Mexico. We also investigated the relationship of HPV DNA positivity with socioeconomic, gynecologic, and obstetric risk factors. Methodology: We screened pregnant and age-matched nonpregnant women for high-risk HPV infection. The study population was clients of the family medicine healthcare services of the Mexican Institute of Social Security in Cuernavaca, Morelos, Mexico. A total of 274 pregnant and 1060 nonpregnant study participants were screened for the presence of high-risk HPV DNA in self-collected specimens by the Hybrid Capture 2 test (HC2; Digene Corp., Gaithersburg, MD). Results: High-risk HPV DNA was detected in 37.2% (95% confidence interval [CI], 31–43%) of pregnant women and in 14.2% (95% CI, 12–16%) of nonpregnant women. Combining both groups for the multivariate analysis, pregnancy was associated with an increased risk for HPV infection (odds ratio, 3.5; CI, 2.7–4.9). Conclusions: Our results are consistent with other studies reporting increased high-risk HPV detection rates among pregnant women. HPV-positive status in pregnant and nonpregnant women appears to be influenced by age. The decrease in HPV positivity by number of pregnancies in both currently pregnant and nonpregnant women is consistent with a possible effect of immune protection as a result of earlier HPV infections. Despite lack of information about a woman’s history of sexual behavior, these data support the hypothesis that an alteration of immunologic responses during pregnancy may be associated with an increased risk of HPV acquisition or reactivation.

Trends in Helicobacter pylori infection and gastric cancer in Mexico.

Infection by Helicobacter pylori affects about 50% of the human population. Of those infected, 10% to 15% will develop peptic ulcer and up to 3% will present with gastric cancer. These estimates suggest that around 7% of the worlds population will eventually develop H. pylori –associated

Design and methods of the evaluation of an HPV-based cervical cancer screening strategy in Mexico: the Morelos HPV study

OBJECTIVE The purpose of this paper is to describe the design and methodology of the Morelos HPV Study. The main objective of this study is to examine the use of two different methods for obtaining HPV DNA specimens, self-collected vaginal and clinician-collected cervical, to detect pre-invasive cervical lesions and cancer. MATERIAL AND METHODS This study was conducted within the regular population-based framework of the Mexican Institute of Social Security (IMSS) cervical cancer screening program in Morelos. A total of 7,868 women were recruited between May and October 1999 and are representative of the population of women attending cervical cancer screening services at the 23 IMSS clinics in the state of Morelos in 1999. Women were provided with a detailed description of the study before signing an informed consent form. Basic data were obtained from all participants using a standard IMSS registration form. During the initial recruitment visit, a randomly selected subsample of 1,069 participants were interviewed to collect additional information about cervical cancer risk factors, acceptability of the HPV and Pap tests, as well as patient costs. Before the pelvic exam, participants were asked to provide a self-collected vaginal specimen for HPV testing. All participants underwent a pelvic examination that involved collecting a cervical sample for the Pap smear and a clinician-collected HPV specimen. Data were evaluated from 7,732 women with complete information for the three tests. The 1,147 women who received at least one positive result (Pap, self- and/or clinician-HPV tests) were invited to return for a colposcopic examination. During colposcopy, biopsies were taken as appropriate, to histologically confirm a diagnosis of cervical intraepithelial neoplasia (CIN) 2/3 or invasive cancer. A total of 1,015 women attended colposcopy, and 101 women received a histologically-confirmed CIN 2/3 or cervical cancer diagnosis. CONCLUSIONS The initial enrollment activities of the Morelos HPV study are the basis for a prevalent case-control study and a prospective cohort study that will investigate the natural history of HPV infections and determine if an HPV-based screening strategy is a safe and cost-effective alternative to Pap screening. The English version of this paper is available too at: http://www.insp.mx/salud/index.html.

Knowledge and Adoption of Community Mitigation Efforts in Mexico During the 2009 H1N1 Pandemic

BACKGROUND The publics ability and willingness to adopt community mitigation efforts during a pandemic are debated in the literature. PURPOSE Awareness and adoption of community mitigation efforts in Mexico during the 2009 pandemic influenza A (H1N1) (pH1N1) outbreak were measured to evaluate if the population received, understood, and acted on public health messages. METHODS A cross-sectional representative household survey in Mexico City; San Luis Potosi (high case ratio); and Queretaro (low case ratio) was conducted in May and June 2009. Accounting for the complex survey design, percentages and 95% CI for answers to all questions were generated and compared based on living inside or outside Mexico City, high versus low prevalence of infection in the community, and perceived severity and knowledge of the virus. RESULTS Greater than 90% of respondents received community mitigation messages and adopted one or more community mitigation efforts. There were few differences among cities. Respondents reported high cost of masks, soaps, and gels as barriers to community mitigation-effort adoption. Nearly one fifth of respondents, disproportionally from the lower socioeconomic tertile, found some messages confusing. Half of all households reported a negative economic impact resulting from the outbreak. CONCLUSIONS Mexicos community mitigation campaign reached the majority of the population in three surveyed cities. Confusion regarding messages and economic barriers to community mitigation-effort adoption were sometimes reported.

Prevalencia de infección por virus de papiloma humano (VPH) de alto riesgo y factores asociados en embarazadas derechohabientes del IMSS en el estado de Morelos

Objective. Some studies suggest the possibility that the physiological process of pregnancy modifies certain characteristics of the mother, increasing the risk of both, infection and persistence of infection with HPV. This association, however, has not been firmly established. This study seeks to determine the prevalence of oncogenic HPV infecton in a sample of pregnant Mexican women and its possible risk factors. Material and Methods. A cross-sectional study was conducted using a sample of 274 pregnant women sought first level of care services during the year 2000 at the antenatal clinic of the Mexican Institute of Social Security (IMSS) in Cuernavaca, Morelos, Mexico. Samples of vaginal cells were obtained through self-collected specimens, for the high-risk HPV DNA test using the Hybrid Capture 2 test (HC2). A structured questionnaire was administered regarding sociodemographic, gynecologic, obstetric and sexual behavior characteristics. Results. The mean age was 25.7 years. The average time of pregnancy when the study was conducted was 6 months. The principal risk factors associated with high-risk HPV infection were: ages between 20 and 29 (OR= 2.82; CI95% 1.02‐7.76)), age 30 and over (OR= 6.85,CI95% 1.22-38.2); partners having sexual relatio