Cristina Muñoz

Cross-sectional study of HPV-16 infection in a population-based subsample of Hispanic adults

Objective This study aimed to estimate the prevalence and correlates of seropositivity to human papillomavirus (HPV)-16 in a subsample of adults who participated in the parent study Epidemiology of Hepatitis C in the adult population of Puerto Rico (PR). Setting The parent study was a population-based household survey aimed to estimate the seroprevalence of hepatitis C and other viral infections (hepatitis A, hepatitis B, HIV, and herpes simplex type 2) in PR (n=1654) between 2005 and 2008. Participants A subsample of the last 450 consecutive adults aged 21–64 years, recruited between February 2007 and January 2008, who participated in the parent study and agreed to participate in HPV testing. Primary and secondary outcome measures The samples were tested by ELISA for HPV-16 viral-like particle-specific immunoglobulin G. Information on sociodemographic, health, and lifestyle characteristics was collected. Logistic regression modelling was used to estimate the prevalence odds ratio (POR) to assess factors associated to HPV-16 seropositivity. Results Prevalence of seropositivity to HPV-16 was 11.3%. Seroprevalence was higher in women (15.8%) than men (5.6%; p=0.001). After adjusting for age and sex, ever smokers (POR 2.06, 95% CI 1.08 to 3.92) and participants with at least five lifetime sexual partners (POR 2.91, 95% CI 1.24 to 6.81) were more likely to be HPV-16 seropositive. Conclusions HPV-16 seropositivity is similar to that reported in the USA (10.4%) for NHANES 2003–2004 participants, although different assays were used in these studies. While future studies should evaluate HPV seroprevalence using a larger population-based sample, our results highlight the need to further understand the burden of HPV infection and HPV-related malignancies in PR, population with a low vaccine uptake.

Prevalence, genotyping, and correlates of anogenital HPV infection in a population-based sample of women in Puerto Rico

Background Oncogenic HPV infection is associated to anogenital cancer. We estimate the prevalence and correlates of anogenital HPV infection among a population-based sample of women aged 16–64 years living in the metropolitan area of Puerto Rico. Methods 564 women completed face-to-face and computer assisted interviews and self-collected anal and cervical specimens. HPV DNA testing used MY09/MY11 consensus HPV L1 primers and beta-globin as an internal control for sample amplification. Positive specimens were typed by dot-blot hybridization. Results Weighted prevalence of cervical, anal, and cervical/anal co-infection was 29.4%, 38.6%, and 17.1%, respectively. The commonest oncogenic HPV types detected in the cervix and anus were: 68 (8% vs. 7%) and 16 (5.5% vs. 5.1%), correspondingly. Having ≥3 lifetime sexual partners (OR: 2.3; 95% CI: 1.5–3.5) and last year anal intercourse (OR: 1.6; 95% CI: 1.1–2.5) increased the odds of anogenital HPV infection. Cervical infection was independently associated to anal infection (OR: 3.0; 95% CI: 2.0–4.6). Conclusions Similar to others, our results confirm the burden of anogenital HPV infection in women and its relationship with sexual behavior. As vaccination increases, future studies should monitor changing trends in HPV infection in this population, and the relationship between anal and cervical HPV-related disease.

Periodontitis and oral human papillomavirus infection among Hispanic adults

Introduction Research on the association between periodontitis and oral human papilloma virus (HPV) infection is inconsistent. The cross-sectional association of severe periodontitis with oral HPV infection was investigated in a sample of Hispanic adults. Methods Data from the 2014–2016 San Juan Overweight Adults Longitudinal Study (n = 740) was analyzed. Periodontitis assessment and self-collection of oral HPV samples followed the National Health and Nutrition Examination Survey methodology. Periodontitis was defined using the Centers of Disease Control and Prevention/American Academy of Periodontology definition. HPV typing was performed using polymerase chain reaction. Multivariate logistic regression models were used to calculate odds ratios (ORs) and 95% confidence intervals (CIs). Results 5.7% of participants had oral HPV infection and 20.3% had severe periodontitis. Adults with severe periodontitis had higher odds of oral HPV infection than those with none/mild disease (OR=2.9, 95% CI: 1.0–8.4, p < 0.05) in multivariable analysis. Adults with clinical attachment loss≥ 7 mm and pocket depth PD≥ 6 mm had 2- to 3-fold higher odds of HPV infection. Conclusions Severe periodontitis was positively associated to oral HPV infection. Longitudinal evaluation of periodontal inflammations role in acquisition and persistence of oral HPV infection is needed, as periodontitis screening could identify individuals at increased risk of HPV-related oral malignancies.

Seroprevalence of HPV 6, 11, 16 and 18 and correlates of exposure in unvaccinated women aged 16–64 years in Puerto Rico

Background To understand risk factors for HPV exposure in Puerto Rican women, we evaluated HPV 6, 11, 16, and 18 serology in women aged living in the San Juan metropolitan area. Methods As part of a cross-sectional study, a population-based sample of 524 HPV unvaccinated Hispanic women ages 16–64 years completed face-to-face and computer assisted interviews and provided blood and self-collected anal and cervical specimens. Serology used multiplex virus-like particle based-IgG ELISA and HPV DNA was detected with L1-consensus PCR. Results 32% and 47% were seropositive to HPV types included in the bivalent (16/18) and quadrivalent (6/11/16/18) vaccines, respectively. Type-specific seroprevalence was HPV6 − 29%, HPV11 − 18%, HPV16 − 23%, and HPV18 − 17%; seroprevalence was high in the youngest age-group (16–19: 26–37%). HPV seropositivity was associated with having ≥ 3 lifetime sexual partners (OR=2.5, 95% CI=1.7–3.9) and detection of anogenital HPV DNA (OR=1.8, 95% CI=1.2–2.6). Conclusions The high cumulative exposure of HPV vaccine types 6/11/16/18 in this Hispanic population was influenced by factors related to HPV exposure through sexual behavior. High seroprevalence in the youngest age-group indicates early age of exposure to HPV in Puerto Rico, highlighting the need for HPV vaccination starting prior to age 16.

Same-Sex Behavior and its Relationship with Sexual and Health-Related Practices Among a Population-Based Sample of Women in Puerto Rico: Implications for Cancer Prevention and Control

ABSTRACT This secondary data analysis aimed to estimate the prevalence of same-sex behavior and sexual and health-related practices of a population-based sample (n = 560) of women aged 16–64 years in Puerto Rico (PR). Data collection included interviews and biologic samples. Seven percent of the sample had had sex with other women (WSW). Age-adjusted logistic regression models indicated that WSW had higher odds of history of cancer, having ≥ 7 lifetime sexual partners, using sex toys and sharing them, and use of tobacco and illicit drugs. Future research is needed to address the health needs of WSW, including cancer-related risk factors and sexual practices.

Abstract B29: Case-control study of metabolic syndrome and breast cancer in Puerto Rico

Background: Breast cancer is the leading cancer type among women in the United States (US) and Puerto Rico (PR); incidence rates of breast cancer have increased in both of these populations in the last decades. In fact, Puerto Rico has highest prevalence of diabetes among all US states and territories. Diabetes, obesity and the metabolic syndrome (MS) are rapidly increasing in Hispanic populations, and research on the impact of these conditions on breast cancer among Hispanics is scarce. Objectives: This study assessed the association of MS with breast cancer among Hispanic women in PR. The secondary aim was to assess the association of the individual components of the MS (hyperglycemia, dyslipidemia, abdominal obesity and elevated blood pressure) with breast cancer. Methods: A matched clinic-based case-control study of 226 Hispanic women was performed between 2011 and 2013. One hundred thirteen cases and 113 controls were recruited in four clinics/hospitals in Puerto Rico and were individually matched by age (±5 years), menopausal status and recruitment site (response rate of 83% for cases and 84% of controls). Data collection procedures included a structured questionnaire, anthropometric and blood pressure measurements. According to the AHA/NHLBI definition, a woman was defined to have the MS if she had at least 3 of the following risk factors: waist circumference ≥35 inches, 2) triglycerides ≥150 mg/dL, 3) HDL Results: Mean age of participants was 54.5 ±12.6 years. Prevalence of the MS was 53.2% among cases and 42.0% among controls. No significant differences were observed between cases and controls with regard to income, health care coverage, parity or smoking habits. Nonetheless, cases had significantly (p Conclusions: This pilot study found marginal evidence of an association of the MS and elevated fasting glucose with breast cancer in a population of Hispanic origin. Future studies should assess this association using a larger sample size and considering the impact of tumor subtypes on breast cancer risk. Grant Support: The project was supported by U54CA96297 and U54CA96300 from the UPR/MDACC Partnership for Excellence in Cancer Research, NCI & by the RCMI-Clinical Research Center grant G12RR03051 from the UPR Medical Sciences Campus. Citation Format: Ana Patricia Ortiz, Cynthia Perez, Edna Mora, Damarys Santiago, Carola T. Sanchez, Cristina Munoz, Marievelisse Soto, Mong-Hong Lee. Case-control study of metabolic syndrome and breast cancer in Puerto Rico. [abstract]. In: Proceedings of the Sixth AACR Conference: The Science of Cancer Health Disparities; Dec 6–9, 2013; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2014;23(11 Suppl):Abstract nr B29. doi:10.1158/1538-7755.DISP13-B29

Abstract 4783: Expression of genes panel related to WNT- signaling in colorectal cancer Human Papillomavirus-positive colorectal cancer.

Proceedings: AACR 104th Annual Meeting 2013; Apr 6-10, 2013; Washington, DC The Wnt signaling pathway is conserved in various species and plays significant roles in development, cellular proliferation and differentiation. WNT signaling comprises three pathways: the canonical pathway and two non-canonical pathways. Moreover, it is generally accepted that both dysfunction of the Wnt signaling pathway, including mutations in the adenomatous polyposis coli (APC) and b-catenin genes, and genetic instability play important roles in colorectal carcinogenesis. However, alterations of the components of the Wnt signaling pathways in CRC have not been totally elucidated. Several studies support a possible role of Human Papillomavirus in colorectal carcinogenesis. The aim of this study was to comprehensively investigate the expression profiles of Wnt signaling components in HPV-positive and HPV-negative CRC cases using real-time PCR analysis. Methods: To determine the expression profile of the association of HPV and CRC, we conducted an age-matched case study in four HPV-positive and four HPV-negative CRC cases. We employed the Human WNT Signaling Pathway RT² Profiler PCR Array (Qiagen) to assay the expression of 84 genes related to WNT-mediated signal transduction. This array contains WNT signaling ligands and receptors as well as other downstream signaling molecules for all three WNT pathways. Results were evaluated with the RT² PCR Data Analysis Software provided by Qiagen. Results: Four male HPV-positive CRC cases (mean ages was 56 ± 2 years) and four HPV-negative CRC cases (mean ages 57 ± 2 years) were analyzed using the RT² Profiler™ PCR Array Human WNT Signaling Pathway (Qiagen). We detected a decrease in the expression levels of three WNT-canonical signaling molecules in HPV-positive CRC cases when compared to HPV-negative cases. The BCL9, LRP5 and WNT3 showed a 39% (p = 0.049), 43% (p = 0.020) and 60% (p=0.038) decrease in expression in HPV-positive cases, respectively. Reduced expression of three WNT signaling negative regulator genes was also observed: CTMP1 decreased 49% (p= 0.006), CXX4 decreased 49% (p=0.029) and FBXW11 expression decreased 41% (p = 0.041). Conclusion: Our findings suggest that colorectal tumors infected with HPV could define a non-described subtype of CRC based in the expression of a focused panel of genes related to WNT-mediated signal transduction. These results suggest an alteration of the WNT canonical pathway as a consequence of HPV infection in CRC. Citation Format: Raul D. Bernabe-Dones, Sharon C. Fonseca-Williams, Mercedes Y. Lacourt-Ventura, Cristina Munoz, Maribel Tirado-Gomez, Marcia R. Cruz-Correa. Expression of genes panel related to WNT- signaling in colorectal cancer Human Papillomavirus-positive colorectal cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4783. doi:10.1158/1538-7445.AM2013-4783

Abstract 3609: Factors associated to concurrent anal and cervical HPV infection: Results from a population-based study among Hispanics.

Objective: Persistent infection with certain types of HPV is associated with cervical and anal cancer, accounting for 96% and 93% of these tumors in the US. Population-based data on anal and cervical HPV co-infection among Hispanics is limited. We aimed to estimate the concordance between cervical and anal HPV infection among a population-based sample of 600 women aged 16 to 64 years living in the San Juan Metropolitan area of Puerto Rico (PR). Methods: The study population for this cross-sectional study (2010-2012) was identified through a cluster probability sampling design of households in the San Juan Metropolitan Area, and included non-institutionalized women aged 16-64 years old residing in this area. Women completed a face-to-face interview conducted by female trained data collectors and a computer-assisted self-interview, using the Audio CASI system for the collection of demographic and lifestyle variables. Anal and cervical specimens were collected through previously tested self-collection methods and HPV DNA testing was performed using a modified pool of MY09/MY11 consensus HPV L1 primers as well as primers for amplification of the human beta-globin gene. PCR products from positive samples were typed by dot-blot hybridization using 39 individual type-specific probes. Logistic regression models were used to assess factors associated to concurrent cervical and anal HPV infection. Results: Mean age of participants is 42.0 years (±13.4 SD), 19.3% have Conclusions: Co-infection with HPV infection in the cervix and anus is common among Hispanic women in PR, and is associated with younger age and increased number of sexual partners. Given the current low uptake of the HPV vaccine in PR, public health interventions that increase vaccine accessibility and uptake in this population are warranted, as a method for cervical and anal cancer prevention. Citation Format: Ana P. Ortiz-Martinez, Edmir Marrero-Estrada, Marievelisse Soto-Salgado, Cynthia Perez, Erick Suarez, Josefina Romaguera, Cristina Munoz, Maria Da Costa, Joel Palefsky, Guillermo Tortolero-Luna. Factors associated to concurrent anal and cervical HPV infection: Results from a population-based study among Hispanics. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3609. doi:10.1158/1538-7445.AM2013-3609

Abstract 5569: DNA methylation status of MLH1, p16, SOCS1, ER and CDH1 in Puerto Rican patients with acute myeloid leukemia

Proceedings: AACR 103rd Annual Meeting 2012‐‐ Mar 31‐Apr 4, 2012; Chicago, IL Background: DNA methylation of gene promoters have been show to play a role in the pathogenesis of acute myeloid leukemia (AML). We present in this study a preliminary report of the methylation status of MLH1, p16, SOCS1, ER and CDH1 in Puerto Rican patients with AML. Methods: Peripheral blood was obtained from 24 patients with diagnosis of acute myeloid leukemia before and after their induction treatments. DNA was isolated and further modified with sodium bisulfite. Methylation-specific polymerase (MSP) chain reaction was performed to detect aberrant promoter methylation of MLH1, p16, SOCS1, ER and CDH1. Results: Samples from a total of 24 patients were analyzed. The mean age was 47 years (range 22-70) with 21/24 patients younger than 60 years (88%). Most of the patients were female (13/24, 54%). Ten patients had diploid cytogenetics (42%), 4 had low risk cytogenetics (17%) and 10 had high risk cytogenetics (42%). Nineteen patients were de Novo AML (79%). Sixteen patients (67%) presented with WBC counts higher than 10 x 109/L. Seventeen patients (71%) achieved a complete response at the end of the induction therapy. Frequencies of gene methylation before treatment were as follows: MLH: 3/24 (13%); p16: 6/24 (25%); SOCS1:13/24 (54%); ER: 16/24 (67%) and CDH1: 4/24 (16.7%). Conclusions: No correlation between methylation status of p16 and MLH1 before treatment and clinicopathological characteristics was noted. Unmethylated CDH1 was more common among the novo AML patients. Methylation of SOCS1 was more common among patients that achieve a CR after induction therapy. This sample is a small one, so any correlation must be further tested in a more ample sample. Collection of more patients samples and correlation with clinical data and patients ultimate outcome is ongoing. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5569. doi:1538-7445.AM2012-5569

Abstract 2766: DNA methylation status of MLH1, p16 and SOCS1 in Puerto Rican patients with acute myeloid leukemia

Proceedings: AACR 102nd Annual Meeting 2011‐‐ Apr 2‐6, 2011; Orlando, FL Background: DNA methylation of gene promoters have been show to play a role in the pathogenesis of acute myeloid leukemia. We present in this study a preliminary report of the methylation status of MLH1, p16 and SOCS1 in Puertorrican patients with acute myeloid leukemia Methods: Peripheral blood was obtained from 24 patients with diagnosis of acute myeloid leukemia before their induction treatments. DNA was isolated and further modified with sodium bisulfite. Methylation-specific polymerase (MSP) chain reaction was performed to detect aberrant promoter methylation of MLH1, p16 and SOCS1. Results: A total of 24 samples were analyzed. The mean age was 49 years (range 22-71) with 17/24 patients younger than 60 years (71%). Most of the patients were female (13/24, 54%). Six patients had diploid cytogenetics (25%), 6 had low risk cytogenetics (25%) and 12 had high risk cytogenetics (50%). Fifteen patients were de Novo AML (63%). Nine patients (38%) presented with WBC counts higher than 10 × 109/L. Thirteen patients (54%) achieved a complete response at the end of the induction therapy. Methylation of MLH1 was detected in 3/24 patients (13%). Methylation of p16 was detected in 5/24 patients (21%). Methylation of SOCS1 was detected in 2/24 patients (8%). Conclusions: A tendency toward an association of methylated p16 with treatment resistance was noted. Also, methylation of SOCS1 was more common among relapsed AML patients. No correlation between methylated MLH1 gene and clinicopathological characteristics was noted. Collection of more patients samples and correlation with clinical data and patients ultimate outcome is ongoing. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2766. doi:10.1158/1538-7445.AM2011-2766