Claudia Hopenhayn

Arsenic exposure from drinking water and birth weight

Background: Arsenic exposures from drinking water increase the risk of various cancers and noncancer health endpoints. Limited evidence suggests that arsenic may have adverse human reproductive effects. We investigated the association between drinking water arsenic exposure and fetal growth, as manifest in birth weight. Methods: We conducted a prospective cohort study in two Chilean cities with contrasting drinking water arsenic levels: Antofagasta (40 &mgr;g/L) and Valparaíso (<1 &mgr;g/L). Study subjects completed in-depth interviews and provided urine samples for exposure analysis. We obtained pregnancy and birth information from medical records. The birth weight analysis was restricted to liveborn, singleton infants born between December 1998 and February 2000. Results: The final study group consisted of 424 infants from Antofagasta and 420 from Valparaíso. After controlling for confounders, results of the multivariable analysis indicated that Antofagasta infants had lower mean birth weight (–57 g; 95% confidence interval = –123 to 9). Conclusion: This study suggests that moderate arsenic exposures from drinking water (<50 &mgr;g/L) during pregnancy are associated with reduction in birth weight, similar in magnitude to that resulting from other environmental exposures such as environmental tobacco smoke and benzene.

US Assessment of HPV Types in Cancers: Implications for Current and 9-Valent HPV Vaccines

BACKGROUND This study sought to determine the prevaccine type-specific prevalence of human papillomavirus (HPV)-associated cancers in the United States to evaluate the potential impact of the HPV types in the current and newly approved 9-valent HPV vaccines. METHODS The Centers for Disease Control and Prevention partnered with seven US population-based cancer registries to obtain archival tissue for cancers diagnosed from 1993 to 2005. HPV testing was performed on 2670 case patients that were fairly representative of all participating cancer registry cases by age and sex. Demographic and clinical data were evaluated by anatomic site and HPV status. Current US cancer registry data and the detection of HPV types were used to estimate the number of cancers potentially preventable through vaccination. RESULTS HPV DNA was detected in 90.6% of cervical, 91.1% of anal, 75.0% of vaginal, 70.1% of oropharyngeal, 68.8% of vulvar, 63.3% of penile, 32.0% of oral cavity, and 20.9% of laryngeal cancers, as well as in 98.8% of cervical cancer in situ (CCIS). A vaccine targeting HPV 16/18 potentially prevents the majority of invasive cervical (66.2%), anal (79.4%), oropharyngeal (60.2%), and vaginal (55.1%) cancers, as well as many penile (47.9%), vulvar (48.6%) cancers: 24 858 cases annually. The 9-valent vaccine also targeting HPV 31/33/45/52/58 may prevent an additional 4.2% to 18.3% of cancers: 3944 cases annually. For most cancers, younger age at diagnosis was associated with higher HPV 16/18 prevalence. With the exception of oropharyngeal cancers and CCIS, HPV 16/18 prevalence was similar across racial/ethnic groups. CONCLUSIONS In the United States, current vaccines will reduce most HPV-associated cancers; a smaller additional reduction would be contributed by the new 9-valent vaccine.

Arsenic Methylation and Bladder Cancer Risk in Case-Control Studies in Argentina and the United States

Objective: We sought to assess whether the metabolism of arsenic impacts a persons susceptibility to bladder cancer. Methods: Urinary methylation products were measured in subjects from Argentina (114 cases and 114 controls) and the United States (23 cases and 49 controls). Results: In Argentina, the adjusted odds ratio (OR) for subjects with a high proportion of ingested arsenic excreted as monomethylarsonate (%MMA) was 2.17 (95% confidence interval [CI] = 1.02–4.63) in smokers and 0.48 (95% CI = 0.17–1.33) in nonsmokers. In the United States, the adjusted ORs for high %MMA in subjects with arsenic intakes less than and greater than 100 &mgr;g/d were 1.20 (95% CI = 0.27–5.38) and 2.70 (95% CI = 0.39–18.6). Conclusions: Overall, these results are consistent with data from Taiwan suggesting that some individuals who excrete a higher proportion of ingested arsenic as MMA are more susceptible to arsenic-related cancer.

Genetic Polymorphisms in MTHFR 677 and 1298, GSTM1 and T1, and Metabolism of Arsenic

Methylation is the primary route of metabolism of inorganic arsenic in humans, and previous studies showed that interindividual differences in arsenic methylation may have important impacts on susceptibility to arsenic-induced cancer. To date, the factors that regulate arsenic methylation in humans are mostly unknown. Urinary arsenic methylation patterns and genetic polymorphisms in methylenetetrahydrofolate reductase (MTHFR) and glutathione S-transferase (GST) were investigated in 170 subjects from an arsenic-exposed region in Argentina. Previous studies showed that subjects with the TT/AA polymorphisms at MTHFR 677 and 1298 have lower MTHFR activity than others. In this study, it was found that subjects with the TT/AA variant of MTHFR 677/1298 excreted a significantly higher proportion of ingested arsenic as inorganic arsenic and a lower proportion as dimethylarsinic acid. Women with the null genotype of GSTM1 excreted a significantly higher proportion of arsenic as monomethylarsonate than women with the active genotype. No associations were seen between polymorphisms in GSTT1 and arsenic methylation. This is the first study to report (1) associations between MTHFR and arsenic metabolism in humans, and (2) gender differences between genetic polymorphisms and urinary arsenic methylation patterns. Overall, this study provides evidence that MTHFR and GSTM1 are involved in arsenic metabolism in humans, and polymorphisms in the genes that encode these enzymes may play a role in susceptibility to arsenic-induced cancer.

Violence against Women Raises Risk of Cervical Cancer

BACKGROUND An emerging literature suggests that violence against women (VAW), particularly sexual violence, may increase the risk of acquiring a sexually transmitted infection (STI) and, therefore, may be associated with cervical cancer development. The purpose of this cross-sectional analysis was to determine if women who had experienced violence had higher prevalence rates of invasive cervical cancer. METHODS Women aged 18-88 who joined the Kentucky Womens Health Registry (2006-2007) and completed a questionnaire were included in the sample. Multivariate logistic regression analyses were used to adjust odds ratio (OR) for confounders (e.g., age, education, current marital status, lifetime illegal drug use, and pack-years of cigarette smoking). RESULTS Of 4732 participants with no missing data on violence, cervical cancer, or demographic factors, 103 (2.1%) reported ever having cervical cancer. Adjusting for demographic factors, smoking, and illegal drug use, experiencing VAW was associated with an increased prevalence of invasive cervical cancer (adjusted OR [aOR] = 2.6, 95% CI = 1.7-3.9). This association remained significant when looking at three specific types of VAW: intimate partner violence (IPV) (aOR = 2.7, 95% CI = 1.8-4.0), adult exposure to forced sex (aOR = 2.6, 95% CI = 1.6-4.3), and child exposure to sexual abuse (aOR = 2.4, 95% CI = 1.4-4.0). CONCLUSIONS Rates of cervical cancer were highest for those experiencing all three types of VAW relative to those never experiencing VAW. Because VAW is common and has gynecological health effects, asking about VAW in healthcare settings and using this information to provide tailored healthcare may improve womens health outcomes.

Human papillomavirus vaccine: knowledge and attitudes in two Appalachian Kentucky counties

ObjectiveA vaccine against common high-risk types of human papillomavirus (HPV) associated with cervical cancer risk was recently approved. We assessed women’s acceptance of HPV vaccination for themselves and for adolescent girls, in an Appalachian population with cervical cancer incidence and mortality rates among the highest in the United States.MethodsWe conducted a population-based, random-digit telephone survey of over 600 adult women residing in two Appalachian Kentucky counties. The analysis focused on questions of HPV vaccine acceptance, and their relationship to several factors.ResultsThe majority of women indicated an interest in HPV vaccination for themselves (85.2%), but they were less accepting of a vaccine being administrated to girls of ages 10–15 (67.6%). Women who were younger, lower-income and smokers were more likely to support vaccination.ConclusionsAlthough a relatively high percentage of women found the HPV vaccination acceptable for their own use, there was less enthusiasm for supporting vaccination to girls. This finding is of concern since the vaccine is being recommended for adolescent girls and young women, prior to sexual initiation. Educational campaigns will be needed for a successful vaccine implementation.

Human Papillomavirus Prevalence in Oropharyngeal Cancer before Vaccine Introduction, United States

We conducted a study to determine prevalence of HPV types in oropharyngeal cancers in the United States and establish a prevaccine baseline for monitoring the impact of vaccination. HPV DNA was extracted from tumor tissue samples from patients in whom cancer was diagnosed during 1995–2005. The samples were obtained from cancer registries and Residual Tissue Repository Program sites in the United States. HPV was detected and typed by using PCR reverse line blot assays. Among 557 invasive oropharyngeal squamous cell carcinomas, 72% were positive for HPV and 62% for vaccine types HPV16 or 18. Prevalence of HPV-16/18 was lower in women (53%) than in men (66%), and lower in non-Hispanic Black patients (31%) than in other racial/ethnic groups (68%–80%). Results indicate that vaccines could prevent most oropharyngeal cancers in the United States, but their effect may vary by demographic variables.

Acceptance of the HPV vaccine for adolescent girls: analysis of state-added questions from the BRFSS.

PURPOSE Previous research regarding human papillomavirus (HPV) awareness and vaccine acceptance has relied on convenience or other selected samples of the population. To assess the prevalence of HPV awareness and vaccine acceptance in Kentucky we added questions to the 2006 Kentucky Behavioral Risk Factor Survey System (BRFSS), a population-based survey of health behaviors. METHODS Women who participated in the statewide BRFSS were asked two HPV-related questions: one assessed previous awareness of HPV, and another assessed vaccine acceptance for girls 10 to 15 years old. We used crosstabulations and multivariate logistic regression to determine which factors were associated with HPV awareness and vaccine acceptance. Because the HPV vaccine Gardasil was approved in June 2006, we conducted an analysis of pre- and postapproval HPV awareness and vaccine acceptance. We also compared results across Appalachian and non-Appalachian counties, two distinct regions of Kentucky. RESULTS Overall, 57.6% of women had heard of HPV, and 70.2% accepted vaccination for girls. HPV awareness increased after Gardasils approval, but the increase was much smaller among Appalachian women. Prevalence of vaccine acceptance was unchanged in both regions. Awareness of HPV was not associated with vaccine acceptance, and factors significantly associated with vaccine acceptance in multivariate analysis differed by Appalachian status. CONCLUSIONS This population-based survey of Kentucky women found relatively high vaccine acceptance for girls. Also, many respondents reported not knowing whether they accept vaccination, and factors associated with vaccine acceptance varied by Appalachian status. These findings suggest that acceptance of the HPV vaccine for girls may improve with targeted interventions.

Prevalence of human papillomavirus types in invasive vulvar cancers and vulvar intraepithelial neoplasia 3 in the United States before vaccine introduction.

Objective The study aimed to determine the baseline prevalence of human papillomavirus (HPV) types in invasive vulvar cancer (IVC) and vulvar intraepithelial neoplasia 3 (VIN 3) cases using data from 7 US cancer registries. Materials and Methods Registries identified eligible cases diagnosed in 1994 to 2005 and requested pathology laboratories to prepare 1 representative block for HPV testing on those selected. Hematoxylin-eosin–stained sections preceding and following those used for extraction were reviewed to confirm representation. Human papillomavirus was detected using L1 consensus polymerase chain reaction (PCR) with PGMY9/11 primers and type-specific hybridization, with retesting of samples with negative and inadequate results with SPF10 primers. For IVC, the confirmatory hematoxylin-eosin slides were re-evaluated to determine histological type. Descriptive analyses were performed to examine distributions of HPV by histology and other factors. Results Human papillomavirus was detected in 121/176 (68.8%) cases of IVC and 66/68 (97.1%) cases of VIN 3 (p < .0001). Patients with IVC and VIN 3 differed by median age (70 vs 55 y, p = .003). Human papillomavirus 16 was present in 48.6% of IVC cases and 80.9% of VIN 3 cases; other high-risk HPV was present in 19.2% of IVC cases and 13.2% of VIN 3 cases. Prevalence of HPV differed by squamous cell carcinoma histological subtype (p < .0001) as follows: keratinizing, 49.1% (n = 55); nonkeratinizing, 85.7% (n = 14), basaloid, 92.3% (n = 14), warty 78.2% (n = 55), and mixed warty/basaloid, 100% (n = 7). Conclusions Nearly all cases of VIN 3 and two thirds of IVC cases were positive for high-risk HPV. Prevalence of HPV ranged from 49.1% to 100% across squamous cell carcinoma histological subtypes. Given the high prevalence of HPV in IVC and VIN 3 cases, prophylactic vaccines have the potential to decrease the incidence of vulvar neoplasia.

Variability of cervical cancer rates across 5 Appalachian states, 1998–2003†‡

Although the rates of invasive cervical cancer (ICC) have decreased substantially in the US since the advent of the Papanicolaou (Pap) test, Appalachian women remain at increased risk compared with the nation as a whole. The ICC incidence rates were compared in 5 Appalachian states with population‐based cancer registries to investigate variability within the Appalachian region.