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.

Human papillomavirus genotype prevalence in invasive vaginal cancer from a registry-based population.

OBJECTIVE: To describe the human papillomavirus (HPV) genotype distribution in invasive vaginal cancers diagnosed before the introduction of the HPV vaccine and evaluate if survival differed by HPV status. METHODS: Four population-based registries and three residual tissue repositories provided formalin-fixed, paraffin-embedded tissue from microscopically confirmed primary vaginal cancer cases diagnosed between 1994 and 2005 that were tested by L1 consensus polymerase chain reaction with type-specific hybridization in a central laboratory. Clinical, demographic, and all-cause survival data were assessed by HPV status. RESULTS: Sixty cases of invasive vaginal cancer were included. Human papillomavirus was detected in 75% (45) and 25% (15) were HPV-negative. HPV 16 was most frequently detected (55% [33/60]) followed by HPV 33 (18.3% [11/60]). Only one case was positive for HPV 18 (1.7%) Multiple types were detected in 15% of the cases. Vaginal cancers in women younger than 60 years were more likely to be HPV 16- or HPV 18-positive (HPV 16 and 18) than older women, 77.3% compared with 44.7% (P=.038). The median age at diagnosis was younger in the HPV 16 and 18 (59 years) group compared with other HPV-positive (68 years) and no HPV (77 years) (P=.003). The HPV distribution did not significantly vary by race or ethnicity or place of residence. The 5-year unadjusted all-cause survival was 57.4% for women with HPV-positive vaginal cancers compared with 35.7% among those with HPV-negative tumors (P=.243). CONCLUSION: Three fourths of all vaginal cancers in the United States had HPV detected, much higher than previously found, and 57% could be prevented by current HPV vaccines.

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.

Human papillomavirus genotype prevalence in invasive penile cancers from a registry-based United States population.

BACKGROUND: Human papillomavirus (HPV) is estimated to play an etiologic role in 40-50% of penile cancers worldwide. Estimates of HPV prevalence in U.S. penile cancer cases are limited. METHODS: HPV DNA was evaluated in tumor tissue from 79 invasive penile cancer patients diagnosed in 1998-2005 within the catchment areas of seven U.S. cancer registries. HPV was genotyped using PCR-based Linear Array and INNO-LiPA assays and compared by demographic, clinical, and pathologic characteristics and survival. Histological classification was also obtained by independent pathology review. RESULTS: HPV DNA was present in 50 of 79 (63%) of invasive penile cancer cases. Sixteen viral genotypes were detected. HPV 16, found in 46% (36/79) of all cases (72% of HPV-positive cases) was the most prevalent genotype followed equally by HPV 18, 33, and 45, each of which comprised 5% of all cases. Multiple genotypes were detected in 18% of viral positive cases. HPV prevalence did not significantly vary by age, race/ethnicity, population size of geographic region, cancer stage, histology, grade, penile subsite, or prior cancer history. Penile cases diagnosed in more recent years were more likely to be HPV-positive. Overall survival did not significantly vary by HPV status. CONCLUSION: The relatively high prevalence of HPV in our study population provides limited evidence of a more prominent and, possibly, increasing role of infection in penile carcinogenesis in the U.S. compared to other parts of the world.

Prevalence of human papillomavirus types in invasive cervical cancers from 7 US cancer registries before vaccine introduction.

OBJECTIVE: We conducted a baseline study of human papillomavirus (HPV) type prevalence in invasive cervical cancers (ICCs) using data from 7 cancer registries (CRs) in the United States. Cases were diagnosed between 1994 and 2005 before the implementation of the HPV vaccines. MATERIALS AND METHODS: Cancer registries from Florida, Kentucky, Louisiana, Michigan, Hawaii, Iowa, and Los Angeles, California identified eligible ICC cases and obtained sections from representative blocks of archived tumor specimens for DNA extraction. All extracts were assayed by linear array and, if inadequate or HPV negative, retested with INNO-LiPA Genotype test. Clinical and demographic factors were obtained from the CRs and merged with the HPV typing data to analyze factors associated with different types and with HPV negativity. RESULTS: A total of 777 ICCs were included in this analysis, with broad geographic, age, and race distribution. Overall, HPV was detected in 91% of cases, including 51% HPV-16, 16% HPV-18 (HPV-16-negative), and 24% other oncogenic and rare types. After HPV-16 and -18, the most common types were 45, 33, 31, 35, and 52. Older age and nonsquamous histology were associated with HPV-negative typing. CONCLUSIONS: This study provides baseline prevaccine HPV types for postvaccine ICC surveillance in the future. HPV-16 and/or -18 were found in 67% of ICCs, indicating the potential for vaccines to prevent a significant number of cervical cancers.

Human papillomavirus prevalence in invasive anal cancers in the United States before vaccine introduction.

OBJECTIVE: This study aimed to conduct a representative survey of human papillomavirus (HPV) prevalence and its genotype distribution in invasive anal cancer specimens in the United States. MATERIALS AND METHODS: Population-based archival anal cancer specimens were identified from Florida, Kentucky, Louisiana, and Michigan cancer registries and Surveillance, Epidemiology, and End Results (SEER) tissue repositories in Hawaii, Iowa, and Los Angeles. Sections from 1 representative block per case were used for DNA extraction. All extracts were assayed first by linear array and retested with INNO-LiPA if inadequate or HPV negative. RESULTS: Among 146 unique invasive anal cancer cases, 93 (63.7%) were from women, and 53 (36.3%) were from men. Human papillomavirus (any type) was detected in 133 cases (91.1%) and 129 (88.4%) contained at least 1 high risk-type, most (80.1%) as a single genotype. Human papillomavirus type 16 had the highest prevalence (113 cases, 77.4%); HPV types 6, 11, 18, and 33 were also found multiple times. Among HPV-16-positive cases, 37% were identified as prototype variant Ep, and 63% were nonprototypes: 33% Em, 12% E-G131G, 5% Af1, 4% AA/NA-1, 3% E-C109G, 3% E-G131T, 2% As, and 1% Af2. No significant differences in the distributions of HPV (any), high-risk types, or HPV-16/18 were seen between sex, race, or age group. CONCLUSIONS: The establishment of prevaccine HPV prevalence in the United States is critical to the surveillance of vaccine efficacy. Almost 80% of anal cancers were positive for the vaccine types HPV-16 or HPV-18, and in 70%, these were the only types detected, suggesting that a high proportion might be preventable by current vaccines.

Factors associated with smoking abstinence after diagnosis of early stage lung cancer.

Smoking cessation after a diagnosis of lung cancer is associated with improved outcomes, including quality of life and survival. The research presented here is based on data obtained from sequential interviews with early stage lung cancer patients in Kentucky, on their smoking patterns at four time points: (1) six months before enrollment in the study, before diagnosis, (2) at enrollment (shortly after surgical resection), (3) three months post-enrollment, and (4) six months post-enrollment. A number of covariates were considered to examine the factors associated with smoking abstinence and rebound trajectories. The results indicate that, while about 75% of patients who were smoking at six months before enrollment had quit by the first post-surgery interview, almost 50% of them had returned to smoking six months later. Multivariate analysis to evaluate the relative contribution of covariates indicated that low household income, exposure to environmental tobacco smoke at home and evidence of depression were positively associated with returning to smoking. Furthermore, even after controlling for these factors, patients from the Appalachian region of Kentucky, an area with substantially high smoking prevalence and very high lung cancer incidence rates, were less likely to abstain from smoking throughout the study than subjects in the rest of the state. Future research is suggested to investigate in more detail the tobacco-related behaviors and cessation attempts of patients and their families, which can lead to more targeted, successful smoking cessation interventions for lung cancer patients.

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.

Atrazine exposure in public drinking water and preterm birth.

OBJECTIVES: Approximately 13% of all births occur prior to 37 weeks gestation in the U.S. Some established risk factors exist for preterm birth, but the etiology remains largely unknown. Recent studies have suggested an association with environmental exposures. We examined the relationship between preterm birth and exposure to a commonly used herbicide, atrazine, in drinking water. METHODS: We reviewed Kentucky birth certificate data for 2004-2006 to collect duration of pregnancy and other individual-level covariates. We assessed existing data sources for atrazine levels in public drinking water for the years 2000-2008, classifying maternal county of residence into three atrazine exposure groups. We used logistic regression to analyze the relationship between atrazine exposure and preterm birth, controlling for maternal age, race/ethnicity, education, smoking, and prenatal care. RESULTS: An increase in the odds of preterm birth was found for women residing in the counties included in the highest atrazine exposure group compared with women residing in counties in the lowest exposure group, while controlling for covariates. Analyses using the three exposure assessment approaches produced odds ratios ranging from 1.20 (95% confidence interval [CI] 1.14, 1.27) to 1.26 (95% CI 1.19, 1.32), for the highest compared with the lowest exposure group. CONCLUSIONS: Suboptimal characterization of environmental exposure and variables of interest limited the analytical options of this study. Still, our findings suggest a positive association between atrazine and preterm birth, and illustrate the need for an improved assessment of environmental exposures to accurately address this important public health issue.

Concentrations of arsenic, chromium, and nickel in toenail samples from Appalachian Kentucky residents.

Lung cancer rates in Appalachian Kentucky are almost twice national rates; colorectal cancer rates are also elevated. Although smoking prevalence is high, it does not explain all excess risk. The area is characterized by poverty, low educational attainment, and unemployment. Coal production is a major industry. Pyrite contaminants of coal contain established human carcinogens, arsenic (As), chromium (Cr), and nickel (Ni). We compared biological exposure to As, Cr, and Ni for adults living in Appalachian Kentucky with residents of Jefferson, a non-Appalachian, urban county. We further compared lung and colon cancer rates, demographics, and smoking prevalence across the study areas. Toenail clipping analysis measured As, Cr, and Ni for residents of 23 rural Appalachian Kentucky counties and for Jefferson County. Reverse Kaplan-Meier statistical methodology addressed left-censored data. Appalachian residents were exposed to higher concentrations of As, Cr, and Ni than Jefferson County residents. Lung cancer incidence and mortality rates in Appalachia are higher than Jefferson County and elsewhere in the state, as are colorectal mortality rates. Environmental factors may contribute to the increased concentration of trace elements measured in residents of the Appalachian region. Routes of human exposure need to be determined.

Exploring geographic variation in lung cancer incidence in Kentucky using a spatial scan statistic: elevated risk in the Appalachian coal-mining region.

OBJECTIVES: We examined geographic patterns of lung cancer incidence in Kentucky. Recent research has suggested that the coal-mining industry contributes to lung cancer risk in Appalachia. We focused on the southeastern portion of the state, which has some of the highest lung cancer rates in the nation. METHODS: We implemented a spatial scan statistic to identify areas with lung cancer incidence rates that were higher than expected, after adjusting for age, gender, and smoking. The Kentucky Cancer Registry supplied information on cases (1995-2007). The U.S. Census (2000) and several years of Behavioral Risk Factor Surveillance System data (1996-2006) provided county-level population and smoking data. We compared the results with coal-mining data from the Mining Safety and Health Administration and public water utility data from the Kentucky Division of Water. RESULTS: We identified three clusters of counties with higher-than-expected rates. Cluster 1 (relative risk [RR] = 1.21, p<0.01) included 12 counties in southeastern Kentucky. Cluster 2 (RR=1.17, p<0.01) included three nearby counties in the same region. Several of the 15 counties in Cluster 3 (RR=1.04, p=0.01) were part of the Louisville, Kentucky, or Cincinnati, Ohio, metropolitan areas. All of the counties in Clusters 1 and 2 produced significant amounts of coal. CONCLUSION: Environmental exposures related to the coal-mining industry could contribute to the high incidence of lung cancer in southeastern Kentucky. Lack of evidence for this effect in western Kentucky could be due to regional differences in mining practices and access to public water utilities. Future research should collect biological specimens and environmental samples to test for the presence of trace elements and other lung carcinogens.

Exposure to indoor biomass fuel pollutants and asthma prevalence in Southeastern Kentucky: results from the Burden of Lung Disease (BOLD) study.

BACKGROUND: Asthma is a chronic inflammatory respiratory disease, characterized by episodic and reversible airflow obstruction and airway hyperresponsiveness and is influenced by both genetic and environmental factors. METHODS: The Burden of Obstructive Lung Disease (BOLD) survey was used to determine the prevalence of self-reported asthma in a target population of 325,000 adults aged > or =40 in Southeastern Kentucky. Postbronchodilator spirometry was used to classify subjects based on lung function. Risk factors for asthma in this population, in particular indoor usage of biomass fuels, were evaluated. RESULTS: The overall study population was comprised of 508 individuals, with 15.5% reporting current asthma and 5.8% reporting former asthma. In this population, the following risk factors for asthma were identified: female sex, smoking, less than a high school education, increasing body mass index (BMI), and a history of cooking indoors with coal and wood. Cooking indoors with wood and coal for more than 6 months of one's life was shown to significantly increase the odds of reporting current asthma (odds ratio (OR) = 2.3, confidence interval (CI) 1.1, 5.0), whereas no effect was seen from a history of heating indoors with wood and coal (OR = 0.8, CI 0.4, 1.8). CONCLUSIONS: Current or former asthma was reported by 21.3% of the adult population. A history of using biomass fuels when cooking indoors significantly increased the risk of reporting current asthma in this population.

Self-reported mental health status and recent mammography screening.

OBJECTIVE: The purpose of this study was to assess the association between self-perceived mental health status and mammography screening in Kentucky. METHODS: Using a cross-sectional design, we examined survey data from the 2002 Kentucky Behavioral Risk Factor Surveillance System (BRFSS) for women aged > or =40. Mental health status was measured by the reported number of days that mental health was not good; the number of days feeling sad, blue, or depressed; and the number of days feeling worried, tense, or anxious. The outcome was mammography within the last 2 years. Three logistic regression analyses were performed, one with each of the mental health status questions as the predictor variable. Analyses controlled for age, race, marital status, education, income, and health insurance status. RESULTS: The numbers of poor mental health days, depressed days, and anxious days were found to be significant or near-significant predictors of recent mammography. Odds ratios (ORs) comparing women reporting 30 poor mental health days, depressed days, or anxious days with similar women reporting zero days were estimated to be 1.68 (95% confidence interval [CI] 1.08-2.63), 1.49 (0.93-2.40), and 1.46 (0.96-2.23), respectively. CONCLUSIONS: Self-reported poor mental health, depression, and anxiety may be associated with nonreceipt of regular mammography screening. How mental health symptoms and self-reported poor mental health status contribute to decreased mammography screening should be explored.

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 Women's 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 women's health outcomes.

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 Gardasil's 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.

Smoking and survival among Kentucky women diagnosed with invasive cervical cancer: 1995-2005.

OBJECTIVES: To determine whether smokers with cervical cancer were more likely to die from cervical cancer compared with non smokers after adjusting for confounding factors. METHODS: A population-based survival analysis was conducted among 2661 women diagnosed with invasive cervical cancer and reported to the Kentucky Cancer Registry from 1995-2005 and linked with state vital records and the National Death Index through 12/31/2005. A standard Kaplan - Meier approach was used in this survival analysis and Cox Proportional Hazards modeling was used to estimate adjusted hazard [aHR] ratios and 95% confidence intervals [CI] for smoking and survival for all cause and cervical cancer specific cause of death. RESULTS: Almost half of women diagnosed with cervical cancer (48.6%) were known to be current smokers based the medical record review and reporting to KCR. For another 19.4% no tobacco status was documented (missing) and 32.1% were known non smokers. After adjustment for age and stage at diagnosis, cell type, rural residence, race, insurance coverage, and treatment received, current smoker were 35% more likely to die of any cause (aHR=1.35; 95% CI=1.17-1.56) and 21% more likely to die of cervical cancer (aHR=1.21; 95% CI=1.01-1.46) compared with known non smoking cases. CONCLUSION: These data strongly suggest that smoking reduces cervical cancer survival.

Variability of cervical cancer rates across 5 Appalachian states, 1998-2003.

BACKGROUND: 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. METHODS: Alabama, Kentucky, Ohio, Pennsylvania, and West Virginia were selected for the analysis on the basis of their having high-quality cancer registry data for 1998 through 2003. Incidence rates were calculated by state and by Appalachia/non-Appalachia, urban/rural, and black/nonblack within each state, following the standard case definition and inclusion criteria used in this supplement. Data from the Behavioral Risk Factor Surveillance System (BRFSS) were used to characterize the prevalence of Pap testing and smoking. RESULTS: The ICC incidence rates varied among the 5 states, being highest in West Virginia (10.9 of 100,000) and Kentucky (10.7 of 100,000), and lowest in Ohio (8.2 of 100,000). The Appalachian regions of Kentucky, West Virginia, and Ohio had considerably higher rates than those of Alabama and Pennsylvania. These variations reflected patterns in the rates of poverty, education, smoking, and Pap testing. CONCLUSIONS: The variability in ICC risk across subgroups of Appalachia should be considered in the planning of preventive strategies, including reduction in risk factors and promotion of screening and vaccination.

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

OBJECTIVE: A 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. METHODS: We 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. RESULTS: The 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. CONCLUSIONS: Although 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.

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.