Search

Background: Few studies have examined prostate cancer incidence and aggressiveness in urban-rural Appalachian populations. We examined these rates in urban-rural Appalachia and non-Appalachia Pennsylvania (PA), and the association between these areas and more aggressive prostate cancer at diagnosis. Methods: Men, ages ≥ 40 years with a primary prostate cancer diagnosis, were identified from the 2004–2014 Pennsylvania Cancer Registry. Age-adjusted incidence rates for prostate cancer and more aggressive prostate cancer at diagnosis were calculated by urban-rural Appalachia status. Multivariable Poisson regressions were conducted. Multiple logistic regressions were used to examine the association between the geographic areas and more aggressive prostate cancer, after adjusting for confounders. Results: There were 94,274 cases, ages 40–105 years, included. Urban non-Appalachia had the highest 2004–2014 age-adjusted incidence rates of prostate cancer and more aggressive prostate cancer (293.56 and 96.39 per 100,000 men, respectively) and rural Appalachia had the lowest rates (256.48 and 80.18 per 100,000 men, respectively). Among the cases, urban Appalachia were more likely [OR = 1.12; 95% confidence interval (CI) = 1.08–1.17] and rural Appalachia were less likely (OR = 0.92; 95% CI = 0.87–0.97) to have more aggressive prostate cancer at diagnosis compared with urban non-Appalachia. Conclusions: Lower incidence rates and the proportion of aggressive disease in rural Appalachia may be due to lower prostate cancer screening rates. More aggressive prostate cancer at diagnosis among the cases in urban Appalachia may be due to exposures that are prevalent in the region. Impact: Identifying geographic prostate cancer disparities will provide information to design programs aimed at reducing risk and closing the disparity gap.

Background To assess: (a) cancer treatment in prostate cancer survivors (PCS) by age at diagnosis (ADx) and prostate cancer (PC) aggressiveness; (b) potential impact on PC mortality; and (c) these results in the context of environmental/behavioral risk factors on PCS in Pennsylvania. Methods Prostate cancer survivors ages ≥40 years were identified from the 2004‐2014 Pennsylvania Cancer Registry (PCR). Demographic/clinical descriptors and PC treatment were extracted from PCR. Prostate cancer aggressiveness was defined by clinical/pathologic Gleason score and tumor stage. Logistic and Cox regression analyses tested associations between treatment received and PC‐specific mortality. County‐level data from the Pennsylvania BRFSS were used to estimate cancer‐related behavioral risk factors (eg, smoking, physical inactivity, fruit/vegetable consumption [FV], alcohol use) and used as covariates. Results There were 90 694 PCS ages 40‐105 years (mean age = 66.19 years, SD = 9.25) included. Most were non‐Hispanic white men (83%). Prostate cancer survivors ≥75 years were least likely to receive any treatment but men ages 65‐74 were more likely to receive combined therapies (OR = 1.47; 95% CI 1.28, 1.69) vs PCS ages 40‐54 years, controlling for covariates. Prostate cancer survivors 55‐75+ with aggressive PC who received any treatment vs no definitive treatment had significantly reduced mortality. Men from counties with high obesity and smoking rates were significantly less likely to receive any treatment than men living in counties with lower rates of these risk factors. Prostate cancer survivors who lived in counties with high rates of physical inactivity and had high rates of sufficient FV consumption were slightly more likely to receive cancer treatment vs no definitive treatment compared to men who lived in counties with high rates of physical activity and lower FV consumption. Conclusions We observed a general age‐related decline in receipt of treatment. Prostate cancer survivors ages ≥75 years were significantly less likely to get any cancer treatment compared to younger PCS. However, most men with more aggressive disease who received any treatment had greatly reduced PC mortality, regardless of age. Considering environmental/behavioral risk factors may attenuate PC risk and inform treatment options., We analyzed prostate cancer registry data for >90 000 men ages 40‐105 to understand age‐related associations with disease aggressiveness, treatment and potential role of environmental/behavioral risk factors in understanding likelihood of treatment recommendations and impact on mortality. Men older than 75 years were more likely to have aggressive disease but less likely to receive any treatment. The oldest men also had the greatest survival benefits from any treatment. We also provide insight on whether where you live impacts your treatment and ultimate survival.

Few studies have reported temporal and spatial trends of aggressive prostate cancer (PC) among black men who are known to have more aggressive disease. We examined these trends for highly aggressive PC at diagnosis among black and white men in Pennsylvania (PA). Men, aged ≥ 40 years, with a primary, clinical PC diagnosis were identified from the Pennsylvania Cancer Registry, 2004–2014. Joinpoint analysis was used to evaluate the temporal trend of highly aggressive PC (clinical/pathologic Gleason score ≥ 7 [4 + 3], clinical/pathologic tumor stage ≥ T3, or distant metastasis) and identify change points by race in which annual percent change (APC) was calculated. Logistic regression analyses were used to examine the association between race and highly aggressive PC, after adjusting for covariates with and without spatial dependence. There were 89,133 PC cases, which included 88.7% white and 11.3% black men. The APC of highly aggressive PC was 8.7% from 2011 to 2014 among white men and 3.6% from 2007 to 2014 among black men (p values ≤ 0.01). The greatest odds of having highly aggressive PC among black compared to white men were found in counties where the black male population was ≤ 5.3%. Highly aggressive PC increased for both black and white men in PA between 2004 and 2014. Black men had more aggressive disease, with the greatest odds in counties where the black male population was small. The increase in highly aggressive PC may be due to less screening for PC, resulting in more advanced disease at diagnosis.

Exposures to heavy metals have been linked to prostate cancer risk. The relationship of these exposures with serum prostate-specific antigen (PSA), a marker used for prostate cancer screening, is unknown. We examined whether total urinary arsenic, urinary dimethylarsonic acid, blood cadmium, blood lead, and total blood mercury levels are associated with elevated PSA among presumably healthy U.S. men. Prostate cancer-free men, aged ≥40 years, were identified from the 2003–2010 National Health and Nutrition Examination Survey. Logistic regression analyses with survey sample weights were used to examine the association between heavy metal levels and elevated PSA for the total population and stratified by black and white race, after adjusting for confounders. There were 5,477 men included. Approximately 7% had elevated PSA. Men with an elevated PSA had statistically significantly higher levels of blood cadmium and blood lead compared to men with a normal PSA (p-values ≤ 0.02), with black men having higher levels. After adjusting for age, race/ethnicity, body mass index, smoking, and education, there was no association found between any of the heavy metal levels and elevated PSA for the total population. In addition, there was no association found when stratified by black and white race. Further investigation is warranted in a larger cohort of men who persistently are exposed to these heavy metals.

Background Spatial heterogeneity of prostate cancer-specific mortality in Pennsylvania remains unclear. We utilized advanced geospatial survival regressions to examine spatial variation of prostate cancer-specific mortality in PA and evaluate potential effects of individual- and county-level risk factors. Methods Prostate cancer cases, aged ≥40 years, were identified in the 2004–2014 Pennsylvania Cancer Registry. The 2018 County Health Rankings data and the 2014 U.S. Environmental Protection Agency’s Environmental Quality Index were used to extract county-level data. The accelerated failure time models with spatial frailties for geographical correlations were used to assess prostate cancer-specific mortality rates for Pennsylvania and by the Penn State Cancer Institute (PSCI) 28-county catchment area. Secondary assessment based on estimated spatial frailties was conducted to identify potential health and environmental risk factors for mortality. Results There were 94,274 cases included. The 5-year survival rate in PA was 82% (95% confidence interval, CI: 81.1–82.8%), with the catchment area having a lower survival rate 81% (95% CI: 79.5–82.6%) compared to the non-catchment area rate of 82.3% (95% CI: 81.4–83.2%). Black men, uninsured, more aggressive prostate cancer, rural and urban Appalachia, positive lymph nodes, and no definitive treatment were associated with lower survival. Several county-level health (i.e., poor physical activity) and environmental factors in air and land (i.e., defoliate chemical applied) were associated with higher mortality rates. Conclusions Spatial variations in prostate cancer-specific mortality rates exist in Pennsylvania with a higher risk in the PSCI’s catchment area, in particular, rural-Appalachia. County-level health and environmental factors may contribute to spatial heterogeneity in prostate cancer-specific mortality.

BACKGROUND MicroRNAs (miRNAs or miR-) have been linked to factors associated with aggressive prostate cancer such as biochemical recurrence and metastasis. We investigated whether circulating miRNAs in plasma could be used as diagnostic biomarkers for more aggressive prostate cancer at prostate biopsy. METHODS Men, aged 40 years and above, newly diagnosed with prostate cancer were categorized into two risk groups, low-grade (Gleason score, 6 or 7 [3 + 4] and serum prostate-specific antigen [PSA]

Background: The survival from breast cancer in Africa is poor and yet the incidence rate is on the rise. Causes of variations in survival from breast cancer are not well understood. We aimed to do a systematic review and meta-analysis on 5-year survival rates of breast cancer on the entire continent of Africa and to examine trends over time, and investigate sources of variations across the region. Methods: We searched MEDLINE, Embase, Cochrane Library to identify studies on breast cancer survival in African men and women published before October 17, 2018, and in any language. Random-effects meta-analyses were done to investigate between-study heterogeneity in 5-year survival rates of breast cancer and meta-regression analyses to identify potential sources of variation. 5-year survival rates of breast cancer in Africa were compared with similar estimates for black and white population in the USA from the Surveillance, Epidemiology, and End Results database. Findings: 54 studies were included, which consisted of 18,970 women and men from 13 African countries, 8 of which were from sub-Saharan region. There was wide between-study heterogeneity in the survival rates (mean 52.9%, range 7-91%, I2=99.1%; p

Purpose MicroRNAs (miRNAs/miRs) as circulating biomarkers for prostate cancer have yet to be determined. We examined whether circulating miRNAs in plasma could be employed as biomarkers of disease among men treated for prostate cancer by radical prostatectomy (RP). Methods The expression of 17 preselected circulating miRNAs associated with prostate cancer (miR-381, -34a, -365, -122, -375, -1255b, -34b, -450b-5p, -885-5p, -1260, -150, -378, -671-3p, -148a, and -224) or high-grade prostate cancer (miR-28 and -100) in plasma at prostate biopsy was examined in pre- and post-RP plasma of prostate cancer patients using real-time PCR and compared using Wilcoxon signed-ranked test. Wilcoxon rank sum test was used to compare the expression of miRNAs in pre-RP plasma between pathologic tumor stage (T2 vs. T3) and Gleason score (6–7 [3 + 4] vs. ≥ 7 [4 + 3]) groups. Partial correlation coefficient between the expression of miRNAs in pre-RP plasma and serum prostate-specific antigen (PSA) level at RP, adjusting for age, was calculated. Results Twenty-nine men, aged 43 to 77 years, were included. Median follow-up time after RP was 55 days. There was no significant change in the expression of miRNAs in plasma from before to after RP. However, higher expression of miR-34a, -378, and 450b-5p in pre-RP plasma was observed among T3 compared to T2 patients (P values = 0.01). Overall, there were no statistically significant relationships observed between the expression of these circulating miRNAs and Gleason score and serum PSA at RP. Conclusions There was no significant change in the expression of circulating miRNAs in plasma from before to approximately 2 months after RP. This finding may be due to the lack of immediate effect RP may have on the expression of circulating miRNAs. However, higher expression of miR-34a, -378, and -450b-5p in plasma was found among patients with more advanced disease at RP. A longer follow-up time after RP is warranted to investigate RP's possible influence on circulating miRNAs among men treated for prostate cancer and to evaluate miRNAs’ diagnostic potential for prostate cancer.

Background MicroRNAs (miRNAs) have been linked to prostate cancer (PC) risk; however, their role as a screening biomarker for PC has yet to be determined. We examined whether circulating miRNAs in plasma could be potential biomarkers for the early detection of PC among men undergoing prostate needle biopsy. Methods Men who had a prostate biopsy due to an abnormal screening test were recruited. Linear regression was used to examine the association between miRNAs in plasma and PC status and to model individual miRNA expression on serum PSA and age to calculate the partial correlation coefficient (r). Results There were 134 men, aged 46-86 years, included, with 66 men with a PC diagnosis (cases), eight men with no PC diagnosis but atypical lesion, and 60 men without a PC diagnosis (controls). The most statistically significant PC circulating miRNAs were miR-381, miR-34a, miR-523, miR-365, miR-122, miR-375, miR-1255b, miR-34b, miR-450b-5p, and miR-639 after adjusting for age (P-values ≤0.05); however, they were no longer statistically significant after P-value adjustment for multiple comparisons. MiR-671-3p was differentially expressed between black and white cases (P-value = 0.03). Moderate positive correlations with serum PSA were observed for miR-381 overall and among controls (r = 0.43-0.60; P-values ≤0.05) and miR-34a among cases (r = 0.46; P-value = 0.02). Conclusions There was no miRNA associated with PC diagnosis after adjusting for age and P-values; however, moderate correlations between miRNAs and serum PSA were observed. Further investigation between miRNAs and PC risk is warranted in a larger population at high risk for PC.

Human herpesvirus 8 (HHV-8) is the causal agent of Kaposi's sarcoma (KS). In Tobago, KS is not common; however, HHV-8 seropositivity has been reported to be 39.9% in men with prostate cancer compared to

Black men are known to have a higher risk for prostate cancer (PC). Carotenoids and retinol, linked to PC, have not been compared in different black populations at risk. We examined serum carotenoid and retinol levels between PC-free African-Caribbean (AC) Tobagonian men with a high PC risk (high-grade prostatic intraepithelial neoplasia, atypical foci or repeated abnormal PC screenings) and African-American (AA) men with elevated serum prostate-specific antigen (PSA) levels (≥4 ng/ml). AC men who participated in the 2003 lycopene clinical trial and AA men who participated in the 2001–2006 National Health and Nutrition Examination Survey were compared. Serum specimens were analysed for carotenoid (β-carotene,α-carotene,β-cryptoxanthin, lutein/zeaxanthin and lycopene) and retinol levels by isocratic HPLC. Quantile regression was used to examine the association between serum carotenoid and retinol levels and black ethnicity, overall and among men with elevated serum PSA. There were sixty-nine AC men and sixty-five AA men, aged 41–79 years, included. AC men were associated with lower serum lycopene and retinol levels, and higher serumα- andβ-carotenes and lutein/zeaxanthin levels compared with AA men, after adjusting for age, BMI, ever smoked cigarettes, education and hypertension (P≤0·03). Among men with elevated PSA, serum retinol was no longer statistically significant with ethnicity (P=0·06). Possible differences may be attributed to dietary intake, genetics and/or factors that influence bioavailability of these micronutrients. Prospective studies are warranted that investigate whether these differences in micronutrients between AC Tobagonian and AA men influence PC risk.

Background Serum prostate specific antigen (PSA) may be elevated in otherwise healthy men; systemic inflammation has been associated with cancer. The study of systemic inflammatory markers in men without clinical prostate disease, but with elevated PSA may characterize the subgroup of men at higher risk for subsequent prostate cancer. Methods We investigated the associations between systemic inflammatory markers and serum PSA in 3,164 healthy men without prostatic disease, aged >40 years, from the 2001 to 2008 U.S. National Health and Nutrition Examination Survey (NHANES). Serum total PSA levels and concentrations of serum C-reactive protein (CRP) and plasma fibrinogen, neutrophil count, lymphocyte count, and platelet count were recorded. Neutrophil-lymphocyte ratio (NLR) ratio and platelet-lymphocyte (PLR) ratio were calculated. PSA elevation was defined as levels equal or greater than 4 ng/ml. Results Elevated serum PSA (194 men, 6.1% of the total), was significantly associated with plasma fibrinogen (ORmultiv = 1.88; 95% CI, 1.09-3.25), and NLR (ORmultiv = 1.14; 95% CI, 1.03-1.26), after adjustment for age, smoking, body mass index, education, race, co-morbidities, and use of medications. Conclusions Markers of systemic inflammation were associated with elevated PSA in men without known prostatic disease. Future studies are needed to examine these markers' relationship with prostate cancer occurrence and progression.

Introduction: The incidence of prostate cancer (PC) is known to vary within Appalachia, with Northern Appalachia and Southern Appalachia having higher and lower rates, respectively. However, the geographical disparity for aggressive PC has not been investigated. The objective of this study was to determine whether having more aggressive PC was associated with residing in an Appalachian/non-Appalachian county and rural/urban community. Methods: A cross-sectional study was conducted among men, aged &gt = 40 years, who had a primary, clinical PC diagnosis identified in the Pennsylvania Cancer Registry between 2004 and 2014. PC aggressiveness was defined as less aggressive (Gleason score 6 or 7 [3+4] and clinical/pathologic tumor stage T1-T2) and more aggressive (Gleason score &gt = 7 [4+3], clinical/pathologic tumor stage T3-T4, or distant metastasis) PC. Logistic regression analysis was used to examine the association between having aggressive PC (less vs more aggressive PC - dependent variable) and residing in a geographical region (Appalachian versus non-Appalachian county - independent variable), stratified by rural/urban, after adjusting for age, race, ethnicity, insurance status, marital status, serum PSA, positive lymph node status, and cancer treatment. Results: There were 94,264 PC cases, aged 40 to 105 years, included in the study. The majority of the PC cases were white (83.9%) followed by black race (10.7%). PC cases from urban Appalachian counties (35.42%) had the highest frequency of aggressive PC followed by rural non-Appalachian (34.18%), rural Appalachian (32.12%), and urban non-Appalachian counties (32.08%). In urban areas, Appalachian PC cases were more likely to be aggressive compared to non-Appalachian PC cases, after adjusting for confounders (odds ratio [O.R.] =1.16; 95% confidence interval [C.I.], 1.13-1.21). Conversely, in rural areas, Appalachian PC cases were less likely to be aggressive compared to non-Appalachian PC cases, after adjusting for confounders (O.R. =0.91; 95% C.I., 0.85-0.98). Conclusion: Differences in having more aggressive PC was observed for Appalachian populations by rural/urban status, with urban Appalachian PC cases more likely and rural Appalachian PC cases less likely to have more aggressive disease, compared to their non-Appalachian counterparts. Further investigation on the underlying mechanisms of aggressive PC in urban Appalachia in PA is warranted. Citation Format: Alicia C. McDonald, Emily Wasserman, Eugene J. Lengerich, Jay D. Raman, Nathaniel Geyer, Raymond Hohl, Ming Wang. Aggressive prostate cancer among men in Pennsylvania: Differences between Appalachian and non-Appalachian counties [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4186.

Introduction: MicroRNAs (miRNAs) have been linked to advanced prostate cancer; however, their role as circulating biomarkers of prostate cancer (PC) status has yet to be determined. We examined whether circulating miRNAs in plasma could be employed as biomarkers of disease among men treated for PC by radical prostatectomy (RP). Methods: Men with clinically localized PC scheduled for a RP were recruited. Demographics, medical history, clinical information, pre-RP blood, and post-RP blood within 1 year after RP were collected. Pre- and post-RP blood were processed into plasma and the expression of the 16 most statistically significant PC circulating miRNAs in plasma identified from our previous study (miR- 381, 34a, 523, 365, 122, 375, 1255b, 34b, 450b-5p, 639, 885-5p, 1260, 150, 378, 671-3p, 148a) were examined using real-time PCR. Wilcoxon signed ranked test was used to compare the median expression of these miRNAs between pre- and post-RP plasma. Results: There were 29 men, aged 43 to 77 years, included. Majority were white men (79.3%). The median preoperative serum PSA was 6.3 ng/mL. Majority had a pathologic Gleason score of 7 (3+4) (56%) and a pathologic tumor stage of T3 (60.7%). There was no statistically significant difference in miRNA expression between pre- and post-RP plasma. Conclusion: No difference in miRNA expression before and immediately after RP was observed, possibly due to the lack of impact of tumor removal on miRNA expression and the timing of plasma collections. Future studies that examine post-RP plasma miRNA expression over time with PC recurrence are warranted. Citation Format: Alicia C. McDonald, Jay D. Raman, Jing Shen, Jason Liao, Manish Vira. Comparison of circulating microRNAs in plasma before and after radical prostatectomy among men treated for prostate cancer [abstract]. In: Proceedings of the AACR Special Conference: Prostate Cancer: Advances in Basic, Translational, and Clinical Research; 2017 Dec 2-5; Orlando, Florida. Philadelphia (PA): AACR; Cancer Res 2018;78(16 Suppl):Abstract nr A002.

Introduction: Although microRNAs (miRNAs) have been linked to prostate cancer risk, their role as a screening biomarker for prostate cancer (PC) has yet to be determined. We examined whether circulating miRNAs in plasma could be potential biomarkers for the early detection of PC among men undergoing prostate needle biopsy. Methods: Men who had a prostate biopsy due to an abnormal screening test were recruited. Demographics, medical history, clinical information, and blood processed into plasma were collected. TaqMan Low Density Arrays were used for the expression profiling of 733 miRNAs in plasma. Wilcoxon test was used to compare expression levels between men with and without a PC diagnosis. Logistic regression was used to examine the association between miRNAs and PC status, after adjusting for age and Bonferroni-correction. Results: There were 131 men, aged 46 to 86 years, included in the final analysis, with 66 men diagnosed with PC on prostate biopsy and 65 men without a PC diagnosis. Majority were white (72.5%) followed by black race (13.5%). Men with PC were older (median: 64 vs. 62 years; p-value = 0.16) and had statistically significantly higher serum PSA (median: 5.8 vs. 5.1 ng/mL; p-value = 0.01) compared to men without a PC diagnosis. The most statistically significant PC circulating miRNAs in plasma were miR-381, miR-523, miR-450B-5p, miR-34a, miR-34b, miR-639, and miR-365, after adjusting for age (p-values ≤ 0.05). The detection rate of these miRNAs in plasma ranged from 23.7% to 83.2%. These miRNAs were no longer statistically significant with PC diagnosis, after adjusting for multiple comparison (FDR q-value = 1.00). Conclusion: Among the 733 miRNAs evaluated, there was no miRNA found to be associated with PC diagnosis after adjusting for multiple comparison. Studies that examine a larger number of miRNAs which include the discovery of new miRNAs and their relationship with PC risk are warranted. Citation Format: Alicia C. Mcdonald, Jing Shen, Manish Vira, Martin Sanda, Jason Liao, Martin L. Lesser, Dattatraya Patil, Jay D. Raman, Emanuela Taioli. Circulating microRNAs in plasma of men screened for prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4241. doi:10.1158/1538-7445.AM2017-4241

Objective: HIV-positive women are known to be at high risk of Human Papillomavirus (HPV) infection and its associated cervical pathology. Here we describe the prevalence and distribution of HPV genotypes among HIV-positive and negative women in South Africa, with and without cervical intraepithelial neoplasia (CIN). Methods: We report data on 1,371 HIV-positive women and 8,050 HIV-negative women, aged 17-65 years, recruited into three sequential studies in Cape Town, South Africa, conducted among women who had no history of cervical cancer screening recruited from the general population. All women were tested for HIV. Cervical samples were tested for high risk HPV DNA (Hybrid Capture 2) with positive samples tested to determine the specific genotype (Line Blot). CIN status was determined based on colposcopy and biopsy. Results: The HPV prevalence was higher among HIV-positive women (52.4%) than among HIV-negative women (20.8%) overall and in all age groups. Younger women, aged 17-19 years, had the highest HPV prevalence regardless of HIV status. HIV-positive women were more likely to have CIN 2 or 3 than HIV-negative women. HPV 16, 35, and 58 were the most common high-risk HPV types with no major differences in the type distribution by HIV status. HPV 18 was more common in older HIV-positive women (40-65 years) with no or low grade disease, but less common in younger women (17-29 years) with CIN 2 or 3, compared to HIV-negative counterparts (p< 0.03). Infections with multiple high-risk HPV types were more common in HIV-positive than HIV-negative women controlling for age and cervical disease status. Conclusion: HIV-positive women were more likely to have high risk HPV than HIV-negative women but among those with HPV, the distribution of HPV types was similar by HIV status. Screening strategies incorporating HPV genotyping and vaccination should be effective in preventing cervical cancer in both HIV-positive and negative women living in sub-Saharan Africa.

ObjectiveLarge studies describing the profile of high-risk Human papillomavirus (hrHPV) genotypes among women in sub-Saharan Africa are lacking. Here we describe the prevalence and distribution of hrHPV genotypes among HIV-negative women in South Africa, with and without cervical intraepithelial neoplasia (CIN).MethodsWe report data on 8,050 HIV-negative women, aged 17-65 years, recruited into three sequential studies undertaken in Cape Town, South Africa. Women had no history of previous cervical cancer screening. Cervical samples were tested for hrHPV DNA using the Hybrid Capture 2 (HC2) assay and all positive samples were genotyped using a PCR-based assay (Line Blot). Women underwent colposcopy and biopsy/endocervical curettage to determine CIN status. The prevalence and distribution of specific hrHPV genotypes were examined by age and CIN status.ResultsOverall, 20.7% (95% CI, 19.9-21.6%) of women were hrHPV-positive by HC2, with women with CIN having the highest rates of positivity. Prevalence decreased with increasing age among women without CIN; but, a bimodal age curve was observed among women with CIN. HPV 16 and 35 were the most common hrHPV genotypes in all age and CIN groups. HPV 45 became more frequent among older women with CIN grade 2 or 3 (CIN2,3). Younger women (17-29 years) had more multiple hrHPV genotypes overall and in each cervical disease group than older women (40-65 years).ConclusionHPV 16, 35, and 45 were the leading contributors to CIN 2,3. The current HPV vaccines could significantly reduce HPV-related cervical disease; however, next generation vaccines that include HPV 35 and 45 would further reduce cervical disease in this population.

Background We previously reported a cross-sectional association between the presence of human herpesvirus 8 (HHV-8) serum antibodies and screen-detected prostate cancer in men living in Tobago. In the same study population, we examined the association between HHV-8 seropositivity and incident prostate cancer discovered at later screenings. Methods In 40-81 year-old men without prostate cancer discovered at initial digital rectal examination (DRE) and prostate-specific antigen (PSA) screening, a case-cohort design measured the association between baseline HHV-8 seropositivity (modified immunofluorescence assay for antibodies against HHV-8 lytic antigens) and incident prostate cancer detected at DRE and PSA screenings three or five years later. Results Analyses included 486 unique individuals, 96 incident prostate cancer cases, and 415 randomly selected subjects representing an at-risk cohort. By design, the random sub-cohort contained 25 incident prostate cancer cases. In the sub-cohort, the frequency of HHV-8 seropositivity increased across age groupings (40-49 years: 3.5%, 50-59 years: 13.6%, and ≥ 60 years: 22.9%). HHV-8 seropositivity was higher in men with elevated (≥ 4.0 ng/mL) than men with non-elevated PSA at initial screening (30.4% vs. 9.9% seropositive; crude odds ratio (OR) 3.96, 95% confidence interval (CI) 1.53-10.2; age-adjusted OR 2.42, 95% CI 0.91-6.47). HHV-8 seropositivity did not increase incident prostate cancer risk (age-adjusted hazard ratio (HR) 0.88, 95% CI 0.46-1.69). Conclusions Case-cohort analysis did not identify association between HHV-8 seropositivity and incident prostate cancer. However, analyses uncovered possible association between HHV-8 and PSA (a marker of prostate inflammation). Co-occurrence of HHV-8 seropositivity and PSA elevation may explain cross-sectional association between HHV-8 and PSA screen-detected prostate cancer.

This unblinded, randomized, Phase I clinical trial was conducted to determine whether lycopene supplementation lowered serum prostate specific antigen (PSA), surrogate endpoint for prostate cancer initiation or progression, in men with elevated prostate cancer risk. Afro-Caribbean men (n=81) with high-grade prostatic intraepithelial neoplasia, atypical foci or repeated non-cancerous biopsies, ascertained in a population-based screening program, were randomized to four months intervention with 30 mg/day lycopene (Lyc-O-Mato) plus a multivitamin, or to multivitamin, only. Serum PSA and lycopene were compared at randomization, 1, and 4 mo using two-sided chi2 and t-tests for independent samples. Treatment groups were similar at baseline. Serum lycopene levels approximately doubled in the lycopene intervention group. Serum PSA declined during the first month of treatment, but returned to randomization level by month 4. The PSA response was nearly identical in both treatment groups. No adverse effects attributed to lycopene supplementation were documented. We conclude that the PSA lowering response to antioxidant supplementation observed in previous 3-wk studies in men awaiting prostatectomy may have been a transient response, perhaps not specific to lycopene. Lowering of serum PSA may not be an appropriate endpoint for the long-term studies needed to evaluate lycopene supplementation for reducing prostate cancer initiation or progression.

Objective: Persistent high-risk human papillomavirus (HPV) infections are associated with cervical pre-malignant lesions and cervical cancer. Women in sub-Saharan Africa are at high risk of advanced cervical disease as well as cervical cancer. We examined the prevalence and distribution of high-risk HPV types (16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, and 66) among HIV-negative Black women enrolled in three cervical cancer screening studies in Cape Town, South Africa. Knowledge of the epidemiology of high-risk HPV types in this population will help target prevention interventions. Methods: Black women, aged 17-65 years, were tested for high risk HPV DNA using the Hybrid Capture 2 (HC2) assay and positive samples were typed by PCR to determine the specific genotype. Cervical disease status was determined by colposcopy and cervical biopsy. The prevalence and distribution of high-risk HPV types as well as the frequency of multiple high-risk HPV types were examined by age and cervical disease. Results: Among 8,073 HIV-negative women included in the study, 20.9% (n=1689) were HC2 HPV DNA positive; and, in 73.62% (n=1223/1661) of these positives, a specific high-risk HPV type was detected. Overall, the prevalence of high-risk types was 19.94%. The most common high-risk types across cervical disease status were HPV 16 and 35. Among women without cervical disease, younger women, aged 17-29 years, had the highest prevalence of high-risk types in comparison to older women. Among women with CIN 2 or CIN 3, a higher prevalence of HPV 16 and 45 was observed among older women, aged 40-65 years, than among younger women, aged 17-29 years; as for HPV 35, the prevalence was stable across age groups. The distribution of HPV 16, 35, and 33 were statistically significantly higher among HC2 DNA positive, high-risk HPV positive women with advanced cervical disease than women with no cervical disease or CIN 1 (p-values < 0.02). Younger women, aged 17-29 years, had more multiple types overall and across all cervical disease status than older women, aged 40-65 years. Conclusion: HPV 16 and 35 are the leading contributors of cervical disease among HIV-negative Black South African women. Therefore, the HPV vaccine has the capacity to result in significant reduction in HPV-related cervical disease in this population. Citation Information: Cancer Prev Res 2010;3(12 Suppl):B77.