Cancer control in the Pacific: big challenges facing small island states.

This Series paper describes the current state of cancer control in Pacific island countries and territories (PICTs). PICTs are diverse but face common challenges of having small, geographically dispersed, isolated populations, with restricted resources, fragile ecological and economic systems, and overburdened health services. PICTs face a triple burden of infection-related cancers, rapid transition to lifestyle-related diseases, and ageing populations; additionally, PICTs are increasingly having to respond to natural disasters associated with climate change. In the Pacific region, cancer surveillance systems are generally weaker than those in high-income countries, and patients often present at advanced cancer stage. Many PICTs are unable to provide comprehensive cancer services, with some patients receiving cancer care in other countries where resources allow. Many PICTs do not have, or have poorly developed, cancer screening, pathology, oncology, surgical, and palliative care services, although some examples of innovative cancer planning, prevention, and treatment approaches have been developed in the region. To improve cancer outcomes, we recommend prioritising regional collaborative approaches, enhancing cervical cancer prevention, improving cancer surveillance and palliative care services, and developing targeted treatment capacity in the region.

Population attributable risks of modifiable reproductive factors for breast and ovarian cancers in Korea.

BACKGROUND: Breast and ovarian cancers are predominant female cancers with increasing prevalence. The purpose of this study was to estimate the population attributable risks (PARs) of breast and ovarian cancer occurrence based on the relative risks (RRs) of modifiable reproductive factors and population-specific exposure prevalence. METHODS: The PAR was calculated by using the 1990 standardized prevalence rates, the 2010 national cancer incidence with a 20 year lag period, the meta-analyzed RRs from studies conducted in the Korean population for breast cancer, and the meta-analyzed RRs from a Korean epithelial ovarian cancer study and a prior meta-analysis, and ovarian cancer cohort results up to 2012. For oral contraceptive and hormone replacement therapy use, we did not consider lag period. RESULTS: The summary PARs for modifiable reproductive factors were 16.7% (95% CI 15.8-17.6) for breast cancer (2404 cases) and 81.9% (95% CI 55.0-100.0) for ovarian cancer (1579 cases). The modifiable reproductive factors included pregnancy/age at first birth (8.0%), total period of breastfeeding (3.1%), oral contraceptive use (5.3%), and hormone replacement therapy use (0.3%) for breast cancer and included breastfeeding experience (2.9%), pregnancy (1.2%), tubal ligation (24.5%), and oral contraceptive use (53.3%) for ovarian cancer. CONCLUSIONS: Despite inherent uncertainties in the risk factors for breast and ovarian cancers, we suggest that appropriate long-term control of modifiable reproductive factors could reduce breast and ovarian cancer incidences and their related burdens by 16.7% and 81.9%, respectively.

Prevention of infection-related cancers in the WHO Western Pacific Region.

A considerable number of infectious agents have been classified as human carcinogens Group 1 by the International Agency for Research on Cancer. Major infection-related cancers such as cancers of nasopharynx (53%), stomach (60%) and liver (63%) occur in the World Health Organization Western Pacific Region. Many infection-related cancers are preventable, particularly those associated with human papilloma virus, Helicobacter pylori, human immunodeficiency virus-I, hepatitis B virus and hepatitis C virus and liver flukes. Mongolia shows the highest prevalence of hepatitis B virus and hepatitis C virus, and China shows the highest prevalence of Helicobacter pylori. Chronic infection is attributable for 17-28% of overall cancer incidence or mortality in China, Japan and Korea. Through infant immunization for hepatitis B, 30 of 37 countries and areas in the Western Pacific Region have reached the 2012 milestone of chronic hepatitis B virus infection prevalence of <2% in 5-year-old children and countries and areas of the region are now striving toward reaching the regional goal of <1% by 2017. Human papilloma virus immunization program is implemented either by government funding or, in some low-income countries, by public and private sector organizations. Cervical cancer screening via visual inspection with acetic acid or Pap smear is available in many Western Pacific Region Member States. More efforts are needed to implement new World Health Organization guide to vaccinate 9- to 13-year-old girls with two doses of human papilloma virus vaccine, and use human papilloma virus tests to screen women to prevent and control cervical cancer including guaranteed monitoring and appropriate follow-up for abnormal results.

Osteopontin and latent-TGF ß binding-protein 2 as potential diagnostic markers for HBV-related hepatocellular carcinoma.

Chronic Hepatitis B (HB) is the main risk factor for chronic liver disease (CLD) and hepatocellular carcinoma (HCC) in many low-resource countries, where diagnosis is constrained by lack of clinical, histopathological and biomarker resources. We have used proteomics to detect plasma biomarkers that outperform α-Fetoprotein (AFP), the most widely used biomarker for HCC diagnosis in low-resource contexts. Deep-plasma proteome analysis was performed in HCC patients, patients with CLD and in HB-carrier controls from Thailand (South-East Asia) and The Gambia (West-Africa). Mass spectrometry profiling identified latent-transforming growth factor ß binding-protein 2 (LTBP2) and Osteopontin (OPN) as being significantly elevated in HCC versus CLD and controls. These two proteins were further analyzed by ELISA in a total of 684 plasma samples, including 183 HCC, 274 CLD and 227 asymptomatic controls. When combined, LTBP2 and OPN showed an area under the receiver operating curve of 0.85 in distinguishing HCC from CLD in subjects with AFP <20 ng/mL. In a prospective cohort of 115 CLD patients from Korea, increased plasma levels of LTBP2 and/or OPN were detected in plasma collected over 2 years prior to diagnosis in 21 subjects who developed HCC. Thus, the combination of LTBP2 and OPN outperformed AFP for diagnosis and prediction of HCC and may therefore improve biomarker-based detection of HBV-related HCC.

Human papillomavirus DNA prevalence and type distribution in anal carcinomas worldwide.

Knowledge about human papillomaviruses (HPV) types involved in anal cancers in some world regions is scanty. Here, we describe the HPV DNA prevalence and type distribution in a series of invasive anal cancers and anal intraepithelial neoplasias (AIN) grades 2/3 from 24 countries. We analyzed 43 AIN 2/3 cases and 496 anal cancers diagnosed from 1986 to 2011. After histopathological evaluation of formalin-fixed paraffin-embedded samples, HPV DNA detection and genotyping was performed using SPF-10/DEIA/LiPA25 system (version 1). A subset of 116 cancers was further tested for p16(INK4a) expression, a cellular surrogate marker for HPV-associated transformation. Prevalence ratios were estimated using multivariate Poisson regression with robust variance in the anal cancer data set. HPV DNA was detected in 88.3% of anal cancers (95% confidence interval [CI]: 85.1-91.0%) and in 95.3% of AIN 2/3 (95% CI: 84.2-99.4%). Among cancers, the highest prevalence was observed in warty-basaloid subtype of squamous cell carcinomas, in younger patients and in North American geographical region. There were no statistically significant differences in prevalence by gender. HPV16 was the most frequent HPV type detected in both cancers (80.7%) and AIN 2/3 lesions (75.4%). HPV18 was the second most common type in invasive cancers (3.6%). p16(INK4a) overexpression was found in 95% of HPV DNA-positive anal cancers. In view of the results of HPV DNA and high proportion of p16(INK4a) overexpression, infection by HPV is most likely to be a necessary cause for anal cancers in both men and women. The large contribution of HPV16 reinforces the potential impact of HPV vaccines in the prevention of these lesions.

Impact of alcohol drinking on gastric cancer development according to Helicobacter pylori infection status.

BACKGROUND: Helicobacter pylori are major carcinogen of gastric cancer, but the associations among gastric cancer, H. pylori infection status, and alcohol consumption are not fully described. This study aimed to clarify how H. pylori infection status affects the association between alcohol consumption and gastric cancer risk. METHODS: We selected 949 case-cohort participants from the 18,863 Korean Multi-center Cancer Cohort (KMCC) populations. Gastric cancer incidence inside and outside of the subcohort were 12 and 254 cases, respectively. Seropositivities for CagA, VacA, and H. pylori infection were determined by performing immunoblot assays. Weighted Cox regression models were used to calculate hazard ratios and 95% confidence intervals (CIs). RESULTS: Relative to non-drinking, heavy drinking (⩾7 times a week), and binge drinking (⩾55 g alcohol intake per occasion) showed a 3.48-fold (95% CI, 1.13-10.73) and 3.27-fold (95% CI, 1.01-10.56) higher risk in subjects not previously infected by H. pylori. There was no significant association between drinking pattern and gastric cancer risk in H. pylori IgG seropositive subjects. An increased risk for gastric cancer in heavy- and binge-drinking subjects were also present in subjects not infected by CagA- or VacA-secreting H. pylori. CONCLUSIONS: Heavy and binge alcohol consumption is an important risk factor related to an increasing incidence of gastric cancer in a population not infected by H. pylori.

Gene polymorphisms in the ornithine decarboxylase-polyamine pathway modify gastric cancer risk by interaction with isoflavone concentrations.

BACKGROUND: The study aimed to examine the association between genes encoding molecules in the ornithine decarboxylase (ODC)-polyamine pathway (ODC1, AMD1, NQO1, NOS2A, and OAZ2) and gastric cancer risk and whether the gene-phytoestrogen interaction modifies gastric cancer risk. METHODS: Among 76 gastric cancer cases and their 1:4 matched controls within the Korean Multi-center Cancer Cohort, a total of 30 SNPs in five genes involved in the ODC pathway were primarily analyzed. The second-stage genotyping in 388 matched case-control sets was conducted to reevaluate the significant SNPs interacting with phytoestrogens during the primary analysis. The summary odds ratios (ORs) [95 % confidence intervals (CIs)] for gastric cancer were estimated. Interaction effects between the SNPs and plasma concentrations of phytoestrogens (genistein, daidzein, equol, and enterolactone) were evaluated. RESULTS: In the pooled analysis, NQO1 rs1800566 showed significant genetic effects on gastric cancer without heterogeneity [OR 0.83 (95 % CI 0.70-0.995)] and a greater decreased risk at high genistein/daidzein levels [OR 0.36 (95 % CI 0.15-0.90) and OR 0.26 (95 % CI 0.10-0.64), respectively; p interaction < 0.05]. Risk alleles of AMD1 rs1279599, AMD1 rs7768897, and OAZ2 rs7403751 had a significant gene-phytoestrogen (genistein and daidzein) interaction effect to modify the development of gastric cancer. They had an increased gastric cancer risk at low isoflavone levels, but a decreased risk at high isoflavone levels (p interaction < 0.01). CONCLUSIONS: Our findings suggest that common variants in the genes involved in the ODC pathway may contribute to the risk of gastric cancer possibly by modulating ODC polyamine biosynthesis or by interaction between isoflavones and NQO1, OAZ2, and AMD1.

Time trends of human papillomavirus types in invasive cervical cancer, from 1940 to 2007.

Contribution over time of human papillomavirus (HPV) types in human cancers has been poorly documented. Such data is fundamental to measure current HPV vaccines impact in the years to come. We estimated the HPV type-specific distribution in a large international series of invasive cervical cancer (ICC) over 70 years prior to vaccination. Paraffin embedded ICC cases diagnosed between 1940 and 2007 were retrieved from eleven countries in Central-South America, Asia and Europe. Included countries reported to have low-medium cervical cancer screening uptake. Information on age at and year of diagnosis was collected from medical records. After histological confirmation, HPV DNA detection was performed by SPF-10/DEIA/LiPA25 (version1). Logistic regression models were used for estimating the adjusted relative contributions (RC) of HPV16 and of HPV18 over time. Among 4,771 HPV DNA positive ICC cases, HPV16 and HPV18 were the two most common HPVs in all the decades with no statistically significant variations of their adjusted-RC from 1940-59 to 2000-07 (HPV16-from 61.5 to 62.1%, and HPV18-from 6.9 to 7.2%). As well, the RC of other HPV types did not varied over time. In the stratified analysis by histology, HPV16 adjusted-RC significantly increased across decades in adenocarcinomas. Regarding age, cases associated to either HPV16, 18 or 45 were younger than those with other HPV types in all the evaluated decades. The observed stability on the HPV type distribution predicts a high and stable impact of HPV vaccination in reducing the cervical cancer burden in future vaccinated generations.

Attributable fraction of alcohol consumption on cancer using population-based nationwide cancer incidence and mortality data in the Republic of Korea.

BACKGROUND: In the Republic of Korea, cancer is the most common cause of death, and cancer incidence and mortality rates are the highest in East Asia. As alcoholic beverages are carcinogenic to humans, we estimated the burden of cancer related to alcohol consumption in the Korean population. METHODS: The cancer sites studied were those for which there is convincing evidence of a positive association with alcohol consumption: oral cavity, pharynx, esophagus, colon, rectum, liver, larynx and female breast. Sex- and cancer-specific population attributable fractions (PAF) were calculated based on: 1) the prevalence of alcohol drinkers among adults ≥ 20 years of age in 1989; 2) the average daily alcohol consumption (g/day) among drinkers in 1998; 3) relative risk (RR) estimates for the association between alcohol consumption and site-specific cancer incidence obtained either from a large Korean cohort study or, when more than one Korean study was available for a specific cancer site, meta-analyses were performed and the resulting meta-RRs were used; 4) national cancer incidence and mortality data from 2009. RESULTS: Among men, 3% (2,866 cases) of incident cancer cases and 2.8% (1,234 deaths) of cancer deaths were attributable to alcohol consumption. Among women, 0.5% (464 cancer cases) of incident cancers and 0.1% (32 deaths) of cancer deaths were attributable to alcohol consumption. In particular, the PAF for alcohol consumption in relation to oral cavity cancer incidence among Korean men was 29.3%, and the PAFs for pharyngeal and laryngeal cancer incidence were 43.3% and 25.8%, respectively. Among Korean women, the PAF for colorectal cancer incidence was the highest (4.2%) and that for breast cancer incidence was only 0.2%. Avoiding alcohol consumption, or reducing it from the median of the highest 4th quartile of consumption (56.0 g/day for men, 28.0 g/day for women) to the median of the lowest quartile (2.80 g/day for men, 0.80 g/day for women), would reduce the burden of alcohol-related cancers in Korea. CONCLUSIONS: A reduction in alcohol consumption would decrease the cancer burden and a significant impact is anticipated specifically for the cancers oral cavity, pharynx, and larynx among men in the Republic of Korea.

Attributable fraction of tobacco smoking on cancer using population-based nationwide cancer incidence and mortality data in Korea.

BACKGROUND: Smoking is by far the most important cause of cancer that can be modified at the individual level. Cancer incidence and mortality rates in Korea are the highest among all Asian countries, and smoking prevalence in Korean men is one of the highest in developed countries. The purpose of the current study was to perform a systematic review and provide an evidence-based assessment of the burden of tobacco smoking-related cancers in the Korean population. METHODS: Sex- and cancer-specific population-attributable fractions (PAF) were estimated using the prevalence of ever-smoking and second-hand smoking in 1989 among Korean adults, respectively, and the relative risks were estimated from the meta-analysis of studies performed in the Korean population for ever-smoking and in the Asian population for passive smoking. National cancer incidence data from the Korea Central Cancer Registry and national cancer mortality data from Statistics Korea for the year 2009 were used to estimate the cancer cases and deaths attributable to tobacco smoking. RESULTS: Tobacco smoking was responsible for 20,239 (20.9%) cancer incident cases and 14,377 (32.9%) cancer deaths among adult men and 1,930 (2.1%) cancer incident cases and 1,351 (5.2%) cancer deaths among adult women in 2009 in Korea. In men, 71% of lung cancer deaths, 55%-72% of upper aerodigestive tract (oral cavity, pharynx, esophagus and larynx) cancer deaths, 23% of liver, 32% of stomach, 27% of pancreas, 7% of kidney and 45% of bladder cancer deaths were attributable to tobacco smoking. In women the proportion of ever-smoking-attributable lung cancer was 8.1%, while that attributable to second-hand smoking among non-smoking women was 20.5%. CONCLUSIONS: Approximately one in three cancer deaths would be potentially preventable through appropriate control of tobacco smoking in Korean men at the population level and individual level. For Korean women, more lung cancer cases and deaths were attributable to second-hand than ever-smoking. Effective control programs against tobacco smoking should be further developed and implemented in Korea to reduce the smoking-related cancer burden.

Control of clonorchiasis in Korea: effectiveness of health education for community leaders and individuals in an endemic area.

OBJECTIVES: To develop effective intervention programmes to control Clonorchis sinensis infection, three interventions were evaluated in a clonorchiasis-endemic area of Korea. METHODS: Four thousand two hundred and sixty-seven voluntary participants in Sancheong county were tested at baseline and two follow-up surveys after 1 and 3 years. Faecal samples were examined for C. sinensis eggs using the Kato-Katz method. Participants were divided into three intervention groups by areas and year recruited: national prevention programme only (mass health campaign and praziquantel treatment) for Group A; health education for community leaders added for Group B; and individual health education added for Group C. RESULTS: The prevalence of C. sinensis infection fell substantially in all three intervention groups between baseline and 3-year follow-up: from 31.1% to 14.9% in Group A, from 29.6% to 6.8% in Group B and from 21.9% to 8.6% in Group C. The control effectiveness was highest in Group B with 76.8%. The new infection rate was 16.3%, 12.8% and 7.6% in Group A, B and C, respectively. The reinfection rate was lower in Group B (3.8%) than Group C (12.2%). CONCLUSIONS: To control C. sinensis infection in endemic areas of Korea, health education for community leaders or individuals on prevention of C. sinensis infection should be added to national control programmes.

Soluble c-Met protein as a susceptible biomarker for gastric cancer risk: A nested case-control study within the Korean Multicenter Cancer Cohort.

This study was conducted to evaluate the relevance of the soluble form of c-Met protein, a truncated form of the c-Met membrane receptor involved in the CagA pathway, as a potential biomarker for gastric cancer. Among 290 gastric cancer case-control sets selected from the Korean Multicenter Cancer Cohort, the plasma concentrations of soluble c-Met protein were measured with enzyme-linked immunosorbent assays. Using analysis of variance and covariance models with age, sex, smoking, Helicobacter pylori infection, and CagA seropositivity, the mean concentrations of soluble c-Met protein between cases and controls were compared. To evaluate the association between gastric cancer and a c-Met protein level, odds ratios and 95% confidence intervals were estimated using conditional logistic regression models. Interactions between CagA-related genes and the soluble c-Met protein concentration were also investigated. The overall median plasma concentration of soluble c-Met among cases was significantly lower than those of controls (1.390 vs. 1.610 ng/mL, p < 0.0001). Closer to the onset of gastric cancer, the soluble c-Met protein level decreased linearly in a time-dependent manner (p for trend = 0.0002). The combined effects between the CagA-related genes and the soluble c-Met protein concentration significantly intensified risks for gastric cancer. Restricted analyses including cases that had been diagnosed within 1 year after entering the cohort had a fair degree of ability (area under the receiver operating characteristic curve of 0.73-0.77) to discriminate gastric cancer cases from normal controls. Our findings demonstrate the potential of the soluble form of c-Met protein as a novel biomarker for gastric cancer. The beneficial effects of a high soluble c-Met concentration in human plasma are strongly supported.

Laser capture microdissection shows HPV11 as both a causal and a coincidental infection in cervical cancer specimens with multiple HPV types.

AIMS: To identify, by laser capture microdissection (LCM), the cellular localization of HPV11 when present with carcinogenic HPV in invasive cervical cancer (ICC) specimens, and to relate this to p16(INK) (4a) expression. METHODS AND RESULTS: Three squamous cell ICC specimens showing coinfection with HPV11 and carcinogenic HPV16 or HPV31 were selected from the Institut Català d'Oncologia international survey of anogenital carcinomas, and coinfection was confirmed by SPF10 -DEIA-LiPA25 analysis. In two cases LCM-PCR identified HPV11 in low-grade and high-grade squamous intraepithelial lesions (SILs) adjacent to the ICC, and HPV16 or HPV31 in the ICC. In one case, HPV11 was the only genotype found in the ICC. P16(INK) (4a) expression was diffuse in ICC associated with carcinogenic HPV, but focal in ICC with HPV11. CONCLUSIONS: Our results confirm that a single cervical, cancerous or precancerous lesion is associated with a single HPV type. Detecting low-risk HPV as a coinfection in whole tissue from ICC does not prove a causal association. HPV11 may be found only in an adjacent SIL with carcinogenic HPV in the ICC. It is also found alone in carcinoma. LCM-PCR and differential P16(INK) (4a) expression can clarify the causal role of each type when multiple HPVs are present in whole tissue from carcinomas.

Intake of soy products and other foods and gastric cancer risk: a prospective study.

BACKGROUND: Gastric cancer, the most common cancer in the world, is affected by some foods or food groups. We examined the relationship between dietary intake and stomach cancer risk in the Korean Multi-Center Cancer Cohort (KMCC). METHODS: The KMCC included 19 688 Korean men and women who were enrolled from 1993 to 2004. Of those subjects, 9724 completed a brief 14-food frequency questionnaire at baseline. Through record linkage with the Korean Central Cancer Registry and National Death Certificate databases, we documented 166 gastric cancer cases as of December 31, 2008. Cox proportional hazard models were used to estimate relative risks (RRs) and 95% CIs. RESULTS: Frequent intake of soybean/tofu was significantly associated with reduced risk of gastric cancer, after adjustment for age, sex, cigarette smoking, body mass index, alcohol consumption, and area of residence (P for trend = 0.036). We found a significant inverse association between soybean/tofu intake and gastric cancer risk among women (RR = 0.41, 95% CI: 0.22-0.78). Men with a high soybean/tofu intake had a lower risk of gastric cancer, but the reduction was not statistically significant (RR = 0.77, 95% CI: 0.52-1.13). There was no interaction between soybean/tofu intake and cigarette smoking in relation to gastric cancer risk (P for interaction = 0.268). CONCLUSIONS: Frequent soybean/tofu intake was associated with lower risk of gastric cancer.

Multiplicative synergistic risk of hepatocellular carcinoma development among hepatitis B and C co-infected subjects in HBV endemic area: a community-based cohort study.

BACKGROUND: There has been limited study on the effect of infection with different hepatitis C virus (HCV) genotypes on the risk of hepatocellular carcinoma (HCC) in hepatitis B virus (HBV) endemic regions of Asia. METHODS: Hazard ratios of HCC development were estimated for HBV and HCV co-infected subjects among a community-based prospective cohort. HCV genotype was determined in HCV RNA-positive samples. Incident HCC cases were identified through linkage to the cancer registry. RESULTS: HCC incidence was 79 per 100,000 person-years in the study population (50 incident cases among 6,694 individuals within 63,170 person-years with an average of 9.4 years of follow-up); seroprevalence of HBsAg and anti-HCV was 5.2% and 5.6%. Adjusted hazard ratios of HCC by HBsAg positivity and anti-HCV positivity were 13.3 (CI: 7.3-24.4) and 6.7 (CI: 3.6-12.6). HRs of HBV and HCV monoinfection, and HBV/HCV coinfection were 17.1 (CI: 8.4-34.8), 10.4 (CI: 4.9-22.1) and 115.0 (CI: 32.5-407.3). Multiplicative synergistic effect of HBV/HCV coinfection on HCC risk was also observed (synergy index: 4.5, CI: 1.3-15.5). Infection with HCV genotype 1 (HR: 29.7, CI: 13.6-46.8) and mixed infection with genotype 1 and 2 (HR: 68.7, CI: 16.4-288.4) significantly elevated HCC risk, much higher than HBV infection. CONCLUSIONS: The effect of differences in HCV genotype and the multiplicative synergistic effect of HBV/HCV coinfection on HCC risk shown in the present study underline the need for comprehensive identification of hepatitis infection status in order to prevent and control HCC in this HBV endemic area.

Cancer control in the Asia Pacific region: current status and concerns.

Cancer is becoming an increasingly important health problem in the low- and middle-income countries in the Asia Pacific region, as well as in high-income countries because of ageing populations and changes in lifestyle associated with economic development and epidemiologic transition. This paper reviews the cancer burden and control in the Asia Pacific region (limited to East Asia, South Eastern Asia and Pacific Islands countries, territories and other areas), with relevant information primarily extracted from the GLOBOCAN 2008, Cancer Incidence in Five Continents series and WHO websites. Most low- and middle-income countries have a cancer control strategy and/or an action plan; however, coverage of cancer registration is still very low and does not meet the international standard in terms of quality. Therefore, only limited data were available for the recent global estimation of cancer burden. Large variations, in both cancer incidence and mortality, were observed in the populations in the different sub-regions of Asia. The most common cancer in males is lung cancer in the Eastern and South Eastern sub-regions, while prostate cancer comes close to lung cancer in the Pacific Island countries. In females, breast cancer is the most common in all three regions. The predominance of lung, stomach, colorectal, prostate, breast and cervical cancers makes cancer control more amenable in the Asia Pacific region. Up-to-date statistics on cancer occurrence and outcome are essential for the planning and evaluation of cancer control programmes. Priority can be given to population-based cancer registration, risk reduction, especially tobacco control, and primary health care based enhancement of health care systems to diagnose and manage cancer specifically in low- and middle-income countries.

Prevalence and seroprevalence of low-risk human papillomavirus in Korean women.

Little is known about the prevalence and seroprevalence of low-risk human papillomavirus (HPV) and the risk factors for HPV infection in Korean women. We determined the prevalence of low-risk HPV among 902 women aged 20-59 yr and the seroprevalence of low-risk HPV subtypes 6 and 11 among 1,094 women aged 9-59 yr in the general population. Genital low-risk HPV DNA was assessed by liquid hybridization and polymerase chain reaction. Antibody titers against HPV 6 and 11 were measured by a multiplexed competitive luminex technique. The prevalence of genital low-risk HPV was 4.9%. It reached its highest peak of 10.3% at 20-29 yr of age and a second peak of 3.2% at 50-59 yr of age. The seroprevalence of HPV 6 or 11 was 9.4%. It reached its highest peak of 12.7% at 25-29 yr of age and a second peak of 12.3% at 50-59 yr of age. In multivariable analysis, the number of lifetime sexual partners and past history of sexually transmitted diseases were associated with the seroprevalence but not prevalence of HPV. It is suggested that younger women should receive prophylactic HPV vaccination before they become sexually active and exposed to HPV in their 20s. This study provides baseline data for developing HPV vaccination programs and monitoring vaccine efficacy in Korea.

Coinfection of hepatitis B and C viruses and risk of hepatocellular carcinoma: systematic review and meta-analysis.

A subadditive effect of hepatitis B virus (HBV) and hepatitis C virus (HCV) coinfection is possible because superinfection of one virus tends to inhibit infection of the other virus. However, studies have reported inconsistent findings, and two meta-analyses of studies from various countries (1998) and China (2005) reported a supraadditive effect for hepatocellular carcinoma (HCC) risk. Thus, we reevaluate HBV/HCV monoinfection and coinfection. Of 411 reports, we included 59 studies that assessed the association between HBV/HCV monoinfection and coinfection for HCC risk. HCC risk because of high/detectable HBV DNA and HBeAg infection was higher than HBsAg infection, whereas anti-HCV vs anti-HCV/HCV RNA was not different. Geographically, HCC risk was significantly higher in nonendemic than in HBV or HCV endemic areas. Subadditive effect for HCC risk was presented in recently published studies, cohort studies and studies conducted in HBV/HCV nonendemic areas; an additive effect was presented in studies conducted in HBV endemic areas; a supraadditive effect was presented in previously published studies, case-control studies and studies conducted in HCV endemic areas. Our results suggest HBV/HCV coinfection for HCC risk is not significantly greater than HBV/HCV monoinfection, and HCC risk due to HBV or HCV is higher in nonendemic than endemic areas. The p-heterogeneity was significant for most analyses, except HBV(+)/HCV(+) and HBV biomarker analyses. Prevention strategies targeted toward HBV or HCV monoinfected patients are needed. In addition, tailored prevention to reduce infectivity such as HBV markers (HBeAg, HBV DNA) is needed.

High prevalence of hepatitis B and hepatitis C virus infections in Korean patients with hematopoietic malignancies.

We performed a large case-control study (3,932 cases, 15,562 controls) to investigate the association of hepatitis B virus (HBV) and hepatitis C virus (HCV) with hematopoietic malignancies in Korea, where HBV is endemic. HBV was present in 636 control patients (4.1%), 333 lymphoma patients (12.4%), and 75 leukemia patients (6.0%). HCV infection was present in 173 control patients (1.1%), 76 lymphoma patients (2.8%), and 18 leukemia patients (1.4%). Co-infection of HBV and HCV was present in one (0.007%) control patient, seven lymphoma patients (0.3%), and one leukemia patient (0.08%). HBV infection was associated with increased risks for most subtypes of B and T/NK-cell lymphomas, Hodgkin's lymphoma, and acute myeloid leukemia. HCV infection was associated with increased risks for diffuse large B cell lymphoma, extranodal marginal zone B cell lymphoma, peripheral T cell lymphoma, and acute lymphoid leukemia B cell early pre-B type. HBV seems to have a more important role than HCV in the pathogenesis of specific hematologic malignancies in Korea.