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Infections with certain viruses, bacteria, and parasites have been identified as strong risk factors for specific cancers. An update of their respective contribution to the global burden of cancer is warranted. We considered infectious agents classified as carcinogenic to humans by the International Agency for Research on Cancer. We calculated their population attributable fraction worldwide and in eight geographical regions, using statistics on estimated cancer incidence in 2008. When associations were very strong, calculations were based on the prevalence of infection in cancer cases rather than in the general population. Estimates of infection prevalence and relative risk were extracted from published data. Of the 12·7 million new cancer cases that occurred in 2008, the population attributable fraction (PAF) for infectious agents was 16·1%, meaning that around 2 million new cancer cases were attributable to infections. This fraction was higher in less developed countries (22·9%) than in more developed countries (7·4%), and varied from 3·3% in Australia and New Zealand to 32·7% in sub-Saharan Africa. Helicobacter pylori, hepatitis B and C viruses, and human papillomaviruses were responsible for 1·9 million cases, mainly gastric, liver, and cervix uteri cancers. In women, cervix uteri cancer accounted for about half of the infection-related burden of cancer; in men, liver and gastric cancers accounted for more than 80%. Around 30% of infection-attributable cases occur in people younger than 50 years. Around 2 million cancer cases each year are caused by infectious agents. Application of existing public health methods for infection prevention, such as vaccination, safer injection practice, or antimicrobial treatments, could have a substantial effect on the future burden of cancer worldwide. Fondation Innovations en Infectiologie (FINOVI) and the Bill & Melinda Gates Foundation (BMGF).

Although most of Helicobacter pylori-related diseases are associated with male gender, the role of gender as a risk factor for H. pylori infection is still debated. To assess the true association between H. pylori and gender, we conducted a meta-analysis of large, population-based studies where the measure of association had been adjusted at least for age and socioeconomic status, and obtained primary data from authors when information on gender associations were not presented. In 18 adult populations, the test of heterogeneity was not significant and male gender was significantly associated with H. pylori infection (summary odds ratio [OR] 1.16 [95% confidence interval (CI) 1.11, 1.22]). In 10 pediatric populations, the test of heterogeneity was of borderline significance, and the summary OR computed using a random effect model was close to 1 (summary OR 1.03 [95% CI 0.91, 1.17]). This study confirms the male predominance of H. pylori infection in adults as a global and homogeneous phenomenon; such predominance is not apparent in children. Differential antibiotic exposure or differential protective immunity between genders may explain the different results observed between children and adult studies.

► 1 in 10 women worldwide carries an HPV infection at any point in time. ► 610,000 incident cancers per annum are attributable to HPV infection globally. ► 80.6% of HPV associated cancers occur in less developed regions of the world. ► Cervix is the predominant HPV-associated cancer with 530,000 incident cases p.a. ► Genital warts are caused by HPV with an annual incidence of 0.1 to 0.2%. The worldwide prevalence of infection with human papillomavirus (HPV) in women without cervical abnormalities is 11–12% with higher rates in sub-Saharan Africa (24%), Eastern Europe (21%) and Latin America (16%). The two most prevalent types are HPV16 (3.2%) and HPV18 (1.4%). Prevalence increases in women with cervical pathology in proportion to the severity of the lesion reaching around 90% in women with grade 3 cervical intraepithelial neoplasia and invasive cancer. HPV infection has been identified as a definite human carcinogen for six types of cancer: cervix, penis, vulva, vagina, anus and oropharynx (including the base of the tongue and tonsils). Estimates of the incidence of these cancers for 2008 due to HPV infection have been calculated globally. Of the estimated 12.7 million cancers occurring in 2008, 610,000 (Population Attributable Fraction [PAF]=4.8%) could be attributed to HPV infection. The PAF varies substantially by geographic region and level of development, increasing to 6.9% in less developed regions of the world, 14.2% in sub-Saharan Africa and 15.5% in India, compared with 2.1% in more developed regions, 1.6% in Northern America and 1.2% in Australia/New Zealand. Cervical cancer, for which the PAF is estimated to be 100%, accounted for 530,000 (86.9%) of the HPV attributable cases with the other five cancer types accounting for the residual 80,000 cancers. Cervical cancer is the third most common female malignancy and shows a strong association with level of development, rates being at least four-fold higher in countries defined within the low ranking of the Human Development Index (HDI) compared with those in the very high category. Similar disparities are evident for 5-year survival—less than 20% in low HDI countries and more than 65% in very high countries. There are five-fold or greater differences in incidence between world regions. In those countries for which reliable temporal data are available, incidence rates appear to be consistently declining by approximately 2% per annum. There is, however, a lack of information from low HDI countries where screening is less likely to have been successfully implemented. Estimates of the projected incidence of cervical cancer in 2030, based solely on demographic factors, indicate a 2% increase in the global burden of cervical cancer, i.e., in balance with the current rate of decline. Due to the relative small numbers involved, it is difficult to discern temporal trends for the other cancers associated with HPV infection. Genital warts represent a sexually transmitted benign condition caused by HPV infection, especially HPV6 and HPV11. Reliable surveillance figures are difficult to obtain but data from developed countries indicate an annual incidence of 0.1 to 0.2% with a peak occurring at teenage and young adult ages. This article forms part of a special supplement entitled “Comprehensive Control of HPV Infections and Related Diseases” Vaccine Volume 30, Supplement 5, 2012.

The stomach is a common site for extranodal non-Hodgkin’s lymphoma. While Helicobacter pylori ( H. pylori ) is the main established risk factor for primary gastric lymphoma, a fraction could be aetiologically associated with Epstein–Barr virus (EBV), a known haematolymphoid carcinogen. We systematically searched five databases from 1 January 1990 until 31 May 2022 for studies reporting EBV prevalence in gastric lymphoma tumour tissue by in-situ hybridisation (ISH) for EBV-encoded small RNA (PROSPERO CRD42020164473). We included representative series of more than five gastric lymphoma cases. Pooled prevalence and corresponding 95% confidence intervals (CI) of EBV in gastric tumour cells were calculated for two major gastric B-cell lymphoma types, mucosa-associated lymphoid tissue (MALT) lymphoma and diffuse large B-cell lymphoma (DLBCL). When available, we also extracted data on H. pylori prevalence and survival by EBV status. We found ten studies including 194 cases of gastric MALT lymphoma and 11 studies including 643 cases of gastric DLBCL. EBV prevalence was 2.2% (95% CI: 0.5–13.3) in gastric MALT lymphoma and 11.0% (95% CI: 5.2–20.0) in gastric DLBCL. In a subset of studies, the prevalence of H. pylori was higher in gastric MALT lymphoma (51/69) compared to gastric DLBCL (62/102). Overall, our findings suggest that EBV is rarely seen in MALT lymphoma but is associated with around 10% of gastric DLBCL, similar to the proportion observed at other primary sites. EBV-related lymphoma adds a small number of cases to the burden of cancer that could be prevented by the future development of a vaccine against EBV.

BackgroundAn increase in the incidence of esophageal adenocarcinoma has coincided with a decrease in the prevalence of Helicobacter pylori infection. Whether these 2 phenomena are associated is unknown MethodsWe conducted a nested case-control study of 128,992 members of an integrated health care system who had participated in a multiphasic health checkup (MHC) during 1964–1969. During follow-up, 52 patients developed esophageal adenocarcinoma. Three randomly chosen control subjects from the MHC cohort were matched to each case subject, on the basis of age at the MHC, sex, race, and the date and site of the MHC. Data on cigarette smoking, alcohol consumption, body mass index (BMI), and education level were obtained at the MHC. Serum samples collected at the MHC were tested for IgG antibodies to H. pylori and to the H. pylori CagA protein ResultsSubjects with H. pylori infections were less likely than uninfected subjects to develop esophageal adenocarcinoma (odds ratio [OR], 0.37 [95% confidence interval (CI), 0.16–0.88]). This significant association was restricted to case subjects and control subjects <50 years old at the MHC (OR, 0.20 [95% CI, 0.06–0.68]). In patients with H. pylori infections, the OR for those who tested positive for IgG antibodies to the CagA protein was similar to that for those who tested negative for it. BMI ⩾25 and cigarette smoking were strong independent risk factors for development of esophageal adenocarcinoma ConclusionThe absence of H. pylori infection, independent of cigarette smoking and BMI, is associated with a markedly increased risk of development of esophageal adenocarcinoma

ObjectiveChina concentrates a large part of the global burden of HBV infection, playing a pivotal role in achieving the WHO 2030 global hepatitis elimination target.MethodsWe searched for studies reporting HBV surface antigen (HBsAg) seroprevalence in five databases until January 2023. Eligible data were pooled using a generalised linear mixed model with random effects to obtain summary HBsAg seroprevalence. Linear regression was used to estimate annual percentage change (APC) and HBsAg prevalence in 2021.Results3740 studies, including 231 million subjects, were meta-analysed. HBsAg seroprevalence for the general population decreased from 9.6% (95% CI 8.4 to 10.9%) in 1973–1984 to 3.0% (95% CI 2.1 to 3.9%) in 2021 (APC=−3.77; p<0.0001). Decreases were more pronounced in children <5 years (APC=−7.72; p<0.0001) and 5–18 years (−7.58; p<0.0001), than in people aged 19–59 years (−2.44; p<0.0001), whereas HBsAg seroprevalence increased in persons ≥60 years (2.84; p=0.0007). Significant decreases were observed in all six major Chinese regions, in both men (APC=−3.90; p<0.0001) and women (−1.82; p<0.0001) and in high-risk populations. An estimated 43.3 million (95% uncertainty interval 30.7–55.9) persons remained infected with HBV in China in 2021 (3.0%), with notable heterogeneity by region (<1.5% in North China to>6% in Taiwan and Hong Kong) and age (0.3%, 1.0%, 4.7% and 5.6% for <5 years, 5–18 years, 19–59 years and ≥60 years, respectively).ConclusionsChina has experienced remarkable decreases in HBV infection over the last four decades, but variations in HBsAg prevalence persist in subpopulations. Ongoing prevention of HBV transmission is needed to meet HBV elimination targets by 2030.Trial registration numberPROSPERO (CRD42021284217)

BackgroundThe subtypes of gastric cancer (GC) and oesophageal cancer (EC) manifest distinct epidemiological profiles. Here, we aim to examine correlations in their incidence rates and to compare their temporal changes globally, both overall and by subtype.MethodsLong-term incidence data were obtained from population-based registries available from the Cancer Incidence in Five Continents series. Variation in the occurrence of EC and GC (overall and by subtype) was assessed using the GC:EC ratio of sex-specific age-standardised rates (ASR) in 2008–2012. Average annual per cent changes were estimated to assess temporal trends during 1998–2012.ResultsASRs for GC and EC varied remarkably across and within world regions. In the countries evaluated, the GC:EC ratio in men exceeded 10 in several South American countries, Algeria and Republic of Korea, while EC dominated in most sub-Saharan African countries. High rates of both cardia gastric cancer and oesophageal squamous cell carcinoma (ESCC) were observed in several Asian populations. Non-cardia gastric cancer rates correlated positively with ESCC rates (r=0.60) and negatively with EAC (r=−0.79). For the time trends, while GC incidence has been uniformly decreasing by on average 2%–3% annually over 1998–2012 in most countries, trends for EC depend strongly on histology, with several but not all countries experiencing increases in EAC and decreases in ESCC.ConclusionsCorrelations between GC and EC incidence rates across populations are positive or inverse depending on the GC subsite and EC subtype. Multisite studies that include a combination of populations whose incidence rates follow and deviate from these patterns may be aetiologically informative.

To provide an assessment of the burden of cancer in France in 2015 attributable to infectious agents. A systematic literature review in French representative cancer cases series was undertaken of the prevalence of infectious agents with the major associated cancer types. PubMed was searched for original studies published up to September 2016; random-effects meta-analyses were performed. Cancer incidence data were obtained from the French Cancer Registries Network, thereby allowing the calculation of national incidence estimates. The number of new cancer cases attributable to infectious agents was calculated using population-attributable fractions according to published methods. Of the 352,000 new cancer cases in France in 2015, 14,336 (4.1% of all new cancer cases) were attributable to infectious agents. The largest contributors were human papillomavirus (HPV) and Helicobacter pylori, responsible for 6333 and 4406 new cancer cases (1.8 and 1.3% of all new cancer cases) respectively. Infectious agents caused a non-negligible number of new cancer cases in France in 2015. Most of these cancers were preventable. The expansion of vaccination (i.e., for hepatitis virus and HPV) and screen-and-treat programs (for HPV and hepatitis virus, and possibly for H. pylori) could greatly reduce this cancer burden.

To systematically assess the sero-prevalence and associated factors of major infectious pathogens in China, where there are high incidence rates of certain infection-related cancers. Cross-sectional study. 10 (5 urban, 5 rural) geographically diverse areas in China. A subcohort of 2000 participants from the China Kadoorie Biobank. Sero-prevalence of 19 pathogens using a custom-designed multiplex serology panel and associated factors. Of the 19 pathogens investigated, the mean number of sero-positive pathogens was 9.4 (SD 1.7), with 24.4% of participants being sero-positive for >10 pathogens. For individual pathogens, the sero-prevalence varied, being for example, 0.05% for HIV, 6.4% for human papillomavirus (HPV)-16, 53.5% for ( ) and 99.8% for Epstein-Barr virus . The sero-prevalence of human herpesviruses (HHV)-6, HHV-7 and HPV-16 was higher in women than men. Several pathogens showed a decreasing trend in sero-prevalence by birth cohort, including hepatitis B virus (HBV) (51.6% vs 38.7% in those born <1940 vs >1970), HPV-16 (11.4% vs 5.4%), HHV-2 (15.1% vs 8.1%), (65.6% vs 28.8%) and (22.0% vs 9.0%). Across the 10 study areas, sero-prevalence varied twofold to fourfold for HBV (22.5% to 60.7%), HPV-16 (3.4% to 10.9%), (16.2% to 71.1%) and (32.5% to 66.5%). Participants with chronic liver diseases had >7-fold higher sero-positivity for HBV (OR=7.51; 95% CI 2.55 to 22.13). Among Chinese adults, previous and current infections with certain pathogens were common and varied by area, sex and birth cohort. These infections may contribute to the burden of certain cancers and other non-communicable chronic diseases.

Several large studies have shown a negative association between Helicobacter pylori (H. pylori) infection and esophageal adenocarcinoma. Diminution of gastric ghrelin secretion by H. pylori could protect against esophageal malignancy by decreasing appetite, food intake, and acid production, thereby decreasing weight and gastroesophageal reflux. We evaluated the association of ghrelin with esophageal adenocarcinoma using a population from a previous nested case-control study. Among 128,992 enrolled in a multiphasic health checkup (MHC) between 1964 and 1969, 52 patients developed esophageal adenocarcinoma by the year 2000. Three random controls from the MHC cohort were matched to each case by age, sex, race, and the date and site of their MHC. Serum samples collected at the MHC had been previously tested for IgG antibodies against H. pylori and the CagA protein. Serum ghrelin concentrations were determined by a commercial EIA on 52% of the initial subjects (31 cases and 79 controls). A concentration of ghrelin greater than 3,200 pg/mL at MHC (fourth quartile) was associated with a lower risk of esophageal cancer (H. pylori and body mass index [BMI] adjusted OR=0.18 [CI 0.04-0.78]). This inverse association was seen only in overweight subjects (BMI>or=25, P value for interaction=0.09). The effects of H. pylori and ghrelin were independent. Contrary to the original hypothesis, high rather than low serum ghrelin was associated with protection against esophageal adenocarcinoma but only among overweight subjects.