We confirm the early decline of HPV infection with age but note increased prevalence after menopause, which could be related to a second peak of HSILs, an observation that warrants further investigation. At least 80% of HPVs involved in cervical carcinogenesis in this population have been characterized. Polyvalent vaccines including the main cancer-associated HPV types may be able to prevent most cases of cervical disease in this region.

Infection with human papillomavirus (HPV) is recognized as one of the major causes of infection-related cancer worldwide, as well as the causal factor in other diseases. Strong evidence for a causal etiology with HPV has been stated by the International Agency for Research on Cancer for cancers of the cervix uteri, penis, vulva, vagina, anus and oropharynx (including base of the tongue and tonsils). Of the estimated 12.7 million new cancers occurring in 2008 worldwide, 4.8% were attributable to HPV infection, with substantially higher incidence and mortality rates seen in developing versus developed countries. In recent years, we have gained tremendous knowledge about HPVs and their interactions with host cells, tissues and the immune system; have validated and implemented strategies for safe and efficacious prophylactic vaccination against HPV infections; have developed increasingly sensitive and specific molecular diagnostic tools for HPV detection for use in cervical cancer screening; and have substantially increased global awareness of HPV and its many associated diseases in women, men, and children. While these achievements exemplify the success of biomedical research in generating important public health interventions, they also generate new and daunting challenges: costs of HPV prevention and medical care, the implementation of what is technically possible, socio-political resistance to prevention opportunities, and the very wide ranges of national economic capabilities and health care systems. Gains and challenges faced in the quest for comprehensive control of HPV infection and HPV-related cancers and other disease are summarized in this review. The information presented may be viewed in terms of a reframed paradigm of prevention of cervical cancer and other HPV-related diseases that will include strategic combinations of at least four major components: 1) routine introduction of HPV vaccines to women in all countries, 2) extension and simplification of existing screening programs using HPV-based technology, 3) extension of adapted screening programs to developing populations, and 4) consideration of the broader spectrum of cancers and other diseases preventable by HPV vaccination in women, as well as in men. Despite the huge advances already achieved, there must be ongoing efforts including international advocacy to achieve widespread—optimally universal—implementation of HPV prevention strategies in both developed and developing countries. This article summarizes information from the chapters presented in a special ICO Monograph ‘Comprehensive Control of HPV Infections and Related Diseases’ Vaccine Volume 30, Supplement 5, 2012. Additional details on each subtopic and full information regarding the supporting literature references may be found in the original chapters.

Background Helicobacter pylori infection is a major cause of non-cardia gastric cancer (NCGC), but its causal role in cardia gastric cancer (CGC) is unclear. Moreover, the reported magnitude of association with NCGC varies considerably, leading to uncertainty about population-based H pylori screening and eradication strategies in high-risk settings, particularly in China, where approximately half of all global gastric cancer cases occur. Our aim was to assess the associations of H pylori infection, both overall and for individual infection biomarkers, with the risks of NCGC and CGC in Chinese adults.Methods A case-cohort study was done in adults from the prospective China Kadoorie Biobank study, aged 30-79 years from ten areas in China

An advantage of multicenter cohort studies on diet and cancer is that these may include populations over a wide range of dietary exposure. With some simplifying assumptions, the information from such multicenter studies may be divided into 1) estimated relationships within each of the separate cohorts, between individual-level measurements of dietary exposure and disease outcome, and 2) an estimated between-cohort relationship, between the mean intake measurements and mean incidence rates. Errors in the dietary exposure measurements may lead to different amounts of bias in each of these estimated relationships, in particular when dietary questionnaire methods cannot easily be standardized. A calibration approach can be used to adjust for such differences in bias. This will improve the relative weighting of within- and between-cohort components of evidence for a diet-disease association.

This paper discusses design issues in 'ecological studies' -epidemiological studies in which the relationship between disease and behavioural and environmental determinants is studied at the population rather than the individual level. The number of study populations has little relevance beyond a certain point, the power and precision being limited by the total number of disease events and by the size of the sample surveys used to estimate the distributions of determinants within populations. In most circumstances, optimal design requires the size of the sample surveys in each population to be related to the number of disease events which will occur in it, and for sampling to be stratified by age and/or sex.

Although Helicobacter pylori (HP) infection has been acknowledged to play an etiological role in gastric carcinogenesis, its relatively weak association particularly in developing countries suggests critical roles of cofactors. Among a population with an extremely high prevalence of HP infection (≈95%) in Venezuela, we examined the relationship of household characteristics, smoking, alcohol drinking, dietary consumption, and plasma nutrient levels with the prevalence of three different stages of gastric precancerous lesions, chronic atrophic gastritis (AG; n = 337), intestinal metaplasia (IM; n = 551), and dysplasia (n = 157), in comparison with those without any of these lesions (n = 1154). Length of refrigerator use was marginally inversely associated with the prevalence of the precursor lesions studied. The association was most pronounced for AG followed by dysplasia. On the other hand, smoking status was a significant predictor for IM and dysplasia. Those smoking ≥10 cigarettes/day had 1.8-fold risk of IM and 3.6-fold risk of dysplasia compared with never smokers. There were no associations with alcohol consumption. When six food groups known to be associated with stomach cancer risk in Venezuela were tested, the prevalence of these lesions progressively increased with increasing starchy vegetable consumption and decreasing fresh fruit/fruit juice consumption. The association with fruits was more evident for dysplasia and AG and that with starchy vegetables for IM and AG. However, there were no inverse associations with plasma antioxidant vitamins. These findings offer important public health implications in preventing progression of HP-associated gastric precancerous lesions in high-risk populations.

Meta‐analysis provides important insights for evidence‐based medicine by synthesizing evidence from multiple studies which address the same research question. Within the Bayesian framework, meta‐analysis is frequently expressed by a Bayesian normal‐normal hierarchical model (NNHM). Recently, several publications have discussed the choice of the prior distribution for the between‐study heterogeneity in the Bayesian NNHM and used several “vague” priors. However, no approach exists to quantify the informativeness of such priors, and thus, we develop a principled reference analysis framework for the Bayesian NNHM acting at the posterior level. The posterior reference analysis (post‐RA) is based on two posterior benchmarks: one induced by the improper reference prior, which is minimally informative for the data, and the other induced by a highly anticonservative proper prior. This approach applies the Hellinger distance to quantify the informativeness of a heterogeneity prior of interest by comparing the corresponding marginal posteriors with both posterior benchmarks. The post‐RA is implemented in the freely accessible R package ra4bayesmeta and is applied to two medical case studies. Our findings show that anticonservative heterogeneity priors produce platykurtic posteriors compared with the reference posterior, and they produce shorter 95% credible intervals (CrI) and optimistic inference compared with the reference prior. Conservative heterogeneity priors produce leptokurtic posteriors, longer 95% CrI and cautious inference. The novel post‐RA framework could support numerous Bayesian meta‐analyses in many research fields, as it determines how informative a heterogeneity prior is for the actual data as compared with the minimally informative reference prior.

Chronic inflammation induced by Helicobacter pylori is a key process in gastric carcinogenesis. We hypothesized that genetic polymorphisms in important mediators of H. pylori-induced inflammation may influence the risk of developing various grades of precancerous lesions. We studied the associations between single nucleotide polymorphisms (SNPs) in cyclooxygenase 1 and 2 (PTGS1 and PTGS2), inducible nitric oxide synthase (NOS2A), interferon gamma (IFNG) and its receptor (IFNGR1), and risk of gastric precancerous lesions in a Venezuelan population characterized by high rates of H. pylori infection. We found no association of precancerous lesions with SNPs in PTGS1 and in IFNG. A nonsynonymous SNP of NOS2A (Ser608Leu) and an SNP located in the promoter of IFNGR1 (C-56T) were associated with higher risk of atrophic gastritis [odds ratio (OR)=1.37, 95% confidence interval (CI)=1.01-1.86, and OR=1.49, 95% CI=1.01-2.19, respectively]. Two SNPs of PTGS2 were associated with risk of dysplasia (OR=1.60, 95% CI=1.01-2.54, and OR=0.66, 95% CI=0.43-0.99). We conclude that genetic variability in the genes we studied does not play a major role in the early stages of gastric carcinogenesis.