Background The primary goal of human papillomavirus (HPV) vaccination is to reduce morbidity and mortality from HPV-associated disease, especially cervical cancer. We determined the real-world effectiveness of HPV vaccination against cervical cancer. Methods The study included women 17–30 years living in Denmark October 2006–December 2019. From nationwide registries, information on HPV vaccination and cervical cancer diagnoses were retrieved. Incidence rate ratios (IRRs) with 95% confidence intervals (CI) for cervical cancer according to vaccination status were estimated using Poisson regression with HPV vaccination treated as a time-varying variable and stratified by age at vaccination. We adjusted for attained age, education, and ethnicity. To address the effect of prevalent disease, different buffer periods were used, with one-year buffer period as primary analysis. Results The cohort comprised 867,689 women. At baseline, 36.3% were vaccinated at ≤ 16 years, and during follow-up, 19.3% and 2.3% were vaccinated at 17–19 and 20–30 years, respectively. For women vaccinated at ≤ 16 or 17–19 years, the IRRs of cervical cancer were 0.14 (95% CI:0. 04–0.53) and 0.32 (95% CI: 0.08–1.28), respectively, compared to unvaccinated women. In women 20–30 years at vaccination, the IR was higher than among unvaccinated women (IRR=1.19, 95% CI: 0.80–1.79), but slightly decreased with increasing buffer period (IRR=0.85 (95% CI: 0.55–1.32) with four-year buffer period). Conclusion HPV vaccine effectiveness against cervical cancer at the population-level is high among girls vaccinated before age 20 years. The lack of immediate effect in women vaccinated at age 20–30 years points to the importance of early age at vaccination.

To get insight into still elusive pathomechanisms of pediatric obesity and non-alcoholic fatty liver disease (NAFLD) we explored the interplay among GC-MS studied urinary metabolomic signature, gut liver axis (GLA) abnormalities, and food preferences (Kid-Med). Intestinal permeability (IP), small intestinal bacterial overgrowth (SIBO), and homeostatic model assessment-insulin resistance were investigated in forty children (mean age 9.8 years) categorized as normal weight (NW) or obese (body mass index <85th or >95th percentile, respectively) ± ultrasonographic bright liver and hypertransaminasemia (NAFLD). SIBO was increased in all obese children (p = 0.0022), IP preferentially in those with NAFLD (p = 0.0002). The partial least-square discriminant analysis of urinary metabolome correctly allocated children based on their obesity, NAFLD, visceral fat, pathological IP and SIBO. Compared to NW, obese children had (1) higher levels of glucose/1-methylhistidine, the latter more markedly in NAFLD patients; and (2) lower levels of xylitol, phenyl acetic acid and hydroquinone, the latter especially in children without NAFLD. The metabolic pathways of BCAA and/or their metabolites correlated with excess of visceral fat centimeters (leucine/oxo-valerate), and more deranged IP and SIBO (valine metabolites). Urinary metabolome analysis contributes to define a metabolic fingerprint of pediatric obesity and related NAFLD, by identifying metabolic pathways/metabolites reflecting typical obesity dietary habits and GLA perturbations.

Increased permeability, endogenous ethanol and systemic endotoxin concentrations reflect some GLA dysfunction in obesity and its hepatic complications. Pending further results to establish their potential causative roles, the modulation of the GLA appears to represent a possible target for the prevention and treatment of these conditions.

Pediatric obesity-related metabolic syndrome (MetS) and nonalcoholic fatty liver disease (NAFLD) are increasingly frequent conditions with a still-elusive diagnosis and low-efficacy treatment and monitoring options. In this study, we investigated the salivary metabolomic signature, which has been uncharacterized to date. In this pilot-nested case-control study over a transversal design, 41 subjects (23 obese patients and 18 normal weight (NW) healthy controls), characterized based on medical history, clinical, anthropometric, and laboratory data, were recruited. Liver involvement, defined according to ultrasonographic liver brightness, allowed for the allocation of the patients into four groups: obese with hepatic steatosis ([St+], n = 15) and without hepatic steatosis ([St–], n = 8), and with (n = 10) and without (n = 13) MetS. A partial least squares discriminant analysis (PLS-DA) model was devised to classify the patients’ classes based on their salivary metabolomic signature. Pediatric obesity and its related liver disease and metabolic syndrome appear to have distinct salivary metabolomic signatures. The difference is notable in metabolites involved in energy, amino and organic acid metabolism, as well as in intestinal bacteria metabolism, possibly reflecting diet, fatty acid synthase pathways, and the strict interaction between microbiota and intestinal mucins. This information expands the current understanding of NAFLD pathogenesis, potentially translating into better targeted monitoring and/or treatment strategies in the future.

Objectives We aimed to provide pooled estimates of human papillomavirus (HPV) prevalence in oral potentially malignant disorders (OPMD) and evaluate the impact of presence of epithelial dysplasia. Methods We searched PubMed, Embase, and Cochrane Library databases for studies that examined the prevalence of HPV DNA in OPMD tested by polymerase chain reaction (PCR). Results Across 52 eligible studies (2,677 cases), we found an overall pooled HPV prevalence of 22.5% (95% confidence interval [CI] 16.6–29.0). Between‐study heterogeneity was 93%. When stratified by subgroup, the pooled HPV prevalence in leukoplakia (1,232 cases) was 20.2% (95% CI 11.2–31.1), lichen planus (767 cases) 23.0% (95% CI 15.0–32.2), oral submucous fibrosis (238 cases) 28.6% (95% CI 23.0–34.5), proliferative verrucous leukoplakia (60 cases) 24.7% (95% CI 1.8–62.0), and OPMD unspecified (377 cases) 25.4% (95% CI 16.2–35.8). Information on presence of epithelial dysplasia was available in 19 studies, and the results did not vary substantially between non‐dysplastic and dysplastic samples. HPV16 was the predominant genotype among HPV‐positive OPMD cases (48.2%, 95% CI 31.4–65.2). Conclusion We found a pooled HPV DNA prevalence of 22.5% in OPMD cases with great between‐study heterogeneity. The HPV prevalence appeared to be comparable across subgroups and independent of epithelial dysplasia.

We conducted a systematic review and meta-analysis of observational studies evaluating survival in patients with anal cancer, according to human papillomavirus (HPV) DNA, p16 INK4a , and combined HPV DNA/p16 INK4a status. We systematically searched PubMed, EMBASE, and Cochrane Library databases to identify studies published in English until July 25, 2018, directly providing or allowing estimation of survival of patients with anal cancer according to the presence of HPV DNA and/or overexpression of p16 INK4a . We estimated pooled HRs and 95% confidence intervals (CI) for overall survival (OS) using a random-effects model. We included 16 studies, comprising 1,724 patients with anal cancer tested for HPV DNA (65% positive), and 567 patients tested for p16 INK4a (87% positive). The pooled HR for OS was 0.54 (95% CI, 0.33-0.89) for HPV DNA positive versus negative, 0.37 (95% CI, 0.24-0.57) for p16 INK4a positive versus negative, and 0.36 (95% CI, 0.22-0.58) for HPV DNA positive/p16 INK4a positive versus HPV DNA positive/p16 INK4a negative patients with anal cancer. Patients with HPV DNA or p16 INK4a positive anal cancer have significantly better OS compared with HPV DNA or p16 INK4a negative. This points to the possible value of HPV DNA and/or p16 INK4a testing when planning the management and follow-up strategy for patients diagnosed with anal cancer. Data extractionTwo authors (A. Urbute and C.L. Rasmussen) reviewed titles, abstracts, and full-texts, and extracted data independently. Any inconsistency in the evaluation of study eligibility or data extraction was

The purpose of this systematic review and meta‐analysis was to estimate the overall and type‐specific prevalence of human papillomavirus (HPV) DNA in oral epithelial dysplasia and assess p16INK4a overexpression in relation to HPV‐status. A systematic literature search identified 31 eligible studies (832 cases) evaluating the presence of HPV DNA in oral epithelial dysplasia cases by PCR. Of these, six studies evaluated p16INK4a overexpression in relation to HPV‐status. The overall pooled prevalence of HPV DNA in oral epithelial dysplasia was 27.2% (95% CI: 17.6‐38.1). We observed substantial interstudy heterogeneity, which could not be explained by differences in continent, tissue type, or severity of epithelial dysplasia. HPV16 was the predominant genotype detected. Moreover, 62.2% of HPV positive and 17.8% of HPV negative oral epithelial dysplasia samples stained intensively positive for p16INK4a. This meta‐analysis found that 27% of oral epithelial dysplasia harbor HPV DNA. Whether this represents a transient infection or has a carcinogenic role is unknown.

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