Vaccination against HPV: boosting coverage and tackling misinformation

The availability of human papillomavirus (HPV) vaccines and screening tests has raised the possibility of globally eliminating cervical cancer, which is caused by HPV. Cervical cancer is a very common malignancy worldwide, especially among deprived women. High vaccination coverage is key to the containment and eventual elimination of the infection. Public HPV vaccination programmes in Italy and Denmark were swiftly established and are among the most successful worldwide. Still, in both countries, it has been challenging to achieve and maintain the recommended coverage of > 80% in girls. In a well‐studied Italian region, vaccination coverage in girls at age 15 years (World Health Organization''s gold standard) reached 76% in 2015 but decreased to 69% in 2018, likely due to work overload in public immunization centres. In Denmark, doubts about safety and efficacy of the HPV vaccine generated a decline in coverage among girls age 12–17, from 80% in 2013 down to 37% in 2015, when remedial actions made it rise again. Insights from these two countries are shared to illustrate the importance of monitoring coverage in a digital vaccine registry and promptly reacting to misinformation about vaccination.

Abbreviations

CC

cervical cancer

FVG

Friuli Venezia Giulia

HICs

high‐income countries

HPV

human papillomavirus

LMICs

middle‐income countries

WHO

World Health Organization

     

Histological and biological developmental characterization of the human cerebellar cortex

The aim of this study was to investigate the histological and biological features of the human cerebellar cortex development and differentiation. We analyzed 52 brains of fetal and infant death victims, aged from 17 gestational weeks to 12th postnatal month. In particular, in the cerebellar cortex at different ages we evaluated, besides the structural aspects, the expression of several biomarkers implicated in proliferative processes (c-fos, PCNA and apoptosis). We observed morphological patterns progressively evolving every month, from the indefinite structure of the second gestational trimester to the four-layered structure (external granular layer, molecular layer, Purkinje cell layer, internal granular layer) of the late fetal cortex and subsequently to the three-layered postnatal definitive morphology, due to involution of the external granular layer. The evaluation of the biological features of the cerebellar cortex showed high proliferative activity mainly confined to the transient external granular layer in prenatal life, and high apoptotic index after birth. Thus, the histological examination, better with the support of biomarker investigations, allows with accuracy to describe the dynamic sequence of steps that occur in human cerebellar cortex development and to establish in each case the age, namely the pre- or postnatal month of life. Consequently, we can diagnose delayed or altered processes of differentiation during the development of the human cerebellar cortex.     

Refined-sugar intake and the risk of colorectal cancer in humans

The relationship between sugar added to coffee and other hot beverages--as an indicator of taste for sugar and sugar intake outside main meals--and the risk of colorectal cancer was investigated using data from a case-control study conducted in Northern Italy on 953 cases of histologically confirmed colon cancer, 633 of rectal cancer and 2845 controls admitted to hospital for acute, non-neoplastic, non-digestive tract disorders. Compared with subjects who reported adding no sugar to their beverages, the multivariate relative risks (RR) of colon cancer were 1.4 for those adding one spoonful of sugar, 1.6 for those adding 2 spoonsful, and 2.0 for those adding 3 or more. The corresponding RRs for rectal cancer were 1.3, 1.5 and 1.4. For combination of colorectal cancer the RRs were 1.4, 1.5 and 1.8. All the trends in risk were significant, and the results were consistent across strata of study centre, sex and age, and were not appreciably modified by allowance for a number of major identified potential distorting factors, including an estimate of total calorie intake. These findings, if confirmed, would suggest that taste for sugar is a relevant indicator of colorectal cancer risk, and could be interpreted either in terms of a role of sugar in colorectal carcinogens, or of a specific influence of even limited amounts of sugar taken outside meals, which may stimulate the proliferation of the bowel epithelium, and hence enhance colorectal carcinogenesis.     

Dietary factors in the risk of bladder cancer

The relationship between selected dietary factors and the risk of bladder cancer was investigated in a case-control study conducted in northern Italy. The study included 163 cases and 181 controls who were hospitalized for acute, nonneoplastic or urinary tract diseases. The frequency of consumption of green vegetables and carrots was lower in the cases; thus, the estimated relative risks for the upper vs. the lower tertiles were 0.6 for green vegetables and 0.5 for carrots. Significant inverse trends in risk emerged with estimated carotenoid (as well as retinoid) intake. The apparent protection conveyed by vitamin A was stronger in current smokers. The risk of bladder cancer was not related to scores of fat and measures of alcohol consumption; the risk was elevated in coffee drinkers (although there was no tendency to rise with higher consumption), but it was reduced in tea drinkers. These findings were not explainable in terms of selection, information, or confounding bias. Thus, although available information is too uncertain for any precise definition of specific (micro)nutrients related to bladder cancer risk, the confirmation that several aspects of a less-affluent diet adversely affect the risk is still of interest in terms of a better understanding of bladder carcinogenesis.     

Cigarette smoking and the risk of cervical neoplasia

The relationship between cigarette smoking and risk of cervical neoplasia was evaluated in a case-control study of 183 women with cervical intraepithelial neoplasia compared with 183 age-matched outpatient controls, and of 230 cases of invasive cervical cancer compared with 230 controls in hospital for acute conditions unrelated to any of the identified or suspected risk factors for cervical cancer. Current cigarette smoking was associated with an elevated risk of cervical intraepithelial neoplasia (relative risk = 1.76, 95 per cent confidence interval = 1.14-2.27) and of invasive cancer (relative risk = 1.69, 95 per cent confidence interval = 1.08-2.65). This association was only partially accounted for by a large number of identified potential confounding factors, including indicators of socioeconomic status and sexual habits. The risk increased with the number of cigarettes smoked and was apparently greater for women who started smoking at younger ages. The relative risk of intraepithelial neoplasia was elevated within 20 years after the start of smoking and showed little tendency to increase with increasing duration. On the other hand, the risk of invasive cervical cancer was apparently unaffected by smoking less than 20 years and increased steadily thereafter, reaching a point estimate of 3.63 after 40 years or more. If one assumes that intraepithelial neoplasia is an early stage of cervical cancer, this pattern of risk is consistent with the predictions from the multistage theory of carcinogenesis, if the effect of smoking is on one of the earlier stages. No obvious distorting factors, apart from the play of chance, is likely to produce such a risk pattern.     

The risk of pneumonectomy over the age of 70. A case-control study.

OBJECTIVE: A higher mortality has been reported after pneumonectomy over the age of 70. The aim of the study was to quantify the additional risk due to age after standard pneumonectomy for lung cancer by a case-control study. METHODS: Our clinical database was reviewed to search for patients aged 70 years or more who underwent standard pneumonectomy for lung cancer between 1998 and 2005. A control group of patients younger than 70 (one case/two controls) was matched for sex, cardiovascular disease, American Association of Anaesthetists score, respiratory function, side of pneumonectomy, induction chemotherapy and stage. Overall mortality and morbidity were compared. Long-term survival data were also analysed. RESULTS: During the considered period, 35 patients aged 70 years or more underwent pneumonectomy (30 males, median age 73 years, 15 right-sided procedures). The control group was composed of 70 patients. The two groups were homogeneous in the variables used for matching. Overall mortality and morbidity were 11.4 and 54.2% in the elderly group as compared to 4.3 and 41.6% in controls (p-value not significant). Elderly patients experienced a higher rate of respiratory complications (25.7%) as compared to controls (8.3%, p=0.01). At univariate analysis, the only risk factor for death was the occurrence of respiratory complications (OR 6.5, CI 1.8-18.2). At multivariate analysis, age >or=70 years (OR 5.36, CI 1.48-19.3) and preoperative chemotherapy (OR 7.65, CI 2.04-28.6) were confirmed as predictors of respiratory complications. Five-year survival was 17.5% in the elderly group and 53.6% in the control group (p=0.003). Elderly patients with a better respiratory function (FEV1>70%) had a 5-year survival of 45.4%. CONCLUSIONS: In the elderly patients, the risk of respiratory complications after pneumonectomy is increased as compared to younger patients with equivalent respiratory function. Age and preoperative chemotherapy are independent risk factors for respiratory complications. A lower mortality and a better long-term survival are obtained in elderly patients with a better respiratory function (FEV1>or=70%).     

A New Harvest Site for Bone Graft in Anterior Cruciate Ligament Revision Surgery

During revision anterior cruciate ligament (ACL) surgery, femoral interference screws frequently require removal. This may lead to significant tunnel widening and possible graft fixation failure as a result. Solutions include drilling the revision tunnel in a different location, using stacked interference screws, or using bone graft to fill the defect. Autogenous iliac crest graft and allograft are both used, but there are significant comorbidities associated with each. We developed a new technique for harvesting autogenous bone graft that avoids many of the complications associated with other graft sources. By use of the existing surgical incision from the initial harvest of the bone–patellar tendon–bone autograft, bone from the medial tibial metaphyseal safe zone is harvested via an OATS tube harvester (Arthrex, Naples, FL). A bone plug 1 mm larger in size than the femoral defect is harvested and arthroscopically inserted via a press-fit technique. At 3 months after bone grafting, patients undergo revision ACL reconstruction. The proximal tibial metaphysis is a safe bone graft harvest site in revision ACL surgery and offers an effective method for filling large bony defects, allowing anatomic reconstruction of the ACL after bone healing has occurred. Furthermore, it eliminates the problems associated with allograft or use of a remote graft donor site.     

Heterogeneous response of individual multicellular tumour spheroids to immunotoxins and ricin toxin.

The cytoreductive effects of anti-transferrin receptor (anti-TfnR) immunotoxins (ITs) and of ricin toxin against tumour micromasses have been evaluated in a multicellular tumour spheroid (MTS) model. More than 600 (656) MTSs obtained with human breast carcinoma (MCF7) or rat glioblastoma (9L) cell lines were treated individually with ITs or toxin and the effects induced by the treatment were measured for each MTS as volume variation vs time by applying the Gompertz growth model. Two dose-dependent patterns of MTS growth were observed in MTSs of both cell lines in response to IT or toxin treatment: (1) complete inhibition of MTS growth (''sterilisation''); and (2) partial/complete inhibition (''heterogeneous response''). Within the range of IT or toxin concentrations resulting in partial inhibition of MTS growth, the sensitivity of treated MTSs was extremely heterogeneous (the cytoreductive effects varying between 0.1 and 4 logs of cells killed for a given IT or toxin concentration). Analysis of the post-treatment regrowth kinetics indicated that treated non-sterilised and control MTSs reached the same final limiting volumes. However, the doubling time estimated for the surviving cells of treated MCF7 and 9L MTSs ranged between 15 and 50 h, indicating that each MTS had individual growing potential. In conclusion, our results indicate that at substerilising IT concentrations individual heterogenicity of MTSs may greatly influence the cytoreductive potential of ITs. An implication of our study is that the efficacy of an IT treatment in eradicating disseminated micrometastases may not be predictable a priori. The MTS model that we describe in this paper may help in dissecting out factors limiting the effect of ITs in three-dimensional tumours.