Australia Postgraduate Award PhD Scholarship, Translational Cancer Research Network Top-up scholarship (supported by Cancer Institute NSW) and Cancer Council NSW.

BackgroundRadiofrequency ablation (RFA) and microwave ablation (MWA) are widely accepted techniques to eliminate small unresectable colorectal liver metastases (CRLM). Although previous studies labelled thermal ablation inferior to surgical resection, the apparent selection bias when comparing patients with unresectable disease to surgical candidates, the superior safety profile, and the competitive overall survival results for the more recent reports mandate the setup of a randomized controlled trial. The objective of the COLLISION trial is to prove non-inferiority of thermal ablation compared to hepatic resection in patients with at least one resectable and ablatable CRLM and no extrahepatic disease.MethodsIn this two-arm, single-blind multi-center phase-III clinical trial, six hundred and eighteen patients with at least one CRLM (≤3 cm) will be included to undergo either surgical resection or thermal ablation of appointed target lesion(s) (≤3 cm). Primary endpoint is OS (overall survival, intention-to-treat analysis). Main secondary endpoints are overall disease-free survival (DFS), time to progression (TTP), time to local progression (TTLP), primary and assisted technique efficacy (PTE, ATE), procedural morbidity and mortality, length of hospital stay, assessment of pain and quality of life (QoL), cost-effectiveness ratio (ICER) and quality-adjusted life years (QALY).DiscussionIf thermal ablation proves to be non-inferior in treating lesions ≤3 cm, a switch in treatment-method may lead to a reduction of the post-procedural morbidity and mortality, length of hospital stay and incremental costs without compromising oncological outcome for patients with CRLM.Trial registrationNCT03088150, January 11th 2017.

Viral transmissibility and natural resistance to infection are key determinants in assessing the population impact of human papillomavirus (HPV) vaccination, yet information on these parameters is scarce. Using data from 2 large-scale surveys on sexual behavior in the Netherlands (carried out in 2005-2006), the authors employed a Bayesian framework to fit a transmission model to the cross-sectional age-dependent prevalence of HPV DNA in cervical smears (data collected in 1992-2002), assuming that the prevaccine situation reflected an endemic equilibrium, and calculated type-specific estimates of transmissibility and infection-induced resistance. The posterior median transmission probability per heterosexual partnership covered a range of 0.43-0.94 among the 14 high-risk types of HPV. The transmission probability of HPV-16 was estimated at 0.80 (95% posterior interval: 0.60, 0.99) and that of HPV-18 at 0.93 (95% posterior interval: 0.72, 1). The model predicted that the decrease in HPV prevalence with age could not solely be explained by sexual activity and screening but also by resistance to reinfection, which is lost at a rate of 0.014-0.047 (1%-5%) per year. These results support the notion that HPV infection is highly transmissible, and they suggest a gradual loss of type-specific immunity over time. Because high transmission potential is associated with a low impact of herd immunity, extensive vaccination coverage will be required to substantially reduce cervical cancer incidence.

We determined the prevalence of type-specific hrHPV infections in the Netherlands on cervical scrapes of 45 362 women aged 18 -65 years. The overall hrHPV prevalence peaked at the age of 22 with peak prevalence of 24%. Each of the 14 hrHPV types decreased significantly with age (P-values between 0.0009 and 0.03). The proportion of HPV16 in hrHPV-positive infections also decreased with age (OR ¼ 0.76 (10-year scale), 95% CI ¼ 0.67 -0.85), and a similar trend was observed for HPV16 when selecting hrHPV-positive women with cervical intraepithelial neoplasia grade 2 or worse (CIN2 þ ) (OR ¼ 0.76, 95% CI ¼ 0.56 -1.01). In women eligible for routine screening (age 29 -61 years) with confirmed CIN2 þ , 65% was infected with HPV16 and/or HPV18. When HPV16/18-positive infections in women eligible for routine screening were discarded, the positive predictive value of cytology for the detection of CIN2 þ decreased from 27 to 15%, the positive predictive value of hrHPV testing decreased from 26 to 15%, and the predictive value of a double-positive test (positive HPV test and a positive cytology) decreased from 54 to 41%. In women vaccinated against HPV16/18, screening remains important to detect cervical lesions caused by non-HPV16/18 types. To maintain a high-positive predictive value, screening algorithms must be carefully re-evaluated with regard to the screening modalities and length of the screening interval. British Journal of Cancer (2008) . Prophylactic vaccines are now available that are effective against incident and persistent HPV16 and 18 infections (Koutsky et al, 2002;Munoz et al, 2003;Harper et al, 2006; Villa et al, 2006). Mass vaccination can have a substantial impact on the cervical cancer incidence, even in developed countries where the incidence is already low because of implementation of organised cervical screening. To make a well-judged decision about the future role of both vaccination and screening in cervical cancer prevention, detailed information about type-specific hrHPV distribution is required. Data on hrHPV prevalence and type distribution in the Netherlands have been reported previously, but only for a relatively small cohort of 3305 women (Jacobs et al, 2000a;Clifford et al, 2005). To obtain reliable estimates of the hrHPV type distribution in relation to age, both for women with normal and for women with abnormal cytology, data from a far larger cohort are needed. In this study, we determined the age-dependent prevalence of 14 hrHPV types and the age-dependent type distribution within hrHPV-positive women from a cohort of 45 362 women in the Netherlands aged 18 -65 years. The results from the current study give an impression of the potential benefits that can be achieved from HPV16/18 vaccination. They can also be used to gain insight into the effects of partial cross-protection against HPV types 31 and 45 (Harper et al, 2006). Furthermore, the figures will serve as inputs for simulation models in which different vaccination and screening strategies will be compared. MATERIALS AND METHOD...

EATL is a rare disease with an incidence of 0.10 per 100,000 inhabitants per year, occurring in older age, with a peak incidence in the 7th decade. The tumour is mainly localized in the proximal small intestine. Although uncomplicated CD is twice as frequent in female patients, EATL is more prevalent in males.