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Aim: Prophylactic human papillomavirus (HPV) vaccines are highly effective at preventing pre–cancerous cervical lesions when given in a three–dose schedule. Some post–hoc trial data suggest that one dose prevents HPV infection. If one dose could prevent pre–cancerous cervical lesions, then global cervical cancer prevention would be greatly facilitated. We assessed the effectiveness of quadrivalent HPV vaccine by number of doses against cervical intraepithelial neoplasia (CIN) 2 or 3/adenocarcinoma–in–situ (AIS)/cancer in Australia up to seven years post vaccination. Methods: We linked registry data from all 8 jurisdictional cervical screening registers, with the national HPV vaccination register, death index and cancer registers for all Australian women aged 15 or under when eligible for vaccine who screened between April 2007 (when vaccination commenced) and 31 December 2014. We performed Cox proportional hazard regression, adjusted a priori for age, socioeconomic status, and area of residence, to estimate hazard ratios of histologically confirmed CIN2/CIN3/AIS/cancer. Results: We included 250,648 women: 48,845 (19·5%) unvaccinated, 174,995 (69·8%) had received three doses, 18,190 (7·3%) two doses and 8,618 (3·4%) one dose. The adjusted hazard ratio was significantly lower for all dose groups compared to unvaccinated women (1 dose 0·65 (95%CI 0·52–0·81), 2 doses 0·61 (0·52–0·72) and 3 doses 0·59 (0·54–0·65).) With adjustment for age at vaccination amongst the vaccinated group, the adjusted hazard ratios for one dose and two dose recipients were comparable to three dose recipients (one dose 1.01 (95%CI 0.81–1.26), two doses 1.00 (0.85–1.17).) Multiple sensitivity analyses, including use of different dose assignment methods, produced consistent findings. Comparison with a historical cohort of age matched women showed that the result was not due to herd protection alone. Conclusions: One dose had comparable effectiveness as two or three doses in preventing high–grade disease in a high coverage setting. These findings support the hypothesis that one dose vaccination may be a viable strategy when working towards the global elimination of cervical cancer. Keywords: Human papillomavirus, Vaccination, Effectiveness, Cervical intraepithelial neoplasia, Australia

This investigation quantitatively compared lumenal dimensions of 1 mm end-to-side anastomoses with longitudinal or transverse arteriotomies into host arteries 1.5-2 mm in diameter. In 27 rats, 6–7 mm sections of iliac arteries (1 mm in diameter) were sutured as small bypasses onto abdominal aortae (1.5-2 mm in diameter). Half the anastomoses were performed on transverse, and half on longitudinal arteriotomies. Between 1 and 20 weeks following surgery intravascular methacrylate casts were made of the aortae and bypasses, and detailed measurements taken from the casts. The success rate (patency) of the bypasses was 78%; 18 successful casts (36 anastomotic sites) were analysed; 6 failed due to stenosis (3 other successful bypasses were used to develop the techniques). From these, five sites developed small dilations (“aneurysms”), which did not occur preferentially on either longitudinal or transverse arteriotomy sites. Despite a trend towards a greater diameter in the transverse compared with the longitudinal arteriotomies, they were not statistically different. Therefore, the authors recommend for technical reasons that for small end-to-side vascular anastomoses the transverse arteriotomy is preferable: it produces a simple incision which opens the artery and facilitates suturing. With a longitudinal arteriotomy in such small vessels it is often necessary to remove an elliptical area of tissue, which may produce an excessive defect.