High sustained efficacy of a prophylactic quadrivalent human papillomavirus types 6/11/16/18 L1 virus-like particle vaccine through 5 years of follow-up

Human papillomavirus (HPV) causes cervical, vulvar, and vaginal cancers, precancerous dysplasia, and genital warts. We report data for the longest efficacy evaluation to date of a prophylactic HPV vaccine. In total, 552 women (16–23 years) were enrolled in a randomised, placebo-controlled study of a quadrivalent HPV 6/11/16/18 L1 virus-like-particle vaccine with vaccination at months 0, 2, and 6. At regular intervals through 3 years, subjects underwent gynaecologic examination, cervicovaginal sampling for HPV DNA, serum anti-HPV testing, and Pap testing, with follow-up biopsy as indicated. A subset of 241 subjects underwent two further years of follow-up. At 5 years post enrolment, the combined incidence of HPV 6/11/16/18-related persistent infection or disease was reduced in vaccine-recipients by 96% (two cases vaccine versus 46 placebo). There were no cases of HPV 6/11/16/18-related precancerous cervical dysplasia or genital warts in vaccine recipients, and six cases in placebo recipients (efficacy=100%; 95% CI:12–100%). Through 5 years, vaccine-induced anti-HPV geometric mean titres remained at or above those following natural infection. In conclusion, a prophylactic quadrivalent HPV vaccine was effective through 5 years for prevention of persistent infection and disease caused by HPV 6/11/16/18. This duration supports vaccination of adolescents and young adults, which is expected to greatly reduce the burden of cervical and genital cancers, precancerous dysplasia, and genital warts

Induction of immune memory following administration of a prophylactic quadrivalent human papillomavirus (HPV) types 6/11/16/18 L1 virus-like particle (VLP) vaccine

Background: The duration of protection afforded by vaccines represents a critical test of their utility as public health interventions. Some vaccines induce long-term immunity, while others require booster doses. Vaccines that induce long-term protection are usually characterized by the generation of immune memory. Recent trials of a quadrivalent (types 6, 11, 16, 18) human papillomavirus (HPV) vaccine have demonstrated high efficacy through 5 years of follow-up. We evaluated the extent to which the vaccine is able to generate HPV type-specific immune memory. Methods: A total of 552, 16-23-year-old women were enrolled in a double-blind, placebo-controlled study. At enrollment, subjects were randomized in a 1:1 ratio to receive three-dose regimens of quadrivalent HPV vaccine or placebo with 3 years' follow-up. A subset of 241 subjects (n = 114 in the quadrivalent HPV vaccine group and n = 127 in the placebo group) underwent 2 further years of follow-up. All extension subjects received quadrivalent HPV vaccine at month 60 to examine the extent of immune memory in response to the primary vaccination series.25264931493

On the Origin of r-concavity and Related Concepts

In a less widely known contribution, Béla Martos (1966, Hungarian Academy of Sciences) introduced a generalized notion of concavity that is closely related to what is nowadays known as r-concavity in the operations research literature, and that is identical to what is nowadays known as ρ-concavity in the economics literature. The present paper aims at making the original contribution accessible to a wider audience and illustrating its importance from a modern perspective. To this end, we offer a translation of those parts of Martos (1966) that are directly related to generalized concavity. Reviewing the virtues of r-concavity and ρ-concavity, we find a surprisingly short proof of the univariate Prékopa-Borell theorem. We also survey a number of applications of the considered concepts in operations research and economics