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SummaryBackgroundAn increase in worldwide HPV vaccination could be facilitated if fewer than three doses of vaccine are as effective as three doses. We originally aimed to compare the immunogenicity and frequency of persistent infection and cervical precancerous lesions caused by vaccine-targeted HPV after vaccination with two doses of quadrivalent vaccine on days 1 and 180 or later, with three doses on days 1, 60, and 180 or later, in a cluster-randomised trial. Suspension of the recruitment and vaccination due to events unrelated to our study meant that some enrolled girls could not be vaccinated and some vaccinated girls received fewer than the planned number of vaccinations by default. As a result, we re-analysed our data as an observational cohort study.MethodsOur study was designed to be done in nine locations (188 clusters) in India. Participants were unmarried girls aged 10–18 years vaccinated in four cohorts: girls who received three doses of vaccine on days 1, 60, and 180 or later, two doses on days 1 and 180 or later, two doses on days 1 and 60 by default, and one dose by default. The primary outcomes were immunogenicity in terms of L1 genotype-specific binding antibody titres, neutralising antibody titres, and antibody avidity after vaccination for the vaccine-targeted HPV types 16, 18, 6, and 11 and incident and persistent infections with these HPVs. Analysis was per actual number of vaccine doses received. This study is registered with ISRCTN, number ISRCTN98283094; and with ClinicalTrials.gov, number NCT00923702.FindingsVaccination of eligible girls was initiated on Sept 1, 2009, and continued until April 8, 2010. Of 21 258 eligible girls identified at 188 clusters, 17 729 girls were recruited from 178 clusters before suspension. 4348 (25%) girls received three doses, 4979 (28%) received two doses on days 1 and 180 or later, 3452 (19%) received two doses at days 1 and 60, and 4950 (28%) received one dose. Immune response in the two-dose HPV vaccine group was non-inferior to the three-dose group (median fluorescence intensity ratio for HPV 16 1·12 [95% CI 1·02–1·23] and for HPV 18 1·04 [0·92–1·19]) at 7 months, but was inferior in the two-dose default (0·33 [0·29–0·38] for HPV 16 and 0·51 [0·43–0·59] for HPV 18) and one-dose default (0·09 [0·08–0·11] for HPV 16 and 0·12 [0·10–0·14] for HPV 18) groups at 18 months. The geometric mean avidity indices after fewer than three doses by design or default were non-inferior to those after three doses of vaccine. Fewer than three doses by design and default induced detectable concentrations of neutralising antibodies to all four vaccine-targeted HPV types, but at much lower concentration after one dose. Cervical samples from 2649 participants were tested and the frequency of incident HPV 16, 18, 6, and 11 infections was similar irrespective of the number of vaccine doses received. The testing of at least two samples from 838 participants showed that there was no persistent HPV 16 or 18 infections in any study group at a median follow-up of 4·7 years (IQR 4·2–...

Population-based screening for early detection and treatment of colorectal cancer (CRC) and precursor lesions, using evidence-based methods, can be effective in populations with a significant burden of the disease provided the services are of high quality. Multidisciplinary, evidence-based guidelines for quality assurance in CRC screening and diagnosis have been developed by experts in a project co-financed by the European Union. The 450-page guidelines were published in book format by the European Commission in 2010.They include 10 chapters and over 250 recommendations, individually graded according to the strength of the recommendation and the supporting evidence. Adoption of the recommendations can improve and maintain the quality and effectiveness of an entire screening process, including identification and invitation of the target population, diagnosis and management of the disease and appropriate surveillance in people with detected lesions. To make the principles, recommendations and standards in the guidelines known to a wider professional and scientific community and to facilitate their use in the scientific literature, the original content is presented in journal format in an open-access Supplement of Endoscopy. The editors have prepared the present overview to inform readers of the comprehensive scope and content of the guidelines. IntroductionAccording to recent estimates by the International Agency for Research on Cancer [1], colorectal cancer (CRC) is the most common cancer in Europe with 432 000 new cases reported annually in men and women combined. It is the second most common cause of cancer deaths in Europe with 212 000 deaths reported in 2008.Worldwide, CRC ranks third in incidence and fourth in mortality with an estimated 1.2 million cases and 0.6 million deaths annually. In the 27 Member States of the European Union (EU), CRC ranks first in incidence and second in mortality, with approximately 334000 new cases and 149000 deaths estimated in 2008.Even in those Member States in the lower range for age-standardized rates of CRC, the burden of disease is significantly greater when compared with many other HHS Public Access Author Manuscript Author ManuscriptAuthor ManuscriptAuthor Manuscript regions of the world (see reference [1]). CRC is therefore an important health problem across the EU.Screening can be effective in cancer control in populations with a significant burden of CRC, provided the services are of high quality [2]. The aim of CRC screening is to lower the burden of cancer in the population by discovering disease in its early, latent stages [3]. Evidence-based methods permit treatment that is more effective than if disease is diagnosed later when symptoms have occurred. Early treatment of invasive lesions, for example by endoscopic resection of early CRC, can also be less detrimental for quality of life. The endoscopic removal of pre-malignant lesions also reduces the incidence of CRC by avoiding the progression to cancer. Randomized trials in people of average risk invite...

Background A randomised trial designed to compare three and two doses of quadrivalent human papillomavirus (HPV) vaccine in adolescent girls in India was converted to a cohort study after suspension of HPV vaccination in trials by the Indian Government. In this Article, the revised aim of the cohort study was to compare vaccine efficacy of single dose to that of three and two doses in protecting against persistent HPV 16 and 18 infection at 10 years post vaccination. MethodsIn the randomised trial, unmarried girls aged 10-18 years were recruited from nine centres across India and randomly assigned to either two doses or three doses of the quadrivalent HPV vaccine (Gardasil [Merck Sharp & Dohme, Whitehouse Station, NJ, USA]; 0•5 mL administered intramuscularly). After suspension of recruitment and vaccination, the study became a longitudinal, prospective cohort study by default, and participants were allocated to four cohorts on the basis of the number vaccine doses received per protocol: the two-dose cohort (received vaccine on days 1 and 180 or later), three-dose cohort (days 1, 60, and 180 or later), two-dose default cohort (days 1 and 60 or later), and the single-dose default cohort. Participants were followed up yearly. Cervical specimens were collected from participants 18 months after marriage or 6 months after first childbirth, whichever was earlier, to assess incident and persistent HPV infections. Married participants were screened for cervical cancer as they reached 25 years of age. Unvaccinated women age-matched to the married vaccinated participants were recruited to serve as controls. Vaccine efficacy against persistent HPV 16 and 18 infections (the primary endpoint) was analysed for single-dose recipients and compared with that in two-dose and three-dose recipients after adjusting for imbalance in the distribution of potential confounders between the unvaccinated and vaccinated cohorts. This trial is registered with ISRCTN, ISRCTN98283094, and ClinicalTrials.gov, NCT00923702. Findings Vaccinated participants were recruited between Sept 1, 2009, and April 8, 2010 (date of vaccination suspension), and followed up over a median duration of 9•0 years (IQR 8•2-9•6). 4348 participants had three doses, 4980 had two doses (0 and 6 months), and 4949 had a single dose. Vaccine efficacy against persistent HPV 16 and 18 infection among participants evaluable for the endpoint was 95•4% (95% CI 85•0-99•9) in the single-dose default cohort (2135 women assessed), 93•1% (77•3-99•8) in the two-dose cohort (1452 women assessed), and 93•3% (77•5-99•7) in three-dose recipients (1460 women assessed).Interpretation A single dose of HPV vaccine provides similar protection against persistent infection from HPV 16 and 18, the genotypes responsible for nearly 70% of cervical cancers, to that provided by two or three doses.Funding Bill & Melinda Gates Foundation.

We conducted a study to document the impact of COVID‐19 pandemic on cancer screening continuum in selected low‐ and middle‐income countries (LMICs). LMICs having an operational cancer control plan committed to screen eligible individuals were selected. Managers/supervisors of cancer screening programs were invited to participate in an online survey and subsequent in‐depth interview. Managers/supervisors from 18 programs in 17 countries participated. Lockdown was imposed in all countries except Brazil. Screening was suspended for at least 30 days in 13 countries, while diagnostic‐services for screen‐positives were suspended in 9 countries. All countries except Cameroon, Bangladesh, India, Honduras and China managed to continue with cancer treatment throughout the outbreak. The participants rated service availability compared to pre‐COVID days on a scale of 0 (no activities) to 100 (same as before). A rating of ≤50 was given for screening services by 61.1%, diagnostic services by 44.4% and treatment services by 22.2% participants. At least 70% participants strongly agreed that increased noncompliance of screen‐positive individuals and staff being overloaded or overwhelmed with backlogs would deeply impact screening programs in the next 6 months at least. Although many of the LMICs were deficient in following the “best practices” to minimize service disruptions, at least some of them made significant efforts to improve screening participation, treatment compliance and program organization. A well‐coordinated effort is needed to reinitiate screening services in the LMICs, starting with a situational analysis. Innovative strategies adopted by the programs to keep services on‐track should be mutually shared.