Efficacy and safety of therapeutic HPV vaccines to treat CIN 2/CIN 3 lesions: a systematic review and meta-analysis of phase II/III clinical trials.

OBJECTIVES: We aim to assess the efficacy and safety of therapeutic human papillomavirus (HPV) vaccines to treat cervical intraepithelial neoplasia of grade 2 or 3 (CIN 2/3). DESIGN: Systematic review and meta-analysis, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses recommendations. DATA SOURCES: PubMed, Embase, Web of Science, Global Index Medicus and CENTRAL Cochrane were searched up to 31 January 2022. ELIGIBILITY CRITERIA: Phase II/III randomised controlled trials (RCTs) and single-arm studies reporting the efficacy of therapeutic vaccines to achieve regression of CIN 2/3 lesions were included. Studies evaluating only safety and side effects of the vaccine were excluded. DATA EXTRACTION AND SYNTHESIS: Two independent reviewers extracted data and evaluated study quality. A random-effect model was used to pool the proportions of regression and/or HPV clearance. RESULTS: 12 trials met the inclusion criteria. Out of 734 women (all studies considered) receiving therapeutic HPV vaccine for CIN 2/3, 414 regressed to normal/CIN 1 with an overall proportion of regression of 0.54 (95% CI 0.39 to 0.69) for vaccinated group; 166 women (from five RCTs) receiving placebo only achieving a pooled normal/CIN 1 regression of 0.27 (95% CI 0.20 to 0.34). When including only the five two-arm studies, the regression proportion for the 410 vaccine group participants was higher than that of the 166 control group participants (relative risk (RR) 1.52; 95% CI 1.14 to 2.04). The pooled proportion of high-risk human papillomavirus (hrHPV) clearance was 0.42 (95% CI 0.32 to 0.52) in the vaccine group (six studies with a total of 357 participants) and 0.17 (95% CI 0.11 to 0.26) in the control group (three RCTs with a total of 104 participants). Based on these three RCTs, the hrHPV clearance was significantly higher in the vaccinated group (250 participants) compared with the control group (RR 2.03; 95% CI 1.30 to 3.16). Similar results were found regarding HPV 16/18 clearance. No significant unsolicited adverse events have been consistently reported. CONCLUSIONS: The efficacy of the therapeutic vaccines in the treatment of CIN 2/3 was modest. Implementation issues such as feasibility, acceptability, adoption and cost-effectiveness need to be further studied. PROSPERO REGISTRATION NUMBER: CRD42022307418.

Colorectal Cancer Screening Pilot Project in Tehran-Iran, a Feasibility Study.

BACKGROUND: Colorectal cancer (CRC) is the third most common cancer in Iran, where there is no organised CRC-screening programme. This study aimed to evaluate feasibility of CRC screening using a qualitative fecal immunochemical test (FIT) among Iranian average-risk adults. METHODS: In this feasibility study, 7039 individuals aged 50-75 years were invited by community health workers (CHWs) in southern Tehran and its suburban districts between April 2018 and November 2019. The CHWs performed a qualitative FIT with cut-off level 50 ng Hb/mL buffer and referred those with positive-FIT for colonoscopy to the endoscopy center of Shariati hospital in Tehran. Outcomes included acceptance rate, FIT positivity rate, colonoscopy compliance, detection rates and positive predictive values (PPVs) with 95% confidence interval for CRC and advanced adenomas (AAs). RESULTS: Acceptance rate at initial invitation was 71.7%. From 4974 average-risk adults (1600 males and 3374 females) who were offered FIT, 96.8% (n=4813) provided valid samples, of whom 471 (9.8%) tested positive. Among FIT-positive participants, 150 (31.8%) underwent colonoscopy; CRC was detected in 2.0% (n=3) and adenomas in 27.3% (n=41). Detection rate of CRC and AAs per 1000-FIT-screened participants was 0.6 (0.1-1.8) [males: 0.7 (0.01-3.6), females: 0.6 (0.07-2.0)] and 4.2 (2.5-6.4) [males: 5.9 (2.6-11.0), females: 3.4 (1.7-6.0)], respectively. PPVs were 2.0% (0.4-5.7) for CRC and 13.3% (8.3-19.8) for AAs. There was no association between gender and the studied outcomes. CONCLUSION: Our results partially support the feasibility of scaling up organized CRC-screening through the existing healthcare system in Iran; it remains to be discussed carefully to ensure the capacity of healthcare system for adequate colonoscopy services.

Analysis of the Mortality Trends of 23 Major Cancers in the Indian Population Between 2000 and 2019: A Joinpoint Regression Analysis.

PURPOSE: Cancer mortality trends have not been documented across the population of India. We, therefore, analyzed the overall and individual cancer mortality trends for 23 major cancers between 2000 and 2019 on the basis of Global Health Observatory (GHO) database. MATERIALS AND METHODS: This study examined cancer mortality trends for 23 major cancer sites on the basis of 12.85 million cancer deaths obtained from the GHO of the WHO between 2000 and 2019. A joinpoint regression model was used to analyze the long-term trends of cancer mortality. Annual percentage change (APC) and average APC were estimated for various cancer sites. RESULTS: Between 2000 and 2019, 12.85 million deaths occurred in India from 23 major cancers. The most common lethal cancers were mouth and oropharyngeal (15.6%), stomach (10.6%), lung (9.6%), breast (9%), and colorectal (8%) cancers. The mortality trend decreased by 0.19% annually among men and increased nonsignificantly by 0.25% among women; an increase of 0.02% was observed among combined sexes. Increasing mortality trends were seen among cancers of the lung, breast, colorectum, lymphoma, multiple myeloma, gallbladder, pancreas, kidney, and mesothelioma between 2000 and 2019. The highest annual increase in mortality was observed in pancreatic cancer among both sexes: 2.7%, 2.1% among men, and 3.7% in women. The cancers of the stomach, esophagus, leukemia, larynx, and melanoma showed a declining cancer mortality trend irrespective of sex. CONCLUSION: A multifaceted strategy is required to tackle the rising cancer mortality rates in India; the best long-term strategy could be implementing awareness on cancer symptoms among the population as well as cancer prevention policies with improved health infrastructure and specifically dedicated human resources.

Average lifespan shortened due to cancer in selected countries of North America, Europe, Asia and Oceania, 2006 and 2016.

PURPOSE: We applied a novel measure of average lifespan shortened (ALSS) to examine changes in lifespan among patients who died of cancer over a 10-year period from 2006 to 2016 in 20 selected high-income countries from North America, Europe, Asia, and Oceania. METHODS: We retrieved cancer deaths in each country from the World Health Organization mortality database. We calculated ALSS as a ratio of years of life lost to the expected lifespan among patients who died from cancer. RESULTS: Between 2006 and 2016, we observed modest changes in ALSS for overall cancer deaths over the study in many countries. The changes in the ALSS over time due to any cancer ranged between -1.7 and +0.4 percentage points (pps) among men and between -1.9 and +0.6 pps among women. Across countries, overall cancer deaths led to an average loss between 16% and 22% of their lifespan in men, and between 18% and 24% in women. Across cancer sites, patients who died of central nervous system cancers, for instance, lost a large proportion of their lifespan. CONCLUSIONS: In this study, we demonstrated the use of ALSS across selected high-income countries, which enables population-level assessment of premature mortality among cancer patients over time.

Evaluation of immune response to single dose of quadrivalent HPV vaccine at 10-year post-vaccination.

BACKGROUND: The recent World Health Organization recommendation supporting single-dose of HPV vaccine will significantly reduce programmatic cost, mitigate the supply shortage, and simplify logistics, thus allowing more low- and middle-income countries to introduce the vaccine. From a programmatic perspective the durability of protection offered by a single-dose will be a key consideration. The primary objectives of the present study were to determine whether recipients of a single-dose of quadrivalent HPV vaccine had sustained immune response against targeted HPV types (HPV 6,11,16,18) at 10 years post-vaccination and whether this response was superior to the natural antibody titres observed in unvaccinated women. METHODS: Participants received at age 10-18 years either one, two or three doses of the quadrivalent HPV vaccine. Serology samples were obtained at different timepoints up to 10 years after vaccination from a convenience sample of vaccinated participants and from age-matched unvaccinated women at one timepoint. The evolution of the binding and neutralizing antibody response was presented by dose received. 10-year durability of immune responses induced by a single-dose was compared to that after three doses of the vaccine and in unvaccinated married women. RESULTS: The dynamics of antibody response among the single-dose recipients observed over 120 months show stabilized levels 18 months after vaccination for all four HPV types. Although the HPV type-specific (binding or neutralizing) antibody titres after a single-dose were significantly inferior to those after three doses of the vaccine (lower bounds of GMT ratios < 0.5), they were all significantly higher than those observed in unvaccinated women following natural infections (GMT ratios: 2.05 to 4.04-fold higher). The results correlate well with the high vaccine efficacy of single-dose against persistent HPV 16/18 infections reported by us earlier at 10-years post-vaccination. CONCLUSION: Our study demonstrates the high and durable immune response in single-dose recipients of HPV vaccine at 10-years post vaccination.

Implementation of visual inspection with acetic acid and Lugol's iodine for cervical cancer screening in rural China.

OBJECTIVE: To address the value of visual inspection where HPV-based screening is not yet available, we evaluated the real-world effectiveness of visual inspection with acetic acid (VIA) and with Lugol's iodine (VILI) as a primary screening method for cervical cancer in rural China. METHODS: A total of 206 133 women aged 30-59 years received two rounds of VIA/VILI screening for cervical cancer in 2006-2010. Women with positive screening results underwent colposcopy and direct biopsy, and were treated if cervical intraepithelial neoplasia grade 2 or worse (CIN2+) was diagnosed. Clinical effectiveness of VIA/VILI was evaluated by process and outcome measures. RESULTS: The VIA/VILI positivity rate, biopsy rate and detection rate of CIN2+ in the second round were significantly lower than in the first round. The 2-year cumulative detection rate of CIN2+ varied from 0.53% to 0.90% among the four cohorts initiated in 2006, 2007, 2008, and 2009. The first round of screening detected 60%-83% of CIN2, 70%-86% of CIN3, and 88%-100% of cervical cancer. Over 92% of CIN2+ were found at the early stage. CONCLUSION: Multiple rounds of visual inspection with continuous training and quality assurance could act as a temporary substitutional screening method for cervical cancer in resource-restricted settings.

Efficacy, acceptability and safety of ablative versus excisional procedure in the treatment of histologically confirmed CIN2/3: A systematic review.

BACKGROUND: Outcomes of earlier systematic reviews of the efficacy of ablative and excisional techniques to treat cervical intraepithelial neoplasia grade 2 or 3 (CIN2/3) were biased, as most of the included studies did not compare the techniques head-to-head. OBJECTIVE: To systematically review the outcomes of studies comparing ablative and excisional techniques to treat CIN2/3 head-to-head. SEARCH STRATEGY: Medline, Embase and Global Index Medicus were searched from inception until May 2021. SELECTION CRITERIA: Studies directly comparing the efficacy and safety of excisional and ablative treatments on histologically confirmed CIN2/3. Eligibility criteria for the women treated with ablation had to be same as those treated with excision. DATA COLLECTION AND ANALYSIS: A total of 323 articles were archived. Data on the risk of persistence/recurrence and safety were extracted from the original trials. Comparison between the two procedures was reported by forest plots, stratified by follow-up intervals and by HIV status. MAIN RESULTS: Six publications were included. The risk of persistence/recurrence following ablation was significantly higher than that following excision (overall, RR 1.65, 95% CI 1.25-2.19; at 6-month follow-up, RR 1.94, 95% CI 1.29-2.91; at 12-month follow-up, RR 1.78, 95% CI 1.27-2.51; at 24-month follow-up, RR 1.57, 95% CI 1.11-2.23). The findings remained similar among women living with HIV (WLHIV). Both procedures were equally safe. CONCLUSIONS: Excisional treatment was more effective than ablative treatment, with both procedures having similar safety profiles. Other programmatic considerations will guide the selection of technique, especially in resource-limited settings.

Lessons Learnt From Pilot Cervical Cancer Screening and Treatment Programmes Integrated to Routine Primary Health Care Services in Benin, Cote d'Ivoire, and Senegal.

PURPOSE: The project aimed to implement pilot screening and treatment services for cervical cancer integrated with existing primary health centers (PHCs) in Benin, Cote d'Ivoire, and Senegal and evaluate these services using implementation research outcomes such as reach, effectiveness, adoption, and acceptability. MATERIALS AND METHODS: The Ministry of Health in each country took the lead in setting up a stakeholder's group that designed a protocol tailored to the local context. The target age was 25-49 years in Benin and Cote d'Ivoire and 30-49 years in Senegal. Visual inspection with acetic acid (VIA) was the screening test, and thermal ablation (TA) was the ablative treatment of choice in all. The Ministry in each country identified 4-5 PHCs to set up screening and ablation services and one higher-level center for colposcopy referral. After a master-trainer led training program, nurses, midwives, or general practitioners screened opportunistically the eligible women attending the clinics. The VIA-positive women eligible for ablation were offered immediate treatment. RESULTS: Between May 2018 and January 2021, 16,530 women were screened opportunistically. VIA positivity was 8.1% with huge variability within and between countries. Sixty-one percent of all VIA-positive cases were eligible for immediate TA, and 88% of them accepted same-day treatment. Compliance to TA at PHCs was 99%. Majority of women treated with TA complained of minor side effects. Significant dropouts occurred as the women were referred to colposcopy clinics. CONCLUSION: Opportunistic screening provided as part of routine PHC service can screen many women and treat a significant proportion of screen-positive women with TA with minimal side effects. Primary concerns are the hard-to-reach women who remain out of opportunistic screening coverage and noncompliance of the screen-positive women referred to higher-level centers.

Evolution of the joint International Atomic Energy Agency (IAEA), International Agency for Research on Cancer (IARC), and WHO cancer control assessments (imPACT Reviews).

Before 2005, cancer and other non-communicable diseases were not yet health and development agenda priorities. Since the 2005 World Health Assembly Resolution, which encouraged WHO, the International Agency for Research on Cancer (IARC), and the International Atomic Energy Agency (IAEA) to jointly work on cancer control, progress was achieved in low-income and middle-income countries on a small scale. Recently, rapid acceleration in UN collaboration and global cancer activities has focused attention in global cancer control. This Policy Review presents the evolution of the IAEA, IARC, and WHO joint advisory service to help countries assess needs and capacities throughout the comprehensive cancer control continuum. We also highlight examples per country, showcasing a snapshot of global good practices to foster an exchange of experiences for continuous improvement in the integrated mission of Programme of Action for Cancer Therapy (imPACT) reviews and follow-up support. The future success of progress in cancer control lies in the high-level political and financial commitments. Linking the improvement of cancer services to the strengthening of health systems after the COVID-19 pandemic will also ensure ongoing advances in the delivery of care across the cancer control continuum.

Effectiveness of Artificial Intelligence-Assisted Decision-making to Improve Vulnerable Women's Participation in Cervical Cancer Screening in France: Protocol for a Cluster Randomized Controlled Trial (AppDate-You).

BACKGROUND: The French organized population-based cervical cancer screening (CCS) program transitioned from a cytology-based to a human papillomavirus (HPV)-based screening strategy in August 2020. HPV testing is offered every 5 years, starting at the age of 30 years. In the new program, women are invited to undergo an HPV test at a gynecologist's, primary care physician's, or midwife's office, a private clinic or health center, family planning center, or hospital. HPV self-sampling (HPVss) was also made available as an additional approach. However, French studies reported that less than 20% of noncompliant women performed vaginal self-sampling when a kit was sent to their home. Women with lower income and educational levels participate less in CCS. Lack of information about the disease and the benefits of CCS were reported as one of the major barriers among noncompliant women. This barrier could be addressed by overcoming disparities in HPV- and cervical cancer-related knowledge and perceptions about CCS. OBJECTIVE: This study aimed to assess the effectiveness of a chatbot-based decision aid to improve women's participation in the HPVss detection-based CCS care pathway. METHODS: AppDate-You is a 2-arm cluster randomized controlled trial (cRCT) nested within the French organized CCS program. Eligible women are those aged 30-65 years who have not been screened for CC for more than 4 years and live in the disadvantaged clusters in the Occitanie Region, France. In total, 32 clusters will be allocated to the intervention and control arms, 16 in each arm (approximately 4000 women). Eligible women living in randomly selected disadvantaged clusters will be identified using the Regional Cancer Screening Coordinating Centre of Occitanie (CRCDC-OC) database. Women in the experimental group will receive screening reminder letters and HPVss kits, combined with access to a chatbot-based decision aid tailored to women with lower education attainment. Women in the control group will receive the reminder letters and HPVss kits (standard of care). The CRCDC-OC database will be used to check trial progress and assess the intervention's impact. The trial has 2 primary outcomes: (1) the proportion of screening participation within 12 months among women recalled for CCS and (2) the proportion of HPVss-positive women who are "well-managed" as stipulated in the French guidelines. RESULTS: To date, the AppDate-You study group is preparing and developing the chatbot-based decision aid (intervention). The cRCT will be conducted once the decision aid has been completed and validated. Recruitment of women is expected to begin in January 2023. CONCLUSIONS: This study is the first to evaluate the impact of a chatbot-based decision aid to promote the CCS program and increase its performance. The study results will inform policy makers and health professionals as well as the research community. TRIAL REGISTRATION: ClinicalTrials.gov NCT05286034; https://clinicaltrials.gov/ct2/show/NCT05286034. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/39288.

Evaluation of effectiveness, acceptability and safety of thermal ablation in the treatment of cervical neoplasia in Burundi.

This longitudinal study aimed at evaluating the effectiveness, acceptability and safety of the thermal ablation procedure (TA) in the treatment of cervical neoplasia. Women referred to the Gynaecology ward for symptoms or for opportunistic screening were assessed by visual inspection with acetic acid (VIA) and colposcopy. Those with lesions eligible to ablation were counselled and treated by TA. They were inquired about the level of pain during the procedure, and their level of satisfaction. Patients were followed up at 6 weeks for any complication and reassessed by VIA and colposcopy at 12 months for any persistent or recurrent lesion and for any adverse event. A total of 86 women with a positive VIA test were included in the study. The mean age was 46 years (28-61 years). Most of the women did not complain about any adverse event during treatment; one-third presented mild pain or cramp. At the 6-week visit, watery discharge was the main adverse event reported. All women were highly satisfied with TA and most of them would recommend it. At the 12-month visit, 82 women were examined (95% follow-up rate), and the overall cure rate was 96% (low-grade lesions: 98%; high-grade lesions: 94%). Three women presented low- and high-grade lesions that were treated by TA. No major adverse event or hospitalisation after the treatment was reported. In conclusion, TA was an effective procedure with a high cure rate at the 1-year follow-up visit. It was acceptable and safe, with only minor short-term side-effects reported and with a high satisfaction rate among the patients.

Evolution of patterns of care for women with cervical cancer in Morocco over a decade.

BACKGROUND: We conducted a Pattern-of-care (POC) study at two premier-most public-funded oncology centers in Morocco to evaluate delays in care continuum and adherence to internationally accepted treatment guidelines of cervical cancer. METHOD: Following a systematic sampling method, cervical cancer patients registered at Centre Mohammed VI (Casablanca) and Institut National d'Oncologie (Rabat) during 2 months of every year from 2008 to 2017, were included in this retrospective study. Relevant information was abstracted from the medical records. RESULTS: A total of 886 patients was included in the analysis; 59.5% were at stage I/II. No appreciable change in stage distribution was observed over time. Median access and treatment delays were 5.0 months and 2.3 months, respectively without any significant temporal change. Concurrent chemotherapy was administered to 57.7% of the patients receiving radiotherapy. Surgery was performed on 81.2 and 34.8% of stage I and II patients, respectively. A very high proportion (85.7%) of operated patients received post-operative radiation therapy. Median interval between surgery and initiation of radiotherapy was 3.1 months. Only 45.3% of the patients treated with external beam radiation received brachytherapy. Radiotherapy was completed within 10 weeks in 77.4% patients. An overall 5-year disease-free survival (DFS) was observed in 57.5% of the patients - ranging from 66.1% for stage I to 31.1% for stage IV. Addition of brachytherapy to radiation significantly improved survival at all stages. The study has the usual limitations of retrospective record-based studies, which is data incompleteness. CONCLUSION: Delays in care continuum need to be further reduced. Increased use of chemoradiation and brachytherapy will improve survival further.

An international consensus on the essential and desirable criteria for an 'organized' cancer screening programme.

BACKGROUND: High variability in the definition and interpretation of organized cancer screening needs to be addressed systematically. Moreover, the relevance of the current practice of categorizing screening programmes dichotomously into organized or non-organized needs to be revisited in the context of considerable heterogeneity that exists in the delivery of cancer screening in the real world. We aimed to identify the essential and desirable criteria for organized cancer screening that serve as a charter of best practices in cancer screening. METHODS: We first did a systematic review of literature to arrive at an exhaustive list of criteria used by various publications to describe or define organized cancer screening, based on which, a consolidated list of criteria was generated. Next, we used a Delphi process comprising of two rounds of online surveys to seek agreement of experts to categorize each criterion into essential, desirable, or neither. Consensus was considered to have been achieved based on a predetermined criterion of agreement from at least 80% of the experts. The outcomes were presented before the experts in a virtual meeting for feedbacks and clarifications. RESULTS: A total of 32 consolidated criteria for an organized screening programme were identified and presented to 24 experts from 20 countries to select the essential criteria in the Delphi first round. Total 16 criteria were selected as essential with the topmost criteria (based on the agreement of 96% of experts) being the availability of a protocol/guideline describing at least the target population, screening intervals, screening tests, referral pathway, management of positive cases and a system being in place to identify the eligible populations. In the second round of Delphi, the experts selected eight desirable criteria out of the rest 16. The most agreed upon desirable criterion was existence of a specified organization or a team responsible for programme implementation and/or coordination. CONCLUSIONS: We established an international consensus on essential and desirable criteria, which screening programmes would aspire to fulfil to be better-organized. The harmonized criteria are a ready-to-use guide for programme managers and policymakers to prioritize interventions and resources rather than supporting the dichotomous and simplistic approach of categorizing programmes as organized or non-organized.

Delivering colorectal cancer screening integrated with primary health care services in Morocco: Lessons learned from a demonstration project.

BACKGROUND: Colorectal cancer (CRC) incidence and mortality rates are increasing rapidly in many low-income and middle-income countries. A demonstration project was implemented in Morocco in collaboration with the Ministry of Health to assess the feasibility, acceptability, and challenges of implementing CRC screening through routine primary care facilities. METHODS: The objective of the project was to screen 10,000 men and women aged 50 to 75 years through 10 primary health centers (PHCs) in 2 provinces. All eligible men and women attending the selected PHCs were offered the fecal immunochemical test (FIT). Stool specimens brought to the PHCs were tested immediately by trained nurses. FIT-positive individuals were referred to the National Oncology Institute for colonoscopy. RESULTS: In total, 9763 eligible men and women were screened by FIT between June 2017 and May 2019; most (73.3%) were women. The test was positive in 460 participants (4.7%). Among the individuals who had positive FIT results, 62.6% underwent colonoscopy. The main reasons for noncompliance to colonoscopy were competing life priorities (15.4%), other health problems (13%), and fear of getting a cancer diagnosis (12.3%). As the number of referrals to colonoscopy increased, the waiting time for the procedure increased, resulting in a drop in compliance. The detection rates of advanced adenomas and CRC were 4.0 in 1000 and 0.5 in 1000 individuals screened, respectively. CONCLUSIONS: An effective strategy to reach the target populations (especially men), a pragmatic assessment of the health system's capacity to deal with large numbers of referrals, and a formal cost-effectiveness analysis are essential before making any decision to introduce CRC screening in Morocco.

Vaccine efficacy against persistent human papillomavirus (HPV) 16/18 infection at 10 years after one, two, and three doses of quadrivalent HPV vaccine in girls in India: a multicentre, prospective, cohort study.

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. METHODS: In 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.

Patterns of care of breast cancer patients in Morocco - A study of variations in patient profile, tumour characteristics and standard of care over a decade.

Guided by a national cancer plan (2010-19), Morocco made significant investments in improving breast cancer detection and treatment. A breast cancer pattern-of-care study was conducted to document the socio-demographic profiles of patients and tumour characteristics, measure delays in care, and assess the status of dissemination and impact of state-of-the-art management. The retrospective study conducted among 2120 breast cancer patients registered during 2008-17 at the two premier-most oncology centres (Centre Mohammed VI or CM-VI and Institut National d'Oncologie or INO) also measured temporal trends of the different variables. Median age (49 years) and other socio-demographic characteristics of the patients remained constant over time. A significant improvement in coverage of the state-financed health insurance scheme for indigent populations was observed over time. Median interval between onset of symptoms and first medical consultation was 6 months with a significant reduction over time. Information on staging and molecular profile were available for more than 90% and 80% of the patients respectively. Approximately 55% of the patients presented at stage I/II and proportion of triple-negative cancers was 16%; neither showing any appreciable temporal variation. Treatment information was available for more than 90% of the patients; 69% received surgery with chemotherapy and/or radiation. Treatment was tailored to stage and molecular profiles, though breast conservation therapy was offered to less than one-fifth. When compared using the EUSOMA quality indicators for breast cancer management, INO performed better than CM-VI. This was reflected in nearly 25% difference in 5-year disease-free survival for early-stage cancers between the centres.

Factors associated with birthweight decline in Japan (1980-2004).

BACKGROUND: Birthweight has been declining consistently for more than 30 years in Japan. This rapid rise in low birthweight is one of the worst among the countries of the Organization for Economic Co-operation and Development. We examined potential determinants of birthweight decline in Japan. METHODS: We used population-based birth certificate data from vital statistics records and retrieved 40,968,266 birth certificates of neonates born between 1980 and 2004. We analyzed time trends using linear regression analysis in examining whether the decline in birthweight could be explained by obstetrical variables such as gestational age and multiple gestations. RESULTS: From 1980 to 2004, we observed a decline in mean birthweight with a yearly effect of - 8.07 g, which became steeper after 1985, persisted until 1999, and plateaued thereafter. After adjusting for gestational age, gender, birth order, multiple gestations, and fathers' age, the yearly effect between 1980 and 2004 persisted at - 5.13 g. CONCLUSION: Recent decreases in birthweight among Japanese neonates were not fully explained by trends in gestational age, gender, birth order, multiple gestations, and fathers' age. Thus, additional factors such as pre-pregnancy maternal body mass index (BMI) and maternal diet should be considered. Reducing the rate of induced deliveries and improving the BMI or diet of young women should be a public health priority.

Cross-sectional survey of the impact of the COVID-19 pandemic on cancer screening programs in selected low- and middle-income countries: Study from the IARC COVID-19 impact study group.

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.