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National cancer control planning is crucial for countries in the WHO Eastern Mediterranean region. This region is challenged with an increase in cancer incidence leading to substantial disease burden, premature deaths, and increasing health-care costs in most countries. Huge inequity in cancer control planning and implementation exists between and within the countries. Over half of the countries (12 [55%] of 22) have standalone comprehensive National Cancer Control Plans and six (27%) have non-communicable disease plans that include cancer. The implementation of cancer plans has common challenges related to weak governance structure, few coordination mechanisms within countries, and inadequate human and financial resources. In most countries, the plan is not costed. Yet, the majority of countries (20 [91%]) reported having fully or partially funded plans. Additionally, political instability and conflicts affecting over half of the countries in the Eastern Mediterranean region have enormously affected cancer planning and implementation, both among the affected countries and those that host large numbers of refugees. In this Policy Review, we used the WHO regional framework for action on cancer to systematically analyse the status of cancer control planning and implementation across the six domains of cancer control, from prevention to palliation. We highlight the gaps, and the opportunities for bridging these gaps, to achieve scale-up on implementation of cancer control programmes in the Eastern Mediterranean region.

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.

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., Highlights • Morocco achieved significant progress in quality of breast cancer care in last decade. • Access delay reduced significantly over time but was still high at median 6 months. • More than 80% breast cancer patients had complete molecular profiles. • Many gaps still exist in quality of treatment

Objective Thermal ablation (TA) was implemented in public sector cervical cancer prevention services in Zambia in 2012. Initially introduced as a treatment modality in primary healthcare clinics, it was later included in mobile outreach campaigns and clinical research trials. We report the feasibility, acceptability, safety, and provider uptake of TA in diverse clinical contexts. Methods Screening services based on visual inspection with acetic acid were offered by trained nurses to non-pregnant women aged 25-59 years. Women with a type 1 transformation zone (TZ) were treated with same-visit TA. Those with a type 2 or 3 TZ, or suspicious for cancer, were managed with same-visit electrosurgical excision or punch biopsy, respectively. A provider survey was conducted. Results Between 2012 and 2020, 2123 women were treated with TA: primary healthcare clinics, n = 746; mobile outreach clinics, n = 1127; research clinics, n = 250. Of the 996 women treated in primary healthcare and research clinics, 359 (48%) were HIV positive. Mild cramping during treatment was the most common adverse effect. No treatment interruptions occurred. No major complications were reported in the early (6 weeks) follow-up period. Providers expressed an overwhelming preference for TA over cryotherapy. Conclusion TA was feasible, safe, and acceptable in diverse clinical contexts. It was the preferred ablation method of providers when compared with cryotherapy.

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., What's new? Reductions in non‐emergency health services and diversion of resources during the coronavirus disease (COVID‐19) pandemic have greatly affected all areas of health care, including cancer care. Here, the authors investigated the impact of the COVID‐19 pandemic specifically on cancer screening in low‐ and middle‐income countries. Nearly all countries investigated experienced suspensions in cancer screening lasting at least one month, owing to lockdown restrictions, changes in health priorities, and reduced patient visits. Upon reopening, cancer services generally operated at significantly reduced capacities, emphasizing a need for highly coordinated re‐initiation efforts to ensure continuity of cancer care following lockdown.

Objectives: We are reporting the evaluation of an opportunistic point of care cervical cancer screening initiative in Pune, India using a mobile screening unit (MSU). Methods: We conducted 290 cervical cancer screening outreach clinics in the MSU. Screening was performed by trained nurses/ health care providers using visual inspection with 5% acetic acid (VIA). Screen positive women when eligible were treated by thermal ablation during the same sitting. Women with large lesions not eligible for treatment with thermal ablation were referred for colposcopy and treatment. Results: A total of 10, 925 women were screened between Nov 2016 and June 2019 in 290 outreach clinics in the MSU. The overall screen positivity was 6.6% (95% CI 6.1, 7.0) with a declining trend over time. A total of 304/717 (42.4%, 95% CI 38.7, 46.1) women received treatment with thermal ablation. About 3.6% (11/304) reported minor side effects and 1.6% (5/304) reported lower abdominal pain and all of them subsided after treatment. Among the 413 women who were advised colposcopy, only 84 (20.33%) women underwent the procedure. Of these 84 women, 64 (76.19%) had normal colposcopy/ histopathology, 7 (8.33%) had CIN1, 2 (2.38%) had CIN 2, 9 (10.71%) had CIN 3 disease and 2 (2.38%) women were diagnosed with invasive cancer. Conclusion: MSUs are useful for providing cervical cancer screening services, using the ‘screen and treat’ strategy. Thermal ablation is safe in the field clinics. Additional efforts are needed to improve the compliance for referral of those with large lesions requiring additional visits.

Cervical cancer, caused by HPV infection, is responsible for more than 311 000 preventable deaths every year. A global call to accelerate efforts to eliminate this disease has generated a new global strategy proposing ambitious, but achievable, targets for HPV vaccination of girls, and screening and treatment of women. The present paper addresses the suboptimal access to HPV vaccination in low‐income and lower‐middle‐income countries (LICs/LMICs), where the burden of disease weighs most heavily, in part through co‐infection with HIV. A proposed framework for action was formulated by first reviewing the reasons underlying gaps in HPV vaccine coverage. Good practices from recent introductions of HPV vaccine at scale in LICs/LMICs were then assessed based on targeted literature reviews and the experience and views of the authors. Difficulties in uptake and coverage of the HPV vaccine relate to the costs of the vaccine and service delivery, lack of prioritization, the challenges of vaccinating adolescents, and shortage of vaccines as the supply failed to keep pace with the rapid expansion in global demand, including from LICs/LMICs. The framework for action calls for new strategic thinking to consolidate global learning and invigorate operationalization at a country level., The elimination of cervical cancer calls for better innovation, investment, integration, information, and influence to boost vaccination against human papilloma virus infection.

The call for elimination of cervical cancer as a public health problem by the World Health Organization has led to intense focus on the burden of disease, available resources, and the possibility of introducing efficient systems for screening and treatment that allow effective cancer control in limited-resource settings. Presently, the focus is on the introduction of rapid, technologically less-demanding, affordable HPV testing. However, until such tests become widely available, the momentum that has been gained using visual inspection with acetic acid (VIA) should not be lost. Countries with limited resources and a heavy burden of cervical cancer, such as Bangladesh and India, introduced and scaled up VIA-based programs with varying degrees of programmatic organization and performance. Despite its limitations, VIA's simplicity and affordability has allowed these countries to build infrastructure, increase numbers of trained healthcare personnel, and develop a system of multilevel coordination within the health system. Such efforts will have long-term advantages provided that countries have access to an appropriate HPV test and build on their efforts to improve program organization through a strengthened health system, translating lessons learned in program implementation, logistics, and compliance with the new paradigm.

PURPOSE Detection of high-risk human papillomavirus (HPV) in self-collected vaginal samples can significantly improve participation of hard-to-reach women; however, the implementation of such an approach in a real-life setting, especially in countries with limited resources, has certain challenges. Our study aimed to evaluate the feasibility, acceptability, and efficacy of implementing an HPV self-sampling–based approach to screen a socioeconomically disadvantaged, unscreened population with support from community health workers (CHWs) for community mobilization, counseling, and navigation. Different triaging options for HPV-positive women were also assessed. METHODS Women age 30 to 65 years from low socioeconomic periurban areas who had never been screened before were motivated by CHWs to attend local community centers and provide self-collected vaginal samples for careHPV testing. Screen-positive women were informed and navigated by CHWs to attend colposcopy clinics where cervical biopsy and same-day ablative treatment were offered. RESULTS Women readily accepted to provide self-collected samples after counseling by CHWs. Screen positivity was 6.4%, and CHWs successfully navigated 65% of HPV-positive women to colposcopy. Cervical intraepithelial neoplasia (CIN) 2+ detection rate was 9.7 per 1,000 women screened. The HPV test had a positive predictive value of 15.3% to detect CIN 2+ lesions. Triage using visual inspection with acetic acid significantly improved the positive predictive value (49.5% to detect CIN 2+), but missed a significant number of CIN 2+ lesions. Colposcopy sensitivity was also suboptimal. Of 51 women with lesions, 80% underwent ablative treatment and the majority accepted same-day treatment. CONCLUSION CHW-driven self-sampling for HPV testing is feasible, well-accepted, and effective for screening unscreened hard-to-reach women. The screen-and-treat approach can ensure strong linkage between screening and treatment.

Background Portable devices that can be used to perform colposcopy may improve cervical cancer screening in low- and middle-income countries (LMIC) where access to colposcopy is limited. The objective of this study was to systematically review the diagnostic test accuracy (DTA) of these devices for the detection of cervical intraepithelial neoplasia grade 2 or higher (CIN2+). Methods In accordance with our protocol (Prospero CRD42018104286), we searched Embase, Medline and the Cochrane Controlled Register of Trials up to 9/2019. We included DTA studies, which investigated portable devices with moderate-to-high optical magnification (≥ 6×) for colposcopy, as described in the manual for Colposcopy and Treatment by the International Agency for Research on Cancer, with a histopathological reference standard. We used the QUADAS-2 tool to assess study quality. We examined results for sensitivity and specificity in paired forest plots, stratified by stages in the clinical pathway. We pooled estimates of test accuracy for the index test, used as an add-on to other tests, using a bivariate random-effect model. Results We screened 1737 references and assessed 239 full-text articles for eligibility. Five single-gate DTA studies, including 2693 women, met the inclusion criteria. Studies evaluated two devices (Gynocular™ and Pocket) at different stages of the screening pathway. In three studies, which used the index test in an add-on capacity in 1273 women, we found a pooled sensitivity of 0.79 (95% CI 0.55–0.92) and specificity of 0.83 (95% CI 0.59–0.94). The main sources of bias were partial verification, incorporation and classification bias. Conclusion Few studies have evaluated portable devices able to perform colposcopy, so their accuracy for the detection of CIN2+ remains uncertain. Future studies should include patient-relevant and long-term outcomes, including missed cases, overtreatment, residual and recurrent disease. To meet the challenge of eliminating cervical cancer in LMIC, methods for visual assessment of the cervix need urgent redress.

Given that high-risk human papillomavirus (HPV) is the necessary cause of virtually all cervical cancer, the clinical meaning of HPV-negative cervical precancer is unknown. We, therefore, conducted a literature search in Ovid MEDLINE, PubMed Central, and Google Scholar to identify English-language studies in which (i) HPV-negative and -positive, histologically confirmed cervical intraepithelial neoplasia grade 2 or more severe diagnoses (CIN2+) were detected and (ii) summarized statistics or deidentified individual data were available to summarize proportions of biomarkers indicating risk of cancer. Nineteen studies including 3,089 (91.0%) HPV-positive and 307 (9.0%) HPV-negative CIN2+ were analyzed. HPV-positive CIN2+ (vs. HPV-negative CIN2+) was more likely to test positive for biomarkers linked to cancer risk: a study diagnosis of CIN3+ (vs. CIN2; 18 studies; 0.56 vs. 0.24; P < 0.001) preceding high-grade squamous intraepithelial lesion cytology (15 studies; 0.54 vs. 0.10; P < 0.001); and high-grade colposcopic impression (13 studies; 0.30 vs. 0.18; P = 0.03). HPV-negative CIN2+ was more likely to test positive for low-risk HPV genotypes than HPV-positive CIN2+ (P < 0.001). HPV-negative CIN2+ appears to have lower cancer risk than HPV-positive CIN2+. Clinical studies of human high-risk HPV testing for screening to prevent cervical cancer may refer samples of HPV test–negative women for disease ascertainment to correct verification bias in the estimates of clinical performance. However, verification bias adjustment of the clinical performance of HPV testing may overcorrect/underestimate its clinical performance to detect truly precancerous abnormalities.

Thermal ablation is a point-of-care ablative treatment technique for cervical intraepithelial neoplasia (CIN). However, limited information is available about its efficacy in low- and middle-income countries. We evaluated the efficacy of thermal ablation in treatment of CIN detected through high-risk human papillomavirus (HPV) screening in China. Women positive on high-risk HPV and having colposcopically suspected lesions eligible for ablation underwent colposcopy, biopsy and thermal ablation in one visit. Women ineligible were recalled for large loop excision of transformation zone (LLETZ) when histopathology results were high-grade CIN. Posttreatment follow-up at 6 months or more was with HPV test and cytology followed by colposcopy and biopsy for HPV and/or cytology-positive women. Cure was defined as either negative cytology and HPV test or absence of histopathology proved CIN in any positive women. Of total 218 HPV-positive women treated with thermal ablation (n = 170) or LLETZ (n = 48), 196 reported for follow-up evaluation. For women with histologically confirmed CIN at baseline (thermal ablation-104; LLETZ-38), cure rates were 84.6% for thermal ablation and 86.8% for LLETZ. Cure rates after thermal ablation were 90.3% for CIN grade one (CIN1) and 76.2% for CIN grade two or worse (CIN2+). HPV clearance rate was 80.4% in women undergoing thermal ablation, which was lower for HPV16/18 compared to other oncogenic types (67.6% vs 85.7%). HPV test had a negative predictive value (NPV) of 98.7% to detect CIN2+ at follow-up and the positive predictive value (PPV) was 40.4%. Thermal ablation is effective to treat CIN as well as to clear the high-risk HPV infection. HPV test has high PPV and NPV in following up patients posttreatment.

INTRODUCTION: Whether existing serological assays are sufficiently robust to measure the lower antibody levels expected following single-dose HPV vaccination is unknown. METHODS: We evaluated seven assays measuring HPV-16/18 immunological responses overall and by number of doses in 530 serum samples from participants receiving varying doses of Cervarix or Gardasil up to 36-months post-vaccination. Serum was evaluated by simplex (HPV-16 ELISA, HPV-18 ELISA), multiplex (LIA-4, VLP-MIA, M9ELISA, GST-L1), and high-throughput pseudovirion-based neutralization assays (HT-PBNA), and results were compared to the gold standard HPV-16/18 secreted alkaline phosphatase neutralization assay (SEAP-NA). Reproducibility was assessed by the coefficient of variation (CV) and intraclass correlation coefficient (ICC). Percent agreement, Pearson correlation and weighted-kappa were used to assess validity. Determinants of seronegativity were evaluated by chi-squared test. RESULTS: HPV-16: Seropositivity range was 97.1–99.5% for single dose and 98.8–99.8% overall. CV range was 4.0–18.0% for single dose and 2.9–19.5% overall. ICC range was 0.77–0.99 for single dose and 0.74–0.99 overall. Correlation with SEAP-NA range was 0.43–0.85 for single dose and 0.51–0.90 overall. Weighted-kappa range was 0.34–0.82 for single dose and 0.45–0.84 overall. HPV-18: Seropositivity range was 63.9–94.7% for single dose and 86.2–97.9% overall. CV range was 8.1–18.2% for single dose and 4.6–18.6% overall. ICC range was 0.75–0.99 for single dose and 0.83–0.99 overall. Correlation with SEAP-NA range was 0.31–0.99 for single dose and 0.27–0.96 overall. Weighted-kappa range was 0.35–0.83 for single dose and 0.45–0.84 overall. HPV-16 seronegativity was 10%, the strongest correlates of seronegativity were receiving a single vaccine dose and receiving Gardasil. CONCLUSIONS: These results support the utility of existing serological assays to monitor antibody responses following single-dose HPV vaccination.

Human papillomavirus (HPV) vaccination offers an excellent prospect for the primary prevention of cervical cancer. The bivalent and quadrivalent vaccines are both available in India. The nonavalent vaccine is licensed but not yet available. However, there still remain controversies regarding the vaccination of older women, immunocompromised females and other special groups. To provide recommendations for HPV vaccination in India. The Federation of Obstetric and Gynecological Societies of India (FOGSI) convened an expert group on cervical cancer prevention to formulate good clinical practice recommendations (GCPR) with respect to vaccine efficacy and safety, target groups, optimal timing and dosing schedules. HPV vaccines are licensed for females aged 9-45 years in India and have been seen to be safe and effective. FOGSI recommends HPV vaccination of all girls15 years of age as the best target group, in whom two-doses at an interval of 6 months, extendable to 18 months, are recommended. Three-doses are recommended in girls15 years of age, immunocompromised persons and sexual assault survivors. Older women and women with abnormal screening results may be vaccinated with an understanding that vaccination does not protect against already acquired infections and screening has to continue. Single-dose vaccination results are promising. Increased awareness is required to reduce vaccine hesitancy. HPV vaccination should be the priority to achieve the elimination of cervical cancer. The introduction of affordable HPV vaccines and reduced dose schedules will improve coverage.

Background The prospective randomized study aimed to compare the safety, acceptability and efficacy of thermal ablation (TA) to that of cryotherapy in screen and treat setting. Methods The participants were recruited prospectively in a community-based screening clinic in India. Women positive on visual inspection with acetic acid (VIA) test and/or Human Papillomavirus (HPV) test were assessed for eligibility for ablative treatment. Total 286 eligible women were randomized to receive either cryotherapy (N=150) or TA (N=136) performed by health workers. Colposcopy and cervical biopsy were performed on all, prior to treatment. Post-treatment follow-up was after one year with colposcopy and biopsy. Results Both the treatment methods had high acceptability. Significantly higher proportion of women treated by cryotherapy reported pain compared to women treated by TA, though intensity was mild in vast majority of them. Approximately 30% of women in both arms had histologic abnormalities, mainly CIN 1, and among those who attended follow-up 74.1% and 81.0% didn't have any CIN after cryotherapy and TA respectively. Conclusion TA is as acceptable and safe as cryotherapy in screen and treat setting. TA has the logistic advantages for the low-resourced settings as the machines are more portable, do not require costly refrigerant gas and battery-driven models are available. The cure rates for CIN 1+ lesions in our study were comparable between cryotherapy and TA.

As an adjunct to mammography, ultrasound can improve the detection of breast cancer in women with dense breasts. We aimed to evaluate the diagnostic performance of automated breast ultrasound system (ABUS) and handheld ultrasound (HHUS) in Chinese women with dense breasts, both in combination with mammography and separately. This is a cross-sectional multicenter clinical research study. Nine hundred and thirty-seven women with dense breasts underwent ABUS, HHUS, and mammography at one of five tertiary-care hospitals. The diagnostic performance of ABUS and HHUS was evaluated in combination with mammography, or separately in women with mammography-negative dense breasts. The agreement between ABUS and HHUS in breast cancer detection was also assessed. The sensitivity of the combination of ABUS or HHUS with mammography was 99.1% (219/221), and the specificities were 86.9% (622/716) and 84.9% (608/716), respectively. The area under the curve was 0.93 for ABUS combined with mammography and 0.92 for that of HHUS combined with mammography. Statistically significant agreement between ABUS and HHUS in breast cancer detection was observed (percent agreement = 0.94, κ = 0.85). The incremental cancer detection rate in mammography-negative dense breasts was 42.8 per 1000 ultrasound examinations. Both ABUS and HHUS as adjuncts to mammography can significantly improve the breast cancer detection rate in women with dense breasts, and there is a strong correlation between them. Given the high prevalence of dense breasts and the multiple advantages of ABUS over HHUS, such as less operator dependence and reproducibility, ABUS showed great potential for use in breast cancer early detection, especially in resource-limited areas.

Comparable performance indicators for breast cancer screening in the European Union (EU) have not been previously reported. We estimated adjusted breast cancer screening positivity rate (PR) and detection rates (DR) to investigate variation across EU countries. For the age 50-69 years, the adjusted EU-pooled PR for initial screening was 8.9% (cross-programme variation range 3.2-19.5%) while DR of invasive cancers was 5.3/1,000 (range 3.8-7.4/1,000) and DR of ductal carcinoma in situ (DCIS) was 1.3/1,000 (range 0.7-2.7/1,000). For subsequent screening, the adjusted EU-pooled PR was 3.6% (range 1.4-8.4%), the DR was 4.0/1,000 (range 2.2-5.8/1,000) and 0.8/1,000 (range 0.5-1.3/1,000) for invasive and DCIS, respectively. Adjusted performance indicators showed remarkable heterogeneity, likely due to different background breast cancer risk and awareness between target populations, and also different screening protocols and organisation. Periodic reporting of the screening indicators permits comparison and evaluation of the screening activities between and within countries aiming to improve the quality and the outcomes of screening programmes. Cancer Screening Registries would be a milestone in this direction and EU Screening Reports provide a fundamental contribution to building them.

Human papillomavirus (HPV) test, self-sampling and thermal ablation for cervical intraepithelial neoplasia (CIN) have been developed separately to increase screening coverage and treatment compliance of cervical cancer screening programmes. A large-scale study in rural China screened 9,526 women with their combinations to explore the optimal cervical cancer-screening cascade in the real-world. Participants received careHPV and polymerase chain reaction (PCR) HPV tests on self-collected samples. Women positive on either HPV test underwent colposcopy, biopsy and thermal ablation in a single visit. Samples positive on either HPV test were retested for genotyping. Absolute and relative performance of HPV tests, triage strategies, 'colposcopy and thermal ablation' approach were statistically evaluated. PCR HPV test detected 33.3% more CIN grade two or worse (CIN2+) at a cost of 28.1% more colposcopies compared to careHPV. Sensitivities of PCR HPV and careHPV tests to detect CIN2+ were 96.7 and 72.5%. Specificities for the same disease outcome were 82.1 and 86.0%. Triaging HPV-positive women with HPV16/18 genotyping considerably improved the positive predictive value for CIN2+ (4.8-5.0 to 18.2-19.2%). Ninety-six women positive on HPV and having abnormal colposcopy were eligible for thermal ablation and all accepted same-day treatment, contributing to 64.6% being treated appropriately (CIN1+ on histopathology), which reached up to 84.8% among women positive on HPV 16/18 triage. No serious side-effects/complications were reported. The combination of PCR HPV test followed by HPV 16/18 triaging on self-collected samples and colposcopy of triage positive women followed by immediate thermal ablation might be the appropriate screening cascade for rural China.

Background: Cryotherapy is standard practice for treating patients with cervical precancer in see-and-treat programmes in low-income and middle-income countries (LMICs). Because of logistical difficulties with cryotherapy (eg, the necessity, costs, and supply chain difficulties of refrigerant gas; equipment failure; and treatment duration >10 min), a battery-operated thermal ablator that is lightweight and portable has been developed. We aimed to compare thermal ablation using the new device with cryotherapy. Methods: We report the pilot phase of a randomised controlled trial in routine screen-and-treat clinics providing cervical screening using visual inspection with acetic acid (VIA) in Lusaka, Zambia. We recruited non-pregnant women, aged 25 years or older, who were eligible for ablative therapy. We randomly assigned participants (1:1:1) to thermal ablation, cryotherapy, or large loop excision of the transformation zone (LLETZ), using computer-generated allocation. The randomisation was concealed but the nurses providing treatment and the participants were unmasked. Thermal ablation was achieved using the Liger thermal ablator (using 1–5 overlapping applications of the probe heated to 100°C, each application lasting for 40 s), cryotherapy was carried out using the double-freeze technique (freeze for 3 min, thaw for 5 min, and freeze again for 3 min), and LLETZ (using a large loop driven by an electro-surgical unit to excise the transformation zone) was done under local anaesthesia. The primary endpoint was treatment success, defined as either human papillomavirus (HPV) type-specific clearance among participants who were positive for the same HPV type at baseline, or a negative VIA test at 6-month follow-up, if the baseline HPV test was negative. Per protocol analyses were done. Enrolment for the full trial is ongoing. Here, we present findings from a prespecified pilot phase of the full trial. The final analysis of the full trial will assess non-inferiority of the groups for the primary efficacy endpoint. The study is registered with ClinicalTrials.gov, number NCT02956239. Findings: Between Aug 2, 2017, and Jan 15, 2019, 750 participants were randomly assigned (250 per group). 206 (84%) participants in the cryotherapy group, 197 (81%) in the thermal ablation group, and 204 (84%) in the LLETZ group attended the 6-month follow-up examination. Treatment success was reported in 120 (60%) of 200 participants in the cryotherapy group, 123 (64%) of 192 in the thermal ablation group, and 134 (67%) of 199 in the LLETZ group (p=0·31). Few participants complained of moderate to severe pain in any group immediately after the procedure (six [2%] of 250 in the cryotherapy group, four [2%] of 250 in the thermal ablation group, and five [2%] of 250 in the LLETZ group) and 2 weeks after the procedure (one [

Human papillomaviruses (HPV)-related gynecological cancers are a major health care issue, and a leading cause of cancer death in low- and middle-income countries (LMIC). In 2020, the World Health Organization launched a program aimed at cervical cancer elimination, by screening and vaccination strategies. Offering the best possible care to women diagnosed with invasive cancer is a complementary objective. Treatment of cervical cancer as per modern standards is complex and multimodal, mainly relying on surgery, external-beam radiotherapy (+/−chemotherapy) and brachytherapy. In parallel with the pivotal role of multidisciplinary discussion, international societies provide guidance to define the most effective and least toxic anti-cancer strategy, homogenize treatment protocols and provide benchmark quality indicators as a basis for accreditation processes. The challenge is to offer the appropriate diagnostic workup and treatment upfront and to avoid non- evidence-based treatment that consumes resources, impairs quality of life (QoL), and compromises oncological outcome. Various strategies may be applied for improving treatment quality: development of surgical mentorship, companion-training programs and international cooperation. The lack of radiotherapy/brachytherapy facilities is a major concern in LMIC. Reinforcing international support in terms of education, training, research and development and technical cooperation with national projects is required to increase access to minimum requirements but also introduce modern techniques, upgrade radiotherapy/brachytherapy services, and expand access to modern systemic treatments. In countries with robust economies, compliance to standards should also be increased. Integrative cancer care and multidisciplinary approaches are needed to tackle the dual challenge of increasing cure rates while minimizing QoL impairment. Appropriate dimensioning of the resources to avoid harmful treatment delays and access to expert referral centers is also a priority.

The increase in cancer incidence and mortality is challenging current cancer care delivery globally, disproportionally affecting low- and middle-income countries (LMICs) when it comes to receiving evidence-based cancer prevention, treatment, and palliative and survivorship care. Patients in LMICs often rely on traditional, complementary, and integrative medicine (TCIM) that is more familiar, less costly, and widely available. However, spheres of influence and tensions between conventional medicine and TCIM can further disrupt efforts in evidence-based cancer care. Integrative oncology provides a framework to research and integrate safe, effective TCIM alongside conventional cancer treatment and can help bridge health care gaps in delivering evidence-informed, patient-centered care. This growing field uses lifestyle modifications, mind and body therapies (eg, acupuncture, massage, meditation, and yoga), and natural products to improve symptom management and quality of life among patients with cancer. On the basis of this review of the global challenges of cancer control and the current status of integrative oncology, the authors recommend: 1) educating and integrating TCIM providers into the cancer control workforce to promote risk reduction and culturally salient healthy life styles; 2) developing and testing TCIM interventions to address cancer symptoms or treatment-related adverse effects (eg, pain, insomnia, fatigue); and 3) disseminating and implementing evidence-based TCIM interventions as part of comprehensive palliative and survivorship care so patients from all cultures can live with or beyond cancer with respect, dignity, and vitality. With conventional medicine and TCIM united under a cohesive framework, integrative oncology may provide citizens of the world with access to safe, effective, evidence-informed, and culturally sensitive cancer care.

Multiple barriers impede the transformation of evidence-based research into implementation of cervical cancer screening in ASEAN countries. This review is the first of its kind to show the disease burden of cervical cancer, progress till date to implement screening and corresponding challenges, and propose tailored solutions to promote cervical cancer prevention in ASEAN. In 2020, approximately 69 000 cervical cancer cases and 38 000 deaths happened in ASEAN, and more than 44% and 63% increases on new cases and deaths are expected in 2040. Only four countries have initiated population-based cervical cancer screening programs, but the participation rate is less than 50% in some countries and even lower than 10% in Myanmar and Indonesia. Inequity and unavailability in service delivery, lack of knowledge and awareness, limited follow-up and treatment capacity, and funding sustainability affect successful scale-up of cervical cancer screening most in ASEAN. Implementing HPV detection-based primary screening, appropriate management of screen-positives, enhancing health education, integrating health services can accelerate reduction of cervical cancer burden in ASEAN. Achieving high screening coverage and high treatment compliance will help ASEAN countries remain aligned to cervical cancer elimination strategies.

Summary Efforts are being made to scale up human papillomavirus (HPV) vaccination for adolescent girls in India. Bivalent and quadrivalent HPV vaccines were licensed in the country in 2008, and a nonavalent vaccine was licensed in 2018. Demonstration projects initiated in Andhra Pradesh and Gujarat in 2009 introduced HPV vaccination in public health services in India. Following a few deaths in these projects, although subsequently deemed unrelated to vaccination, HPV vaccination in research projects was suspended. This suspension by default resulted in some participants in a trial evaluating two versus three doses receiving only one dose. Since 2016, the successful introduction of HPV vaccination in immunisation programmes in Punjab and Sikkim (with high coverage and safety), government-sponsored opportunistic vaccination in Delhi, prospects of a single dose providing protection, and future availability of an affordable Indian vaccine shows promise for future widespread implementation and evaluation of HPV vaccination in India.

Unconventional natural gas extraction by hydraulic fracturing requires millions of gallons of water and generates flowback water, produced water and recycled fluids of varying chemical composition. Ion chromatography (IC) is a relatively low cost and efficient means to determine the anionic composition, however, the wide range in anionic content of these fluids poses a challenge to analytical methods developed for "natural" waters. We report here that the combination of UV and conductivity detectors increased detection sensitivity (e.g., 10-50 ppb) and expanded the number of anions detectable in a single sample run. Samples from four unconventional shale gas wells, two impoundments, nine conventional oil wells, two freshwater streams and mine drainage samples were analyzed in this study. All produced water samples and impoundment samples had high chloride (17,500-103,000 mg L

Objective Cervical cancer is the second most common cancer in Thai women; human papillomavirus (HPV) is the main cause. This study aimed to determine the clinical performance of HPV mRNA compared with HPV DNA testing. Methods Cervical specimens were collected from women aged 35 to 60 who attended the routine organized screening programme. We compared accuracy parameters of standalone HPV mRNA and HPV DNA tests, and those of triaging with liquid-based cytology or HPV genotyping and liquid-based cytology for those positive only for the less oncogenic HPV types. Test accuracy parameters were estimated using latent class analysis using Bayesian models. Results Of the 5046 women enrolled, 174 (3.4%) were HPV DNA positive and 141 (2.8%) HPV mRNA positive. Colposcopy compliance was 95.4% ( n = 166) among HPV DNA-positive women and 94.3% ( n = 133) among those HPV mRNA positive. The estimated sensitivity, specificity, and positive predictive value for detection of CIN2 or worse were 67.4%, 97.1%, 12.1% for HPV DNA testing, and 73.1%, 97.8%, 16.3% for HPV mRNA testing. These estimates for triaging of HPV DNA-positive women with liquid-based cytology were 64.4%, 98.8%, and 19.0%, respectively, and slightly better for liquid-based cytology triage of HPV mRNA-positive women, at 71.8%, 98.9%, and 22.1%. Conclusion A triaging strategy based on HPV genotyping and liquid-based cytology for those positive only for the less oncogenic HPV types had test characteristics comparable with that of liquid-based cytology triage. The HPV mRNA detection-based strategies had non-significant advantages over the HPV DNA detection-based strategies.

The aim of this study was to describe the compliance of the population-based cancer screening programmes in the European Union Member States to the invitation strategies enumerated in the European Guidelines and the impact of such strategies on the invitational coverage. Experts in screening programme monitoring from the respective countries provided data. Coverage by invitation was calculated as the proportion of individuals in the target age range receiving a screening invitation over the total number of annualized eligible population. The invitation strategies of 30 breasts, 25 cervical and 27 colorectal national or regional population-based screening programmes are described. Individual mail invitations are sent by 28 breasts, 20 cervical and 25 colorectal screening programmes. Faecal occult blood test kits are sent by post in 17 of the colorectal cancer screening programmes. The majority of programmes claimed to have a population registry, although some use health insurance data as the database for sending invitations. At least 95% invitation coverage was reached by 16 breast, six cervical and five colorectal screening programmes. Majority of the programmes comply with the invitation strategies enumerated in the European guidelines, although there is still scope for improvements. Coverage by invitation is below the desirable level in many population-based cancer screening programmes in European Union.

Objectives To report the key outcomes of evaluation of the national cervical cancer screening program in Morocco, and describe its organization, status of implementation, performance, and major challenges. Methods An evaluation team conducted program manager interviews and screening provider focus group discussions, supervisory visits to primary health and diagnostic centers, and review of published documents. Aggregated performance data collected by the Ministry of Health from the screening and diagnostic centers were analyzed. Results Screening is conducted using visual inspection with acetic acid. The program is opportunistic, with no mechanism to identify and invite eligible women. Coverage of the target population was very low (6.6% in 2015 and 7.7% in 2016). Positivity rates were 5.3% and 8.9% in 2015 and 2016 respectively, and varied widely between regions. Detection rate of cervical intraepithelial neoplasia (CIN) 2 or worse in 2016 was very low (0.9/1,000), with more invasive cancers detected than CIN 2/3. Lack of histopathology and treatment facilities at the Cancer Early Detection Centers is a major short-coming, and there is a need for service-provider refresher training. Without a computerized health information system tracking screen positive women, ensuring high treatment compliance and performing regular quality assurance are challenging. Conclusions The screening program in Morocco requires better organization, a pragmatic system of inviting the target population, improved compliance to diagnosis, treatment, and follow-up, improved provider training, better quality assurance systems, and an effective health information system with appropriate linkages for monitoring and evaluation.

Cancer screening programs from majority of the low- and middle-income countries (LMICs) report screening coverage as the only performance indicator, and that too measured through population-based sample surveys. Such information is unreliable and has very little value in assessing programmatic quality and impact. Regular monitoring of key process and outcome indicators based on data collected through a robust information system is essential to ensure quality of a screening programme. Fragmented health systems, limited resources and absence of a culture of systematic evaluation are the major hindrances for most of the LMICs to build electronic information systems to manage screening. The COVID-19 pandemic has created an impetus for the countries to customize the freely available District Health Information Software (DHIS2) to collect electronic data to track the outbreaks and manage containment measures. In the present article we present Bangladesh as an exemplar LMIC that has a (DHIS2) based integrated health information system gradually upgraded to collect individual data of the participants to the national cervical cancer screening program. Such efforts paid rich dividends as the screening program was switched from opportunistic to a population-based one. Moreover, the electronic system could report impact of the pandemic on cancer screening on a monthly basis. The aggregate number of women screened in the year 2020 was 14.1% less compared to 2019. The monthly rate of screening during peak of the outbreak was only 5.1% of the previous year. The rate rapidly recovered as the program intensified screening in the hard-to-reach regions less affected by the pandemic and expanded the outreach services. Other LMICs may emulate Bangladesh example. Customizing the information system developed for pandemic surveillance to collect cancer screening data will help them build back the screening programs better.

Background The World Health Assembly has adopted a global strategy to eliminate cervical cancer. However, neither the optimal pathway nor the corresponding economic and health benefits have been evaluated. We take China as an example to assess the optimal pathway towards elimination and the cost-effectiveness of tailored actions. Methods A validated hybrid model was used to assess the costs and benefits of alternative strategies combining human papillomavirus vaccination, cervical screening, and treatment of pre-invasive lesions and invasive cancer for females with different immunization history. All Chinese females living or projected to be born during 2015–2100, under projected trends in aging, urbanization, and sexual activity, were considered. Optimal strategies were determined by cost-effectiveness efficiency frontiers. Primary outcomes were cervical cancer cases and deaths averted and incremental cost-effectiveness ratios (ICERs). We employed a lifetime horizon from a societal perspective. One-way and probabilistic sensitivity analyses evaluate model uncertainty. Results The optimal pathway represents an integration of multiple tailored strategies from females with different immunization history. If China adopts the optimal pathway, the age-standardized incidence of cervical cancer is predicted to decrease to fewer than four new cases per 100,000 women (i.e., elimination) by 2047 (95% confidence interval 2043 to 2050). Compared to the status quo, the optimal pathway would avert a total of 7,509,192 (6,922,744 to 8,359,074) cervical cancer cases and 2,529,873 (2,366,826 to 2,802,604) cervical cancer deaths in 2021–2100, with the discounted ICER being $− 339 (− 687 to − 79) per quality-adjusted life-year. Conclusions By adopting an optimal pathway from 2021 (namely, the year of the first Chinese Centennial Goals) onwards, cervical cancer could be eliminated by the late 2040s (namely, ahead of the second Chinese Centennial Goals) while saving net economic costs in China.

The COVID-19 pandemic, caused by the SARS-CoV-2 coronavirus, poses a clear and present danger to the health and well-being of populations. Here we discuss its indirect impact on global cancer prevention and control efforts, particularly for cervical cancer. We suggest some comparisons between the COVID-19 pandemic and the human papillomavirus–induced cancer burden, as well as opportunities for translating pandemic-control strategies into effective cancer control.

PURPOSE The coronavirus-induced pandemic has put great pressure on health systems worldwide. Nonemergency health services, such as cancer screening, have been scaled down or withheld as a result of travel restrictions and resources being redirected to manage the pandemic. The present article discusses the challenges to cancer screening implementation in the pandemic environment, suggesting ways to optimize services for breast, cervical, and colorectal cancer screening. METHODS The manuscript was drafted by a team of public health specialists with expertise in implementation and monitoring of cancer screening. A scoping review of literature revealed the lack of comprehensive guidance on continuation of cancer screening in the midst of waxing and waning of infection. The recommendations in the present article were based on the advisories issued by different health agencies and professional bodies and the authors' understanding of the best practices to maintain quality-assured cancer screening. RESULTS A well-coordinated approach is required to ensure that essential health services such as cancer management are maintained and elective services are not threatened, especially because of resource constraints. In the context of cancer screening, a few changes in invitation strategies, screening and management protocols and program governance need to be considered to fit into the new normal situation. Restoring public trust in providing efficient and safe services should be one of the key mandates for screening program reorganization. This may be a good opportunity to introduce innovations (eg, telehealth) and consider de-implementing non–evidence-based practices. It is necessary to consider increased spending on primary health care and incorporating screening services in basic health package. CONCLUSION The article provides guidance on reorganization of screening policies, governance, implementation, and program monitoring.

Objectives: A randomized control trial of a battery-operated thermocoagulator for the treatment of precancerous cervical lesions is ongoing in Lusaka, Zambia. We describe preliminary results of treatment efficacy in HIV-positive women. Methods: Visual inspection with acetic acid (VIA) screen-positive women eligible for ablative treatment are randomized to receive thermal ablation (TA), cryotherapy or large loop excision of the transformation zone (LLETZ). Demographic information is collected, including human immunodeficiency virus (HIV) status and antiretroviral therapy (ART) use. Human papillomavirus (HPV) DNA sampling for known or suspected oncogenic HPV types is performed at baseline and follow-up. Treatment efficacy is based on VIA and HPV status at 6- and/or 12-month follow-up. Side-effects, pain and client satisfaction are scored and recorded, however, these data are not included in this analysis. Results: Of the 1,683 women who have been randomized to treatment, 994 (59%) are HIV-positive with the vast majority (97%) on anti-retroviral therapy (ART). HIV-positive women were equally distributed between treatment arms (p=0.28). Among the 1328 (79%) eligible for follow-up, follow-up data are available on 722 women (54%), of which 383 are HIV-positive. Based on VIA results alone for cure, HIV positive women had lower overall cure rates than HIV-negative women (77% vs 88%, respectively, p 2yrs, 55%; p=0.072). Download : Download high-res image (215KB) Download : Download full-size image Conclusions: In May 2020, the 173rd World Health Assembly adopted the Global Strategy to Eliminate Cervical Cancer. This sub-analysis of data from a randomized control trial of locally ablative methods for cervical precancer highlights the challenges in eradicating this disease in women living with HIV. Investigations are underway to determine the underlying causes of these findings. (NCI Grant No. 4UH3CA202721-03)

Breast cancer is the most frequently diagnosed cancer among women in both transitioned and transitioning countries and has become a major women's health problem. Although recent advances in our understanding of the biological nature of cancer, improved awareness coupled with better early detection facilities, use of chemotherapy, hormone therapy, and targeted therapy have significantly improved survival from cancer, there are many gaps in providing individual-centric, holistic care. Integrative medicine refers to the use of traditional medicine alongside conventional preventive or therapeutic interventions (allopathic medicine) as a comprehensive, individual-centered, evidence-based care. The three pillars of complementary medicine (lifestyle modifications, mind-body practices, and use of natural products) have the potential for cancer prevention and improving quality-of-life and even treatment response in cancer patients when combined with conventional oncology care. Therefore, continued research into integrative therapies is required to extend the benefits to a broader patient population and improve outcomes in breast and other common cancers. In the present review article, the possible role of integrative medicine across the breast cancer care continuum has been discussed along with the concept of integrating complementary practices into mainstream health delivery. We have focused on breast cancer as a model cancer that is well amenable to prevention, early detection and stage appropriate treatment. However, our observations are pertinent for other common cancers, for which there are several opportunities for improving the continuum of care, especially in developing countries like India.

In context of the ongoing multi-centric HPV vaccine study in India, unvaccinated married women (N = 1484) aged 18–23 years were recruited in 2012–2015 as age-matched controls to the vaccinated women and followed up yearly. We assess type-specific prevalence, natural history and potential determinants of human papillomavirus (HPV) infection in these unvaccinated women. Cervical samples were collected yearly for at least four consecutive years. A Multiplex Type-Specific E7-Based polymerase chain reaction assay was used to detect 21 HPV types. HPV prevalence was 36.4% during 6 years. Most common HPV types were 16 (6.5%) and 31 (6.1%). Highest persistence were observed for HPV 35 (62.5%) and 52 (25%). New HPV acquisition rate was 5.6/1000 person-months of observation (PMO), highest for HPV 16 (1.1/1000 PMO). Type-specific clearance rates ranged between 2.9–5.5/100 PMO. HPV 16 and/or 18 infections were 41% (95% CI 4–63%) lower among women with 2

Interpretation of histopathology of cervical premalignant lesions suffers from marked interobserver variability due to its subjective nature. We aimed to evaluate the usefulness of the biomarkers p16 and Ki-67 in improving the diagnostic accuracy of cervical histopathology and assess the correlation between p16 expression and human papillomavirus test in different grades of cervical intraepithelial neoplasia (CIN). Cervical tissue specimens with a diagnosis of CIN 1 or worse (CIN 1+) on hematoxylin and eosin staining were selected for immunohistochemistry (IHC) staining for p16 and Ki-67. The IHC slides were examined by a gynecologic pathologist along with a review of hematoxylin and eosin slides. The review histopathology diagnosis was used to correlate with the IHC results. We observed that the proportion of women with overexpression of p16 increased with increasing histologic severity: 0% in women with normal histology; 33.3% in women with CIN 1; 58.1% in women with CIN 2; and 73.8% in women with CIN 3. Among the human papillomavirus-positive women, 76.3% (58/76) women with CIN 2/CIN 3 expressed p16, and only 8.9% (4/45) women with normal histopathology or CIN 1 expressed the same. A combination of p16 positivity and abnormal expression of Ki-67 beyond the lower third of the epithelium was observed in 0% of normal/CIN 1 and 60.5% (40/66) of CIN 3 detected on routine histopathology. We concluded that dual staining could be used as an adjunctive test to improve the diagnostic accuracy of histopathology. In addition, p16/Ki-67 IHC has a role in guiding management decisions in cases with discordant colposcopy and histopathology diagnoses.

We performed an independent comparison of neutralizing and cross-neutralizing antibody (ab) levels seven months after initiation of three-dose, six-month vaccination schedules with the bivalent and quadrivalent human papillomavirus (HPV) vaccines in adolescent Finnish and Indian females, respectively. We used a semi-automated Pseudovirion-Based Neutralization Assay and observed significantly higher HPV16/18 peak ab-levels in bivalent as compared to quadrivalent vaccine recipients. Bivalent vaccine induced cross-neutralizing HPV31/33/45/52/58 antibodies significantly more frequently and to higher levels than the quadrivalent vaccine. The correlation of bivalent vaccine-induced HPV45 ab-levels with HPV16/18 ab-levels was stronger than that of corresponding quadrivalent vaccine-induced ab-levels, suggesting a qualitatively different cross-reactive response. Our findings on the comparison of the immunogenicity of two HPV vaccine tested in two different populations indicate that further head-to-head studies are warranted.

Limited health system capacities and competing health priorities in low and middle income countries (LMICs) necessitate a pragmatic approach to population-based cancer screening. Thus, the challenges faced by LMICs to implement a 'western' model of screening for common cancers and the possible means to overcome these challenges are presented. Breast cancer is the number one cancer with a rising trend in the majority of LMICs. Implementation of mass-scale mammography-based screening is not feasible and sustainable in most of them. While some LMICs have introduced breast cancer screening based on clinical breast examination (CBE), the programs need to be of appropriate quality. All LMICs should improve the capacity for early diagnosis of breast cancer along with other common cancers through community education, training of frontline health workers, facilitating prompt referrals and improving the infrastructure for cancer diagnosis and treatment. Resources permitting, the LMICs with high burden of cervical cancer may consider human papillomavirus (HPV) detection-based screening; a simple low-cost alternative is visual inspection with acetic acid (VIA). Regardless of the choice, a strong linkage should be established between screening and treatment with implementation of robust quality assurance. The few LMICs with a rising trend of colorectal cancers and adequate resources may implement demonstration projects to screen with fecal immunochemical tests (FIT). Oral cancer screening of habitual tobacco and/or alcohol users using oral visual examination (OVE) may be implemented in countries with high burden of the cancer, but primary prevention (i.e., tobacco/alcohol cessation) should be prioritized. Screenings for other cancers are not recommended for LMICs.

The objective was to describe the cervical cancer cases in Brazil by the age-group and stage at diagnosis, and to associate them with the human development index (HDI), where the women live. This was a retrospective study that used data from the Brazilian hospital-based cancer registry from 2005 to 2014. The data were accessed by 5-year age/groups and the federal units. The association between the proportion of cases at Stage I and HDI was estimated in an adjusted linear regression analysis. Among the staged cases, the proportions of cases diagnosed at FIGO Stage I, II, III and IV were 21.2%, 30.7%, 39.9% and 8.2%, respectively. The cases were diagnosed mostly in women aged 45-49 years. There was a significant increase in the proportion of Stage I cases with an increasing HDI (coefficient, 0.46; 95% confidence interval, 0.17-0.76). In conclusion, most of the cases were diagnosed at late stages. The stage at the diagnosis was associated with the human development level. Impact Statement What is already known on this subject? The stage at diagnosis varies according to the level of organisation of the cancer control programme. It is expected that in well-developed programmes there will be a shift to an early stage diagnosis. What the results of this study add? The stage at a diagnosis was associated with the human development level where the women live in Brazil, where most cases were diagnosed at the late stages. What the implications are of these findings for clinical practice and/or further research? This analysis can help with better planning strategies for cancer control. Regional strategies would improve the efficiency of cancer care interventions in countries with large socioeconomic disparities.

Breast Cancer Screening Program was introduced and rolled out in Morocco in 2010. Women between 40 and 69 years are screened at the primary health centers (PHC) with clinical breast examination (CBE). A comprehensive evaluation of the program was conducted in 2016–2017 for quality assurance and mid‐term course correction. The evaluation process involved: in‐depth interviews of program managers; focus group discussions with service‐providers of screening, diagnosis and treatment; supportive supervisory visits to randomly selected PHCs and diagnostic centers; desk review of the national guidelines and other published documents; and analysis of the performance data compiled by the program‐in‐charge. We found that the program has strong political support, a well‐organized management structure and documented national policy and protocol. In absence of a mechanism to identify and invite the eligible women individually, the program is opportunistic in nature. Every PHC is provided with an annual target to be screened. A highly visible annual campaign to educate and motivate women has a major impact on participation. Record keeping and data collection are paper‐based. In the years 2015 and 2016, 1.1 and 1.5 million women were screened, respectively. In the year 2015, 62.8% of the annual target population was covered, CBE positivity was 3.2%, a further assessment rate of screen‐positive women was 34.1% and the breast cancer detection rate was 1.0/1000 women. Systematic paper‐based data collection enabled the assessment of some of the process and outcome indicators. The screening coverage was moderate and the cancer detection rate was low., What's new? The rising incidence of breast cancer is a tremendous public health challenge in the developing world. Clinical breast examination is a promising approach provided effective diagnosis, timely treatment, and adequate resources. Here, the authors conducted a comprehensive evaluation of the Breast Cancer Screening Program in Morocco, where systematic data collection is challenging in absence of a computerized information system. They found that the program has strong political support and a well‐organized management structure. Systematic paper‐based data collection showed a moderate screening coverage and low cancer detection rate. The experience will be useful for all developing countries implementing clinical breast examination.

In India, there are marked variations in resources for cervical cancer screening. For the first time, resource-stratified screening guidelines have been developed that will be suitable for low middle-income countries with similar diversities. The current article describes the process and outcomes of these resource stratified guidelines for screening and treatment of preinvasive lesions of cervix. Evidence from literature was collated and various guidelines were reviewed by an expert panel. Based on the level of evidence, guidelines were developed for screening by human papillomavirus (HPV) testing, cytology and visual inspection after application of acetic acid (VIA), and management of screen positive lesions in different resource settings. Expert opinion was used for certain country-specific situations. The healthcare system was stratified into two resource settings - good or limited. The mode of screening and treatment for each was described. HPV testing is the preferred method for cervical cancer screening. VIA by trained providers is especially suitable for low resource settings until an affordable HPV test becomes available. Healthcare providers can choose the most appropriate screening and treatment modality. A single visit approach is encouraged and treatment may be offered based on colposcopy diagnosis ('see and treat') or even on the basis of HPV test or VIA results ('screen and treat'), if compliance cannot be ensured. The Federation of Obsterician and Gynaecologists of India Good Clinical Practice Recommendations (FOGSI) GCPR are appropriately designed for countries with varied resource situations to ensure an acceptable cervical cancer prevention strategy.

The second report on the implementation status of cancer screening in European Union (EU) was published in 2017. The report described the implementation status, protocols and organization (updated till 2016) and invitation coverage (for index year 2013) of breast, cervical and colorectal cancer screening in the EU. Experts in screening programme monitoring (N=80) from the EU Member States having access to requisite information in their respective countries provided data on breast, cervical and colorectal cancer screening through online questionnaires. Data was collected for screening performed in the framework of publicly mandated programmes only. Filled in questionnaires were received from 26 Member States for all three sites and from one Member State for breast cancer only. Substantial improvement in screening implementation using population-based approach was documented. Among the age-eligible women, 94.7% were residents of Member States implementing or planning population-based breast cancer screening in 2016, compared to 91.6% in 2007. The corresponding figures for cervical cancer screening were 72.3% and 51.3% in 2016 and 2007 respectively. Most significant improvement was documented for colorectal cancer screening with roll-out ongoing or completed in 17 Member States in 2016, compared to only five in 2007. So the access to population-based screening increased to 72.4% of the age-eligible populations in 2016 as opposed to only 42.6% in 2007. The invitation coverage was highly variable, ranging from 0.2%-111% for breast cancer, 7.6%-105% for cervical cancer and 1.8%-127% for colorectal cancer in the target populations. In spite of the considerable progress, much work remains to be done to achieve optimal effectiveness. Continued monitoring, regular feedbacks and periodic reporting are needed to ensure the desired impacts of the programmes. This article is protected by copyright. All rights reserved.

Background Human papillomavirus (HPV) is the necessary cause of cervical cancer. Cervico-vaginal infection with pathogens like Chlamydia is a likely cofactor. The interactions between HPV, Trichomonas vaginalis (TV) and Candida spp. are less understood, though inflammation induced by these pathogens has been demonstrated to facilitate oncogenesis. Objective Our study aimed to evaluate the association between Candida spp . and TV co-infection with HPV in cervical oncogenesis. Study design Women with normal cervix who were high-risk HPV-negative (N = 104) and HPV-positive (N = 105); women with CIN 1 (N = 106) and CIN 2/CIN 3 (N = 62) were recruited from a community based cervical cancer screening program. Cervical cancer patients (N = 106) were recruited from a tertiary care oncology clinic. High-risk HPV was detected by Hybrid Capture II technique; Candida spp. and TV were detected by culturing the high vaginal swabs followed by microscopic examination in all. The disease status was established by histopathology in all the women. Result HPV-positive women had significantly higher risk of having precursor lesions (of any grade) and cancer compared to HPV-negative women. Candida spp. or TV infection did not alter the risk of low grade or high grade lesions among HPV- positive women. HPV positive women co-infected with TV had higher risk of cervical cancer but not those co-infected with Candida spp. Conclusion The higher risk of cancer observed in the women co-infected with HPV and TV without any enhanced risk of CIN 3 suggests secondary infection of the malignant growth by TV rather than any causal role. Co-infection with Candida spp. and/or TV infection did not increase the carcinogenic effect of HPV on cervix.

The 2003 European Council recommendation urging the Member States to introduce or scale up breast, cervical and colorectal cancer screening through an organized population-based approach has had a remarkable impact. We argue that the recommendation needs to be updated for at least two sets of reasons. First, some of the current clinical guidelines include new tests or protocols that were not available at the time of the Council document. Some have already been adopted by organized screening programs, such as newly defined age ranges for mammography screening, Human Papillomavirus (HPV)-based cervical cancer screening, fecal immunochemical test (FIT) and sigmoidoscopy for colorectal cancer screening. Second, the outcomes of randomized trials evaluating screening for lung and prostate cancer have been published recently and the balance between harms and benefits needs to be pragmatically assessed. In the European Union, research collaboration and networking to exchange and develop best practices should be regularly supported by the European Commission. Integration between primary and secondary preventive strategies through comprehensive approaches is necessary not only to maximize the reduction in cancer burden but also to control the rising trend of other noncommunicable diseases sharing the same risk factors.

Flowback and produced water generated by the hydraulic fracturing of unconventional oil and gas plays contain a suite of cations (e.g., metals) typically in a high salt (e.g., NaCl) matrix. Here, we analyzed the chemical (cation) composition of production fluids associated with natural gas and oil development (e.g., flowback, produced water, impoundment fluids), along with mine drainage, and surface and ground water samples using ICP-OES and ICP-MS. ICP-MS and ICP-OES analytical performance and interference effects were evaluated. Both platforms exhibited excellent analytical spike recoveries, detection limits for blank and spiked solutions, and accuracy for standard certified reference materials. Mass ratio analyses using Ca/Sr, Ca/Mg, Ba/Sr, Mg/Sr, and B and Li, were assessed for their efficacy in differentiation among brines from conventional oil wells, produced water from unconventional oil and gas wells and impoundments, mine drainage treatment pond water, groundwater, and surface water. Examination of Mg/Sr ratios when compared with Li concentrations provide clear separation among the different types of samples, while Ca/Mg versus Ca/Sr correlations were useful for distinguishing between conventional and unconventional oil and gas fluids.

This study aimed to systematically review the literature on the efficacy and immunogenicity of single-dose HPV vaccination compared to no vaccination or multi-dose schedules among vaccine trial participants.Medline, EMBASE, Global Health Database and Cochrane Central Register of Controlled Trials were searched for publications and conference abstracts (dated January 1999-August 2018) using MeSH and non-MeSH terms for human papillomavirus AND vaccines AND (immunogenicity OR efficacy/effectiveness) AND dosage. Search results were screened against pre-specified eligibility criteria. Data were extracted from included articles, and a narrative synthesis conducted on efficacy against HPV16/18 infection and humoral immunogenicity.Seven of 6,523 unique records identified were included in the review. Six were nested observational studies of participants randomised to receive two or three doses in three large HPV vaccine trials, in which some participants did not complete their allocated schedules. One small pilot study prospectively allocated participants to receive one or no vaccine dose. Frequency of HPV16/18 infection was low (e.g.1% for 12-month-persistent infection) in all vaccinated participants up to seven years post vaccination and did not significantly differ by number of doses (p 0.05 in all cases). Frequency of infection was significantly lower in one-dose recipients compared to unvaccinated controls (p 0.01 for all infection endpoints in each study). HPV16/18 seropositivity rates were high in all HPV vaccine recipients (100% in three of four studies reporting this endpoint), though antibody levels were lower with one compared to two or three doses.This review supports the premise that one HPV vaccine dose may be as effective in preventing HPV infection as multi-dose schedules in healthy young women. However, it also highlights the paucity of available evidence from purpose-designed, prospectively-randomised trials. Results from ongoing clinical trials assessing the efficacy and immunogenicity of single-dose HPV vaccination compared to currently-recommended schedules are awaited.