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Oral premalignant disorders (OPMDs) are a group of potentially malignant conditions that pose a significant health burden globally. MicroRNAs (miRNAs), small non-coding RNA molecules, have emerged as crucial regulators of gene expression and have been implicated in various biological processes, including carcinogenesis. This review synthesizes existing knowledge to provide a comprehensive understanding of the molecular mechanisms underlying OPMDs and to highlight the potential of miRNAs as promising biomarkers and therapeutic targets. Additionally, this review seeks to explore the potential of miRNA-based diagnostic biomarkers for early detection of OPMDs in the current literature on miRNAs in OPMDs, examining their involvement in disease pathogenesis, diagnostic potential, and therapeutic implications. Dysregulated miRNAs can target genes involved in critical cellular processes, such as cell cycle regulation, apoptosis, and DNA repair, leading to disease progression. Notably, miR-21, miR-31, miR-135b, and miR-486-5p have shown promise as potential biomarkers for early detection of oral premalignant lesions. Furthermore, the paper discusses the therapeutic implications of miRNAs in OPMDs. Preclinical studies have demonstrated the efficacy of miRNA-targeted therapies, such as miRNA mimics and inhibitors, in suppressing the growth of oral premalignant lesions. Early-phase clinical trials have shown promising results, indicating the potential for personalized treatment approaches. The findings underscore the importance of understanding the molecular mechanisms underlying these disorders and provide insights for the development of improved diagnostic and therapeutic strategies. However, they pose certain limitations given their intrinsic variability in expression profiles, the need for optimized isolation and detection methods, and potential hurdles in transitioning from preclinical success to clinical applications. Thus, future clinical studies are warranted to fully exploit the potential of miRNAs in the management of OPMDs., (© 2024. The Author(s), under exclusive licence to The Society of The Nippon Dental University.)

Objective: During the last decade, the management of gastric intestinal metaplasia (GIM) has been addressed by several distinct international evidence-based guidelines. In this review, we aimed to synthesise these guidelines and provide clinicians with a global perspective of the current recommendations for managing patients with GIM, as well as highlight evidence gaps that need to be addressed with future research., Design: We conducted a systematic review of the literature for guidelines and consensus statements published between January 2010 and February 2023 that address the diagnosis and management of GIM., Results: From 426 manuscripts identified, 16 guidelines were assessed. There was consistency across guidelines regarding the purpose of endoscopic surveillance of GIM, which is to identify prevalent neoplastic lesions and stage gastric preneoplastic conditions. The guidelines also agreed that only patients with high-risk GIM phenotypes (eg, corpus-extended GIM, OLGIM stages III/IV, incomplete GIM subtype), persistent refractory Helicobacter pylori infection or first-degree family history of gastric cancer should undergo regular-interval endoscopic surveillance. In contrast, low-risk phenotypes, which comprise most patients with GIM, do not require surveillance. Not all guidelines are aligned on histological staging systems. If surveillance is indicated, most guidelines recommend a 3-year interval, but there is some variability. All guidelines recommend H. pylori eradication as the only non-endoscopic intervention for gastric cancer prevention, while some offer additional recommendations regarding lifestyle modifications. While most guidelines allude to the importance of high-quality endoscopy for endoscopic surveillance, few detail important metrics apart from stating that a systematic gastric biopsy protocol should be followed. Notably, most guidelines comment on the role of endoscopy for gastric cancer screening and detection of gastric precancerous conditions, but with high heterogeneity, limited guidance regarding implementation, and lack of robust evidence., Conclusion: Despite heterogeneous populations and practices, international guidelines are generally aligned on the importance of GIM as a precancerous condition and the need for a risk-stratified approach to endoscopic surveillance, as well as H. pylori eradication when present. There is room for harmonisation of guidelines regarding (1) which populations merit index endoscopic screening for gastric cancer and GIM detection/staging; (2) objective metrics for high-quality endoscopy; (3) consensus on the need for histological staging and (4) non-endoscopic interventions for gastric cancer prevention apart from H. pylori eradication alone. Robust studies, ideally in the form of randomised trials, are needed to bridge the ample evidence gaps that exist., Competing Interests: Competing interests: No conflicts of interest are declared by MD-R, SS, HE-S, MB, NU, HT, LGC, DL, EL, AR, J-YF, LM, JB, EJK, EME-O. PM is a member of advisory board/lecturer of Aboca, Alfasigma, Allergosan, Bayer, Biocodex, Menarini advisory boards/lectures., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose of Review: This review aims to provide a comprehensive overview of the current advances in managing and preventing progression of oral potentially malignant disorders (OPMDs), focusing on their histological and clinicopathological features, and management., Recent Findings: Recent studies, including a multicenter cross-sectional study, have identified oral leukoplakia as the most prevalent form of OPMD, comprising over half of the cases examined. Advances in histological grading, specifically the World Health Organization's three-tier system (mild, moderate, and severe dysplasia), have significantly enhanced the accuracy of risk assessment for malignant transformation. Additionally, treatments such as surgical interventions, photodynamic therapy, and chemopreventive and molecularly targeted agents are being evaluated for their safety and efficacy as well as, immune checkpoint inhibitors being evaluated as potential preventive strategies to halt the progression of OPMDs. The management of OPMDs remains challenging due to the lack of standardized screening protocols and varied clinical management approaches. Despite this, recent advancements in diagnostic grading and therapeutic interventions provide a framework for improved treatment outcomes. Continued research into the molecular and cellular mechanisms driving development and progression of OPMDs and innovative treatment trials are essential to optimize strategies that prevent malignant progression and thereby reduce the global health burden of oral cancer., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Rationale: Despite significant advances in precision treatments and immunotherapy, lung cancer is the most common cause of cancer death worldwide. To reduce incidence and improve survival rates, a deeper understanding of lung premalignancy and the multistep process of tumorigenesis is essential, allowing timely and effective intervention before cancer development. Objectives: To summarize existing information, identify knowledge gaps, formulate research questions, prioritize potential research topics, and propose strategies for future investigations into the premalignant progression in the lung. Methods: An international multidisciplinary team of basic, translational, and clinical scientists reviewed available data to develop and refine research questions pertaining to the transformation of premalignant lung lesions to advanced lung cancer. Results: This research statement identifies significant gaps in knowledge and proposes potential research questions aimed at expanding our understanding of the mechanisms underlying the progression of premalignant lung lesions to lung cancer in an effort to explore potential innovative modalities to intercept lung cancer at its nascent stages. Conclusions: The identified gaps in knowledge about the biological mechanisms of premalignant progression in the lung, together with ongoing challenges in screening, detection, and early intervention, highlight the critical need to prioritize research in this domain. Such focused investigations are essential to devise effective preventive strategies that may ultimately decrease lung cancer incidence and improve patient outcomes.

Cervical cancer, caused due to oncogenic types of human papillomavirus (HPV), is a leading preventable cause of cancer morbidity and mortality globally. Chronic, persistent HPV infection-induced cervical precursor lesions, if left undetected and untreated, can progress to invasive cancer. Cervical cancer screening approaches have evolved from cytology (Papanicolaou test) to highly sensitive HPV-based molecular methods and personalized, risk-stratified, management guidelines. Innovations like self-collection of samples to increase screening access, innovative triage methods to optimize management of screen positives, and scalable and efficacious precancer treatment approaches will be key to further enhance the utility of prevention interventions., Competing Interests: Disclosure The Author has no financial conflicts of interest to disclose. The opinions expressed by the Author are his own and this material should not be interpreted as representing the official viewpoint of the U.S. Department of Health and Human Services, the National Institutes of Health, or the National Cancer Institute., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Gastrointestinal cancers are a leading cause of cancer morbidity and mortality. Many gastrointestinal cancers develop from cancer precursor lesions, which are commonly found in individuals with hereditary cancer syndromes. Hereditary cancer syndromes have advanced our understanding of cancer development and progression and have facilitated the evaluation of cancer prevention and interception efforts. Common gastrointestinal hereditary cancer syndromes, including their organ-specific cancer risk and surveillance recommendations, are reviewed in this article. The management of common gastroesophageal, pancreatic, and colonic precursor lesions is also discussed, regardless of their genetic background. Further research is needed to advance chemoprevention and immunoprevention strategies., Competing Interests: Disclosure Maoz has no disclosures related to this article. N.J. Rodriguez has no disclosures related to this article. M.B. Yurgelun has has Research funding from Janssen; and Consulting/scientific advisory board roles at Nouscom. Syngal has no disclosures related to this article. This study was supported by The Pancreatic Cancer Action Network Catalyst Award (N. Rodriguez) and the K12TR004381 award (N. Rodriguez) through Harvard Catalyst | The Harvard Clinical and Translational Science Center (National Center for Advancing Translational Sciences, National Institutes of Health). The content is solely the responsibility of the authors and does not necessarily represent the official views of Harvard Catalyst, Harvard University, and its affiliated academic health care centers, or the National Institutes of Health. This study was also supported by the Whittaker Family Fund, the Scragg Family Fund, and the Hooley Fund-Lynch Syndrome., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Anal intraepithelial neoplasia (AIN) are precancerous lesions and are sequela of human papilloma virus (HPV) infection. AIN is classified as low-grade squamous intraepithelial lesion or high-grade squamous intraepithelial lesion. Screening with anal cytology and anoscopy should be considered for high-risk populations. Diagnosis is made through high resolution anaoscopy and biopsy. Options for treatment include ablation and several topical therapies; however, recurrence rates are high for all treatment options, and an ongoing surveillance is necessary to prevent progression to anal squamous cell carcinoma. HPV vaccination is recommended to prevent disease., Competing Interests: Disclosure The authors have nothing to disclose., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Barrett's oesophagus is the only known precursor to oesophageal adenocarcinoma, a cancer with very poor prognosis. The main risk factors for Barrett's oesophagus are a history of gastro-oesophageal acid reflux symptoms and obesity. Men, smokers and those with a family history are also at increased risk. Progression from Barrett's oesophagus to cancer occurs via an intermediate stage, known as dysplasia. However, dysplasia and early cancer usually develop without any clinical signs, often in individuals whose symptoms are well controlled by acid suppressant medications; therefore, endoscopic surveillance is recommended to allow for early diagnosis and timely clinical intervention. Individuals with Barrett's oesophagus need to be fully informed about the implications of this diagnosis and the benefits and risks of monitoring strategies. Pharmacological treatments are recommended for control of symptoms, but not for chemoprevention. Dysplasia and stage 1 oesophageal adenocarcinoma have excellent prognoses, since they can be cured with endoscopic or surgical therapies. Endoscopic resection is the most accurate staging technique for early Barrett's-related oesophageal adenocarcinoma. Endoscopic ablation is effective and indicated to eradicate Barrett's oesophagus in patients with dysplasia. Future research should focus on improved accuracy for dysplasia detection via new technologies and providing more robust evidence to support pathways for follow-up and treatment., Competing Interests: Competing interests: MdP participated in the BEST3 screening trial and received consultant fees from Medtronic. JNP was chair of the trial Steering committee of the AspECT trial. NJT participated in the AspECT trial., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Background and Objective: Barrett's esophagus (BE) is a precancerous condition that has the potential to develop into esophageal cancer (EC). Currently, there is a wide range of management options available for individuals at different pathological stages in Barrett's esophagus (BE). However, there is currently a lack of knowledge regarding their comparative efficacy. To address this gap, we conducted a network meta-analysis of published randomized controlled trials to examine the comparative effectiveness of all regimens., Methods: Data extracted from eligible randomized controlled trials were utilized in a Bayesian network meta-analysis to examine the relative effectiveness of BE's treatment regimens and determine their ranking in terms of efficacy. The ranking probability for each regimen was assessed using the surfaces under cumulative ranking values. The outcomes under investigation were complete ablation of BE, neoplastic progression of BE, and complete eradication of dysplasia., Results: We identified twenty-three RCT studies with a total of 1675 participants, and ten different interventions. Regarding complete ablation of non-dysplastic BE, the comparative effectiveness ranking indicated that argon plasma coagulation (APC) was the most effective regimen, with the highest SUCRA value, while surveillance and PPI/H2RA were found to be the least efficacious regimens. For complete ablation of BE with low-grade dysplasia, high-grade dysplasia, or esophageal cancer, photodynamic therapy (PDT) had the highest SUCRA value of 94.1%, indicating it as the best regimen. Additionally, for complete eradication of dysplasia, SUCRA plots showed a trend in ranking PDT as the highest with a SUCRA value of 91.2%. Finally, for neoplastic progression, radiofrequency ablation (RFA) and surgery were found to perform significantly better than surveillance. The risk of bias assessment revealed that 6 studies had an overall high risk of bias. However, meta-regression with risk of bias as a covariate did not indicate any influence on the model. In terms of the Confidence in Network Meta-Analysis evaluation, a high level of confidence was found for all treatment comparisons., Conclusion: Endoscopic surveillance alone or PPI/H2RA alone may not be sufficient for managing BE, even in cases of non-dysplastic BE. However, APC has shown excellent efficacy in treating non-dysplastic BE. For cases of BE with low-grade dysplasia, high-grade dysplasia, or esophageal cancer, PDT may be the optimal intervention as it can induce regression of BE metaplasia and prevent future progression of BE to dysplasia and EC., Competing Interests: The authors declare that they have no conflict of interest., (Copyright: © 2024 Zhang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: In Ethiopia, both incidence and mortality of cervical cancer are relatively high. Screening services, which were implemented during the past few years, are currently being expanded. The World Health Organization recommends patients with a positive VIA (visual inspection with acetic acid) result should immediately receive treatment followed by rescreening after 1 year as precancerous lesions can reoccur or become residential despite treatment., Materials and Methods: Screening logbooks dating between 2017 and 2020 were retrospectively reviewed in 14 health facilities of Addis Ababa and Oromia region. Data for 741 women with a VIA-positive result were extracted and those women were asked to participate in a questionnaire-based phone interview to gain insights about adherence to treatment and follow-up. Data were analyzed using descriptive methods and then fitted into 2 generalized linear models to test variables for an influence on adherence to follow up., Results: Around 13 800 women had received a VIA screening, of which approximately 820 (5.9%) were VIA positive. While over 90% of women with a positive screen received treatment, only about half of the treated patients returned for a follow-up examination. After treatment, 31 women had a VIA-positive re-screen. We found that educational status, age over 40, no/incorrect follow-up appointment, health facility-related barriers, and use of reminders are important drivers of adherence to follow up., Conclusion: Our results revealed that adherence to treatment after VIA positive screening is relatively high whereas adherence to follow up recommendations still needs improvement. Reminders like appointment cards and phone calls can effectively reduce the loss of follow-up., (© The Author(s) 2024. Published by Oxford University Press.)

Background: Clinical guidelines reserve endoscopic surveillance after a gastric intestinal metaplasia (GIM) diagnosis for high-risk patients. However, it is unclear how closely guidelines are followed in clinical practice. We examined the effectiveness of a standardized protocol for the management of GIM among gastroenterologists at a US hospital., Methods: This was a preintervention and postintervention study, which included developing a protocol and education of gastroenterologists on GIM management. For the preintervention study, 50 patients with GIM were randomly selected from a histopathology database at the Houston VA Hospital between January 2016 and December 2019. For the postintervention study, we assessed change in GIM management in a cohort of 50 patients with GIM between April 2020 and January 2021 and surveyed 10 gastroenterologists. The durability of the intervention was assessed in a cohort of 50 GIM patients diagnosed between April 2021 and July 2021., Results: In the preintervention cohort, GIM location was specified (antrum and corpus separated) in 11 patients (22%), and Helicobacter pylori testing was recommended in 11 of 26 patients (42%) without previous testing. Gastric mapping biopsies were recommended in 14% and surveillance endoscopy in 2%. In the postintervention cohort, gastric biopsy location was specified in 45 patients (90%, P <0.001) and H. pylori testing was recommended in 26 of 27 patients without prior testing (96%, P <0.001). Because gastric biopsy location was known in 90% of patients ( P <0.001), gastric mapping was not necessary, and surveillance endoscopy was recommended in 42% ( P <0.001). One year after the intervention, all metrics remained elevated compared with the preintervention cohort., Conclusions: GIM management guidelines are not consistently followed. A protocol for GIM management and education of gastroenterologists increased adherence to H. pylori testing and GIM surveillance recommendations., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: in Senegal, cervical cancer is the leading cause of cancers among women. This study estimated the costs associated with cervical cancer screening and treatment for precancerous lesions from the health system perspective., Methods: we estimated costs for screening, diagnostics, and treatment. We conducted a cross-sectional study in seven regions with primary data collected from 50 health facilities. Data collection included structured questionnaires, with secondary data from the Ministry of Health and other sources. A mixed-methods approach combined ingredients-based costing and financial expenditures to estimate direct medical and non-medical costs. All costs are reported in 2019 USD., Results: average costs were $3.71 for visual inspection with acetic acid, $16.49 for Pap smear, and $46.65 for human papillomavirus deoxyribonucleic acid (HPV DNA) testing. Screening cost drivers were clinical exam supplies and clinical equipment for visual inspection with acetic acid, offsite processing of specimens for Pap smear, and lab equipment costs for HPV DNA procedure. The average cost of diagnosis via colposcopy alone was $25.73, and colposcopy with biopsy/endocervical curettage was $74.96. The average cost of treatment followed by one visit for pre-cancerous lesions was $195.24 for loop electrosurgical excision, $47.35 for cryotherapy, and $32.35 for thermal ablation. Clinical equipment and lab costs were the largest contributors to colposcopy and endocervical curettage/biopsy expenses. Clinical equipment made up the largest portion of cryotherapy, loop electrosurgical excision, and thermoablation costs., Conclusion: this study is the first to estimate the costs of HPV screening and treatment in Senegal, which can be used to inform decision-making on cervical cancer investments., Competing Interests: The authors declare no competing interests., (Copyright: Abdou Diop et al.)

Background: Gastric cancer (GC) stands as one of the most prevalent cancer types worldwide, holding the position of the second leading cause of cancer-related deaths. Gastric lesions represent pathological alterations to the gastric mucosa, with an elevated propensity to advance to gastric cancer. Limited research has explored the potential of stem cells in the treatment of gastric lesions., Methods: This study aimed to explore the potential of intravenous transplantation of labeled bone marrow-derived mesenchymal stem cells (BMMSCs) to inhibit the progression of precancerous gastric lesions., Results: In the gastric lesion disease model group, the rat tissue exhibited noteworthy mucosal atrophy, intestinal metaplasia, dysplasia, and inflammatory cell infiltration. Following the infusion of BMMSCs, a notable decrease in gastric lesions was found, with atrophic gastritis being the sole remaining lesion, which was confirmed by morphological and histological examinations. BMMSCs that were colonized at gastric lesions could differentiate into epithelial and stromal cells, as determined by the expression of pan-keratin or vimentin. The expression of vascular endothelial growth factor was significantly elevated following BMMSC transplantation. BMMSCs could also upregulate the production of humoral immune response cytokines, including interleukin (IL)-4 and IL-10, and downregulate the production of IL-17 and interferon-gamma, which could be highly associated with the cellular immune response and inflammation severity of the lesions., Conclusions: BMMSC transplantation significantly reduced inflammation and reversed gastric lesion progression., Competing Interests: The authors declare no conflict of interest., (© 2024 The Author(s). Published by IMR Press.)

Oral epithelial dysplasia refers to a premalignant lesion of the oral cavity. The diagnosis of dysplasia is rendered via pathologic assessment of diseased tissue. There are many different premalignant conditions identified in the oral cavity. These include leukoplakias, erythroplakias, proliferative verrucous leukoplakia, oral submucosal fibrosis, actinic cheilitis, and lichen planus. This article will discuss these different conditions and how they are diagnosed. It will also review the treatment for these entities., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: Aim: To identify the medical management determinants of the maxillofacial precancerous and benign diseases malignancy., Patients and Methods: Materials and Methods: 150 people with maxillofacial cancer and 100 people with precancerous and benign diseases of the same localization were interviewed., Results: Results: There were revealed: a low percentage of detection during check-up (10.2-15.8%), more than a third of cases (35.8-37.4%) are diagnosed by chance; not all patients undergo histological verification of the diagnosis (25.7% in cancerous and 43.2% in precancerous and benign diseases); not all are under follow up observation (24.7-27.7%). The risk of precancerous and benign diseases malignancy is the highest at 40-59 years of age (OR=4.4; 95% CI: 1.9-10.5), andalso increases with the duration of the disease for more than 5 years (2.2; 1.2-4.10 ), in patients who didn't undergo histological verification (2.2; 1.3-3.8), don't follow doctors' recommendation on visits and treatment (2.4; 1.4-4.1), don't trust doctors and are dissatisfied with medical care (2.1; 1.3-3.6). The risk groups of the maxillofacial oncological, precancerous and benign diseases are men, who are 1.5 times more likely to suffer from them than women and are characterized by lower medical care activity. The risk factors of the maxillofacial precancerous and benign diseases malignancy are low financial (4.6; 1.7-12.4) and territorial (3.3; 1.1-10.3) accessibility of medical care, including dental care (2.8; 1.6-4.8)., Conclusion: Conclusions: It is necessary to improve the prevention and medical care in order to advance the early detection of maxillofacial cancer, taking into account the established medical management determinants of malignancy.

According to the latest statistical data, the incidence and mortality rate of hepatocellular carcinoma in China are still on the rise, posing a major threat to the health of the Chinese population. The occurrence is closely related to the formation of precancerous lesions in the liver. The clinical and basic research on precancerous lesions of hepatocellular carcinoma has developed rapidly, and the concepts and specific techniques for diagnosis and treatment have also undergone new changes and advancements. Therefore, based on the first version in 2020, this consensus has organized multidisciplinary experts to compile and improve a new version by integrating the latest progress in their respective professional fields at home and abroad. It aims to enhance clinicians' understanding of precancerous lesions of hepatocellular carcinoma standardize the pathology, imaging, and molecular diagnostic criteria, broaden early screening methods, formulate scientifically rational treatment plans, and help promote the advancement of diagnosis and treatment strategies and to enhance the overall 5-year survival rate of patients with hepatocellular carcinoma.

Barrett's esophagus (BE) is the condition in which a metaplastic columnar mucosa predisposed to neoplasia replaces the squamous mucosa of the distal esophagus. The current guidelines recommends that diagnosis requires the finding of intestinal metaplasia (IM) with goblet cells of at least 1 cm in length. BE affects approximately 1% of the general population and up to 14% of patients with gastroesophageal reflux disease (GERD). BE is a precursor of esophageal adenocarcinoma (EAC), which has increased in western countries. The main risk factors described for EAC associated with BE are male sex, age > 50 years, central obesity and tobacco use. Annual risk of EAC in patients with BE without dysplasia, low grade (LGD) and high-grade dysplasia is 0,1-0,3%, 0,5% y 5-8%, respectively. Treatment of non-dysplastic BE consists mainly of a healthy lifestyle change, chemoprevention with proton pump inhibitors and surveillance endoscopy every 3 to 5 years. It is recommended that from the presence of LGD patients are referred to an expert center for confirmation of the diagnosis, stage and thus define their management. In patients with BE and dysplasia or early-stage cancer, endoscopic therapy with resection and ablation is successful in about 90% of the patients. The main adverse event is esophageal stricture, which is managed endoscopically.

Abstract: The benefit of treating anal precancerous lesions to reduce anal cancer progression was recently shown in people living with HIV. This will certainly impact the future development of recommendations on anal cancer prevention by including anal precancerous lesions screening and treatment for people living with HIV. However, by bringing this topic to the spotlight, it has also uncovered data that are still missing in this field and that need to be addressed by research.This article will discuss the many unanswered questions about treatment of anal precancerous lesions and future directions for research., Competing Interests: The author has declared that there are no conflicts of interest., (Copyright © 2023, ASCCP.)

Oral potentially malignant disorders (OPMDs) of the oral mucosa include leukoplakia, erythroplakia, erythroleukoplakia, lichen planus, and oral lichenoid lesions, each with varying incidences of dysplastic disease at the time of presentation and each with observed incidences of malignant transformation over time. The primary goal of the management of dysplasia, therefore, includes their early detection and treatment prior to malignant transformation. The recognition and management of these OPMDs and an understanding of their potential progression to oral squamous cell carcinoma will reduce the morbidity and mortality associated with these lesions with expedient and properly executed treatment strategies that will have a positive effect on patient survival. It is the purpose of this position paper to discuss oral mucosal dysplasia in terms of its nomenclature, epidemiology, types, natural history, and treatment to acquaint clinicians regarding the timing of biopsy, type of biopsy, and follow-up of patients with these lesions of the oral mucosa. This position paper represents a synthesis of existing literature on this topic with the intention of closing gaps in our understanding of oral mucosal dysplasia while also stimulating new thinking to guide clinicians in the proper diagnosis and management of OPMDs. The fifth edition of the World Health Organization classification of head and neck tumors published in 2022 represents new information regarding this topic and a construct for this position paper., (Copyright © 2023 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.)

There have been many advancements in the clinical and histologic diagnosis of laryngeal dysplasia (LD), but diagnosis still necessitates invasive histologic evaluation. Furthermore, despite improved histologic identification of dysplastic lesions, the exact details of pathophysiologic progression and the risk of malignant transformation is still uncertain. These unknowns create a barrier to establishing an ideal grading and classification system, which prevents the establishment of a precise and consistent treatment paradigm. Identifying these gaps in knowledge serves to highlight where further studies are warranted, ideally focusing on a better understanding of the biological behavior of LD. This would ultimately allow for the creation of a reliable grading and classification system and for the formalization of management and treatment guidelines for LD., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: The 2021 Chinese Expert Consensus on the Clinical Application of the Human Papillomavirus (HPV) Vaccine recommended vaccination for women who previously received ablative or excisional treatment for high-grade squamous intraepithelial lesion (HSIL). This study evaluates the cost-effectiveness of HPV vaccination in women previously treated for cervical precancerous lesions., Methods: We used a Markov model to simulate the disease progression of both low- and high-risk HPV subtypes. We followed a cohort of 100,000 women aged 18-45 years who received treatment for cervical precancerous lesions for a lifetime (80 years). We used the Incremental Cost-Effectiveness Ratios (ICER) with a 5% discount rate to measure the cost-effectiveness of nine vaccination strategies, including a combination of HPV bivalent (HPV-2), quadrivalent (HPV-4) and nonavalent vaccine (HPV-9), each with three vaccination doses (one-, two- and three-dose). We conducted one-way sensitivity analysis and probabilistic sensitivity analysis. We followed the CHEERS 2022 guidelines., Results: Compared to the status quo, the nine vaccination strategies would result in $3.057-33.124 million incremental cost and 94-1,211 incremental quality-adjusted life-years (QALYs) in 100,000 women previously treated for cervical precancerous lesions. Three vaccination strategies were identified on the cost-effectiveness frontier. In particular, ICER for one-dose HPV-4 vaccination was US$10,025/QALY compared to the status quo (no vaccination); ICER for two-dose HPV-4 vaccination was US$17,641//QALY gained compared to one-dose HPV-4 vaccination; ICER for three-dose HPV-4 vaccination was US$27,785/QALY gained compared with two-dose HPV-4 vaccination. With a willingness-to-pay of three times gross domestic product per capita (US$37655), three-dose HPV-4 vaccination was the most cost-effective vaccination strategy compared with the lower-cost non-dominated strategy on the cost-effectiveness frontier. A probabilistic sensitivity analysis confirmed a 99.1% probability of being cost-effective. If the cost of the HPV-9 is reduced to 50% of the current price, three-dose HPV-9 vaccination would become the most cost-effective strategy., Discussion: Three-dose HPV-4 vaccination is the most cost-effective vaccination strategy for women treated for precancerous cervical lesions in the Chinese setting., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Zou, Liu, Liu, Wang, Zou and Zhang.)

The aim of the present study was to evaluate the incidence of concomitant vulvar cancers or premalignant lesions in women surgically treated for extramammary Paget's disease of the vulva (EMPDV) through a multicenter case series. The medical records of all women diagnosed with and treated for EMPDV from January 2010 to December 2020 were retrospectively analyzed. Women with EMPDV and synchronous vulvar cancer, vulvar intraepithelial neoplasia (VIN) and/or lichen sclerosus (LS) at the histology report were included in the study. A total of 69 women eligible for the present study were considered. Concomitant vulvar lesions occurred in 22 cases (31.9%). A total of 11 cases of synchronous VIN (50%) and 14 cases (63.6%) of concomitant LS were observed. One patient (4.5%) had synchronous vulvar SCC (FIGO stage 1B). Women with EMPDV and concomitant premalignant/malignant vulvar lesions had a significantly higher rate of invasive EMPDV and wider lesions with an extravulvar involvement. The specific meaning of the association between EMPDV, VIN, SCC and LS remains unclear. The potential overlapping features between different vulvar lesions highlight the importance of dedicated gynecologists and pathologists in referral centers.

Appropriate surveillance and treatment of Barrett's esophagus (BE) is vital to prevent disease progression and decrease esophageal adenocarcinoma (EAC)-related mortality. We sought to determine the variation in BE care and identify improvement opportunities. 275 physicians (113 general gastroenterologists, 128 interventional gastroenterologists, 34 gastrointestinal surgeons) cared for 3 simulated patients, one each from 3 BE clinical scenarios: non-dysplastic BE (NDBE), BE indefinite for dysplasia (IND), and BE with low grade dysplasia (LGD), and care scores were measured against societal guidelines. Overall quality-of-care scores ranged from 17% to 85% with mean of 47.9% ± 11.8% for NDBE, 50.8% ± 11.7% for IND, and 52.7% ± 12.2% for LGD. Participants appropriately determined risk of progression 20.3% of the time: 14.4% for NDBE cases, 19.9% for LGD cases, and 26.8% for IND cases (P = .001). Treatment and follow-up care scores averaged 12.9% ± 17.5% overall. For the LGD cases, guideline-recommended twice-daily PPI treatment was ordered only 24.7% of the time. Guideline-based follow-up endoscopic surveillance was done in only 27.7% of NDBE cases and 32.7% of IND cases. For the LGD cases, 45.4% ordered endoscopic eradication therapy while 25.1% chose annual endoscopic surveillance. Finally, participants provided counseling on lifestyle modifications in just 20% of cases. Overall care of patients diagnosed with BE varied widely and showed room for improvement. Specific opportunities for improvement were adherence to guideline recommended surveillance intervals, patient counseling, and treatment selection for LGD. Physicians would potentially benefit from additional BE education, endoscopic advances, and better methods for risk stratification., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Early detection of colorectal cancer and precursor lesions under colonoscopy, and timely and optimal treatment remain the crucial means for reducing colorectal cancer-related deaths. In this article, we focused on the hot spots in recent years, reviewed the progress of endoscopic diagnosis and treatment of serrated lesions and inflammatory bowel disease (IBD)-related dysplasia, the application of endocytoscopy and the management of early colorectal cancer/precancerous lesions, and provided new prospects for future studies.

Gastric adenocarcinoma (GC) is the fourth leading cause of global cancer mortality, and the leading infection-associated cancer. Helicobacter pylori is the dominant risk factor for GC and classified as an IARC class I carcinogen. Surveillance of gastric premalignant conditions is now indicated in high-risk patients. Upper endoscopy is the gold standard for GC diagnosis, and image-enhanced endoscopy increases the detection of gastric premalignant conditions and early gastric cancer (EGC). Clinical staging is crucial for treatment approach, defining early gastric cancer, operable locoregional disease, and advanced GC. Endoscopic submucosal dissection is the treatment of choice for most EGC. Targeted therapies are rapidly evolving, based on biomarkers including MSI/dMMR, HER2, and PD-L1. These advancements in surveillance, diagnostic and therapeutic strategies are expected to improve GC survival rates in the near term., Competing Interests: Disclosure Cancer Prevention Pharmaceuticals and Thorne Research (NCI funded studies, with company donation of study medications) (DRM). CDx Diagnostics (Investigator initiated study, with company donation of disposables) (DRM). Freenome Inc. (Trial participation by the University) (DRM)., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Oral potentially malignant disorders (OPMDs) are a group of diseases involving the oral mucosa and that have a risk of carcinogenesis. The microenvironment is closely related to carcinogenesis and cancer progression by regulating the immune response, cell metabolic activities, and mechanical characteristics. Meanwhile, there are extensive interactions between the microenvironments that remodel and provide favorable conditions for cancer initiation. However, the changes, exact roles, and interactions of microenvironments during the carcinogenesis of OPMDs have not been fully elucidated. Here, we present an updated landscape of the microenvironments in OPMDs, emphasizing the changes in the immune microenvironment, metabolic microenvironment, mechanical microenvironment, and neural microenvironment during carcinogenesis and their carcinogenic mechanisms. We then propose an immuno-metabolic-mechanical-neural interaction network to describe their close relationships. Lastly, we summarize the therapeutic strategies for targeting microenvironments, and provide an outlook on future research directions and clinical applications. This review depicts a vivid microenvironment landscape and sheds light on new strategies to prevent the carcinogenesis of OPMDs.

Objective: To systematically summarize and analyze the clinical research progress of therapeutic vaccines for cervical cancer or precancerous lesions. Methods: English databases (PubMed, Embase, Web of Science, Cochrane library, Proquest, and ClinicalTrails.gov) and Chinese databases (SinoMed, CNKI, WanFang, and VIP Database) were systematically searched to collect literature on therapeutic vaccines for cervical cancer or precancerous lesions from inception to February 18, 2021. After screening, we evaluated the risk of bias of included studies, and combed the basic information of the literature, research designs, information of vaccines, study patients, outcome indicators and so on, qualitatively summarized the clinical research progress. Results: A total of 71 studies were included in this systematic review, including 14 random controlled trials, 15 quasi-random controlled trials, 4 cohort studies, 1 case-control study, 34 case series studies and 3 case reports. The study patients included women aged 15~79 with cervical cancer or precancerous lesions in 18 countries from 1989 to 2021. On the one hand, there were 40 studies on therapeutic vaccines for cervical precancerous lesions (22 867 participants), involving 21 kinds of vaccines in 6 categories. Results showed 3 marketed vaccines (Cervarix, Gardasil, Gardasil 9) as adjuvant immunotherapies were significant effective in preventing the recurrence of precancerous lesions compared with the conization only. In addition, MVA E2 vaccine had been in phase Ⅲ clinical trials as a specific therapeutic vaccine, with relative literature showing it could eliminate most high-grade precancerous lesions. Therapeutic vaccines for precancerous lesions all showed good safety. On the other hand, there were 31 studies on therapeutic vaccines for cervical cancer (781 participants), involving 19 kinds of vaccines in 7categories, with none had been marketed. 25 studies were with no control group, showing the vaccines could effectively eliminate solid tumors, prevent recurrence, and prolong the median survival time. However, the vaccines effectiveness couldn't be statistically calculated due to the lack of a control group. As for the safety of therapeutic vaccines for cervical cancer, 9 studies showed that patients experienced serious adverse events after treatments, where 7 studies reported that serious adverse events occurred in patients couldn't be ruled out as the results of therapeutic vaccines. Conclusions: The literature review shows that the literature evidence for the therapeutic vaccines for cervical precancerous lesions is relatively mature compared with the therapeutic vaccines for cervical cancer. The four kinds of vaccines on the market are all therapeutic vaccines for precancerous lesions, but they are generally used as vaginal infection treatments or adjuvant immunotherapies for cervical precancerous lesions, not used for the specific treatments of cervical precancerous lesions. Other specific therapeutic vaccines are in the early stage of clinical trials, mainly phase Ⅰ/Ⅱ clinical trials with small sample size. The effectiveness and safety data are limited, and further research is still needed.

Oral cancer is usually preceded by oral potentially malignant disorders (OPMDs) and early detection can downstage the disease. The majority of OPMDs are asymptomatic in early stages and can be detected on routine oral examination. Though only a proportion of OPMDs may transform to oral squamous cell carcinoma (OSCC), they may serve as a surrogate clinical lesion to identify individuals at risk of developing OSCC. Currently, there is a scarcity of scientific evidence on specific interventions and management of OPMDs and there is no consensus regarding their management. A consensus meeting with a panel of experts was convened to frame guidelines for clinical practices and recommendations for management strategies for OPMDs. A review of literature from medical databases was conducted to provide the best possible evidence and provide recommendations in management of OPMDs., Competing Interests: None

Gastric cancer (GC) has a good prognosis, if detected at an early stage. The intestinal subtype of GC follows a stepwise progression to carcinoma, which is treatable with early detection and intervention using high-quality endoscopy. Premalignant lesions and gastric epithelial polyps are commonly encountered in clinical practice. Surveillance of patients with premalignant gastric lesions may aid in early diagnosis of GC, and thus improve chances of survival. An expert professional workgroup was formed to summarise the current evidence and provide recommendations on the management of patients with gastric premalignant lesions in Singapore. Twenty-five recommendations were made to address screening and surveillance, strategies for detection and management of gastric premalignant lesions, management of gastric epithelial polyps, and pathological reporting of gastric premalignant lesions.

Background: The incidence of anal cancer is substantially higher among persons living with the human immunodeficiency virus (HIV) than in the general population. Similar to cervical cancer, anal cancer is preceded by high-grade squamous intraepithelial lesions (HSILs). Treatment for cervical HSIL reduces progression to cervical cancer; however, data from prospective studies of treatment for anal HSIL to prevent anal cancer are lacking., Methods: We conducted a phase 3 trial at 25 U.S. sites. Persons living with HIV who were 35 years of age or older and who had biopsy-proven anal HSIL were randomly assigned, in a 1:1 ratio, to receive either HSIL treatment or active monitoring without treatment. Treatment included office-based ablative procedures, ablation or excision under anesthesia, or the administration of topical fluorouracil or imiquimod. The primary outcome was progression to anal cancer in a time-to-event analysis. Participants in the treatment group were treated until HSIL was completely resolved. All the participants underwent high-resolution anoscopy at least every 6 months; biopsy was also performed for suspected ongoing HSIL in the treatment group, annually in the active-monitoring group, or any time there was concern for cancer., Results: Of 4459 participants who underwent randomization, 4446 (99.7%) were included in the analysis of the time to progression to cancer. With a median follow-up of 25.8 months, 9 cases were diagnosed in the treatment group (173 per 100,000 person-years; 95% confidence interval [CI], 90 to 332) and 21 cases in the active-monitoring group (402 per 100,000 person-years; 95% CI, 262 to 616). The rate of progression to anal cancer was lower in the treatment group than in the active-monitoring group by 57% (95% CI, 6 to 80; P = 0.03 by log-rank test)., Conclusions: Among participants with biopsy-proven anal HSIL, the risk of anal cancer was significantly lower with treatment for anal HSIL than with active monitoring. (Funded by the National Cancer Institute; ClinicalTrials.gov number, NCT02135419.)., (Copyright © 2022 Massachusetts Medical Society.)

Objective: To systematically summarize current status and recommendations of the global cervical cancer and precancerous lesions treatment guidelines. Methods: The retrieval for all the Chinese and English literature published before July 8, 2021 was conducted in PubMed, Embase, SinoMed Database, CNKI and Wanfang Database, supplemented by a search of health websites of countries worldwide, with"uterine cervical neoplasms""cervix cancer""cervical neoplasm""cervical precancerous lesions""treat*""guideline*""practice guideline*""consensus" "recommendation*""guidebook*"in English as well as"cervical precancerous lesions""cervical neoplasm""treatment""guideline*""consensus"in Chinese as search keywords. A total of 38 guidelines were included for data extraction and analysis. Results: Guidelines covered Asia, Europe, North America, South America and Oceania. Conservative observation was recommended for the CIN1 population. For the women with CIN2/CIN3, ablation or excision was recommended according to the specific situation and guidelines of developed countries give priority to the latter. In low and middle resource countries, given the availability of medical resources, ablative treatment was recommended as an alternative to excisional treatment if the women were eligible. For women with adenocarcinoma in situ (AIS), cervical conization or total hysterectomy was recommended depending on the patient's desire of fertility. For patients with cervical cancer, most guidelines recommended surgery for early disease and smaller lesions, otherwise concurrent chemoradiotherapy was usually the main treatment modality for advanced cancers. All guidelines recommended long-term follow-up to monitor disease recurrence after treatment. Follow-up methods included human papillomavirus (HPV) testing and/or cytology or colposcopy. Most guidelines recommended follow-up at 6 or 12 months after treatment for cervical precancerous lesions, and 3~4 months for cervical cancer. Conclusions: There are some differences in the treatment and management recommendations for cervical cancer and precancerous lesions issued by different countries and regions around the world. Based on the global treatment guidelines and medical resource of different regions, the treatment and management guidelines for cervical cancer and precancerous lesions suitable for different regions of China should be developed, so as to achieve effective treatment.

Background: Laryngeal dysplasia represents a complex pre-malignant condition characterised by a spectrum of mucosal changes, with a reported malignant transformation rate from dysplasia to invasive carcinoma of 14.0 per cent., Objective: To identify whether increasing glottic dysplasia severity is associated with higher local malignant transformation rates or adverse clinical outcomes., Methods: This retrospective cohort study identified 125 patients with any histopathological grade of glottic dysplasia over a 10-year period who were followed up for a standardised 10-year period., Results: The malignant transformation rate was 21.8 per cent over 10 years, demonstrating a statistically significant greater risk with increasing dysplasia severity. The mean time to transformation was 52 months, with time to transformation statistically associated with increasing dysplasia severity. Rapid progression to carcinoma within 12 months occurred in 40 per cent of cases, and 58 per cent of subsequently diagnosed laryngeal squamous cell carcinomas were tumour stage T1., Conclusion: Laryngeal dysplasia carries a significant malignant potential, appearing greatest within 12 months of diagnosis and with increasing severity of dysplasia.

Clonal hematopoiesis (CH) defines a population of hematopoietic cells with one or more somatic mutations/copy number alterations that can expand with time and under positive clonal selection pressures. The term CH of indeterminate potential (CHIP) operationally describes somatic mutations in leukemia-associated driver genes in hematopoietic stem cells with variant allele frequencies (VAF) of ≥ 2%, without evidence for an underlying hematological malignancy. Risk factors for CHIP include aging, inflammation, male sex, cigarette smoking, history of cancer and cancer treatments, germline predisposition states, among others. CHIP is a premalignant condition, with a low but definite risk of hematologic malignancies and is associated with increased all-cause mortality, largely due to cardiovascular disease and associated endothelial dysfunction. Here we review recent advances in CHIP, including diagnostic, prognostic, and potential therapeutic strategies., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Early testing and treatment is among the successful strategies for the prevention and control of cervical precancerous and invasive cancer, and a paramount for women with HIV. In Ethiopia, visual inspection with acetic acid for screening and cryotherapy treatment is commonly practiced, though the recurrence of the precancerous lesion after treatment has not been well documented., Objective: This study was aimed to estimate the association of HIV status and the recurrence of cervical precancerous lesion after cryotherapy among Ethiopian women., Methods: We conducted a retrospective cohort study from January to April 2021. The time to the incidence of recurrence was compared between HIV positive and HIV negative women. Cox regression models were used to adjust the analyses for potential confounders, and only women treated with cryotherapy after a positive Visual Inspection with Acetic acid (VIA) screening test were included., Results: A total of 140 eligible patient cards were included in the analysis with the median follow-up of 15.5 months. The overall recurrence rate was 15.7% (22/140), with a greater proportion among HIV negative women, 19.0% (4/21) than HIV positive 15.1% (18/119). Prolonged use of corticosteroid and higher age were the major significant predictors of a higher likelihood of recurrence. The recurrence of screening positive lesion was higher among women aged above 39 years (hazard ratio (HR) of 11.94 (95% CI, 1.07-133.04; P = .04), and women with prolonged use of corticosteroid (HR = 7.82, 95% CI = 1.04-58.75; P = .046) than their counterparts., Conclusion: The recurrence of cervical precancerous lesion after cryotherapy was higher than the expert panel report by WHO with a higher proportion among women of old age and prolonged corticosteroid use. Cryotherapy showed a satisfying performance against the recurrence of cervical disease diagnosed through VIA. To substantiate, our findings, further prospective cohort study is also recommended.

Barrett's esophagus (BE) is the precursor lesion for esophageal adenocarcinoma (EAC) development. Unfortunately, BE screening/surveillance has not provided the anticipated EAC reduction benefit. Noninvasive techniques are increasingly available or undergoing testing to screen for BE among those with/without known risk factors, and the use of artificial intelligence platforms to aid endoscopic screening and surveillance will likely become routine, minimizing missed cases or lesions. Management of high-grade dysplasia and intramucosal EAC is clear with endoscopic eradication therapy preferred to surgery. BE with low-grade dysplasia can be managed with removal of visible lesions combined with endoscopic eradication therapy or endoscopic surveillance at present., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Breast cancer (BC) prevention remains the ultimate cost-effective method to reduce the global burden of invasive breast cancer (IBC). To date, surgery and chemoprevention remain the main risk-reducing modalities for those with hereditary cancer syndromes, as well as high-risk non-hereditary breast lesions such as ADH, ALH, or LCIS. Ductal carcinoma in situ (DCIS) is a preinvasive malignant lesion of the breast that closely mirrors IBC and, if left untreated, develops into IBC in up to 50% of lesions. Certain high-risk patients with DCIS may have a 25% risk of developing recurrent DCIS or IBC, even after surgical resection. The development of breast cancer elicits a strong immune response, which brings to prominence the numerous advantages associated with immune-based cancer prevention over drug-based chemoprevention, supported by the success of dendritic cell vaccines targeting HER2-expressing BC. Vaccination against BC to prevent or interrupt the process of BC development remains elusive but is a viable option. Vaccination to intercept preinvasive or premalignant breast conditions may be possible by interrupting the expression pattern of various oncodrivers. Growth factors may also function as potential immune targets to prevent breast cancer progression. Furthermore, neoantigens also serve as effective targets for interception by virtue of strong immunogenicity. It is noteworthy that the immune response also needs to be strong enough to result in target lesion elimination to avoid immunoediting as it may occur in IBC arising from DCIS. Overall, if the issue of vaccine targets can be solved by interrupting premalignant lesions, there is a potential to prevent the development of IBC., Competing Interests: BC has a patent application filed for intellectual property on a human version of DC1. LL has stock in Johnson & Johnson, Pfizer, Eli Lilly, Gilead, and Amgen. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Zachariah, Basu, Gautam, Ramamoorthi, Kodumudi, Kumar, Loftus and Czerniecki.)

Despite being highly preventable, cervical cancer is the fourth most common cancer and cause of cancer death in women globally. In low-income countries, cervical cancer is often the leading cause of cancer-related morbidity and mortality. Women living with human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome are at a particularly high risk of cervical cancer because of an impaired immune response to human papillomavirus, the obligate cause of virtually all cervical cancers. Globally, approximately 1 in 20 cervical cancers is attributable to HIV; in sub-Saharan Africa, approximately 1 in 5 cervical cancers is due to HIV. Here, the authors provide a critical appraisal of the evidence to date on the impact of HIV disease on cervical cancer risk, describe key methodologic issues, and frame the key outstanding research questions, especially as they apply to ongoing global efforts for prevention and control of cervical cancer. Expanded efforts to integrate HIV care with cervical cancer prevention and control, and vice versa, could assist the global effort to eliminate cervical cancer as a public health problem., (© 2021 The Authors. CA: A Cancer Journal for Clinicians published by Wiley Periodicals LLC on behalf of American Cancer Society. This article has been contributed to by US Government employees and their work is in the public domain in the USA.)

Purpose of Review: Gastric intestinal metaplasia (GIM) is an attractive target for surveillance and treatment as it can progress to gastric adenocarcinoma (GAC). Yet, GIM remains a challenging area for clinicians as most patients do not progress to cancer, and there are conflicting data regarding the benefits of surveillance and therapy. This review aims to summarize recently published GIM surveillance guidelines, to discuss, which patients with GIM may benefit from treatment, and to review pivotal and recent literature on GIM therapy., Recent Findings: Guidelines published by American, British, and European gastroenterology societies do not recommend universal surveillance, but do suggest endoscopic surveillance in patients with risk factors for progression to GAC. Although light examination for at least 7 min and mapping biopsies may increase yield for dysplasia and GAC. In randomized trials, Helicobacter pylori eradication reduced risk of dysplasia and cancer. In GIM with visible dysplasia and early-stage GAC, endoscopic resection improves quality of life without reducing survival compared with surgery. Endoscopic ablation therapies have shown promise for invisible or extensive dysplasia., Summary: Endoscopic resection is appropriate for visible dysplasia and early-stage GAC without high-risk features that persists despite H. pylori eradication therapy. Prospective studies are needed to assess the utility of endoscopic ablation in GIM., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Patients with oral potentially malignant disorders (OPMDs), including oral leukoplakia and erythroplakia, proliferative verrucous leukoplakia, oral submucous fibrosis, and oral lichen planus/lichenoid lesions, can be challenging to manage. A small proportion will undergo cancer development and determining a patient's cancer risk is key to making management decisions. Yet, our understanding of the natural history of OPMDs has not been fully elucidated, and a precision approach based on the integration of numerous predictive markers has not been validated by prospective studies. Evidence-based health promotion by clinicians and healthcare systems is not embraced universally. Medical and surgical interventions evaluated by rigorous research measuring important endpoints, such as cancer development, mortality, or survival, are difficult and expensive to run. Most of these studies employ non-ideal surrogate endpoints and have deep methodologic flaws. Diagnostic criteria for enrolling research subjects are not uniform, and patients with the highest risk for cancer development comprise small proportions of those enrolled. Few studies explore quality of life and patient preferences. It is time to rethink how we approach the management of these patients, across each OPMD, and considering the healthcare infrastructure and cost-effectiveness. Global networks with well-characterized patient populations with OPMDs and well-designed interventional trials using validated outcome measures are needed., (© 2021 Wiley Periodicals LLC.)

Background Guidelines such as the Lung CT Screening Reporting and Data System (Lung-RADS) are available for determining when subsolid nodules should be treated within lung cancer screening programs, but they are based on expert opinion. Purpose To evaluate the cost-effectiveness of varying treatment thresholds for subsolid nodules within a lung cancer screening setting by using a simulation model. Materials and Methods A previously developed model simulated 10 million current and former smokers undergoing CT lung cancer screening who were assumed to have a ground-glass nodule (GGN) at baseline. Nodules were allowed to grow and to develop solid components over time according to a monthly cycle and lifetime horizon. Management strategies generated by varying treatment thresholds, including the solid component size and use of the Brock risk calculator, were tested. For each strategy, average U.S. costs and quality-adjusted life years (QALYs) gained per patient were computed, and the incremental cost-effectiveness ratios (ICERs) of those on the efficient frontier were calculated. One-way and probabilistic sensitivity analyses of results were performed by varying several relevant parameters, such as treatment costs or malignancy growth rates. Results Variants of the Lung-RADS guidelines that did not treat pure GGNs were cost-effective. Strategies based on the Brock risk calculator did not reach the efficient frontier. The strategy with the highest QALYs under a willingness-to-pay threshold of $100 000 per QALY included no treatment of GGNs and a threshold of 4-mm solid component size for treatment of subsolid nodules. This strategy yielded an ICER of $52 993 per QALY (95% CI: 44 407, 64 372). Probabilistic sensitivity analysis showed this was the optimal strategy under a range of parameter variations. Conclusion Treatment of pure ground-glass nodules was not cost-effective. Strategies that use modifications of the Lung CT Screening Reporting and Data System guidelines were cost-effective for treating part-solid nodules; an optimal threshold of 4 mm for the solid component yielded the most quality-adjusted life years. © RSNA, 2021 Online supplemental material is available for this article.

Oral cancer has been recognized as a significant challenge to healthcare. In Malaysia, numerous patients frequently present with later stages of cancers to the highly subsidized public healthcare facilities. Such a trend contributes to a substantial social and economic burden. This study aims to determine the cost of treating oral potentially malignant disorders (OPMD) and oral cancer from a public healthcare provider's perspective. Medical records from two tertiary public hospitals were systematically abstracted to identify events and resources consumed retrospectively from August 2019 to January 2020. The cost accrued was used to estimate annual initial and maintenance costs via two different methods- inverse probability weighting (IPW) and unweighted average. A total of 86 OPMD and 148 oral cancer cases were included. The initial phase mean unadjusted cost was USD 2,861 (SD = 2,548) in OPMD and USD 38,762 (SD = 12,770) for the treatment of cancer. Further annual estimate of initial phase cost based on IPW method for OPMD, early and late-stage cancer was USD 3,561 (SD = 4,154), USD 32,530 (SD = 12,658) and USD 44,304 (SD = 16,240) respectively. Overall cost of late-stage cancer was significantly higher than early-stage by USD 11,740; 95% CI [6,853 to 16,695]; p< 0.001. Higher surgical care and personnel cost predominantly contributed to the larger expenditure. In contrast, no significant difference was identified between both cancer stages in the maintenance phase, USD 700; 95% CI [-1,142 to 2,541]; p = 0.457. A crude comparison of IPW estimate with unweighted average displayed a significant difference in the initial phase, with the latter being continuously higher across all groups. IPW method was shown to be able to use data more efficiently by adjusting cost according to survival and follow-up. While cost is not a primary consideration in treatment recommendations, our analysis demonstrates the potential economic benefit of investing in preventive medicine and early detection., Competing Interests: The authors have declared that no competing interests exist.

Anal squamous cell carcinoma is the most common type of anal cancer and is largely associated with anal human papillomavirus infection. The incidence of anal squamous cell carcinoma is increasing, and although still uncommon in the general population, a high incidence has been noted in specific population groups (eg, patients with HIV, men who have sex with men [MSM], recipients of solid organ transplants, women with genital neoplasia, and patients with systemic lupus erythematosus or inflammatory bowel disease). The higher incidence among individuals who are HIV-positive makes anal squamous cell carcinoma one of the most common non-AIDS-defining cancers among HIV-positive individuals. Anal cancer screening in high-risk groups aims to detect high-grade squamous intraepithelial lesions, which are considered anal precancerous lesions, and for which identification can provide an opportunity for prevention. A blind anal cytology is normally the first screening method, and for patients with abnormal results, this approach can be followed by an examination of the anal canal and perianal area under magnification, along with staining-a technique known as high-resolution anoscopy. Digital anorectal examination can enable early anal cancer detection. Several societies are in favour of screening for HIV-positive MSM and recipients of transplants. There are no current recommendations for screening of anal precancerous lesions via endoscopy, but in high-risk groups, a careful observation of the squamocolumnar junction should be attempted. Several treatments can be used to treat high-grade squamous intraepithelial lesions, including argon plasma coagulation or radiofrequency ablation, which are largely limited by high recurrence rates. Gastroenterologists need to be aware of anal squamous cell carcinoma and anal precancerous lesions, given that patients at high risk are frequently encountered in the gastroenterology department. We summarise simple procedures that can help in early anal squamous cell carcinoma detection., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Objectives: There remains a significant risk of recurrence of intraepithelial neoplasia regardless of the type of conservative treatment. The aim's work is to assess this rate., Methods: All women's consenting who had received conservative treatment at the sites identified since for more than 12 months were included in this multicenter cross-sectional study. The outcome measure was a recurrence of precancerous lesions of the cervix during visual inspection with acetic acid performed by a single practitioner to limit interobserver variability. Data collection and analysis were done on the Stata 13 software. We performed an univariate then multivariate analysis with logistic regression., Results: Two hundred and seventy-nine participated in this study with an average age of 37.44 (σ=7.31 years). A total of 52.33% were HIV positive. Moreover, 63.44% were treated by cryotherapy versus 36.66% by loop electrosurgical excision procedure. The overall prevalence of recurrences was 8.96%. Multivariate analysis with logistic regression concluded that the risk of recurrence was 5.72 times (OR=1.69-19.29; P=0.005) higher with cryotherapy and 2.85 times higher (OR=1.04-7.82; P=0.042) in women with HIV., Conclusion: The risk of recurrence is proportionally high with cryotherapy and HIV status. This suggests that an adaptation of the strict monitoring protocols to our African context due to the lack of cytocolposcopic logistical resources., (Copyright © 2020. Published by Elsevier Masson SAS.)

Background: Gastric cancer is one of the most common malignant tumors, which seriously affect peoples quality of life and threaten people's health. Precancerous lesions of gastric cancer (PLGC) are a critical stage in the occurrence and development of gastric cancer. Early effective intervention is an important means to prevent and control gastric cancer. In this study, we will evaluate the efficacy and safety of complementary and alternative therapies in the treatment of PLGC by Bayesian network meta-analysis (NMA)., Methods: We will search PubMed, Cochrane Library, CNKI and other databases to gather randomized controlled trials (RCTs) on the treatment of PLGC with complementary and alternative therapies. Two reviewers will screen the literature and extract the data according to the inclusion and exclusion criteria, and then assess the quality and bias risk according to Cochrane's Risk of Bias Assessment Tool. Bayesian network meta-analysis will be conducted by Stata16.0 and WinBUGS1.4.3., Results: This study will compare and rank the efficacy and safety of different complementary and alternative therapies for PLGC., Conclusion: This study can provide reliable evidence for the efficacy and safety of complementary and alternative therapies in treatment of PLGC. We expect to provide scientific and rigorous evidence support for clinicians and patients, and then assist them to choose the optimum treatment., Protocol Registration Number: INPLASY2020120077., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

The authors conducted a review of the literature of cost-effectiveness analyses regarding management of Barrett's esophagus, including screening, surveillance, and treatment strategies. Because of the presence of multiple systematic reviews on this topic, they chose to focus on more recent economic analyses, with an emphasis on comparative modeling because these analyses have been demonstrated to achieve greater validity and impact when there are multiple competing strategies that are clinically reasonable to pursue. The authors identified areas of consensus across studies regarding management strategies and also areas that require additional empirical data., Competing Interests: Disclosure Research effort provided for J.H. Rubenstein and J.M. Inadomi by the National Institutes for Health (U01CA152926, U01CA199336, U54CA163059). J.H. Rubenstein has served as a consultant to the American Gastroenterological Association Institute for work related to TissueCypher. J.M. Inadomi is on the scientific advisory board of Cernostics, which developed and produces TissueCypher., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objectives: Oral Epithelial Dysplasia (OED) is associated with an increased risk of oral cancer development. The SARS-CoV-2 pandemic is necessitating the suspension or dramatic reduction of face-to-face non-urgent elective services, including OED clinics. Little is known regarding the potential impact of elective services suspension upon the risk of OED progression, and whether alternative strategies (e.g. remote consultations) may be introduced to ensure OED surveillance. The aim of this paper is to provide expert-opinion consensus recommendations for the management of OED during the current and future pandemic outbreaks., Materials and Methods: A working group of nine UK-based senior clinicians and academics in Oral and Maxillofacial Surgery and Oral Medicine was created and twelve consensus statements were developed using a modified-Delphi process. Greater than 80% agreement was considered a consensus., Results: Consensus was achieved for all twelve statements (89-100% agreement). The group agreed that, during the temporary suspension of elective services associated with COVID-19 pandemic outbreaks, patients with OED can be risk stratified to determine the length of accepted delay in face-to-face consultation. Remote consultations with patient-provided clinical photographs may be a useful way of maintaining a level of surveillance in this group of patients., Conclusions: Using an expert working group methodology, we have developed consensus recommendations for the monitoring of individuals with OED during pandemic outbreaks associated with temporary suspension of elective services. This has identified areas of future research and highlighted the need for a stronger evidence base to inform the set-up and delivery of surveillance regimens for patients with OED., (Copyright © 2020 Elsevier Ltd. All rights reserved.)