Chronic active and atrophic gastritis as significant contributing factor to the development of gastric cystica profunda.

Gastric cystica profunda (GCP) is an uncommon but underestimated gastric lesion. Its precancerous potential determines its significance. In addition to previous mucosa injury due to operations, biopsy or polypectomy, chronic active and atrophic gastritis may also lead to the development of GCPs. By carefully examining the stomach and taking biopsy samples from the susceptible regions, the stage of atrophy can be determined. Chronic atrophic gastritis is a risk factor for cancer evolvement and it can also contribute to GCPs formation. GCPs frequently occur close to early gastric cancers (EGCs) or EGC can arise from the cystic glands. Endoscopic resection is an effective and minimally invasive treatment in GCP.

Helicobacter pylori Infection Promotes Gastric Premalignancies and Malignancies Lesions and Demotes Hyperplastic Polyps: A 5 Year Multicentric Study among Cameroonian Dyspeptic Patients.

BACKGROUND: Helicobacter pylori infection is the most well-known risk factor for gastric mucosa abnormalities. However, some geographic regions with persistent high H. pylori infection rates do not suffer from high gastric mucosa lesions incidence. The aim of the study was to establish the relationship between H. pylori infection and gastric pathological features in Cameroon. METHODS: We performed a retrospective study, collecting data from the University Teaching Hospital and the Cameroon Pasteur institute on 1290 patients (mean age 46.31 ± 16.45 years, sex ratio 1.19:1) for whom histological features of the gastric mucosa and H. pylori infection were investigated from 2014 to 2019. Data were extracted from the medical records; hospital computerized databases; or clinical charts of these patients and reviewed according to gender and age of participants. The study was approved by the Ethical Committee of Medical Sciences. RESULT: Approximately 3% (2.56%) of the sample population were with normal gastric mucosa whereas chronic gastritis, atrophic gastritis, intestinal metaplasia, dysplasia, carcinoma, hyperplastic polyps and MALT lymphoma was found in 75.35, 8.2, 7.7, 2.8, 9.3, 1.55 and 0.8% of cases respectively. Unlike hyperplasia (OR= 0.3838), infected participants were in a high risk to develop gastric lesions with an odds ratio of 1.1775, 1.4866, 1.4415, 1.2088, 0.9408 and 0.9075 for gastritis, atrophic gastric, dysplasia, carcinoma, intestinal metaplasia and MALT lymphoma respectively. CONCLUSION: our finding showed that chronic gastritis, gastric premalignancies and malignancies are positively link to Helicobacter pylori infection and that hyperplastic polyp is inversely associated with H. pylori infection in our milieu.

Endoscopic submucosal dissection for early cancers or precancerous lesions of the upper GI tract in cirrhotic patients with esophagogastric varices: 10-year experience from a large tertiary center in China.

BACKGROUND AND AIMS: Treatment strategies for early cancers or precancerous lesions of the upper GI tract in patients with cirrhosis and esophagogastric varices (EGVs) are complicated and risky. The aim of this study was to assess the efficacy and safety of endoscopic submucosal dissection (ESD) in the treatment of such patients and explore optimal treatment strategies. METHODS: We retrospectively enrolled 15 patients with cirrhosis and EGV who underwent ESD for early cancers or precancerous lesions of the upper GI tract from January 2012 to December 2021 at our center. Clinical features, endoscopic findings, treatment methods, adverse events, and follow-up data were analyzed. RESULTS: Of the 15 patients, 1 had a platelet count <30 × 1000/mm3. Five were untreated for EGV, 1 was treated after ESD, 6 were treated before ESD, 1 was treated before and during ESD, and 2 were treated during ESD. The R0 resection rate was 100%. Of the 16 mucosal lesions, 15 were endoscopic resection bleeding (ERB)-0 or ERB-c1, and 1 was ERB-c2. No patient experienced deterioration in liver function. The only adverse events were fever in 2 patients and postoperative bleeding in 2 patients. During a median follow-up of 27 months, 1 patient's esophageal high-grade dysplasia recurred at 19 months. No death resulted from the ESD procedure, liver function injury, or GI tumor itself. CONCLUSIONS: ESD is an effective and safe treatment for early cancers or precancerous lesions of the upper GI tract in patients with cirrhosis and EGV. The incidence of severe adverse events is very low due to the development of individualized clinical treatment strategies.

Prevalence of oral potentially malignant disorders (OPMD) in adults of Western Maharashtra, India: A cross-sectional study.

Background: Oral cavity cancer is estimated to be the third most common malignancy after cancer of cervix and stomach in developing countries. Objectives: The objective of this study is to investigate the relationship between smoking, alcoholic consumption, betel quid chewing, and OPMD in a prospective manner. Materials and Methods: A descriptive, cross-sectional study was conducted among 35-55-year-old adults of Western Maharashtra, India. Oral cavity examination as recommended by the American Dental Association specification was followed. Data recorded were transferred from precoded survey pro forma to the computer. The prevalence of OPMD was assessed by determining the percentage of the study population affected. Analysis was done to find out the risk of oral premalignant disorders. The Chi-square (x2) test and adjusted odds ratio (ORs) with 95% confidence interval (CI) were calculated. The Statistical Package for the Social Sciences (SPSS) software version 21.0 was used for the statistical analysis and significance level was set at P < 0.05. Results: Odds of having OPMD are five times higher for those who smoke (OR = 5.78; 95% CI, [6.18, 7.82]) as compared to those who do not. The odds of suffering from OPMD are about five times higher among those who chew as compared to those who do not (OR = 4.98; 95%CI, [2.91, 7.28]). The mean frequency of tobacco chewing per day and duration in years in participants with OPMDs was significantly higher as compared with normal oral mucosa (P < 0.05 and P < 0.05), respectively, in the use of different tobacco forms. Conclusion: These findings can be used to design case control or cohort studies to further understand the relation between habits and OPMD.

Prognostic factors in the treatment of gastric mucosal atypical hyperplasia by endoscopic submucosal dissection.

BACKGROUND: Endoscopic submucosal dissection (ESD) is becoming increasingly popular as a treatment for precancerous lesions and early cancers of the stomach. However, there have been few studies on the factors associated with the recurrence of precancerous lesions after ESD. METHODS: To investigate the prognostic factors of gastric intraepithelial neoplasia, we retrospectively analyzed 115 patients who were treated with ESD between February 2018 and January 2020. Chi-square test and Fisher's extract test were used to select factors for further investigation, and prognostic analysis was carried out with the Kaplan-Meier method and a Cox regression model. RESULTS: Platelet counts (P = 0.027) and albumin levels (P = 0.011) were both lower in patients with recurrence than in patients without recurrence of gastric mucosal atypical hyperplasia after ESD. CONCLUSIONS: This study reveals that low platelet counts and albumin levels were probably unfavorable prognostic factors in mucosal atypical hyperplasia of the stomach.

Barrett Esophagus: A Review.

Importance: Barrett esophagus is characterized by the replacement of normal esophageal squamous cell epithelium with columnar metaplasia and affects approximately 5% of people in the US and approximately 1% worldwide. Approximately 3% to 5% of patients with Barrett esophagus will be diagnosed with esophageal adenocarcinoma in their lifetime. Observations: Barrett esophagus affects approximately 2.3% to 8.3% of people with gastroesophageal reflux disease (GERD) and approximately 1.2% to 5.6% of people without GERD. Characteristics associated with Barrett esophagus include older age (prevalence of approximately 1.1% in individuals older than 50 years compared with 0.3% in those 50 years or younger), male sex, and smoking (prevalence of approximately 12% in people who smoke cigarettes compared with 1.1% in those who do not smoke cigarettes). The histopathology of Barrett esophagus progresses from metaplasia to dysplasia and, without treatment, can progress to adenocarcinoma. People with Barrett esophagus have approximately a 0.2% to 0.5% annual rate of developing esophageal adenocarcinoma. Management of Barrett esophagus primarily consists of acid-suppressive medications to reduce underlying GERD symptoms and surveillance endoscopy every 3 to 5 years. In patients with Barrett esophagus and dysplasia or early cancer, endoscopic therapy consisting of resection and ablation successfully treats 80% to 90% of patients. Conclusions and Relevance: Barrett esophagus affects approximately 5% of people in the US and approximately 1% worldwide and is associated with an increased risk of esophageal adenocarcinoma. First-line therapy for Barrett esophagus consists of proton-pump inhibitors for control of reflux symptoms, but their role in chemoprevention is unclear. Surveillance with upper endoscopy is recommended by practice guidelines to monitor for progression to esophageal adenocarcinoma, but randomized clinical trials are lacking.

Treatment of Anal High-Grade Squamous Intraepithelial Lesions to Prevent Anal Cancer.

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.).

Oral and gastric microbiome in relation to gastric intestinal metaplasia.

Evidence suggests that Helicobacter pylori plays a role in gastric cancer (GC) initiation. However, epidemiologic studies on the specific role of other bacteria in the development of GC are lacking. We conducted a case-control study of 89 cases with gastric intestinal metaplasia (IM) and 89 matched controls who underwent upper gastrointestinal endoscopy at three sites affiliated with NYU Langone Health. We performed shotgun metagenomic sequencing using oral wash samples from 89 case-control pairs and antral mucosal brushing samples from 55 case-control pairs. We examined the associations of relative abundances of bacterial taxa and functional pathways with IM using conditional logistic regression with and without elastic-net penalty. Compared with controls, oral species Peptostreptococcus stomatis, Johnsonella ignava, Neisseria elongata and Neisseria flavescens were enriched in cases (odds ratios [ORs] = 1.29-1.50, P = .004-.01) while Lactobacillus gasseri, Streptococcus mutans, S parasanguinis and S sanguinis were under-represented (ORs = 0.66-0.76, P = .006-.042) in cases. Species J ignava and Filifactor alocis in the gastric microbiota were enriched (ORs = 3.27 and 1.43, P = .005 and .035, respectively), while S mutans, S parasanguinis and S sanguinis were under-represented (ORs = 0.61-0.75, P = .024-.046), in cases compared with controls. The lipopolysaccharide and ubiquinol biosynthesis pathways were more abundant in IM, while the sugar degradation pathways were under-represented in IM. The findings suggest potential roles of certain oral and gastric microbiota, which are correlated with regulation of pathways associated with inflammation, in the development of gastric precancerous lesions.

Notch signaling in oral pre-cancer and oral cancer.

Notch signaling involves cell to cell contact. It is an ancient signaling mechanism that is conserved throughout the animal kingdom. The basic function of Notch signaling is to decide cell fate and execute asymmetrical division. Notch signaling is indispensable for embryo growth. Aberrant Notch signaling involves in cancer progression by altering cell proliferation rate, tumor micro-environment, stem cell activities. The role of Notch signaling in cancer progression is context-dependent. In breast cancer and T cell lymphoma Notch signaling is highly active, whereas in squamous cell carcinoma (SCC) as oral and skin cancer, the signaling is suppressed. It is believed that in SCC, Notch-mediated tumor growth is due to the cell non-autonomous function. Oral cancer is the 6th most risky cancer worldwide. In many patients, oral cancer is preceded by pre-cancer conditions. In this review, we have summarized the research knowledge related to the role of Notch signaling in oral cancer and pre-cancer conditions and the therapeutic options available targeting different components of Notch pathways.

Risk factors for esophageal squamous cell carcinoma and its histological precursor lesions in China: a multicenter cross-sectional study.

BACKGROUND: Despite research efforts, the causative factors that contribute to esophageal squamous cell carcinoma (ESCC) in high-risk areas have not yet been understood. In this study, we, therefore, aimed to describe the risk factors associated with ESCC and its precursor lesions. METHODS: We performed an endoscopic examination of 44,857 individuals aged 40-69 years from five high incidence regions of China in 2017-2018. Participants were classified as 4 groups of normal control, esophagitis, low-grade intraepithelial neoplasia (LGIN) and high-grade intraepithelial neoplasia/esophageal squamous cell carcinoma (HGIN/ESCC) using an unconditional logistic regression determine risk factors. RESULTS: We identified 4890 esophagitis, 1874 LGIN and 437 HGIN/ESCC cases. Crude odds ratios (ORs) and adjusted odds ratios were calculated using unconditional logistic regression. Drinking well and surface water, salty diet, and positive family history of cancer were the common risk factors for esophagitis, LGIN and HGIN/ESCC. History of chronic hepatitis/cirrhosis was the greatest risk factor of esophagitis (adjusted OR 2.96, 95%CI 2.52-3.47) and HGIN/ESCC (adjusted OR 1.91, 95%CI 1.03-3.22). Pesticide exposure (adjusted OR 1.20, 95%CI 1.05-1.37) was essential risk factor of LGIN. CONCLUSIONS: Among individuals aged 40-69 years in high incidence regions of upper gastrointestinal cancer, the results provided important epidemiological evidence for the prevention of different precancerous lesions of ESCC.

Evaluation and Quantification of Cytomorphometry in Conjunction with Visual Examination and Exfoliative Cytology in Early Diagnosis of Oral Premalignant and Malignant Lesions.

INTRODUCTION: Incidence of oral epithelial dysplasia and oral squamous cell carcinoma (SCC) is very high in south Asian countries as compared to western population owing to a greater use of tobacco in these regions. While visual examination and exfoliative cytology are the most common screening and diagnostic modalities at present, it is a subjective analysis. Quantitative analyses such as nuclear size, cell size, and nuclear-to-cytoplasmic ratio may provide an accurate diagnosis and improve reproducibility. The aim of the study was to evaluate the role of morphometry as a diagnostic adjunct to exfoliative cytology and to derive a significant cutoff to identify the population at risk for development of SCC among chronic tobacco users. MATERIAL AND METHODS: This was an outpatient-based prospective study done in a tertiary hospital over a period of 2 years. Hundred and fifty cases with a history of chronic tobacco use for a minimum period of 5 years were evaluated. Visual inspection using acetic acid was done. Oral scrapes were taken for cytological and morphometric analysis followed by incision biopsy for histopathological evaluation, wherever possible. RESULTS: On morphometrical analysis, mean nuclear area and nuclear:cytoplasmic (N:C) ratio increased, while the cytoplasmic area decreased from smears with normal cytology to oral dysplasia to SCC. Analysis of variance and post hoc Tukey's honest significant difference test showed a statistically significant difference among the 3 groups (p value <0.05). A cutoff value for a significant N:C ratio was calculated as ≥0.08 using Youden's index with a sensitivity and a specificity of 88% and 94%, respectively. CONCLUSION: In high-risk cases, morphometry can be a useful adjunct to exfoliative cytology and visual examination for an early and accurate diagnosis and timely intervention in oral potentially malignant and malignant lesions, thereby improving the prognosis.

Association of Helicobacter pylori vacA polymorphisms with the risk of gastric precancerous lesions in a Moroccan population.

INTRODUCTION: Helicobacter pylori infection is the major risk factor of atrophic gastritis and intestinal metaplasia. The vacA gene is one of the most virulence factors of H. pylori and genetic diversity in its s, m, i, and d regions is associated with gastric lesions severity. This study aimed to investigate the association of vacA s, m, i, and d regions with the risk of atrophic gastritis and intestinal metaplasia in a Casablanca population. METHODOLOGY: A total of 210 patients suffering from gastric lesions (chronic gastritis, atrophic gastritis, and intestinal metaplasia) were enrolled. The type of lesion was diagnosed by histological examination. Detection of H. pylori infection and genotyping of vacA regions were carried out by PCR. RESULTS: The prevalence of H. pylori was 95%. The most common vacA genotypes were s2 (51.5%), m2 (77%), i2 (60.5%), and d2 (58.5%). VacA s1, m1, and i1 genotypes were associated with a high risk of intestinal metaplasia, while the vacA d1 genotype increases the risk of atrophic gastritis and intestinal metaplasia. The most common vacA combination was s2/m2/i2/d2 (52%), and it was more detected in chronic gastritis. The moderate virulent vacA combination (s1/m2/i1/d1) increases the risk of atrophic gastritis, while the most virulent vacA combination (s1/m1/i1/d1) increases the risk of intestinal metaplasia. CONCLUSIONS: Genotyping of vacA d region might be a reliable marker for the identification of vacA virulent strains that represent a high risk of developing precancerous lesions (atrophic gastritis and intestinal metaplasia).

Natural Progression of Helicobacter pylori-Negative Gastritis with Lymphoid Follicles in Children: Prospective Evaluation and Outcome.

BACKGROUND: The association of Helicobacter pylori-negative gastritis with lymphoid follicles (LFs) in children is still unclear. Therefore, we aimed to investigate the natural history and significance of H. pylori-negative gastritis with LFs in children. METHODS: We identified children with histologically proven H. pylori-negative gastritis with LFs between June 2014 and January 2017. The children were invited for a follow-up examination. The clinical, endoscopic, and histological findings of the index esophagogastroduodenoscopy (EGD) were revised and compared to the follow-up findings. RESULTS: A total of 754 children underwent EGD. Among the 48 children diagnosed with H. pylori-negative gastritis, 17 (35.41%) had gastric LFs. Eight agreed to participate in the study. The mean follow-up was 25.58 ± 4.52 (range, 20.53-35.73) months. Three children still had histologic findings of chronic gastritis with LFs. Four children had resolution of the gastritis but still had LFs, and 1 patient had resolution of both the gastritis and LFs. CONCLUSION: LFs were still present in children with H. pylori-negative gastritis after a mean follow-up of 2 years, and in some children, despite resolution of the gastritis. Therefore, this histological finding might be a non-pathological feature in children and does not need any contribution or follow-up.

Oral submucous fibrosis presenting with histopathological lichenoid changes as predominant feature: Report of five cases and review of the literature.

Oral submucous fibrosis (OSF) is a precancerous condition of the oral cavity associated with habitual chewing of quid, with a high incidence among populations of the Indian subcontinent and Southeast Asia. Clinically, its initial manifestation may mimic oral lichen planus or lichen sclerosus. If the habit is not halted, the mucosa gets leathery and thickened, and fibrous bands form causing significant morbidity. Microscopically, it is characterized by atrophic epithelium, loss of rete ridges, and hyalinization of lamina propria. Of note, these hallmark histopathological features may be overlooked in the unusual presence of lichenoid interface changes, which may lead to the wrong diagnosis. We present herein five cases in which the rare joint appearance of OSF and lichenoid reaction features posed a diagnostic challenge. Due to its progressive nature and malignant potential, the presence of oral lichenoid changes overlying submucous hyalinization, in the right clinical and demographic setting, should raise suspicion of OSF and prompt actions directed at quid-chewing discontinuation.

Prevalence and Associated Factors of Precancerous Cervical Lesions among Women in Ethiopia: A Systematic Review and Meta-Analysis.

BACKGROUND: Cervical cancer remains the most common cancer of women worldwide. Its burden is more serious in developing countries. It is also the second common cancer deaths of women in Ethiopia followed by breast cancer. The aim of this study was to determine the pooled prevalence and associated factors of precancerous cervical lesions among women in Ethiopia. METHODS: We systematically searched published and unpublished articles reported from 2010 to 2019 using a comprehensive search of electronic databases including PubMed and Google scholar for grey literature from August 1 to September 1, 2019. The methodological qualities of included studies were evaluated using Joanna Briggs Institute meta-analysis of Statistics Assessment. The pooled prevalence estimate was calculated using MedCalc software-version 19.0.7, and the pooled odd ratios for predictors was calculated using RevMan software version 5.3. RESULTS: The pooled prevalence of precancerous cervical lesions among women in Ethiopia was 13.4% (95% CI:10.63% 16.37%). Statistically significant heterogeneity between studies was detected (I2=83.1%, P < 0.001). Among all measured associated factors: numbers of women life time sexual partners > 1, OR=2.5 (95% CI:3.70,4.76), being HIV positive women, OR=2.4 (95% CI:1.33,4.61) and women having history of STI, OR=2.0 (95% CI:1.02,3.87) had statistically significant association with precancerous cervical lesions among women in Ethiopia. CONCLUSION: The pooled prevalence of precancerous cervical lesions among women in Ethiopia was high as compared to the 5-year worldwide cervical cancer prevalence. Women having more than one life time sexual partners, being HIV positive women and women having history of STI had a statistically significant association with precancerous cervical lesions.

DNA polymerase ß deficiency promotes the occurrence of esophageal precancerous lesions in mice.

Esophageal mucosa undergoes mild, moderate, severe dysplasia, and other precancerous lesions and eventually develops into carcinoma in situ, and understanding the developmental progress of esophageal precancerous lesions is beneficial to prevent them from developing into cancer. DNA polymerase ß (Polß), a crucial enzyme of the base excision repair system, plays an important role in repairing damaged DNA and maintaining genomic stability. Abnormal expression or deletion mutation of Polß is related to the occurrence of esophageal cancer, but the role of Polß deficiency in the esophageal precancerous lesions is still unclear. Here, esophageal mucosa Polß-knockout mice were used to explore the relationship of Polß deficiency with esophageal precancerous lesions. First, we found the degree and number of esophageal precancerous lesions in Polß-KO mice were more serious than those in Polß-Loxp mice after N-nitrosomethylbenzylamine (NMBA) treatment. Whole exome sequencing revealed that deletion of Polß increased the frequency of gene mutations. Gene expression prolife analysis showed that the expression of proteins correlated to cell proliferation and the cell cycle was elevated in Polß-KO mice. We also found that deletion of Polß promoted the proliferation and clone formation as well as accelerated cell cycle progression of human immortalized esophageal epithelial cell line SHEE treated with NMBA. Our findings indicate that Polß knockout promotes the occurrence of esophageal precancerous lesions.

Follicular Epithelial Dysplasia as Hashimoto Thyroiditis-Related Atypia: a Series of 91 Specimens.

Follicular epithelial dysplasia (FED) is described as Hashimoto thyroiditis-related atypia and is thought to be a possible precancerous lesion. Dysplasia as an interface between normal state and carcinoma is described in a wide range of diseases and carcinogenesis chains. On the other hand, inflammation-related atypia and cancerogenesis is also widely studied. In this study, we retrospectively analyzed 91 specimens of thyroid gland surgical resections with FED during a 10-year-period at the university hospital pathology department. The study population consisted of 68 females and 15 males aged between 22 and 86 years. The preoperative cytology diagnoses had mainly been in the indeterminate categories with prevailing AUS/FLUS results in the FED-only group (p = 0.005) and suspicious for malignancy and malignant in the group with FED plus adjacent malignancy. The decision for surgery was malignancy related in 48.2% of the cases. The lesions were sized 0.1-3.5 mm and multifocal in 45.1% of the cases. Immunohistochemically, the atypical cells were cyclin D1-positive in 67.5%, galectin-3 in 72.7%, CK19 in 85.7%, and HBME-1 in 87.0% of cases. In conclusion, FED is suggested to be a pathogenetic link between inflammation-related atypia and papillary carcinoma and thus a premalignant precursor of papillary carcinoma in HT as 36.1% of the specimens contained also papillary carcinoma in the present study. Both histopathological nuclear features and the immunoprofile of FED are widely shared with that of papillary carcinoma.

Can breast cancer be stopped? Modifiable risk factors of breast cancer among women with a prior benign or premalignant lesion.

Physical inactivity, high postmenopausal body mass index, alcohol consumption and use of menopausal hormone therapy are established risk factors for breast cancer. Less is known about whether these factors influence the risk of progression of benign and premalignant breast lesions to invasive breast cancer. This registry-based cohort study was based on women with a precancerous lesion who were followed for breast cancer. The cohort consisted of 11 270 women with a benign lesion, 972 women with hyperplasia with atypia and 2379 women with carcinoma in situ diagnosed and treated after participation in BreastScreen Norway, 2006-2016. Information on breast cancer risk factors was collected by a questionnaire administered with the invitation letter. Cox regression analysis was used to estimate the association between breast cancer and physical activity, body mass index, alcohol consumption, tobacco smoking and menopausal hormone therapy, adjusted for age. During follow-up, 274 women with a benign lesion, 34 women with hyperplasia with atypia and 118 women with carcinoma in situ were diagnosed with invasive breast cancer. We observed an increased risk of breast cancer associated with use of menopausal hormone therapy for women with a benign or premalignant lesion. Alcohol consumption and tobacco smoking showed suggestive increased risk of breast cancer among women with a benign lesion. We were only to a limited degree able to identify associations between modifiable risk factors of breast cancer and the disease among women with a precancerous lesion, and a larger study is needed to confirm or refute associations.

Analysis of HPV Integrations in Mexican Pre-Tumoral Cervical Lesions Reveal Centromere-Enriched Breakpoints and Abundant Unspecific HPV Regions.

Human papillomavirus (HPV) DNA integration is a crucial event in cervical carcinogenesis. However, scarce studies have focused on studying HPV integration (HPVint) in early-stage cervical lesions. Using HPV capture followed by sequencing, we investigated HPVint in pre-tumor cervical lesions. Employing a novel pipeline, we analyzed reads containing direct evidence of the integration breakpoint. We observed multiple HPV infections in most of the samples (92%) with a median integration rate of 0.06% relative to HPV mapped reads corresponding to two or more sequence breakages. Unlike cancer studies, most integrations events were unique (supported by one read), consistent with the lack of clonal selection. Congruent to other studies, we found that breakpoints could occur, practically, in any part of the viral genome. We noted that L1 had a higher frequency of rupture integration (25%). Based on host genome integration frequencies, we found previously reported integration sites in cancer for genes like FHIT, CSMD1, and LRP1B and putatively many new ones such as those exemplified in CSMD3, ROBO2, and SETD3. Similar host integrations regions and genes were observed in diverse HPV types within many genes and even equivalent integration positions in different samples and HPV types. Interestingly, we noted an enrichment of integrations in most centromeres, suggesting a possible mechanism where HPV exploits this structural machinery to facilitate integration. Supported by previous findings, overall, our analysis provides novel information and insights about HPVint.

Pathogenesis of Keratinocyte Carcinomas and the Therapeutic Potential of Medicinal Plants and Phytochemicals.

Keratinocyte carcinoma (KC) is a form of skin cancer that develops in keratinocytes, which are the predominant cells present in the epidermis layer of the skin. Keratinocyte carcinoma comprises two sub-types, namely basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). This review provides a holistic literature assessment of the origin, diagnosis methods, contributing factors, and current topical treatments of KC. Additionally, it explores the increase in KC cases that occurred globally over the past ten years. One of the principal concepts highlighted in this article is the adverse effects linked to conventional treatment methods of KC and how novel treatment strategies that combine phytochemistry and transdermal drug delivery systems offer an alternative approach for treatment. However, more in vitro and in vivo studies are required to fully assess the efficacy, mechanism of action, and safety profile of these phytochemical based transdermal chemotherapeutics.