Low-risk Cancer Research Articles

Role of sentinel lymph node biopsy with indocyanine green and site of injection in endometrial cancer.

The aim of the present narrative review is to summarize the state of art on sentinel lymph node biopsy (SLNB) in endometrial cancer, with a special focus on indocyanine green (ICG) as adopted tracer. Over the years, the surgical nodal staging in patients with endometrial cancer has been intensively investigated. Traditionally, systematic pelvic and para-aortic lymphadenectomy represented the gold standard surgical treatment to assess nodal involvement of the tumor. Through the last two decades, SLNB has gradually replaced lymphadenectomy as a more targeted procedure. A great heterogeneity of tracers and injection techniques have been proposed to perform SLNB. However, no universally accepted recommendations are still available. SLNB has nowadays almost replaced pelvic lymphadenectomy in low-risk endometrial cancers, offering a better safety profile while being related to a comparable nodal involvement sensitivity. Currently, ICG is considered to be the most used tracer among others. Different injection sites have been proposed, with different detection features. While ICG cervical injection is nowadays the suggested technique for SLNB, noncervical injection techniques, such as hysteroscopic and combined procedures, seem to have a better accuracy in para-aortic nodal assessment, which have a role in high-risk endometrial cancers.

Associations of steps per day and step intensity with the risk of cancer: Findings from the Women's Health Accelerometry Collaboration cohort

ObjectiveAccumulating more steps/day is associated with a lower risk of cancer mortality and composite cancer outcomes. However, less is known about the relationship of steps/day with the risk of multiple site-specific cancers. MethodsThis study included >22,000 women from the Women's Health Accelerometry Collaboration Cohort (2011−2022), comprised of women from the Women's Health Study and Women's Health Initiative Objective Physical Activity and Cardiovascular Health Study. Steps/day and step intensity were collected with accelerometry. Incident cancer cases and deaths were adjudicated. Stratified Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) of the associations of steps/day and step intensity with incident breast, colon, endometrial, lung, and ovarian cancers, a composite of 13 physical activity-related cancers, total invasive cancer, and fatal cancer. ResultsOn average, women were 73.4 years old, accumulated 4993 steps/day, and had 7.9 years of follow-up. There were small nonsignificant inverse associations with the risks of colon cancer (HR = 0.94, 95% CI: 0.83, 1.05), endometrial cancer (HR = 0.91, 95% CI: 0.82, 1.01), and fatal cancer (HR = 0.95 95% CI: 0.90, 1.00) per 1000 steps/day. More minutes at ≥40 steps/min and a faster peak 10- and 30-min step cadence were associated with a lower risk of endometrial cancer, but findings were attenuated after adjustment for body mass index and steps/day. ConclusionsAmong women 62–97 years, there were small nonsignificant inverse associations of colon, endometrial, and fatal cancer with more steps/day. Epidemiologic studies with longer follow-up and updated assessments are needed to further explore these associations.

Dietary exposure to polycyclic aromatic hydrocarbons-contaminated Talinum Triangulare grown along polluted river.

The research aims to evaluate the source, dispersion, and human health risk assessment of PAH-contaminated Talinum Triangulare grown along the polluted Ikpoba River. The freeze-dried vegetables were sonicated with dichloromethane for an hour and then concentrated using a rotary evaporator. The extract was purified using a glass column with anhydrous Na2SO4 and silica gel and analyzed using gas chromatography-mass spectrometry (GC-MS). The distribution of the contaminants showed that Pyrene < Benzo(a)anthracene ≤ Fluorene < Phenathrene ≤ Naphthalene ≤ Acenaphthene < Anthracene ≤ Acenaphthylene, while Pyrene < Benzo(a)anthracene < Fluorene < Phenathrene < Acenaphthalene ≤ Naphthalene < Anthracene < Acenaphthylene in wet and dry periods, respectively. The average ∑8 PAHs was 0.85mg/kg and 0.75mg/kg in wet and dry periods, respectively, and showed a decrease of 17.64% from wet to dry periods. The daily average dose revealed that the infant male and the adult female consumed the least and highest doses of T. Triangulare (TT), respectively. Furthermore, the hazard quotient and hazard index were < 1 for all the target groups, with adult females having higher values in both seasons. However, the incremental life cancer risk of the target group was between potential and high-potential cancer risk, with adolescent males and adult females more prone to low and high cancer risk, respectively. The isomer ratio and multivariate statistics revealed the sources of the PAH-contaminated TT to be more from pyrolysis.

Mammography Screening Preferences Among Screening-Eligible Women in Their 40s : A National U.S. Survey.

The U.S. Preventive Services Task Force (USPSTF) recently changed its recommendation for mammography screening from informed decision making to biennial screening for women aged 40 to 49 years. Although many women welcome this change, some may prefer not to be screened at age 40 years. To conduct a national probability-based U.S. survey to investigate breast cancer screening preferences among women aged 39 to 49 years. Pre-post survey with a breast cancer screening decision aid (DA) intervention. (ClinicalTrials.gov: NCT05376241). Online national U.S. survey. 495 women aged 39 to 49 years without a history of breast cancer or a known BRCA1/2 gene mutation. A mammography screening DA providing information about screening benefits and harms and a personalized breast cancer risk estimate. Screening preferences (assessed before and after the DA), 10-year Gail model risk estimate, and whether the information was surprising and different from past messages. Before viewing the DA, 27.0% of participants preferred to delay screening (vs. having mammography at their current age), compared with 38.5% after the DA. There was no increase in the number never wanting mammography (5.4% before the DA vs. 4.3% after the DA). Participants who preferred to delay screening had lower breast cancer risk than those who preferred not to delay. The information about overdiagnosis was surprising for 37.4% of participants versus 27.2% and 22.9% for information about false-positive results and screening benefits, respectively. Respondent preferences may have been influenced by the then-current USPSTF guideline. There are women in their 40s who would prefer to have mammography at an older age, especially after being informed of the benefits and harms of screening. Women who wanted to delay screening were at lower breast cancer risk than women who wanted screening at their current age. Many found information about the benefits and harms of mammography surprising. National Cancer Institute.

Electronic Cigarettes and Tobacco Product Cessation: A Survey of Healthcare Providers' Opinions on Safety and Recommendation.

Background: This study aimed to: (1) assess healthcare providers' opinions on e-cigarette safety and compare them across professions; (2) evaluate providers' recommendations for e-cigarettes as a tobacco product cessation tool and identify any associations with their safety perceptions. Methods: A self-administered questionnaire was completed by 760 healthcare professionals (January-March 2020). The survey included eight opinions on e-cigarette safety with five Likert-scale answers and a question on recommending them for tobacco product cessation. Results: Among 760 healthcare providers (173 physicians/dentists, 69 pharmacists, and 518 nurses), only 20% reported prior experience with tobacco product cessation counseling. Providers expressed uncertainty regarding e-cigarette safety (mean ± SD: 2.5 ± 0.7 on a 5-point Likert scale), with no significant differences between professions (p = 0.836). Similarly, e-cigarette recommendations for tobacco product cessation remained low across professions (13%, 85/637), with no significant differences found (p = 0.072). The recommendation of e-cigarettes for tobacco cessation is associated with perceived safety, lower respiratory irritation, lower coughing, a lower risk of cancer, and a lower risk for secondhand smokers when compared to traditional cigarettes (p < 0.05). Conclusions: Most healthcare providers were unsure about the safety of e-cigarettes; about 13% of providers suggested using them for tobacco product cessation, with safety perceptions influencing recommendations.

Prospective Analysis of Circulating Biomarkers and Ovarian Cancer Risk in the UK Biobank.

Risk factors have a limited ability to predict individuals at high risk of developing ovarian cancer among average-risk women, highlighting the need for discovery of novel biomarkers. In the UK Biobank, we investigated serum biomarkers commonly measured in clinical laboratory tests and ovarian cancer risk. We conducted a prospective analysis of 20 serum biomarkers and ovarian cancer risk in 232,037 female UK Biobank participants (including 1,122 incident ovarian cancer cases diagnosed from 2006 to 2020). Multivariable adjusted Cox proportional hazards models were used to examine associations between biomarkers and ovarian cancer risk overall and by histotype. FDR was used to account for multiple testing. Overall, higher levels of insulin-like growth factor (IGF)-1 [RRquartile 4 vs. 1 = 0.73; 95% confidence interval (CI), 0.60-0.87; P-trend = 0.002/FDR = 0.04], HbA1c (RRquartile 4 vs. 1 = 0.74; 95% CI, 0.62-0.89; P-trend = 0.002/FDR = 0.04), and alanine aminotransferase (RRquartile 4 vs. 1 = 0.76; 95% CI, 0.63-0.91; P-trend = 0.002/FDR = 0.04) were significantly associated with lower ovarian cancer risk. When stratified by histotype, higher IGF1 levels were associated with lower risk of serous (RRquartile 4 vs. 1 = 0.73; 95% CI, 0.58-0.91; P-trend = 0.01/FDR = 0.20) and clear cell tumors (RRquartile 4 vs. 1 = 0.18; 95% CI, 0.07-0.49; P-trend = 0.001/FDR = 0.02), and higher HbA1c levels were associated with lower risk of serous tumors (RRquartile 4 vs. 1 = 0.73; 95% CI, 0.59-0.90; P-trend = 0.004/FDR = 0.08). We observed that higher levels of circulating IGF1, HbA1c, and alanine aminotransferase were associated with lower ovarian cancer risk. These results suggest metabolism of glucose/amino acid and insulin/IGF1 signaling pathway may be contributing to ovarian carcinogenesis. Further research is needed to replicate our findings and elucidate how systemic changes in metabolism impact ovarian carcinogenesis.

Antioxidant Properties of Zinc and Copper-Blood Zinc-to Copper-Ratio as a Marker of Cancer Risk BRCA1 Mutation Carriers.

Pathogenic mutations in BRCA1 (BReast CAncer gene 1) confer high risks of both breast (up to 70%) and ovarian (up to 40%) cancers. Zinc (Zn) and copper (Cu) are essential for various physiological functions, including antioxidant reactions. Their balance, reflected in the Zn/Cu ratio, plays a crucial role in maintaining redox homeostasis, which is vital for cancer prevention. This study examines the antioxidant properties of Zn and Cu, specifically focusing on the blood Zn/Cu ratio as a potential marker for cancer risk among BRCA1 mutation carriers. The study cohort consisted of 989 initially unaffected women, followed up for 7.5 years. Blood samples were analyzed using inductively coupled plasma mass spectrometry. Although individual Zn and Cu levels did not significantly correlate with overall cancer risk, those women with a Zn/Cu ratio above 6.38 experienced a significantly lower cancer risk than women with a ratio below this cut-off point. This suggests that the Zn/Cu ratio may be a valuable biomarker for cancer prevention in this high-risk group. Given the increased cancer risk in BRCA1 mutation carriers, optimizing Zn and Cu levels through dietary and active interventions could provide a preventive strategy.

Predictive factors for adnexal involvement in endometrial cancer FIGO stage IIIA

ObjectiveUnderstanding ovarian involvement incidence and risk factors in women with endometrial cancer may inform the decision of ovary preservation.MethodsOur retrospective study included all consecutive fully surgically staged patients with endometrial...

Grains in a Modern Time: A Comprehensive Review of Compositions and Understanding Their Role in Type 2 Diabetes and Cancer.

Globally, type 2 diabetes (T2D) and Cancer are the major causes of morbidity and mortality worldwide and are considered to be two of the most significant public health concerns of the 21st century. Over the next two decades, the global burden is expected to increase by approximately 60%. Several observational studies as well as clinical trials have demonstrated the health benefits of consuming whole grains to lower the risk of several chronic non-communicable diseases including T2D and cancer. Cereals grains are the primary source of energy in the human diet. The most widely consumed pseudo cereals include (quinoa, amaranth, and buckwheat) and cereals (wheat, rice, and corn). From a nutritional perspective, both pseudo cereals and cereals are recognized for their complete protein, essential amino acids, dietary fibers, and phenolic acids. The bran layer of the seed contains the majority of these components. Greater intake of whole grains rather than refined grains has been consistently linked to a lower risk of T2D and cancer. Due to their superior nutritional compositions, whole grains make them a preferred choice over refined grains. The modulatory effects of whole grains on T2D and cancer are also likely to be influenced by several mechanisms; some of these effects may be direct while others involve altering the composition of gut microbiota, increasing the abundance of beneficial bacteria, and lowering harmful bacteria, increasing insulin sensitivity, lowering solubility of free bile acids, breaking protein down into peptides and amino acids, producing short-chain fatty acids (SCFAs), and other beneficial metabolites that promote the proliferation in the colon which modulate the antidiabetic and anticancer pathway. Thus, the present review had two aims. First, it summarized the recent knowledge about the nutritional composition and bioactive acids in pseudo cereals (quinoa, amaranth, and buckwheat) and cereals (wheat, rice, and corn); the second section summarized and discussed the progress in recent human studies, such as observational (cross-sectional studies, case-control studies, and cohort studies) and intervention studies to understand their role in T2D and cancer including the potential mechanism. Overall, according to the scientific data, whole grain consumption may reduce the incidence of T2D and cancer. Future studies should carry out randomized controlled trials to validate observational results and establish causality. In addition, the current manuscript encourages researchers to investigate the specific mechanisms by which whole grains exert their beneficial effects on health by examining the effects of different types of specific protein, dietary fibers, and phenolic acids that might help to prevent or treat T2D and cancer.

Prevalence of Endoscopically Curable Low-Risk Cancer Among Large (≥20 mm) Nonpedunculated Polyps in the Right Colon

Background and aimsEndoscopic submucosal dissection (ESD) is increasingly promoted for the treatment of all large non-pedunculated colorectal polyps (LNPCP), to cure potential low-risk cancers (superficial submucosal invasion without additional high-risk histopathological features). The effect of a universal en bloc strategy on oncological outcomes for the treatment of LNPCP in the right colon is unknown. We evaluated this in a large Western population. MethodsA prospective cohort of patients referred for endoscopic resection (ER) of LNPCP was analysed. Patients found to have cancer after ER and those referred directly to surgery were included. The primary outcome was to determine the proportion of right colon LNPCP with low-risk cancer. ResultsOver 180 months until June 2023, 3294 sporadic right colon LNPCP in 2956 patients were referred for ER at 7 sites (median size 30mm [IQR 15]). 63 (2.1%) patients were referred directly to surgery and cancer was proven in 56 (88.9%). 2851/2956 (96.4%) LNPCP underwent ER (median size 35mm [IQR 20]) of which 75 (2.6%) were cancers. The overall prevalence of cancer in the right colon was 4.4% (131/2956). Detailed histopathological analysis was possible in 115/131 (88%) cancers (71 after ER, 44 direct to surgery). After excluding missing histopathological data, 23/2940 (0.78%) sporadic right colon LNPCP were low-risk cancers. ConclusionsThe proportion of right colon LNPCP referred for ER containing low-risk cancer amenable to endoscopic cure was <1%, in a large, multicentre Western cohort. A universal ESD strategy for the management of right colon LNPCP is unlikely to yield improved patient outcomes given the minimal impact on oncological outcomes. Clinical TrialAustralian Colonic Endoscopic Resection (ACE) cohort: NCT01368289 (https://classic.clinicaltrials.gov/ct2/show/NCT01368289); NCT02000141 (https://classic.clinicaltrials.gov/ct2/show/NCT02000141)

Direct factor Xa inhibitors and the risk of cancer and cancer mortality: A Danish population-based cohort study.

Preclinical animal studies have suggested that myeloid cell-synthesized coagulation factor X dampens antitumor immunity and that rivaroxaban, a direct factor Xa inhibitor, can be used to promote tumor immunity. This study was aimed at assessing whether patients with atrial fibrillation taking direct factor Xa inhibitors have lower risk of cancer and cancer-related mortality than patients taking the direct thrombin inhibitor dabigatran. This nationwide population-based cohort study in Denmark included adult patients with atrial fibrillation and without a history of cancer, who started taking a factor Xa inhibitor or dabigatran between 2011 and 2015. Data on medical history, outcomes, and drug use were acquired through Danish healthcare registries. The primary outcome was any cancer. Secondary outcomes were cancer-related mortality and all-cause mortality. Outcome events were assessed during 5 years of follow-up in an intention-to-treat analysis. The propensity score-based inverse probability of treatment weighting was used to compute cumulative incidence and subdistribution hazard ratios (SHRs) and corresponding 95% confidence intervals (CIs), with death as a competing event. Propensity scores were estimated using logistic regression and including in the model sex, age group at index date, comorbidities, and use of comedications. A total of 11,742 patients with atrial fibrillation starting a factor Xa inhibitor and 11,970 patients starting dabigatran were included. Mean age was 75.2 years (standard deviation [SD] 11.2) in the factor Xa cohort and 71.7 years (SD 11.1) in the dabigatran cohort. On the basis of the propensity score-weighted models, after 5 years of follow-up, no substantial difference in the cumulative incidence of cancer was observed between the factor Xa inhibitor (2,157/23,711; 9.11%, 95% CI [8.61%,9.63%]) and dabigatran (2,294/23,715; 9.68%, 95% CI [9.14%,10.25%]) groups (SHR 0.94, 95% CI [0.89,1.00], P value 0.0357). We observed no difference in cancer-related mortality (factor Xa inhibitors cohort 1,028/23,711; 4.33%, 95% CI [4.02%,4.68%]. Dabigatran cohort 1,001/23,715; 4.22%, 95% CI [3.83%,4.66%]; SHR 1.03, 95% CI [0.94,1.12]), but all-cause mortality was higher in the factor Xa inhibitor cohort (factor Xa inhibitors cohort 7,416/23,711; 31.31%, 95% CI [30.37%,32.29%]. Dabigatran cohort 6,531/23,715; 27.56%, 95% CI [26.69%,28.45%]; HR 1.17, 95% CI [1.13,1.21]). The main limitations of the study were the possibility of residual confounding and the short follow-up period. In this population based cohort study, factor Xa inhibitor use was not associated with an overall lower incidence of cancer or cancer-related mortality when compared to dabigatran. We did observe an increase in all-cause mortality in the factor Xa inhibitor cohort.

Metformin and statins reduce hepatocellular carcinoma risk in chronic hepatitis C patients with failed antiviral therapy.

Chronic hepatitis C (CHC) patients who failed antiviral therapy are at increased risk for hepatocellular carcinoma (HCC). This study assessed the potential role of metformin and statins, medications for diabetes mellitus (DM) and hyperlipidemia (HLP), in reducing HCC risk among these patients. We included CHC patients from the T-COACH study who failed antiviral therapy. We tracked the onset of HCC 1.5 years post-therapy by linking to Taiwan's cancer registry data from 2003 to 2019. We accounted for death and liver transplantation as competing risks and employed Gray's cumulative incidence and Cox subdistribution hazards models to analyze HCC development. Out of 2,779 patients, 480 (17.3%) developed HCC post-therapy. DM patients not using metformin had a 51% increased risk of HCC compared to non-DM patients, while HLP patients on statins had a 50% reduced risk compared to those without HLP. The 5-year HCC incidence was significantly higher for metformin non-users (16.5%) versus non-DM patients (11.3%; adjusted sub-distribution hazard ratio [aSHR]=1.51; P=0.007) and metformin users (3.1%; aSHR=1.59; P=0.022). Statin use in HLP patients correlated with a lower HCC risk (3.8%) compared to non-HLP patients (12.5%; aSHR=0.50; P<0.001). Notably, the increased HCC risk associated with non-use of metformin was primarily seen in non-cirrhotic patients, whereas statins decreased HCC risk in both cirrhotic and non-cirrhotic patients. Metformin and statins may have a chemopreventive effect against HCC in CHC patients who failed antiviral therapy. These results support the need for personalized preventive strategies in managing HCC risk.

Simple Versus Radical Hysterectomy in Women With Low-Risk Cervical Cancer

(Abstracted from N Engl J Med 2024;390:9) Radical hysterectomy is the standard-of-care treatment for early-stage cervical cancer; however, observational studies suggest no survival benefit between patients who undergo radical hysterectomy versus simple hysterectomy for stage IA2 cervical cancer. Additionally, 2 recent large studies have raised the question of whether simple hysterectomy compares favorably overall with radical hysterectomy in stage IA2 or IB1 disease with mixed evidence.

Association of genetic variants in soy isoflavones metabolism-related genes with decreased lung cancer risk

BackgroundSoy isoflavones have been reported to exhibit anti-tumor effects. We hypothesize that genetic variants in soy isoflavone metabolism-related genes are associated with the risk of lung cancer. MethodsA two-stage case-control study design was conducted in this study. The discovery stage included 300 lung cancer cases and 600 healthy controls to evaluate the association of candidate genetic variants with lung cancer risk. The validation stage involved 1200 cases and 1200 controls to validate the associations found. Furthermore, qPCR was performed to assess the mRNA expression levels of different genotypes of the SNP. ELISA was used to explore the association between genotype and soy isoflavone levels, as well as the association between soy isoflavone levels and lung cancer risk. ResultsA nonlinear association was observed between plasma soy isoflavone levels and lung cancer risk, with higher soy isoflavone levels associated with lower lung cancer risk (P < 0.001). The two-stage case-control study identified that UGT1A1 rs3755319 A > C was associated with decreased lung cancer risk (Recessive model: adjusted OR = 0.69, 95 %CI = 0.57–0.84, P < 0.001). Moreover, eQTL analysis showed that the expression level of UGT1A1 in the rs3755319 CC genotype was lower than in the AA + AC genotype (P < 0.05). The plasma concentration of soy isoflavones in the rs3755319 CC genotype was higher than in the AA + AC genotype (P = 0.008). ConclusionsWe identified a potentially functional SNP, UGT1A1 rs3755319 A > C, as being associated with decreased lung cancer risk. Further experiments will be needed to explore the mechanisms underlying the observed associations.

Oncologic control and predictors of urologic reconstruction after Mohs micrographic surgery for low-risk penile malignancy.

Mohs micrographic surgery (MMS) is a low-risk penile cancer management option. However, contemporary patients' short-term oncologic control and preoperative characteristics predicting reconstruction needs are undefined. This study assesses MMS's oncologic efficacy for low-risk penile cancer and identifies baseline predictors of post-resection reconstruction referral. We retrospectively reviewed 73 adult males with 78 penile cutaneous malignancies treated with MMS from 2005 to 2019. Patients underwent MMS with or without surgical reconstruction. Demographic information, MMS operative details, lesion pathology, and short-term outcomes were recorded. Descriptive statistics for all variables were calculated, and logistic regression identified predictive factors for urologic referral for complex reconstruction. Seventy-three men with 78 lesions, all staged ≤ cT1a prior to MMS, were identified. Twenty-one men were found to have invasive SCC. Median follow-up was 2.0years (IQR 0.8-5.2years). MMS was able to clear the disease in 90.4% of cases. One patient had disease related death following progression. Dermatology closed primarily in 68% of patients. Twenty percent of patients had a complication, most commonly poor wound healing. On univariate and multivariate linear regression analysis, lesion size > 3cm and involvement of the glans independently predicted the need for referral to a reconstructive surgeon. MMS for penile cancer appears to provide sound oncologic control in the properly selected patient. Involvement of a reconstructive surgeon may be needed for glandular and large lesions, necessitating early referral to a comprehensive multidisciplinary care team.

Screening outcome of HPV-vaccinated women: Data from the Danish Trial23 cohort study.

Danish women-who were HPV-vaccinated as girls-are now reaching an age where they are invited to cervical cancer screening. Because of their expected lower cervical cancer risk, we must reassess our screening strategies. We analyzed Danish HPV-vaccinated women's outcomes after the first screening test at age 23. Our study was embedded in Danish routine cytology-based screening. We conducted an observational study and included women born in 1994, offered the 4-valent HPV vaccine at age 14, and subsequently invited to screening at age 23. Cervical cytology was used for diagnostics and clinical management. Residual material was HPV tested with Cobas® 4800/6800. The most severe histology diagnosis within 795 days of screening was found through linkage with the Danish National Pathology Register. We calculated the number of women undergoing follow-up (repeated testing and/or colposcopy) per detected cervical intraepithelial neoplasia (CIN2+). A total of 6021 women were screened; 92% were HPV-vaccinated; 12% had abnormal cytology; 35% were high-risk HPV-positive, including 0.9% HPV16/18 positive, and 20% had follow-up. In women that were cytology-abnormal and HPV-positive (Cyt+/HPV+), 610 (98.5%) had been followed up, and 138 CIN2+ cases were diagnosed, resulting in 4.4 (95% CI 3.9-5.2) women undergoing follow-up per detected CIN2+. In contrast to recommendations, 182 (12.2%) cytology-normal and HPV-positive (Cyt-/HPV+) women were followed up within 795 days, and 8 CIN2+ cases were found, resulting in 22.8 (95% CI 13.3-59.3) women undergoing follow-up per detected CIN2+. Overall, HPV prevalence was high in HPV-vaccinated women, but HPV16/18 had largely disappeared. In the large group of cytology-normal and HPV-positive women, 23 had been followed up per detected CIN2+ case. Our data indicated that primary HPV screening of young HPV-vaccinated women would require very effective triage methods to avoid an excessive follow-up burden. Trial registration number: NCT0304955.

DNA Methylation and p53 Immunohistochemistry as Prognostic Biomarkers for Vulvar Lichen Sclerosus

Vulvar lichen sclerosus (LS) is an inflammatory dermatosis that can progress to human papillomavirus (HPV)-independent vulvar intraepithelial neoplasia (HPVi VIN) and vulvar squamous cell carcinoma (VSCC). Although LS has a much lower cancer risk compared with HPVi VIN (5% vs 50%, respectively), its incidence is significantly higher. Therefore, there is a clinical need to identify LS patients with an increased cancer risk. Our objective was to study the value of DNA methylation and p53 immunohistochemistry (IHC) as prognostic biomarkers for progression to cancer in patients with LS. Vulvar tissues from 236 patients were selected, including 75 LS and 68 HPVi VIN, both with and without cancer development, 32 VSCC, and 61 healthy vulvar controls. Samples were subjected to p53 IHC and DNA methylation analysis of a 3-gene marker panel containing ZNF582, SST, and miR124-2. Methylation levels and p53 IHC status (mutant or wild-type) were assessed and compared among all disease categories. Odds ratios were determined to identify whether the biomarkers were associated with progression to cancer in patients with LS. The highest methylation levels were found in HPVi VIN and VSCC, followed by LS and healthy vulvar controls. The largest heterogeneity in methylation levels was observed in LS cases. In fact, the 3-marker panel tested positive in 70% of LS, which progressed to VSCC vs only 17% of LS in patients without cancer development (P = .002). Also, mutant p53 IHC was observed more frequently in LS with progression to VSCC compared with nonprogressive LS cases (42% vs 3%, respectively, P = .001). Multivariable analysis identified a mutant p53 status as the only independent risk factor for cancer development in LS (odds ratio: 34.0, 95% CI: 1.4-807.4). In conclusion, DNA methylation testing and p53 IHC show strong potential as prognostic biomarkers for the identification of LS patients at high risk of progression to cancer.

Association between polycystic ovary syndrome and the risk of malignant gynecologic cancers (ovarian, endometrial, and cervical): A population-based study from the U.S.A. National Inpatient Sample 2016–2019

ObjectiveThis study aimed to systematically examine the relationship between polycystic ovary syndrome and ovarian, endometrial, and cervical cancers using the National Inpatient Sample (NIS) database. MethodsWe utilized the International Classification of Diseases (ICD-10) system to identify relevant codes from the NIS database (2016–2019). Univariate and multivariable regression analyses (adjusted age, race, hospital region, hospital teaching status, income Zip score, smoking, alcohol use, and hormonal replacement therapy) were conducted to evaluate association between PCOS and gynecologic cancers. Results were summarized as odds ratio (OR) with 95% confidence intervals (CI). ResultsOverall, 15,024,965 patients were analyzed, of whom 56,183 and 14,968,782 patients were diagnosed with and without PCOS, respectively. Among the patients diagnosed with gynecologic cancers (n = 91,599), there were 286 with PCOS and 91,313 without PCOS. Univariate analysis revealed that PCOS was significantly associated with higher risk of endometrial cancer (OR = 1.39, 95 % CI [1.18–1.63], p < 0.0001), but lower risk of ovarian cancer (OR = 0.55, 95 % CI [0.45–0.67], p < 0.0001) and cervical cancer (OR = 0.68, 95 % CI [0.51–0.91], p = 0.009). In contrast, after Bonferroni correction, multivariable analysis depicted that PCOS remained significantly associated with higher risk of endometrial cancer (OR = 3.90, 95 % CI [4.32–4.59], p < 0.0001). There was no significant correlation between PCOS and risk of ovarian cancer (OR = 1.09, 95 % CI [0.89–1.34], p = 0.409) and cervical cancer (OR = 0.83, 95 % CI [0.62–1.11], p = 0.218). ConclusionThis first-ever NIS analysis showed that patients with PCOS exhibited unique gynecologic cancer risk profiles, with higher risk for endometrial cancer, and no significant risk for ovarian or cervical cancers.

Machine Learning and External Validation of the IDENTIFY Risk Calculator for Patients with Haematuria Referred to Secondary Care for Suspected Urinary Tract Cancer

BackgroundThe IDENTIFY study developed a model to predict urinary tract cancer using patient characteristics from a large multicentre, international cohort of patients referred with haematuria. In addition to calculating an individual’s cancer risk, it proposes thresholds to stratify them into very-low-risk (<1%), low-risk (1–<5%), intermediate-risk (5–<20%), and high-risk (≥20%) groups. ObjectiveTo externally validate the IDENTIFY haematuria risk calculator and compare traditional regression with machine learning algorithms. Design, setting, and participantsProspective data were collected on patients referred to secondary care with new haematuria. Data were collected for patient variables included in the IDENTIFY risk calculator, cancer outcome, and TNM staging. Machine learning methods were used to evaluate whether better models than those developed with traditional regression methods existed. Outcome measurements and statistical analysisThe area under the receiver operating characteristic curve (AUC) for the detection of urinary tract cancer, calibration coefficient, calibration in the large (CITL), and Brier score were determined. Results and limitationsThere were 3582 patients in the validation cohort. The development and validation cohorts were well matched. The AUC of the IDENTIFY risk calculator on the validation cohort was 0.78. This improved to 0.80 on a subanalysis of urothelial cancer prevalent countries alone, with a calibration slope of 1.04, CITL of 0.24, and Brier score of 0.14. The best machine learning model was Random Forest, which achieved an AUC of 0.76 on the validation cohort. There were no cancers stratified to the very-low-risk group in the validation cohort. Most cancers were stratified to the intermediate- and high-risk groups, with more aggressive cancers in higher-risk groups. ConclusionsThe IDENTIFY risk calculator performed well at predicting cancer in patients referred with haematuria on external validation. This tool can be used by urologists to better counsel patients on their cancer risks, to prioritise diagnostic resources on appropriate patients, and to avoid unnecessary invasive procedures in those with a very low risk of cancer. Patient summaryWe previously developed a calculator that predicts patients’ risk of cancer when they have blood in their urine, based on their personal characteristics. We have validated this risk calculator, by testing it on a separate group of patients to ensure that it works as expected. Most patients found to have cancer tended to be in the higher-risk groups and had more aggressive types of cancer with a higher risk. This tool can be used by clinicians to fast-track high-risk patients based on the calculator and investigate them more thoroughly.

Comparing Cancer Risks and Mortality between Phytopharmaceuticals and Estrogen-Progestogen Medications for Menopausal Women: A Population-Based Cohort Study.

We evaluated the long-term risks of overall cancer and all-cause mortality associated with five types of phytopharmaceuticals and the most commonly used estrogen-progestogen medications for the treatment of postmenopausal syndrome in women. Using data from Taiwan's National Health Insurance Research Database (NHIRD) from 1 January 2000 to 31 December 2018, we conducted a 1:2 matched cohort study with 12,087 eligible patients. We compared phytopharmaceuticals -only users (n = 4029, phytopharmaceuticals group) with HRT-only users (n = 8058, HRT group) with a washout period of ≥6 months. The phytopharmaceuticals group had significantly lower risks of overall cancer and all-cause mortality than the HRT group (adjusted hazard ratio [95% confidence interval]: 0.60 [0.40-0.9] and 0.40 [0.16-0.99], respectively) after over 180 days of use. Bupleurum and Peony Formula were associated with lower risks of overall cancer and all-cause mortality (aHR: 0.57 [0.36-0.92] and 0.33 [0.11-1.05], respectively). In conclusion, phytopharmaceuticals may serve as an alternative therapy to HRT for alleviating menopausal symptoms and reducing health risks, leading to more favorable long-term health outcomes. Further randomized control trials are necessary to validate the findings of this study.