Search Results (115)

Background: Oral Submucous Fibrosis (OSMF) is a chronic, progressive condition characterized by the fibrosis of the oral mucosa, often associated with the habitual consumption of areca nut and tobacco, leading to significant morbidity. Despite its prevalent occurrence in many parts of the world, the underlying genetic and molecular mechanisms remain poorly understood, highlighting a critical need for research into its molecular genomics. The aim of this literature review is to investigate the molecular genomics of Oral Submucous Fibrosis by analyzing the relevant literature of the past decade. Methods: The search was conducted using MEDLINE (National Library of Medicine)-PubMed, focusing on the period 2015–2025 using the following keywords: Molecular Genomics AND Oral Submucous Fibrosis. This was followed by a manual search, and references were used to identify relevant articles. Results: A total of 12 articles were included in our review according to our inclusion criteria, which illustrated the importance of TGF-β, Wnt inhibitory factor-1, CypA, Hsp-70 1B, Calreticulin, Lumican, Enolase 1, MMP-2, IGF-1R, XIST, Epigallocatechin-3-gallate, Von Hippel-Lindau, and MUC1 and 4. Conclusions: Understanding the molecular pathogenesis of OSMF involves examining the molecular interactions and the roles of specific proteins. Advanced genomic technologies have opened new frontiers in the study of OSMF. As research in OSMF continues to evolve, emerging interdisciplinary approaches may provide therapeutic strategies, aiming to improve management outcomes for the patients. Full article

Background/Objectives: Persistent pulmonary nodules are at higher risk of developing into lung cancers. Assessing their future cancer risk is essential for successful interception. We evaluated the performance of two risk prediction models for persistent nodules in hospital-based cohorts: the Brock model, based on clinical and radiological characteristics, and the Sybil model, a novel deep learning model for lung cancer risk prediction. Methods: Patients with persistent pulmonary nodules—defined as nodules detected on at least two computed tomography (CT) scans, three months apart, without evidence of shrinkage—were included in the retrospective (n = 130) and prospective (n = 301) cohorts. We analyzed the correlations between demographic factors, nodule characteristics, and Brock scores and assessed the performance of both models. We also built machine learning models to refine the risk assessment for our cohort. Results: In the retrospective cohort, Brock scores ranged from 0% to 85.82%. In the prospective cohort, 62 of 301 patients were diagnosed with lung cancer, displaying higher median Brock scores than those without lung cancer diagnosis (18.65% vs. 4.95%, p < 0.001). Family history, nodule size ≥10 mm, part-solid nodule types, and spiculation were associated with the risks of lung cancer. The Brock model had an AUC of 0.679, and Sybil’s AUC was 0.678. We tested five machine learning models, and the logistic regression model achieved the highest AUC at 0.729. Conclusions: For patients with persistent pulmonary nodules in real-world cancer hospital-based cohorts, both the Brock and Sybil models had values and limitations for lung cancer risk prediction. Optimizing predictive models in this population is crucial for improving early lung cancer detection and interception. Full article

Background/Objectives: Despite advancements in treatment options, endometrial cancer remains a significant threat to women, underscoring the importance of early detection of atypical hyperplasia/endometrioid intraepithelial neoplasia (AH/EIN), the widely accepted histological precursor to endometrial carcinoma. Even with refinements in morphological criteria for the diagnosis of AH/EIN, accurate diagnosis remains challenging for pathologists, particularly in cases with secretory changes. Morphological alterations resulting from secretory-related changes further complicate the application of diagnostic criteria, emphasizing the need for reliable biomarkers. Previous studies have demonstrated that a panel consisting of three immunohistochemical markers, PAX2, PTEN, and β-catenin, can be effectively utilized for the identification of AH/EIN in various non-secretory scenarios. Methods: In this study, a total of 69 AH/EIN within secretory endometrium were analyzed using this panel. Benign interval endometrium (n = 57) and secretory phase endometrium (n = 71) were also analyzed for PAX2, PTEN, and β-catenin expression as controls. Results: The 3-marker panel successfully identified 93% of secretory AH/EIN, comparable to its performance in identifying non-secretory bona fide AH/EIN (92.8%) and AH/EIN within endometrial polyps (92.4%). Of note, β-catenin expression in benign interval endometrium commonly displayed weak nuclear staining (67%), which could pose a diagnostic pitfall when using the 3-marker panel. Overall, the results demonstrate the diagnostic utility of the 3-marker panel in clinical practice in identifying AH/EIN within challenging secretory phase endometrium cases. Conclusions: Combined with previous research highlighting its effectiveness in other challenging contexts—such as AH/EIN in polyps, small-sized EIN (subdiagnostic EIN), and progestin-treated EIN—this study provides strong evidence supporting the panel’s broad applicability in resolving major diagnostic challenges related to the precise diagnosis of AH/EIN. Full article

Background/Objectives: Proliferative verrucous leukoplakia (PVL) is an oral disorder with the greatest degree of malignant transformation. However, it is relatively rare. This study compared the clinical characteristics of patients with oral squamous cell carcinoma (OSCC) who had and had not been previously diagnosed with PVL. Methods: This case control study compared the clinical characteristics of patients classified as early (T1 and T2) or advanced (T3 and T4) OSCC according to the T size of the Tumor, Node, Metastasis (TNM) classification, including age, gender, location, and clinical type of oral squamous cell carcinoma. The analysis involved 140 patients. Group 1: 50 OSCC patients with PVL (OSCC-PVL) and Group 2: 90 OSCC patients without PVL (OSCC-noPVL). Results: The patients with OSCC-PVL were younger than those with OSCC-noPVL, but this did not reach statistical significance. Regarding patient gender, those with OSCC-PVL were much more frequently female (70%), while OSCC-noPVL was more prevalent in men (65.5%) (p < 0.01). There were also significant differences in the oral locations between the two groups: the gingiva was most prevalent in OSCC-PVL and the tongue in OSCC-noPVL. Erythroleukoplastic forms were significantly more common in OSCC-PVL (30% vs. 7.7%), while ulcerated forms were more frequent in OSCC-noPVL (63.3% vs. 42%). Finally, early T stages were much more prevalent in our patients with OSCC-PVL. Conclusions: We found that OSCC preceded by PVL was much more frequent in women, had less aggressive clinical forms, and had significantly more frequent early T stages than in OSCC-noPVL. Full article

Objectives: This scoping review aimed to provide both researchers and practitioners with an overview of how machine learning (ML) methods are applied to infrared spectroscopy for the diagnosis and prognosis of head and neck precancer and cancer. Methods: A subject headings and keywords search was conducted in MEDLINE, Embase, and Scopus on 14 January 2024, using predefined search algorithms targeting studies that integrated infrared spectroscopy and ML methods in head and neck precancer/cancer research. The results were managed through the COVIDENCE systematic review platform. Results: Fourteen studies met the eligibility criteria, which were defined by IR spectroscopy techniques, ML methodology, and a focus on head and neck precancer/cancer research involving human subjects. The IR spectroscopy techniques used in these studies included Fourier transform infrared (FTIR) spectroscopy and imaging, attenuated total reflection-FTIR, near-infrared spectroscopy, and synchrotron-based infrared microspectroscopy. The investigated human biospecimens included tissues, exfoliated cells, saliva, plasma, and urine samples. ML methods applied in the studies included linear discriminant analysis (LDA), principal component analysis with LDA, partial least squares discriminant analysis, orthogonal partial least squares discriminant analysis, support vector machine, extreme gradient boosting, canonical variate analysis, and deep reinforcement neural network. For oral cancer diagnosis applications, the highest sensitivity and specificity were reported to be 100%, the highest accuracy was reported to be 95–96%, and the highest area under the curve score was reported to be 0.99. For oral precancer prognosis applications, the highest sensitivity and specificity were reported to be 84% and 79%, respectively. Conclusions: This review highlights the promising potential of integrating infrared spectroscopy with ML methods for diagnosing and prognosticating head and neck precancer and cancer. However, the limited sample sizes in existing studies restrict generalizability of the study findings. Future research should prioritize larger datasets and the development of advanced ML models to enhance reliability and robustness of these tools. Full article

Following cancer treatment, individuals experience a range of physical, mental and social health difficulties that interfere with their ability to resume participation in pre-cancer activities. In Ireland, the National Cancer Strategy recommends community-based services to address post-treatment difficulties. Social prescribing is a community-based, non-medical service that links individuals with health-related activities and supports in their community. This study explored the feasibility and acceptability of social prescribing for cancer survivors. A mixed methods study was undertaken with individuals who had completed curative treatment for any cancer type. Recruitment was carried out in a national cancer centre. Quantitative outcomes included feasibility metrics (recruitment, intervention adherence and retention), the Frenchay Activities Index (FAI), the Hospital Depression and Anxiety Scale (HADS), the Multidimensional Assessment of Fatigue (MAF), and EORTC QLQ-C30. Qualitative interviews explored acceptability of social prescribing. Data were analysed using descriptive statistics (quantitative data) and content analysis (qualitative data). Out of 131 individuals identified as eligible to participate, 43 agreed to participate (32.8% recruitment) and 27 met a link worker and were connected to a local activity (62.7% adherence) and completed follow-up outcome measures (62.7% retention). Improvements were observed in all health-related outcomes and those interviewed identified the intervention as acceptable. Study participants attended a range of community-based activities as a result of link worker support. They also reported increased confidence, improved mental health and reduction in fatigue following attendance at community-based activities. The findings of this study indicate that social prescribing is a feasible and acceptable community-based intervention to improve the physical, mental and social health of individuals living with and beyond cancer. A pilot randomised trial is indicated to inform a definitive intervention trial. Full article

Human papillomavirus (HPV) is a major global health issue and is recognized as the leading cause of cervical cancer. While prophylactic vaccination programs have led to substantial reductions in both HPV infection rates and cervical cancer incidence, considerable burdens of HPV-related diseases persist, particularly in developing countries with inadequate vaccine coverage and uptake. The development of therapeutic vaccines for HPV represents an emerging strategy that has the potential to bolster the fight against cervical cancer. Unlike current prophylactic vaccines designed to prevent new infections, therapeutic vaccines aim to eradicate or treat existing HPV infections, as well as HPV-associated precancers and cancers. This review focuses on clinical studies involving therapeutic HPV vaccines for cervical cancer, specifically in three key areas: the treatment of cervical intraepithelial neoplasia; the treatment of cervical cancer in combination with or without chemotherapy, radiotherapy, or immune checkpoint inhibitors; and the role of prophylaxis following completion of treatment. Currently, there are no approved therapeutic HPV vaccines worldwide; however, active progress is being made in clinical research and development using multiple platforms such as peptides, proteins, DNA, RNA, bacterial vectors, viral vectors, and cell-based, each offering relative advantages and limitations for delivering HPV antigens and generating targeted immune responses. We outline preferred vaccine parameters, including indications, target populations, safety considerations, efficacy considerations, and immunization strategies. Lastly, we emphasize that therapeutic vaccines for HPV that are currently under development could be an important new tool in fighting against cervical cancer. Full article

Background/Objectives: Oral cancers in patients with proliferative verrucous leukoplakia (PVL-OSCC) exhibit different clinical and prognostic outcomes from those seen in conventional oral squamous cell carcinomas (cOSSCs). The aim of the present study is to compare the genome-wide DNA methylation signatures in fresh frozen tissues between oral squamous cell carcinomas in patients with PVL and cOSCC using the Illumina Infinium MethylationEPIC BeadChip. Methods: This case–control study was carried out at the Stomatology and Maxillofacial Surgery Department of the General University Hospital of Valencia. For the epigenomic study, unsupervised exploratory bioinformatic analyses were performed using principal component and heatmap analysis. Supervised differential methylation analyses were conducted using a rank-based regression model and a penalized logistic regression model to identify potential prognostic biomarkers. Results: The unsupervised analyses of the global methylation profiles did not allow us to differentiate between the distinct oral cancer groups. However, the two supervised analyses confirmed the existence of two oral carcinoma phenotypes. We identified 21 differentially methylated CpGs corresponding to 14 genes. Among them, three CpGs had not been previously assigned to any known gene, and the remaining were associated with genes unrelated to oral cancer. The AGL, WRB, and ARL15 genes were identified as potential prognostic biomarkers. Conclusions: This study emphasizes the significant role of epigenetic dysregulation in OSCC, particularly in cases preceded by PVL. We have provided data on differential methylation genes that could be involved in the molecular carcinogenesis of PVL-OSCC. Full article

This study explores the effects of plant compounds on human papillomavirus (HPV)-induced W12 cervical precancer cells and bioelectric signaling. The aim is to identify effective phytochemicals, both individually and in combination, that can prevent and treat HPV infection and HPV associated cervical cancer. Phytochemicals were tested using growth inhibition, combination, gene expression, RT PCR, and molecular docking assays. W12 cells, derived from a cervical precancerous lesion, contain either episomal or integrated HPV16 DNA. Several compounds, including digoxin, tanshinone IIA, dihydromethysticin and carrageenan, as well as fractions of turmeric, ginger and pomegranate inhibited the growth of W12 precancer and cervical cancer cells. Curcumin and tanshinone IIA were the most active and relatively nontoxic compounds. RT-PCR analysis showed that tanshinone IIA activated the expression of p53, while repressing the expression of HPV16 E1, E2, E4, E6, and E7 viral transcripts in W12 (type 1 and 2) integrant cells. In addition, curcumin synergized with tanshinone IIA in HeLa cells. Molecular docking studies suggested tanshinone IIA and curcumin bind to the Na⁺/K⁺-ATPase ion channel, with curcumin binding with higher affinity. Our findings highlight the potential of these multifaceted phytochemicals to prevent and treat HPV-induced cervical cancer, offering a promising approach for combinatorial therapeutic intervention. Full article

In addition to chronic hrHPV anogenital infection, continuing inflammatory cervical changes are intrinsic in the development of precancerous lesions. In younger women, much of this inflammatory background parallels the progressive maturation of squamous metaplasia, often rendering treatment interventions redundant; however, patients with persistent cervical precancer, as well as those harboring invasive bacterial pathogens, might benefit from controlling the active inflammatory process by shortening the HPV natural cycle and avoiding subsequent cervical surgery. In a colposcopy population of 336 predominantly young asymptomatic individuals, we explored the impact of molecularly detected bacterial STIs on HPV DNA and APTIMA positivity rates using validated assays. In the multivariable analysis, several largely anticipated epidemiological factors were related to STI positivity. In this cohort, the HPV DNA test illustrated better performance for the prediction of STI positivity than the corresponding APTIMA test (sensitivity 52.94% vs. 33.82%), while inversely, the APTIMA test was more indicative of bacterial STI negativity than the HPV DNA test (specificity 77% vs. 60%). In addition, no significant differences between these two molecular assays were documented in terms of PPV, NPV, and overall accuracy. Despite the high Ureaplasma urealyticum and low Chlamydia trachomatis prevalence recorded in this study’s population, which is among the first assessing the co-variation of bacterial STI expression with established HPV biomarkers, the APTIMA assay did not predict concurrent bacterial STIs superiorly compared with an established HPV DNA assay. Full article

Cervical cancer is more common in Sub-Saharan Africa (SSA) compared to developed countries, with persistent genital high-risk HPV (HR-HPV) infection identified as the cause. However, other factors contributing to this gap remain unclear. This review explores the potential role of cervicovaginal microbiota (CVM) in genital HPV infection and cervical cancer development among women in SSA. Many women of African descent, including those from SSA, lack lactobacilli dominance in their CVM, which is considered a biomarker of cervicovaginal health. Published literature has associated Lactobacillus-dominated CVM with a lower risk of HPV infection and cervical cancer. The converse is true for women with high diversity non-Lactobacillus-dominated CVM and bacterial vaginosis, the most common form of vaginal disorder. However, findings on the relationship between specific bacterial abundance and cervical disease severity are inconsistent and inconclusive due to differences in study design, study population, sampling, and potential confounders. Thus, there is a need to form consensus to advance research on CVM and HPV-associated cervical disease. Despite the exact mechanisms by which CVM influence HR-HPV persistence and cervical carcinogenesis being unknown, the backbone of the mechanisms appears to be mediated in part by the following: cervicovaginal dysbiosis, elevated vaginal pH, high ratio of L-to-D-lactic acid, cohesive biofilm formation, chronic inflammation, and immune dysregulation. Consequently, these promote cellular proliferation, genetic instability, and evasion of immune surveillance. This review calls for larger, prospective studies to unravel causal links, identify protective features, and integrate CVM interventions into HPV and cervical cancer prevention strategies in SSA. Full article

More common than cervical cancer, cervical intraepithelial neoplasia (CIN) represents a precursor lesion of cervical carcinoma, being associated with HPV infection. Due to the bidirectional relationship between HPV and estrogen and progesterone in pregnancy, most of the published data claim that precancerous lesions remain stable or even regress during pregnancy, although several studies have indicated the tendency of HSILs to persist. It is considered that pregnancy-related cervical precancerous lesions undergo a postpartum regression, due to stimulatory effects of the immune microenvironment. Due to the rarity of publications on this subject, we aimed to offer a concise overview of and new insights into the current knowledge regarding the pathogenesis, diagnosis, and evolution of pregnancy-associated precancerous lesions, as well as their impact upon gestation and fertility. Full article

In this comprehensive review supported by clinical examples, the authors explore the topic of cervical cancer in pregnancy, with emphasis on potential pre-cancer progression, the possibility of coexisting preinvasive and invasive disease, and neoadjuvant chemotherapy. This manuscript addresses the challenges of managing cervical cancer in pregnant women with a pregnancy-preserving approach, including the importance of screening, the timing of surgery, and the impact of pregnancy on the course of the disease. The first case study illustrates the potential for a benign cervical lesion to transform into a malignant one during pregnancy and the possible coexistence of preinvasive lesions together with early-stage cervical cancer. It also questions the rationale behind the non-treatment of pregnant patients initially diagnosed with CIN 2/3 during pregnancy. The second presented clinical example shows the histologically confirmed response to neoadjuvant chemotherapy, resulting in a radiologically diagnosed FIGO stage IIA1 being downgraded to adenocarcinoma in situ in the histology report after surgery performed six weeks postpartum. The treatment of cervical cancer, which is becoming increasingly prevalent among pregnant women, and the necessity for an individualized diagnostic and therapeutic approach represent significant challenges for contemporary medicine. Discrepancies in therapeutic options proposed among centers within the same region lead to the conclusion that there is a need for centralization and unification of evidence-based management in referral centers with both high-level oncological and perinatal care. Full article

Background/Objectives: The diagnosis of oral potentially malignant disorders (OPMDs) and oral squamous cell carcinoma (OSCC) represent a significant challenge in oral medicine. Optical coherence tomography (OCT) shows promise for evaluating oral tissue microstructure but lacks standardized diagnostic protocols tailored to the structural variability and lesions of oral mucosa. Methods: This cross-sectional observational study aims to evaluate the diagnostic accuracy of targeted biopsy-based and site-coded OCT protocols for common OPMDs and OSCC. Adult patients clinically diagnosed with OPMDs, including oral leukoplakia (OL), oral lichen planus (OLP), and OSCC were enrolled. Clinical and OCT evaluation before and after punch scalpel-site registration preceding diagnostic biopsy on the target site was performed. Blinded observers analyzed the OCT scans for OCT-based diagnoses. Sensitivity, specificity, and diagnostic accuracy for OCT evaluations before and after punch scalpel-site registration were statistically compared with histological findings. Results: A dataset of 2520 OCT scans and 210 selected images from 21 patients was obtained. Sensitivity and specificity post-target site registration were high for OSCC (98.57%, 100.00%), OL (98.57%, 98.57%), and OLP (97.14%, 98.57%). The positive predictive values ranged from 97.14% to 100.00%, while negative predictive values ranged from 98.57% to 99.29%. Inter-observer agreements were strong for OSCC (0.84) and moderate for OL (0.54) and OLP (0.47–0.49). Targeted OCT scans significantly improved diagnostic accuracy for all conditions (p < 0.001). Conclusions: This preliminary study supports using site-targeted OCT scans followed by a site-targeted punch biopsy, enhancing precision in oral diagnostics. This approach is foundational for developing pioneering automated algorithms guiding oral cancer and pre-cancer diagnosis via OCT imaging. Full article

Background: Determining the distribution of high-risk human papillomavirus (HR-HPV) types in histologic low-(LSIL) and high-grade (HSIL/CIN2+) squamous intraepithelial lesions through a diagnostic process in a cervical cancer prevention provides one of the key etiological factors behind further progression and persistence. Incorporating novel high-grade cervical lesion biomarkers such as p16/Ki67 dual staining (DS) alongside HPV typing has become important in detecting cervical precancers. Methods: Among 28,525 screening tests and 602 histology results, 559 cases with HR-HPV and histology results obtained from colposcopic biopsy were retrospectively analyzed, together with DS status. The χ² test with Bonferroni correction evaluated the differences in HR-HPV type prevalence and DS positivity across three histologic study groups. Results: A statistically significant difference in the prevalence of HPV 16 was observed between negative and HSIL/CIN2+ (p = 0.00027) groups, as well as between the LSIL/CIN1 and HSIL/CIN2+ groups (p = 0.00041). However, no significant difference was found between the negative and LSIL/CIN1 groups. Similarly, the DS positivity difference was significant between the negative and HSIL/CIN2+ (p < 0.0001) and between the LSIL/CIN1 and HSIL/CIN2+ groups (p < 0.0001), but there was no significant difference between the negative and LSIL/CIN1 groups. Conclusions: The study highlights the heterogeneous nature of HPV-related cervical pathologies, and the distinct risks associated with different cervical lesion grades, emphasizing the importance of HR-HPV type distribution and DS status. Full article