Search Results (81)

Background/Objectives: Structured cytopathology reporting systems attach an evidence-based risk of malignancy (ROM) to every diagnostic category for the thyroid, salivary gland, urinary tract, lung and other sites. None exists for the oral cavity, and the ROM of an oral brush cytology category has not, to our knowledge, been reported. Methods: All oral liquid-based cytology specimens accessioned at one tertiary dental hospital between 2015 and 2024 were reviewed; those with a site-concordant histopathological diagnosis obtained within 90 days formed the analytic cohort (n = 137). Cytological reports were recovered from primary laboratory records and assigned to a five-tier ordinal scale. The target condition was malignancy or high-grade dysplasia, and diagnostic indices were calculated at every ordinal threshold with Wilson 95% confidence intervals. Results: ROM rose monotonically: 15.6% (95% CI 8.7–26.4) for negative, 53.3% (30.1–75.2) for atypical favoring reactive, 76.9% (61.7–87.4) for atypical cells of undetermined significance (ACUS), 87.5% (52.9–97.8) for atypical favoring neoplastic and 100% (74.1–100) for malignancy. The ACUS value far exceeded that of the similarly named tier in the thyroid (22%) and salivary gland (30.5%) systems and fell within the range spanned by their suspicious-for-malignancy tiers (74% and 83.8%). Malignancy was never reported in a histologically benign or low-grade lesions. Sensitivity at the ACUS threshold was 25.0% in keratotic against 79.3% in non-keratotic lesions (p = 0.004). Conclusions: These are, to our knowledge, the first category-specific ROM estimates for oral brush cytology, and they identify a nomenclature problem: a category named for the pathologist’s uncertainty carried a risk equivalent to suspicious for malignancy elsewhere; while a negative report was followed by disease in one lesion in six. Any oral reporting system should attach an explicit ROM to each category; our exploratory data further suggest that the surface keratinization of the sampled lesion should be recorded. Full article

Background: Reliable molecular biomarkers that complement cytomorphological assessment for early identification of high-risk oral epithelial lesions remain limited. Although p53 immunocytochemistry (ICC) is used as a surrogate marker of TP53 abnormalities, p53 protein expression does not always reflect TP53 transcriptional activity. This study investigated the relationships between p53 ICC, TP53 mRNA expression, and p53 immunohistochemical (IHC) staining patterns in the categories of oral high-grade squamous intraepithelial lesions (OHSILs) and oral squamous cell carcinoma (SCC). Methods: We classified 504 liquid-based cytology (LBC) specimens according to the Bethesda System for Reporting Oral Cytology: negative for an intraepithelial lesion or malignancy (NILM) (n = 394), oral low-grade squamous intraepithelial lesion (OLSIL) (n = 72), OHSIL (n = 18), and SCC (n = 20). p53 ICC was performed on cytological specimens, TP53 mRNA expression was quantified by quantitative real-time PCR using residual LBC samples, and corresponding biopsy specimens were evaluated for p53 IHC staining patterns. Associations between p53 ICC and clinicopathological variables were also analyzed. Results: The p53 labeling index significantly increased with cytological severity, and TP53 mRNA expression was significantly higher in OHSIL and SCC than in NILM and OLSIL. In OHSIL and SCC, lesions showing a null-type p53 IHC staining pattern showed significantly lower TP53 mRNA expression than lesions with non-null staining patterns. No significant associations between p53 ICC and clinicopathological variables were observed in OHSIL. In contrast, p53 ICC positivity in SCC was significantly associated with tumor size, depth of invasion, and p53 IHC staining patterns. Conclusions: Negative p53 ICC may result from sampling limitations or null-type TP53 expression. TP53 mRNA analysis provides complementary molecular information that distinguishes false-negative p53 ICC caused by sampling limitations from biologically reduced TP53 expression. Integrating cytomorphology, p53 ICC, histopathology, and TP53 mRNA analysis may improve diagnostic accuracy and risk stratification of high-risk oral epithelial lesions. Full article

Canine urothelial carcinoma (UC) is commonly managed with non-steroidal anti-inflammatory drugs (NSAIDs), alone or combined with cytotoxic chemotherapy. Evidence supporting subcutaneous keyhole limpet hemocyanin (KLH) in canine UC is lacking. We describe two client-owned dogs with presumptive lower urinary tract UC managed with NSAIDs, KLH, and selenium after cytotoxic chemotherapy was declined. Case 1 was an 11-year-7-month-old castrated male Maltese with bladder-neck/proximal-urethral thickening. A positive veterinary bladder tumor antigen test, compatible serial imaging, and low-cellularity urine cytology showing suspected urothelial hyperplasia with dysplasia supported clinical suspicion; however, BRAF and BRAF-PLUS assays were negative and histopathology was unavailable. Case 2 was an 11-year-old neutered male Poodle with a BRAF V595E-positive urethrovesical-junction lesion on imaging, without histopathologic confirmation. Both dogs received NSAIDs, Immucothel^® (1 mg subcutaneously), intravenous sodium selenite (200 μg/kg), and oral selenium (100 μg/dog q24h). Serial CT and ultrasonography documented persistent localized abnormalities over prolonged follow-up, but measurements obtained by different modalities were not treated as directly comparable. Adverse events were assessed retrospectively and not prospectively graded using VCOG-CTCAE criteria. Because the diagnoses were presumptive and the interventions were concurrent and uncontrolled, the independent contribution, efficacy, and safety of KLH cannot be determined. These cases are descriptive and hypothesis-generating. Full article

Background: Chronic pulmonary aspergillosis (CPA) is a slowly progressive pulmonary fungal disease, predominantly caused by Aspergillus fumigatus, which develops in patients with pre-existing structural lung abnormalities. Chronic cavitary pulmonary aspergillosis (CCPA), the most common form of CPA, is characterized by one or more pulmonary cavities, with or without intracavitary fungal balls (aspergillomas), and requires prolonged oral triazole therapy. Long-term treatment may be limited by adverse events, drug–drug interactions, and the need for therapeutic drug monitoring with conventional azoles. Case Presentation: A 69-year-old former smoker with a history of breast cancer and right upper lobectomy for pulmonary adenocarcinoma presented with fever, productive cough, hyporexia, sarcopenia, and an unintentional 6 kg weight loss over three months. Two years earlier, she had undergone atypical pulmonary resection for an Aspergillus fumigatus aspergilloma and had been treated with amphotericin B followed by voriconazole for six months. HRCT revealed a recurrent intracavitary fungal lesion within a residual post-surgical cavity with extensive inflammatory consolidation. Bronchoalveolar lavage demonstrated a positive galactomannan index (4.74) and septate fungal hyphae on cytology, supporting the diagnosis of recurrent CCPA. Treatment with oral isavuconazole resulted in clinical recovery, weight gain, and complete radiological resolution after six months, without treatment-related adverse events or QTc abnormalities. Conclusions: This case highlights the successful outpatient management of CCPA developing within a persistent post-lobectomy cavity despite previous surgical resection and antifungal therapy. The favourable clinical response, excellent tolerability, and absence of treatment-related toxicity support the growing evidence that isavuconazole may represent a valuable therapeutic option for selected patients with recurrent CCPA. Full article

Background/Objectives: Oral cavity squamous cell carcinoma (OSCC) remains a major global health burden, with outcomes strongly dependent on stage at diagnosis. Although the oral cavity is directly accessible to clinical examination, many cases are still detected at advanced stages. This narrative review aimed to summarize current trends in OSCC diagnosis and early monitoring, with emphasis on non-invasive and minimally invasive techniques and biomarkers. Methods: A semi-systematic narrative literature search was conducted in PubMed/MEDLINE, Scopus, and Web of Science using predefined combinations of OSCC-, early-detection-, imaging-, cytology-, liquid-biopsy-, salivaomics-, artificial-intelligence-, and biosensor-related terms. English-language systematic reviews, meta-analyses, reviews of reviews, translational studies, and clinically relevant original articles were prioritized, with explicit attention to oral cavity-specific evidence and clearly identified extrapolation from broader head-and-neck or oropharyngeal cancer settings. Results: Conventional oral examination and histopathological assessment of biopsy specimens remain the diagnostic foundation. Adjunctive methods may support lesion triage, biopsy-site selection, risk stratification, and early monitoring, but cannot replace tissue diagnosis. Narrow-band imaging, optical coherence tomography, and molecular brush cytology appear particularly promising for specialist assessment and surveillance. Liquid biopsy and saliva-based biomarker platforms offer translational potential, particularly for repeatable monitoring, but clinical implementation is limited by methodological heterogeneity, pre-analytical variability, inconsistent thresholds, and insufficient external validation. Artificial intelligence and biosensor platforms remain promising but largely developmental. Conclusions: Progress in early OSCC diagnosis and monitoring will most likely depend on integrated diagnostic models combining clinical examination, adjunctive imaging, minimally invasive sampling, molecular biomarkers, and computational decision-support tools, validated in prospective multicenter studies. Full article

Background/Objectives: Oral potentially malignant disorders (OPMDs) require accurate risk stratification to identify patients at the highest risk for severe oral epithelial dysplasia (OED) or oral squamous cell carcinoma (OSCC). We developed and internally validated the oral cancer numerical index (OCNI), a quantitative risk score derived from clinical features and deep learning-based brush cytology measurements. Methods: This retrospective model development and internal validation study was conducted using data from the multicenter Grand Opportunity study. Prospectively recruited subjects with OPMD with complete data were divided at the subject level into a training set (n = 384) and a holdout test set (n = 164) using a 70:30 diagnosis-stratified split. The primary endpoint was severe OED or OSCC versus benign diagnoses, and mild and moderate OED. Predictors included age, sex, tobacco history, lesion color, lesion size, multiple lesions, ulcerative morphology, and the percentages of differentiated squamous epithelial and small round cells derived from deep learning-based cytology. Prespecified rule-out and rule-in thresholds were selected in the training set to target 90% sensitivity and 90% specificity, respectively, and then applied to the holdout test set. Results: At the prespecified rule-out threshold (OCNI ≤ 37.6), sensitivity was 92% and negative predictive value was 97%. At the rule-in threshold (OCNI > 60.0), specificity was 89% and positive predictive value was 67%. Calibration was good in the holdout set (intercept, −0.07; slope, 1.13; Hosmer–Lemeshow p = 0.36), and OCNI increased significantly with worsening histopathologic severity. Conclusions: OCNI provided an objective, clinically interpretable estimate of risk for severe OED or OSCC, with strong rule-out and rule-in performance and good calibration. These findings support further external validation of OCNI as an adjunctive tool for oral lesion risk stratification. Full article

Periodontitis (P) and Type 2 Diabetes Mellitus (T2DM) are chronic inflammatory diseases that share pathophysiological pathways involving immune dysregulation and oxidative stress. Both conditions have been associated with increased susceptibility to viral infections, including SARS-CoV-2. In this regard, molecules associated with viral infection include angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2). This study aimed to evaluate the clinical periodontal status, oral microbiota composition, and the expression of ACE2 and TMPRSS2 in the oral epithelium and gingival tissue of patients with and without T2DM and P. Methods: This cross-sectional study enrolled 120 participants allocated into four groups based on periodontal and glycemic status: periodontally healthy non-diabetic individuals (PH non-T2DM), periodontitis without diabetes (P non-T2DM), periodontally healthy individuals with type 2 diabetes mellitus (PH T2DM), and periodontitis with T2DM (P T2DM), with 30 participants per group. Full-mouth clinical periodontal parameters were recorded by a calibrated examiner. Oral microbiota was assessed from unstimulated whole saliva, labial swab samples, and subgingival biofilm by selective culture and checkerboard DNA-DNA hybridization. Gingival exfoliative cytology and full-thickness gingival biopsies were obtained for immunohistochemical evaluation of ACE2 and TMPRSS2 expression. Cytomorphometric analysis and polymorphonuclear cell counts were performed on epithelial smears. Additionally, primary human gingival fibroblasts (HGFs) isolated from each group were stimulated with bacterial ligands (LPS, LTA, and PGN) to assess ACE2 and TMPRSS2 modulation by Western blot. Intergroup comparisons were performed using one-way ANOVA with Bonferroni post hoc correction and the Mann–Whitney U test, with statistical significance set at p < 0.05. Results: Diabetic patients exhibited higher plaque accumulation, clinical attachment loss, and bleeding on probing compared with non-diabetic individuals (p < 0.05). The diabetic groups showed significantly higher levels of Actinomyces, Fusobacterium, and Streptococcus spp., with decreased Staphylococcus counts. ACE2 and TMPRSS2 expression were markedly elevated in gingival epithelial cells of P T2DM patients, predominantly in basal and suprabasal layers. The nuclear-to-cytoplasmic ratio and polymorphonuclear cell counts were also increased in diabetic subjects. Conclusions: T2DM and P synergistically upregulate ACE2 and TMPRSS2 expression and alter the oral microbiota. Full article

Background/Objectives: Early detection remains the most decisive factor in improving outcomes for oral cancer and oral potentially malignant disorders. However, reliance on conventional biopsy-based pathways presents some practical and biological limitations. This scoping review aimed to map recent advances in non- and minimally invasive diagnostic approaches and to clarify how these innovations are being positioned within clinical workflows. Methods: Following PRISMA-ScR guidance, PubMed/MEDLINE, Scopus, and Web of Science were searched for English-language original studies published between 2020 and 2025. Two independent reviewers screened and charted data on technologies, biomarkers, sampling sources, and clinical applications. Forty-nine studies were included. The literature clustered around four main domains: enhanced cytology (including liquid-based platforms and DNA ploidy analysis), multilayer liquid biopsy strategies (miRNA, cfDNA/ctDNA, methylation panels, and autoantibodies), optical and nanotechnology-based systems (Raman/SERS and sensor platforms), and artificial intelligence-driven decision support tools. Results: Across modalities, a shared emphasis on rapid triage, risk stratification, and follow-up monitoring was evident. Nonetheless, variability in sampling, processing, analytical thresholds, and reporting standards limited cross-study comparability. Conclusions: Recent innovations point toward integrated, panel-based diagnostic models. Broader clinical adoption will require methodological standardization and robust multicenter validation. Full article

Background: Persistent cervical human papillomavirus (Human papillomavirus) infection remains a significant public health concern, as it is the primary etiological factor in the development of cervical cancer and its precursor lesions. While prophylactic vaccination and standard screening programs are cornerstones of prevention, a substantial proportion of women with established infection are managed conservatively, often with prolonged follow-up and associated psychological burden. Interest has therefore grown in supportive interventions that may facilitate viral clearance during routine clinical management. Methods: This retrospective cohort study included 239 women with confirmed cervical Human papillomavirus infection followed at a tertiary referral center between February 2023 and August 2025. Participants were classified into a treatment group receiving oral Papivir/Pavirona^® twice daily for six months (n = 119) and a control group managed with routine clinical follow-up alone (n = 120). Human papillomavirus DNA testing and cervical cytology were evaluated at baseline and at 6 and 12 months. Results: Human papillomavirus clearance rates were significantly higher in the Papivir/Pavirona^® group compared with controls at both 6 and 12 months. Cytological regression was also more frequent in the treatment group at both time points. In multivariate logistic regression analysis, Papivir/Pavirona^® use emerged as the only independent predictor of both Human papillomavirus clearance and cytological regression, while demographic, reproductive, behavioral, and virological baseline characteristics were not significantly associated with outcomes. Conclusions: Papivir/Pavirona^® supplementation was associated with increased Human papillomavirus clearance and cytological regression rates in women with cervical Human papillomavirus infection, suggesting a potential supportive role alongside standard clinical follow-up. Full article

Cigarette smoke contains a high concentration of carcinogenic substances to which smokers are regularly exposed. Passive smoking is seriously harmful to the health of non-smoking humans and animals. Domestic cats are particularly vulnerable because of their constant grooming activity, which can promote oral ingestion of smoke-derived residues. Cotinine, a nicotine metabolite, is a reliable biomarker for tobacco exposure. Considering these observations, our study aimed to (1) characterize cytological alterations in oral mucosal epithelial cells by conventional morphology and automated digital cytomorphometry; (2) quantify urinary cotinine concentration and investigate its possible correlation with oral epithelial cytological alterations. To this aim, oral smears were collected from 30 cats divided into two groups (20 exposed; 10 non-exposed). Smears were stained with May–Grünwald–Giemsa and Papanicolaou to assess inflammation and dysplasia; digital cytomorphometric analysis was used to quantify the nucleus-to-cytoplasm (N/C) ratio. Urinary cotinine was measured by ELISA. Our results showed that exposed cats had significantly higher urinary cotinine levels and higher N/C ratios (p < 0.01) than non-exposed controls, along with mild-to-severe inflammation and dysplastic-like epithelial alterations. These findings support urinary cotinine as a valid biomarker of household tobacco smoke exposure in domestic cats and suggest that such exposure may be correlated with early cytological and cytomorphometric changes in the oral mucosa. Further studies are needed to better investigate the relationship between exposure duration and cytological, cytomorphometric, and molecular alterations. Full article

Cryptococcosis is a severe systemic mycosis affecting humans and animals, caused primarily by members of the Cryptococcus neoformans/Cryptococcus gattii species complex. In cats, it is the most common systemic fungal infection and may present with non-specific signs involving the upper respiratory tract, skin, lymph nodes, eyes, or the central nervous system. This study presents two feline cases of cryptococcosis diagnosed by cytological examination and provides an updated literature review. Fine-needle aspiration biopsies were performed in two cats with chronic nasal swelling and submandibular enlargement. Cytological smears stained with hematoxylin and eosin revealed spherical to oval yeast-like organisms with a characteristic thick, non-staining capsule, narrow-based budding, and absence of pseudohyphae, consistent with Cryptococcus spp. Based on cytological findings, both patients were treated with oral itraconazole, resulting in favorable clinical outcomes. A limitation of this study is the lack of mycological culture or molecular confirmation, owing to the owners’ refusal of further diagnostic testing. These cases highlight the diagnostic value of cytology as a rapid tool for differentiating fungal infections from neoplastic processes. Early diagnosis and antifungal therapy are crucial for successful management. From a One Health perspective, feline cryptococcosis may indicate shared environmental exposure risks relevant to both animal and human health. Full article

Oral squamous cell carcinoma (OSCC) cytology involves extracting a cell sample consisting of single cells or small clusters of cells from patients’ head and neck area in order to identify abnormal morphological characteristics after staining it. This method is used to screen for early cancer and the formation of metastases within the oral cavity. OSCC diagnosis partly depends on pathologists’ skills and also laboratories’ instrumentation. The use of Raman spectroscopy could support diagnoses performed using traditional methods, providing information based on the cellular biochemical environment. Technical drawbacks related to low signal-to-noise ratios of Raman spectroscopy and the need to obtain diagnostic information within a reasonable time frame have recently led to the analysis of Raman spectra using machine learning (ML) methods in order to obtain reliable information about the correct attribution of unknown cellular spectra. So, we used Raman micro-spectroscopy combined with machine learning methods to build classification models, which allow the diagnosis of different grades of OSCC in cell samples. The Raman spectra were analysed in the 980–1800 cm⁻¹ range by focusing the laser beam onto the nucleus and the cytoplasm regions of single cells from different cell lines modelling healthy (HaCaT) and cancer (Cal-27, SAS and HSC-3) cytological samples. We considered six classification algorithms (k-Nearest Neighbours, Logistic Regression, Naïve Bayes, artificial Neural Network, Random Forest and Support Vector Machine) to classify unknown Raman spectra. We report two classification tasks: a 4-level classification, which encompasses healthy cells, two different types of cancer cells, and one type of metastatic cells, and a 3-level classification, which includes healthy cells, non-metastatic cancer cells, and metastatic cancer cells. Our findings show that both Neural Network and Support Vector Machine algorithms applied to Raman spectra measured in the cytoplasm region can achieve sensitivity, precision and F1-score values larger than 90% in the 3-groups classifications, whereas Support Vector Machine performs better in the 4-groups classification with respect to a Neural Network. These results contribute to increasing confidence in the clinical translation of ML-assisted Raman spectroscopy as a tool to support conventional cytological techniques. Full article

Background/Objectives: Cervical cancer remains a major cause of morbidity and mortality among women worldwide, marked by stark geographic and socioeconomic disparities. Preventable via HPV vaccination and screening, progress toward elimination varies widely across and within countries. This narrative review synthesizes the epidemiology, including incidence, mortality, survival, and stage distribution, as well as risk factors and the coverage/equity of HPV screening and vaccination programs. Methods: Comprehensive searches were performed in PubMed, Web of Science, Scopus, and Google Scholar (no date restrictions; English only). Included were original epidemiological studies, systematic reviews, meta-analyses, and international reports on burden, risk factors, or prevention indicators. Data were qualitatively synthesized into three themes: epidemiological patterns, risk factors, and screening/prevention programs. Results: Persistent high-risk HPV infection causes nearly all cervical cancers, predominantly HPV16/18, with regional variation in other types. Strong co-factors include HIV immunosuppression, early sexual debut, multiple partners, high parity, long-term oral contraceptive use, and smoking. Inequalities in incidence, late diagnosis, and survival are driven by socioeconomic disadvantages, low education, rural residence, and poor health system access. Screening ranges from cytology/VIA to primary HPV testing, but coverage is low and inequitable in high-burden settings. HPV vaccination has expanded yet faces major gaps in low- and middle-income countries. Conclusions: Cervical cancer burden concentrates in low-resource and marginalized populations. Global elimination demands accelerated, equitable scale-up of HPV vaccination and screening, alongside health system strengthening and barrier reduction. Full article

We undertook a preliminary clinical study to compare the efficacy of lime essential oil shampoo with a conventional 2% miconazole/chlorhexidine formulation, both in combination with pulse oral itraconazole, in cats with dermatophytosis caused by M. canis. Sixteen affected cats were randomly assigned to receive either lime essential oil shampoo or a 2% miconazole/chlorhexidine formulation. All cats were bathed twice weekly and received itraconazole (5 mg/kg once daily) using a pulse regimen (1 week for every 2 weeks) for 56 days. Clinical assessments, including cytological, direct hair examinations, Wood’s lamp evaluation, total skin lesion score (TLS), and fungal pathogen score (FPS), were performed on days 0, 28, 42, and 56. Hematological and biochemical analyses were conducted on days 0, 28, and 56. By day 56, no significant differences were observed between groups in the cytological, direct hair examination, or Wood’s lamp results. Both groups had significant reductions in TLS and FPS on days 28, 42, and 56 compared to day 0 (p < 0.05). No cutaneous or systemic adverse effects were observed. These findings suggest that lime essential oil shampoo has clinical efficacy comparable to the conventional formulation and may represent a safe natural alternative for the topical management of feline dermatophytosis. Full article

Background and Objectives: Squamous cell carcinoma (SCC) of the lip is a common malignancy of the oral and maxillofacial region. Medium-to-large post-excisional defects often require reconstructive techniques that preserve oral competence, function, and facial aesthetics. Despite its broad clinical use, the Karapandzic flap lacks comprehensive evidence describing its postoperative outcomes and associated complications. Materials and Methods: This retrospective cohort study evaluated all consecutive patients who underwent lip SCC excision followed by Karapandzic flap reconstruction at a tertiary oncologic center in Greece from 2000 to 2024. Demographic, clinical, pathological, and postoperative data were collected, and complications were categorized as early (wound dehiscence, surgical site infection, hematoma) or late (microstomia, excessive scarring). Statistical analyses included comparative tests and Firth’s logistic regression to explore potential predictors of morbidity. Results: A total of 102 patients met the inclusion criteria. Most were male (82.4%) with a median age of 68.8 years, and 94.1% had lower-lip tumors. Early complications occurred in 9.8% of patients and late complications in 17.7%, with microstomia being the most frequent late event (15.7%). Age was the only variable showing a borderline significant association with overall complications. No demographic, clinical, or pathological factor, including lesion morphology, cytological diagnosis, tumor location, or presence of metastasis, demonstrated a statistically significant association with early or late complications. Conclusions: Karapandzic flap reconstruction represents a reliable single-stage option for lip SCC defects, demonstrating relatively low complication frequencies and generally favorable functional outcomes. Further comparative studies are warranted to evaluate its performance relative to alternative reconstructive techniques. Full article