Bethesda System Research Articles

Cold Knife Conization Vs. Loop Electrosurgical Excision Procedure in Premalignant Cervical Lesions in a Cohort of Females in Romania

Cold knife conization and loop electrosurgical excision procedures (LEEP) are two methods of minimally invasive treatment used in Romania for high-grade cervical dysplasia. The purpose of this study is to identify correlations between the results of the Papanicolaou (PAP) smear and biopsy and to evaluate the positivity of resection margins in both types of conizations: cold knife conization versus LEEP. The 96 cases enrolled in this study were gathered from ‘Prof. Dr. Ioan Pușcaș’ City Hospital of Șimleu Silvaniei, Romania, in a time interval from 01.01.2022 to 01.01.2024. The results of our study showed that out of 20 women who underwent PAP smear for ASC-US, 4 were actually found to have high-grade squamous intraepithelial lesion (H-SIL) according to biopsy results. The estimated risk in females who underwent LEEP procedure with positive margins in the histopathological examination, in the studied population, is almost 0.5 times higher compared to those who underwent cold knife conization. Histopathological examination of cervical specimens is the gold standard method in detecting high-risk cervical lesions. Our study shows that positive deep endocervical margins are more likely to occur in loop electrosurgical excision procedures compared with cold knife conization.

Evaluating the Diagnostic Role of ACR-TIRADS and Bethesda Classifications in Thyroid Nodules Highlighted by Cyto-Histopathological Studies.

To evaluate the accuracy of thyroid imaging reporting and data system (ACR-TIRADS) and the Bethesda system for reporting cytopathology (TBSRCP) classifications for identifying or ruling out thyroid malignancy in relation to the gold standard (post-surgical pathology). This cross-sectional study included 573 patients with single or multiple thyroid nodules. Patients were evaluated using the TIRADS and the TBSRCP classification. The data from a cohort of patients who underwent surgery (77/573, 13.4%) were correlated with post-operative pathology and the relevant clinical features of the patients. Of 573 patients, 545 (95.1%) were euthyroid, 24 (4.1%) were hypothyroid, and 4 (0.8%) were hyperthyroid; 419 (73.1%) had benign nodules (Bethesda II), 115 (20.1%) had intermediate (Bethesda III, IV), and 39 (6.8%) had Bethesda V and VI nodules. Four-hundred twenty (73.3%) patients were categorized as TIRADS 2,3, and 153 (26.7%) were categorized as TIRADS 4,5. The Bethesda and TIRADS classifications concorded significantly in thyroid nodule diagnosis (K=14.9%, P<0.001).Thyroid malignancy was significantly associated with microcalcification and interrupted halo, while benign nodules were significantly associated with macrocalcification and complete halo type (P=0.041, P=0.005, respectively). The TBSRCP could significantly detect malignant thyroid nodules with a sensitivity, specificity, PPV, and NPV of 64.1%, 98.1%, 85.0%, and 94.1%, respectively (K=88.2%, P<0.001), while the respective values for the TIRADS classification were 63.5%, 76.0%, 84.6%, and 50.0% (K=34.8%, P=0.001). The TIRADS and TBSRCP are essential primary steps for evaluating thyroid nodules and both are complimentary. Hence, each patient with thyroid nodules should be evaluated by both approaches before opting for surgery. Highly suspicious TIRADS categories TR4 and TR5 need further evaluation by fine needle aspiration cytology.

Comparative analysis of Paiteling a traditional Chinese medicine (TCM) and CO2 laser therapy for high-risk HPV-associated with LSIL (CIN1) lesions

ObjectivesThis study aims to evaluate the therapeutic outcomes of Paiteling and CO2 laser therapy on high-risk human papillomavirus. MethodsWe retrospectively analyzed the data of 558 patients with HR-HPV low-grade squamous intraepithelial neoplasia (CIN1) from 2021 to 2023. Patients were selected and put into two groups: Paiteling and CO2 laser. Out of the 558 patients who were included in our final study, 239 (42.8 %) were treated with Paiteling, and 319 (57.2 %) were treated with CO2 laser vaporization. The mean age was 49.55 ± 12.10 years old. We observed that 27 (4.83 %) were younger than 30 years and 531 (95.1 %) were older than 30 years. We reviewed the patient’s results at intervals of 3 months, 6 months, 12 months, and 24 months after each therapy. The results of the recurrence rate, effective viral clearance rate, and the effectiveness of both therapies on low-grade cervical lesions were determined using multivariate and univariate cox-regression analysis. The Kaplan-Meier curve was used to determine the HR-HPV conversion rate of each therapy. ResultsThe median time for HR-HPV clearance was 6.00 months (95 % CI: 4.26–6.89) in the Paiteling group and 9.00 months (95 % CI: 15.92–22.67) in the CO2 laser group. There was a significant difference between the two groups (χ2 = 25.118, p-Value = 0.000). The HR-HPV clearance rate during 6–12 months for Paiteling and CO2 laser was 100 (55.6 %) and 80 (44.4 %), respectively. The clearance rate for both therapies from 6 to 18 months was statistically significant (6–12 months: p < 0.010, 12–18 months: p < 0.011). The Paiteling HR-HPV negative rate over 24 months 214 (89.5 %) is higher than CO2 laser 176 (55.2 %). Paiteling has a 5.4 % re-infection rate, which is marginally lower than the 5.6 % rate for CO2 lasers.The clearance rate for both therapies from 12 to 18 months [Paiteling: 20 (4.7 %) to 10 (3.6 %) and CO2 laser: 22 (8.4 %) to 15 (4.2 %)] was also significant (p < 0.011). The percentage of persistent Hr-HPV clearance rate for Paiteling patients was higher than carbon dioxide laser vaporization. No severe side effects were reported by the Paiteling patients compared to laser vaporization. This is due to the fact that Paiteling, as a traditional Chinese medicine, is a topical, non-invasive medicine, thus preserving the integrity of the cervix. ConclusionsPaiteling is an effective noninvasive therapy that can clear persistent HR-HPV associated with cervical low-grade squamous lesions in a relatively shorter period of time compared to CO2 laser ablation.

CAPZB mRNA is a novel biomarker for cervical high-grade squamous lesions

This study aimed to evaluate the potential of capping protein (actin filament) muscle Z-line subunit β (CAPZB) messenger ribonucleic acid (mRNA) levels as a biomarker for distinguishing low-grade squamous intraepithelial lesions of the cervix (LSIL) from high-grade squamous intraepithelial lesions of the cervix (HSIL). We collected a total of 166 cervical exfoliated cells and divided them into five groups based on histopathological results. Each sample was divided into two portions, one for fluorescence in situ hybridization (FISH) detection and the other for bisulfite sequencing polymerase chain reaction (BSP) detection. We found that FISH detection of CAPZB mRNA mean fluorescence intensity (MFI) and BSP detection of CAPZB deoxyribonucleic acid (DNA) percentage of methylation rate (PMR) performed as biomarkers for distinguishing HSIL from LSIL, with an area under the receiver operating characteristic curve (AUC), sensitivity, specificity and cut-off value of 0.893, 81.25%, 80.39% and 0.616, 0.794, 64.06%, 81.37% and 0.454, respectively. Furthermore, FISH detection of CAPZB mRNA exhibited a greater AUC (0.893) for the detection of HSIL than the CAPZB DNA methylation method (0.794), indicating the CAPZB mRNA levels can be used as a biomarker for assessing cervical lesions.

Automated analysis of scattering-based light sheet microscopy images of anal squamous intraepithelial lesions.

We developed an algorithm for automatically analyzing scattering-based light sheet microscopy (sLSM) images of anal squamous intraepithelial lesions. We developed a method for automatically segmenting sLSM images for nuclei and calculating seven features: nuclear intensity, intensity slope as a function of depth, nuclear-to-nuclear distance, nuclear-to-cytoplasm ratio, cell density, nuclear area, and proportion of pixels corresponding to nuclei. 187 images from 80 anal biopsies were used for feature analysis and classifier development. The automated nuclear segmentation method provided reliable performance with the precision of 0.97 and recall of 0.91 when compared with the manual segmentation. Among the seven features, six showed statistically significant differences between high-grade squamous intraepithelial lesion (HSIL) and non-HSIL (non-dysplastic or low-grade squamous intraepithelial lesion, LSIL). A classifier using linear support vector machine (SVM) achieved promising performance in diagnosing HSIL versus non-HSIL: sensitivity of 90%, specificity of 70%, and area under the curve (AUC) of 0.89 for per-image diagnosis, and sensitivity of 90%, specificity of 80%, and AUC of 0.92 for per-biopsy diagnosis.

Unveiling the hidden link: fungi and HPV in cervical lesions.

Cervical cancer, primarily driven by high-risk human papillomavirus (HR-HPV) infection, ranks as the second most common cancer globally. Understanding combined infections' role, including Cervical fungi, is crucial in cervical carcinogenesis. This study aims to explore the potential correlation between HR-HPV, cervical fungi, and cervical cancer, while adjusting for various factors. The study population comprised patients undergoing colposcopy and conization due to abnormal cervical screening results. Clinical data including age, gravidity, HPV (human papillomavirus) genotypes, cervical pathology, and p16/Ki67 expression were extracted. Cervical TCT (ThinPrep Pap Test) and HPV testing are utilized for screening cervical lesions, with fungal presence suggested by TCT results. 5,528 participants were included in this study. Statistical analyses investigated associations between HPV/fungi co-infection and cervical lesions, employing multinomial logistic regression and interaction analysis. Co-infection with fungi and HPV may decrease the risk of cervical lesions compared to HPV infection alone. In the co-infection group, compared with HPV infection alone, the risk of low-grade squamous intraepithelial lesions (LSIL) was reduced by 27% (OR = 0.73, 95% CI: 0.59-0.90), the risk of high-grade squamous intraepithelial lesions (HSIL) was reduced by 35% (OR = 0.65, 95% CI: 0.51-0.82), and the risk of cervical cancer was reduced by 43% (OR = 0.57, 95% CI: 0.35-0.92). The interaction analysis revealed a negative interaction between fungal and HPV infections in the development of cervical cancer (RERI = -6.25, AP = -0.79, SI = 0.52), HSIL (RERI = -19.15, AP = -0.37, SI = 0.72) and LSIL (RERI = -1.87, AP = -0.33, SI = 0.71), suggesting a sub-additive effect, where the combined effect of the two infections was less than the sum of their individual effects. This indicates that fungal infection may attenuate the promoting effect of HPV on cervical lesions. In exploring the potential mechanism, we found that the co-infection group had significantly lower p16 positivity (54.6%) compared to the HPV-only group (60.2%) (p = 0.004), while there was no statistically significant difference in Ki67 positivity. This study unveils the intricate relationship between cervical fungi and HPV in cervical lesions. Co-infection with fungi and HPV against cervical lesions compared to HPV infection alone, indicating a novel clinical interaction. Lower p16 positivity in co-infection hints at a protective mechanism, urging further exploration.

Two Decades of Thyroid Nodule Cytology in Children: Malignancy Risk Assessment at a Tertiary Care Center

Plain Language SummaryPediatric thyroid nodules are less common than those in adults, but they have a higher risk of being cancerous. This study reviews data from the past 20 years at a major healthcare center to understand how often these nodules are malignant in children and how accurate fine-needle aspiration (FNA) biopsies are in diagnosing them. The study analyzed 75 thyroid nodules from 73 children, finding that 62.6% of the nodules were malignant. The FNA biopsy, a key diagnostic tool, was shown to be very accurate, with a sensitivity of 78.38% and a perfect specificity of 100%. This means that FNA is highly reliable for identifying both cancerous and noncancerous nodules in children. One significant finding is that the risk of cancer in thyroid nodules categorized as indeterminate (uncertain) by the Bethesda System is much higher in children than in adults. This suggests that pediatric thyroid nodules behave more aggressively, underscoring the need for careful evaluation and tailored guidelines for children. These results are crucial for medical professionals as they highlight the importance of specialized approaches in managing thyroid nodules in children, ensuring accurate diagnosis and appropriate treatment to avoid overtreatment and unnecessary surgeries.

Radiofrequency ablation of Bethesda category III thyroid nodules with benign molecular testing: Preliminary findings from a single institution

BackgroundThe efficacy of radiofrequency ablation (RFA) in treating thyroid nodules with indeterminate cytology remains less studied. The objective of this study was to determine the efficacy of RFA in treating nodules with Bethesda III that have been molecularly profiled benign (BIII-MPN). MethodsWe included prospectively enrolled patients who underwent RFA for benign and BIII-MPN thyroid nodules. Primary outcome measures were volume reduction ratio (VRR), symptom score (range 0–10), and cosmetic score (range 0–3) at 1, 3, 6, and 12 months after RFA, as well as complication rates. ResultsA total of 258 nodules in 192 patients were included (benign: 238 in 174; BIII-MPN: 20 in 18). The median VRR differed insignificantly, whereas symptom and cosmetic score improvements were similar between two cohorts. BIII-MPN thyroid nodules were associated with lower rates of infection and temporary voice change. ConclusionOur preliminary findings suggest that RFA may be a feasible management option for BIII-MPN thyroid nodules. However, appropriate will be important to address the important risk of potentially missed malignancies.

Automatic Classification of Nodules from 2D Ultrasound Images Using Deep Learning Networks.

In clinical practice, thyroid nodules are typically visually evaluated by expert physicians using 2D ultrasound images. Based on their assessment, a fine needle aspiration (FNA) may be recommended. However, visually classifying thyroid nodules from ultrasound images may lead to unnecessary fine needle aspirations for patients. The aim of this study is to develop an automatic thyroid ultrasound image classification system to prevent unnecessary FNAs. An automatic computer-aided artificial intelligence system is proposed for classifying thyroid nodules using a fine-tuned deep learning model based on the DenseNet architecture, which incorporates an attention module. The dataset comprises 591 thyroid nodule images categorized based on the Bethesda score. Thyroid nodules are classified as either requiring FNA or not. The challenges encountered in this task include managing variability in image quality, addressing the presence of artifacts in ultrasound image datasets, tackling class imbalance, and ensuring model interpretability. We employed techniques such as data augmentation, class weighting, and gradient-weighted class activation maps (Grad-CAM) to enhance model performance and provide insights into decision making. Our approach achieved excellent results with an average accuracy of 0.94, F1-score of 0.93, and sensitivity of 0.96. The use of Grad-CAM gives insights on the decision making and then reinforce the reliability of the binary classification for the end-user perspective. We propose a deep learning architecture that effectively classifies thyroid nodules as requiring FNA or not from ultrasound images. Despite challenges related to image variability, class imbalance, and interpretability, our method demonstrated a high classification accuracy with minimal false negatives, showing its potential to reduce unnecessary FNAs in clinical settings.

The value of endocervical curettage during large loop excision of the transformation zone in combination with endocervical surgical margin in predicting persistent/recurrent dysplasia of the uterine cervix: a retrospective study

BackgroundCervical cancer often originates from cervical cell dysplasia. Previous studies mainly focused on surgical margins and high-risk human papillomavirus persistence as factors predicting recurrence. New research highlights the significance of positive findings from endocervical curettage (ECC) during excision treatment. However, the combined influence of surgical margin and ECC status on dysplasia recurrence risk has not been investigated.MethodsIn this retrospective study, data from 404 women with high-grade squamous intraepithelial lesions (HSIL) who underwent large loop excision of the transformation zone (LLETZ) were analyzed. Records were obtained retrospectively from the hospital’s patient database including information about histopathological finding from ECC, endocervical margin status with orientation of residual disease after LLETZ, recurrent/persistent dysplasia after surgical treatment and need for repeated surgery (LLETZ or hysterectomy).ResultsPatients with cranial (= endocervical) R1-resection together with cells of HSIL in the ECC experienced re-surgery 17 times. With statistical normal distribution, this would have been expected to happen 5 times (p < 0.001). The Fisher’s exact test confirmed a statistically significant connection between the resection status together with the result of the ECC and the reoccurrence of dysplasia after surgery (p < 0,001). 40,6% of the patients with re-dysplasia after primary LLETZ had shown cranial R1-resection together with cells of HSIL in the ECC. Investigating the risk for a future abnormal Pap smear, patients with cranial R1-resection together with dysplastic cells in the ECC showed the greatest deviation of statistical normal distribution with SR = 2.6.ConclusionOur results demonstrate that the future risk of re-dysplasia, re-surgery, and abnormal Pap smear for patients after LLETZ due to HSIL is highest within patients who were diagnosed with cranial (endocervical) R1-resection and with cells of HSIL in the ECC in their primary LLETZ. Consequently, the identification of patients, who could benefit of intensified observation or required intervention could be improved.

Oral cancer screening using cytopathology: An advanced proposal with the Bethesda classification.

Oral cancer screening requires analysis capable of detecting changes preceding the clinical manifestation. Oral cytopathology studies as an oral cancer screening have shown promising results. This study aims to evaluate the use of cytopathology in a quali-quantitative analysis using Papanicoloau staining. Four experimental groups were evaluated: control (CG), exposed to carcinogens (EG), potentially malignant disorder with and without epithelial dysplasia (D-OPMDG and ND-OPMDG) and oral squamous cell carcinoma (OSCCG). Oral smears were collected using a Cytobrush® and conventional exfoliative cytology. Oral Papanicolaou smears from 143 individuals were analysed in 8100 images. Qualitatively, non-lesional groups exhibited minimal suspected cases (20% in CG and 5% in EG), in the OPMD groups the ability to identify altered cells was low (40% in D-OPMDG and 0% in ND-OPMDG). Conversely, a notable100% accuracy was achieved in the OSCCG. Quantitatively, a higher percentage of anucleated and a lower percentage of intermediate cells were observed in the OPMDG; a higher proportion of parabasal/suspicious cells was observed in OSCCG. The optimal threshold for improved accuracy in detecting suspected malignancies occurs when the count of parabasal/suspicious cells exceeds 8/100 cells examined. Cytomorphometric analysis revealed a higher nucleus/cytoplasm ratio (N/C) in OSCCG, with a best cutoff point indicating enhanced accuracy in discerning suspected malignancies when exceeding 17% of cells exhibiting this elevated ratio. It is possible to suggest updates in cytomorphometric and quantitative analysis in the modified Bethesda system for the oral cavity including objective criteria in the risk classification, therefore improving oral cancer screening.

AICyte-alone capabilities as an independent screener for triaging cervical cytology using a 50% negative cutoff value.

AICyte has previously demonstrated a potential role in cervical cytology screening for reducing the workload by using a 50% negative cutoff value. The aim of the current study is to evaluate this hypothesis. The authors used the Ruiqian WSI-2400 (with the registered trademark AICyte) to evaluate a collection of 163,848 original cervical cytology cases from 2018 to 2023 that were collected from four different hospital systems in China. A breakdown of cases included 46,060 from Shenzhen, 67,472 from Zhengzhou, 25,667 from Shijiazhuang, and 24,649 from Jinan. These collected cases were evaluated using the AICyte system, and the data collected were statistically compared with the original interpretative results. In 98.80% of all artificial intelligence cases that were designated as not needing further review, the corresponding original diagnosis was also determined to be negative. For any cases that were designated atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesion or higher, the sensitivity and negative predictive value were 90.77% and 98.80%, respectively. The sensitivity and negative predictive value were greater in cases designated as low-grade squamous intraepithelial lesion or higher at 98.92% and 99.94%, respectively. Of the 49 low-grade squamous intraepithelial lesion or higher that were designed by AICyte as not needing further review, the cytohistologic correlation revealed eight cases of cervical intraepithelial neoplasia 1 and 18 negative cases; and the remaining cases were without histologic follow-up. In practice, AICyte used at a 50% negative cutoff value could reduce the anticipated workload if a protocol were implemented to label cases that qualified within the negative cutoff value as not needing further review, thereby finalizing the case as negative for intraepithelial lesions and malignancy. For pathologic practices that do not have cytotechnologists or in which the workflow is sought to be optimized, the artificial intelligence system AICyte alone to be an independent screening tool by using a 50% negative cutoff value, which is a potential assistive method for cervical cancer screening.

Identification of HPV16 Lineages in South African and Mozambican Women with Normal and Abnormal Cervical Cytology.

Human papillomavirus 16 (HPV16) is an oncogenic virus responsible for the majority of invasive cervical cancer cases worldwide. Due to genetic modifications, some variants are more oncogenic than others. We analysed the HPV16 phylogeny in HPV16-positive cervical Desoxyribonucleic Acid (DNA) samples collected from South African and Mozambican women to detect the circulating lineages. Polymerase chain reaction (PCR) amplification of the long control region (LCR) and 300 nucleotides of the E6 region was performed using HPV16-specific primers on HPV16-positive cervical samples collected in women from South Africa and Mozambique. HPV16 sequences were obtained through Next Generation Sequencing (NGS) methods. Geneious prime and MEGA 11 software were used to align the sequences to 16 HPV16 reference sequences, gathering the A, B, C, and D lineages and generating the phylogenetic tree. Single nucleotide polymorphisms (SNPs) in the LCR and E6 regions were analysed and the phylogenetic tree was generated using Geneious Prime software. Fifty-eight sequences were analysed. Of these sequences, 79% (46/58) were from women who had abnormal cervical cytology. Fifteen SNPs in the LCR and eight in the E6 region were found to be the most common in all sequences. The phylogenetic analysis determined that 45% of the isolates belonged to the A1 sublineage (European variant), 34% belonged to the C1 sublineage (African 1 variant), 16% belonged to the B1 and B2 sublineage (African 2 variant), two isolates belonged to the D1-3 sublineages (Asian-American variant), and one to the North American variant. The African and European HPV16 variants were the most common circulating lineages in South African and Mozambican women. A high-grade squamous intraepithelial lesion (HSIL) was the most common cervical abnormality observed and linked to European and African lineages. These findings may contribute to understanding molecular HPV16 epidemiology in South Africa and Mozambique.

Associations of clinical and modifiable behavioral risk factors with the histological progression of squamous intraepithelial lesions.

Cervical cancer is the third most common cancer in women worldwide. Human papillomavirus (HPV) has been established as a cause of invasive cervical cancer. However, HPV is predominantly transient and only a minority of cases persist and progress clinically. Certain epidemiological factors have been suggested to increase the risk of HPV persistence and progression. In the present study, 893 women were investigated, with an age range from 25 to 60 years old. PAP smears and colposcopy were used for assessment. Of these women, 108 were diagnosed with squamous intraepithelial lesions (SILs) and were further divided into high-grade SIL (HSIL) and low-grade SIL (LSIL). The dietary habits, sleep patterns and gynecological histories of these participants were studied, and it was found that the probability of having <3 meals a day [odds ratio (OR), 4.35; 95% confidence interval (CI), 1.73-10.95], having an unbalanced diet (OR, 3.90; 95% CI, 1.44-10.55), breakfast skipping (OR, 6.32; 95% CI, 2.40-16.61) and disrupted sleep (OR, 4.42; 95% CI, 1.79-10.93) was significantly higher in the HSIL group compared with the probability in the LSIL group. In addition, participants who had pregnancies prior to the age of 20 were 2.85 times more likely to have more advanced disease (OR, 2.85; 95% CI, 1.22-6.71). Cervical erosion was higher in the HSIL group compared with that in the LSIL group (OR, 3.31; 95% CI, 1.36-6.96). The present study highlights the protective effects of meal numbers, nutritious diet and sleep hygiene against HPV and the progression of SIL.

Prevalence of Anal Human Papillomavirus Infection and Anal High-Grade Squamous Intraepithelial Lesions Among Men Who Have Sex With Men 50 Years and Older Living With or Without HIV.

Anal cancer is caused by human papillomavirus (HPV), particularly HPV-16, and is preceded by anal high-grade squamous intraepithelial lesions (HSILs). The incidence of anal cancer is highest among men who have sex with men (MSM) living with HIV (MSMLWH) and increases with age. However, most previous studies of anal HPV infection and anal HSIL were performed on men under 50 years old, and relatively little is known about HSIL among older MSMLWH or MSM not living with HIV (MSM-Not-LWH). We enrolled MSM who were aged 50+ during 2018-2022 in San Francisco, CA. One hundred twenty-nine MSMLWH and 109 MSM-not-LWH participated. All participants had anal HPV DNA testing (Atila Biosystems) and high-resolution anoscopy with a biopsy of visible lesions. Among MSMLWH, 47% had anal HSIL, 19% had HPV-16, and 51% had other oncogenic anal HPV types (excluding HPV-16). Among MSM-not-LWH, 37% had anal HSIL, 22% had HPV-16, and 34% had other oncogenic anal HPV types. Increasing age was not statistically associated with prevalent HSIL, HPV-16, or other oncogenic HPV infections in MSMLWH or MSM-not-LWH. HPV-16 (odds ratio: 45.1, 95% confidence interval: 15.8-129); other oncogenic HPV types (odds ratio: 5.95, 95% confidence interval: 2.74-12.9) were associated with increased odds of anal HSIL, adjusted for age, income, education, and HIV status. The prevalence of oncogenic anal HPV, anal HPV-16, and anal HSIL remains very high in older MSMLWH and MSM-not-LWH. With recent evidence showing that treating anal HSIL prevents anal cancer, MSM aged 50+ should be considered for anal cancer screening.

Unsatisfactory Pap Test Results: A Critical Patient Management Problem Pre-Analytically Addressed by the Cytopathology Laboratory.

The unsatisfactory rate of Pap tests (PT) is an important quality assurance (QA) metric for a cytopathology laboratory. At our institution, an unsatisfactory PT slide is followed by a second ThinPrep (TP) slide. The aim of this study is to evaluate this QA practice. Our laboratory processes an unsatisfactory TP PT with a follow-up second TP slide with or without glacial acetic acid. The correlation between the unsatisfactory rate and the second slide rate test was examined. A total of 2739 cases with a second TP slide were prepared for an unsatisfactory initial TP PT. After second slide preparation, 780 cases (28%) remained unsatisfactory. Using Spearman's rank correlation test, there was a notable negative correlation between the unsatisfactory rate and the second slide rate (rho = -0.42). Of those PTs recategorized as satisfactory TP, 1742 were negative for intraepithelial lesion or malignancy (NILM) (89%), 135 as atypical squamous cells of undetermined significance (ASC-US) (7%), 37 as low-grade squamous intraepithelial lesion (LSIL) (1.9%), 11 as atypical squamous cells cannot exclude high-grade squamous intraepithelial lesion (ASC-H) (0.6%), 8 as high-grade squamous intraepithelial lesion (HSIL) (0.4%), and 20 as atypical glandular cells (AGC) (1%). The final Bethesda categorization for all cases and the human papilloma virus (HPV) data was tabulated. A second slide preparation significantly reduced the unsatisfactory rate of the PT. This also had a significant impact by detecting clinically significant lesions. HPV testing can also be performed on slides reclassified from unsatisfactory to ASC-US or higher.

The significance of extensive HPV genotyping for cervical high-grade neoplasia among women with atypical glandular cells.

To examine the associated risk of cervical intraepithelial neoplasm grade 3+ (CIN3+) lesions in patients with AGC and extensive human papillomavirus (HPV) genotyping. Cases with atypical glandular cell (AGC) interpretation on a Papanicolaou (Pap) test were identified along with associated extensive HPV genotyping and histologic follow-up results. Within this cohort of 469,694 Pap tests, 0.4% were diagnosed as AGCs. In total, 1267 cases had concurrent high-risk HPV (hrHPV) genotyping, and 40.3% were hrHPV positive. The percentage of AGC cases with cervical CIN3+ on histologic follow-up was 52.2% when hrHPV was positive, whereas it was 4.9% with a negative hrHPV result. The top 5 hrHPV genotypes associated with cervical CIN3+ in this cohort were HPV16, HPV18, HPV58, HPV52, and HPV33. Indeed, 92.8% of the hrHPV-associated CIN3+ lesions identified in this cohort were positive for at least one of these HPV genotypes. The sensitivity of detecting cervical CIN3+ lesions was 85.6% with the top 5 hrHPV genotypes (HPV16/18/58/52/33) and only increased to 89.0% when the additional 12 genotypes were included. In patients with an AGC Pap, the risk of having a cervical CIN3+ lesion is greatly increased by positivity for hrHPV types 16, 18, 58, 52, and/or 33. Incorporating comprehensive HPV genotyping into AGC cytology allows for refined risk stratification and more tailored management strategies.

Risk of developing high-grade squamous intraepithelial lesions or anal cancer after anal condylomata treatment in people living with HIV.

To assess the risk and natural history of developing advanced anal disease after diagnosis of anal condyloma in people living with HIV (PLWH). This was a single-centre retrospective cohort study of PLWH and anal condyloma from 2001 to 2021. Patients who developed advanced anal disease (AAD; anal high-grade squamous intraepithelial lesions and/or anal cancer) were compared to those who did not progress (non-AAD). We assessed the potential association between AAD and condyloma location, recurrence, and treatment modality. AAD-free survival was calculated utilizing Kaplan-Meier methods. A total of 118 PLWH and anal condyloma were included. Mean overall follow-up time was 9.3 years. A total of 31% of patients developed AAD (n = 37). Average time to AAD from condyloma diagnosis was 5.6 years. On multivariate analysis, risk for AAD development was associated with perianal location of condyloma (OR 4.39, p = 0.038) and increased time from initial condyloma diagnosis (OR 1.12, p = 0.008). Higher CD4/CD8 ratios were associated with lower risk of AAD (OR 0.15, p = 0.029). Condyloma recurrence and treatment type were not associated with development of AAD. AAD-free survival was longer in those with intra-anal only condyloma versus those with either perianal disease alone or combined intra-anal/perianal disease (mean survival times: 22.8 vs. 8.7 vs. 10.7 years, p = 0.017). Our study demonstrates the need for careful, long-term follow-up of PLWH and condyloma, particularly in the setting of perianal disease and low CD4/CD8 ratio. Risk of anal disease progression is present even in the setting of condyloma regression following treatment.

The use of vacuum fine needle aspiration biopsy of small formations in the diagnosis of thyroid cancer

Introduction. Diagnosis and treatment of lesional pathology of the thyroid are important problems in Russia and worldwide. Currently, fine-needle aspiration (FNA) is the main technique of differential diagnosis of benign and malignant tumors of the thyroid. In 2023, clinical guidelines of the European Thyroid Association (ETA) on thyroid lesion treatment were published noting possible minimally invasive treatment of benign and malignant tumors of the thyroid requiring repeat cytologic verification. Despite the proven effectiveness of FNA, its informativity and specificity vary between 60 and 100 %. Additionally, this method is associated with high risk of false negative and false positive results. Therefore, there is a need to improve FNA and minimize its disadvantages.Aim. To evaluate the capabilities of vacuum FNA of small lesions using multiparameter ultrasound in diagnosis of thyroid cancer.Materials and methods. At the scientific and practical problem laboratory Diagnostic Studies and Minimally Invasive Technologies of the Smolensk State Medical University, a device for vacuum FNA was developed. Between 2023 and 2024, patients with thyroid lesions of size &lt;10 mm underwent 25 vacuum FNAs. Correlation analysis with 51 FNAs performed between 2020 and 2023 was performed.Results. A decrease in the number of nondiagnostic (category I per the Bethesda system, 2017) and undetermined (category III per the Bethesda system, 2017) results was observed. Comparison of preoperative cytologic conclusions (category V per the Bethesda system, 2017) with the results of postoperative histological examination in patients of the control group showed benign lesions in 2 (50 %) cases which correspond to false negative results. Vacuum FNA did not show this discrepancy. These results demonstrate a decrease in the probability of false negative results and effectiveness of vacuum FNA.Conclusion. Use of vacuum FNA expedites ultrasound-guided biopsy for small thyroid lesions. Due to high negative pressure (up to –0.8 bar), single-step retrieval of cytologic material is performed which leads to a decrease in the number of nondiagnostic and undetermined cytologic conclusions by 11.7 and 1.9 %, respectively.

Follicular neoplasms with nuclear atypia versus other types of atypia: Should follicular neoplasms be stratified according to the presence of nuclear atypia?

The third edition of The Bethesda System (TBS) subclassifies the atypia of undetermined significance (AUS) category on the basis of the presence of nuclear atypia (AUS-Nuclear). This approach is supported by studies showing significant differences in the risk of malignancy (ROM) between AUS-Nuclear and those without (AUS-Other). Although aspirates of follicular neoplasms (FNs) are characterized by marked architectural atypia, TBS recognizes the infrequent occurrence of FNs with mild nuclear atypia (FN-Nuclear). Furthermore, limited studies have shown significant differences in ROM between FN-Nuclear and those without (FN-Other). This study explored potential differences in ROM, molecular-derived risk of malignancy (MDROM), and molecular alterations between FN-Nuclear and FN-Other. A retrospective database search identified 93 FN aspirates. Cytology slides, molecular reports, and histologic follow-ups were reviewed. Both groups' benign call rate (BCR), positive call rate (PCR), MDROM, and ROM were computed and compared. Eighty-six percent of aspirates (80 of 93) comprised FN-Other, whereas 14% (13 of 93) were FN-Nuclear. The BCR and PCR for FN-Other were 51% and 49%, respectively. In contrast, they were 23% and 77% for FN-Nuclear, respectively. The MDROM significantly differed between FN-Other (30%) and FN-Nuclear (56%) (p<.05). HRAS mutation was the most common molecular alteration in FN-Nuclear, whereas mutations in NRAS/KRAS and copy number alterations were more common in FN-Other. The ROM1/ROM2 in FN-Other and FN-Nuclear were 16%/31% and 54%/88%, respectively. These results reveal that FN-Nuclear exhibits significantly higher MDROM and ROM than FN-Other, which provides support for a subclassification scheme for FNs based on the presence of nuclear atypia.