Bethesda System Research Articles

A Comparative Study on BRAFV600E Mutation, Sonographic Findings, and Pathologic Characteristics in Non-invasive Follicular Thyroid Neoplasm with Papillary-like Nuclear Features (NIFTP) and Invasive Follicular Variant of Papillary Thyroid Carcinoma (IFVPTC)

Objective: Noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) comprise a new subgroup of thyroid tumors of follicular origin with borderline histologic features that lack evidence of either capsular or vascular invasion. In contrast to the invasive follicular variant of papillary thyroid carcinoma (IFVPTC), adverse events such as cancer-related death, distant or regional metastases, and structural or biochemical recurrence do not occur in patients with NIFTP. Many studies have been done to elucidate these two specific types of papillary thyroid cancer (PTC) and reduce aggressive therapeutic actions. This study compares molecular, cytological, and radiologic features of NIFTP and IFVPTC. Materials and Methods: Two groups of patients with NIFTP and IFVPTC (n = 18 in each group) who were referred to the endocrine clinic, at Imam Reza Hospital, were enrolled in this crosssectional study. Molecular analysis for BRAFV600E mutation of thyroid tissue was evaluated for all cases. Patient data included: age, sex, type of surgery, thyroid sonographic findings, and prior cytological diagnosis with the Bethesda system for reporting thyroid cytopathology. Results: Only two cases in the IFVPTC group were positive for BRAFV600E mutation. The majority of NIFTP cases were diagnosed as benign lesions (8/18). In contrast, the majority of IFVPTC cases were diagnosed as suspicious for malignancy on cytology (7/18). The mean nodule size in ultrasound in the NIFTP group (41.81 ± 20.43 mm) was larger than the IFVPTC group (36.72 ± 20.73 mm) (p =0.47). Most cases in the IFVPTC group had significantly multiple nodules (72.2%), while most cases in the NIFTP group (81.3%) had solitary nodules. Nodule composition in both groups was solid and complex; however, no cystic nodules were detected in ultrasound examinations. Furthermore, no calcification or lymphadenopathy was seen in the majority of cases in ultrasound. In the IFVPTC group, 47.1% and 35.3% of nodules were hyperechoic and hypoechoic, respectively, while 23.1%, 38.5%, and 23.1% of nodules in the NIFTP group were heterogenic, hyperechoic, and hypoechoic, respectively. Conclusion: According to our findings, only 11.1% of IFVPTC cases were BRAFV600E-positive, while none of the patients in the NIFTP group showed this mutation. However, IFVPTC was predominantly associated with a preceding diagnosis of PTC on FNA, and NIFTP was associated with the preceding diagnosis of benign lesions and follicular neoplasm. Sonographic findings failed to distinguish NIFTP from IFVPTC.

Influence of vitamin D supplementation and the vaginal microenvironment on human papillomavirus infection

This was a retrospective study, mainly explored the mediating role of vaginal microenvironment and the influence of vitamin D addition on human papillomavirus (HPV) infection. Five hundred and twelve participants were chosen in this study, followed by dividing into HPV positive (212 cases) and negative groups (300 cases) based on HPV 23 typing results. The high-risk human papillomavirus (HR-HPV) positive group showed higher abnormal rates of lactobacillus, catalase, cleanliness, sialidosidase, and proline aminopeptidase than the HPV negative group. No significant differences were found in pH value, leukocyte esterase, and Acetylglucosaminidase abnormality between 2 groups. The HR-HPV positive group presented a higher percentage of patients with cleanliness III and IV. Relative to low-grade squamous intraepithelial lesion (LSIL) group, HSIL group presented a higher HPV positive infection rate. Mould infection, Gardnerella infection, and catalase were identified as independent risk elements for HR-HPV infection. Vitamin D supplementation was found to potentially reduce HR-HPV infection persistence post-Loop Electrosurgical Excision Procedure (LEEP), improve nutritional health, reduce insulin, insulin resistance (HOMA-IR) and triglyceride levels, as well as reduce high-sensitivity C-reactive protein (hs-CRP) along with malondialdehyde (MDA) levels. Our results indicate that HR-HPV infection is intimately associated with the condition of the vaginal microenvironment, and vitamin D addition potentially reduces the persistence of HR-HPV infection post-LEEP, improves nutritional and metabolic health, reduces inflammation, and be well-tolerated.

Clinicopathologic and Genomic Features of Invasive Stratified Mucin-producing Carcinoma of the Uterine Cervix Coexisting With High-grade Squamous Intraepithelial Lesion.

Invasive stratified mucin-producing carcinoma (ISMC) is a specific type of adenocarcinoma of the cervix, which is associated with human papillomavirus infection and often coexists with other types of carcinomas. However, given its rarity, understanding of this disease remains insufficient. We present a unique case of ISMC of the cervix coexisting with a high-grade squamous intraepithelial lesion (HSIL). In addition to histologic and immunohistochemical feature observation, genomic profiling of the 2 lesions was performed. Histologically, the ISMC and HSIL lesions were independent of each other. Aside from the typical morphology, various architectural features of ISMC were observed. Immunohistochemically, the ISMC and HSIL lesions were strongly and diffusely positive for p16 and exhibited high Ki-67 expression. The ISMC lesion was also positive for CK7, MUC5AC, and MUC6, while it was negative for PAX-8. The HSIL lesion was positive for CK5/6 and p40. The combined positive score of PD-L1 was 55. The other markers were all negative in both lesions, and the p53 was wild-type. Next-generation sequencing analysis revealed multiple gene mutations in the ISMC and HSIL lesions. A total of 88 gene mutations were identified in the ISMC lesion, while 20 gene mutations were identified in the HSIL lesion. Three mutations (ERBB2, histidine decarboxylase gene [HDC], and BSN) were detected in the ISMC and HSIL lesions. Both lesions had a low tumor mutation burden and microsatellite-stable status. No copy number-associated variants or structural variations were identified in either lesion. These results suggest that patients with ISMC may benefit from PD-L1 immunotherapy and targeted therapy.

HPV and HCMV in Cervical Cancer: A Review of Their Co-Occurrence in Premalignant and Malignant Lesions

Cervical cancer remains a significant global health concern, particularly in low- and middle-income countries. While persistent infection with high-risk human papillomavirus (HR-HPV) is essential for cervical cancer development, it is not sufficient on its own, suggesting the involvement of additional cofactors. The human cytomegalovirus (HCMV) is a widespread β-herpesvirus known for its ability to establish lifelong latency and reactivate under certain conditions, often contributing to chronic inflammation and immune modulation. Emerging evidence suggests that HCMV may play a role in various cancers, including cervical cancer, through its potential to influence oncogenic pathways and disrupt host immune responses. This review explores clinical evidence regarding the co-presence of HR-HPV and HCMV in premalignant lesions and cervical cancer. The literature reviewed indicates that HCMV is frequently detected in cervical lesions, particularly in those co-infected with HPV, suggesting a potential synergistic interaction that could enhance HPV’s oncogenic effects, thereby facilitating the progression from low-grade squamous intraepithelial lesions (LSIL) to high-grade squamous intraepithelial lesions (HSIL) and invasive cancer. Although the precise molecular mechanisms were not thoroughly investigated in this review, the clinical evidence suggests the importance of considering HCMV alongside HPV in the management of cervical lesions. A better understanding of the interaction between HR-HPV and HCMV may lead to improved diagnostic, therapeutic, and preventive strategies for cervical cancer.

Relevance of Thyroid Microcarcinoma and Its Diagnosis

Microcarcinoma is a thyroid gland cancer with a size of less than 1 cm. The aim: To determine the frequency of microcarcinoma among malignant pathologies of the thyroid gland based on fine-needle aspiration biopsies (FNAB) data. Materials and Methods: A retrospective analysis of 2490 FNAB data was conducted under ultrasound control from 2007 to 01.07. 2024 at the Ternopil Regional Clinical Hospital. FNAB results were categorized into four groups: the first group – non-diagnostic results, the second – suspicion of thyroid cancer, the third – thyroid cancer, and the fourth – benign lesions. After the Bethesda system was introduced, FNAB classifications were based on this system. Results: Thyroid cancer was diagnosed in 186 cases (7.5%). Among these, macrocarcinoma was identified in 152 cases (81.7%) and microcarcinoma in 34 cases (18.3%). The peak incidence of microcarcinoma is observed in the 40-50 age, with approximately 90% of patients being women. Microcarcinomas in solitary nodules were found in 16 cases (47%); among multinodular goiters in 18 cases (53%). In 8 cases (23.5%), microcarcinoma was associated with larger thyroid cancers (multifocal process) and in 4 cases (11.8%) with benign nodules. In 6 cases (17.7%), microcarcinomas were associated with nodules suspicious for cancer. Conclusions: Indications for FNAB should be guided by the identified sonographic characteristics (solid echostructure of the nodule; hypoechogenicity; vertical orientation of nodules; indistinct margins of the nodule; presence of microcalcifications; regional cervical lymphadenopathy with signs of malignancy).

Liquid-based Cytological Features of Adenocarcinoma Not Otherwise Specified, Extrauterine Adenocarcinoma, and Other Malignant Neoplasms of The Uterine Cervix: A 5-year Single-institutional Experience With 30 Consecutive Patients.

The adenocarcinoma (ADC) and other malignant neoplasm (OMN) terminologies of The Bethesda System represent various histological types of uterine and extrauterine malignancies. This study aimed to clarify the incidences of ADC not otherwise specified (ADC-NOS), ADC extrauterine (ADC-EXT), and OMN in our institution and describe their characteristic cytomorphological features. We searched the database to identify all patients diagnosed with carcinoma, including those diagnosed through cervical liquid-based cytology (LBC), between January 2019 and December 2023. The electronic medical records and all available slides were reviewed. Overall, 30 of the 149,197 (0.02%) patients were diagnosed with ADC-NOS, ADC-EXT, and OMN. All three groups included various histological types of both gynecological and non-gynecological origin. More than two-thirds (23/30; 76.7%) were of uterine origin, but seven patients had metastatic carcinoma of extrauterine organ origin, including the ovary, lung, stomach, breast, colon, urethra, and pancreas. In all patients, the cytological features were concordant with the histological features. In LBC, ADC-NOS does not only encompass uterine cervical tumors, but also various types of extrauterine malignancies. ADC-EXT and OMN also represent both extrauterine and uterine tumors. Awareness of the morphological features observed in LBC samples of non-gynecological malignancies may be helpful in obtaining the correct diagnosis.

A novel methylation-detection panel for HPV associated high-grade squamous intraepithelial lesion and cervical cancer screening

Cervical cancer (CC) was considered to be the most common gynaecological cancer, with an estimated 342,000 deaths worldwide each year, as the majority of patients were diagnosed at an advanced stage of the disease. The purpose of this study was to evaluate the predictive value of multi-locus methylation assay for the early detection of CC. The cervical exfoliated cell samples from 492 HPV-positive females with cervical lesions were collected and subjected to methylation detection of gene FAM19A4, EPB41L3 and PAX1 after bisulfite conversion. The levels of gene methylation in patients with different severity of cervical lesions were evaluated and compared. The receiver-operating characteristic (ROC) curve was established and efficacy indexes such as sensitivity, specificity and area under the curve (AUC) were calculated to assess the diagnostic value of DNA methylation detection at multiple gene loci for CC. The methylation levels of FAM19A4, EPB41L3 and PAX1 were significantly increased with the grade of cervical squamous intraepithelial lesions. The sensitivities of FAM19A4, EPB41L3 and PAX1 alone for high-grade squamous intraepithelial lesion (HSIL) and CC diagnosis were 84.6%, 86.3% and 88.0%, respectively; when three markers were combined by a logistic regression model, the sensitivity was 88.0%, with a high specificity of 97.7% and AUC of 0.957 (95% CI 0.937–0.977). Methylation status of FAM19A4, EPB41L3 and PAX1 were highly specific and effective for monitoring the progression of cervical lesions and the tri-gene methylation assay could be used as a triage tool for CC early screening.

Clinical effect of secondary LEEP combined with transcervical resection of endocervical tissue for cervical precancerous lesions with positive internal margin after the first LEEP

Objective: To preliminarily investigate the clinical outcomes of secondary loop electrosurgical excision procedure (LEEP) combined with transcervical resection of endocervical tissue (i.e., second combined surgeries) in patients with positive endocervical margins following the initial LEEP for high-grade squamous intraepithelial lesion (HSIL) or adenocarcinoma in situ (AIS) of the cervix. Methods: Patients who underwent second combined surgeries due to positive endocervical margins after the initial LEEP for cervical HSIL or AIS at Obstetrics and Gynecology Hospital, Fudan University between August 2015 and September 2023 were included. Postoperative cytological examinations, high-risk human papillomavirus (HR-HPV) testing, colposcopic biopsy results, and cervical canal length were followed up to evaluate the clinical efficacy of second combined surgeries. Results: (1) General clinical data: a total of 67 patients were enrolled, including 34 with cervical HSIL (HSIL group) and 33 with AIS (AIS group). In the HSIL group before the time of initial LEEP, the mean age was (41.3±5.3) years, with all patients positive for HR-HPV preoperatively. Preoperative cytology results revealed ≤low-grade squamous intraepithelial lesion (LSIL) in 13 cases and ≥HSIL in 21 cases. The preoperative cervical canal length was (3.71±0.17) cm. Patients in the AIS group before their the first LEEP were at an average age of (39.1±8.7) years old, with preoperative HR-HPV positive. Among them, 16 cases showed preoperative cytological results of ≤LSIL, while 17 cases showed ≥HSIL. The preoperative cervical canal length was (3.64±0.21) cm. (2) Pathological findings and postoperative follow-up of the HSIL group following second combined surgeries:in the HSIL group, the residual rate of HSIL in the endocervical canal tissue (ECT) was 24% (8/34). Out of the 34 HSIL patients, 10 cases (29%, 10/34) remained with positive endocervical margins post-second combined surgeries. Among these 10 patients, 5 cases (5/10) had no lesion detected in ECT, while the remaining 5 cases (5/10) exhibited HSIL in their ECT. Conversely, 24 patients (71%, 24/34) had negative endocervical margins after second combined surgeries. Of these 24 patients, 3 cases (12%, 3/24) were found to have HSIL in ECT, and 21 cases (88%, 21/24) had no lesion in ECT. During follow-ups conducted at 6 and 12 months post-second combined surgeries, the clearance rates of HR-HPV were 91% (31/34) and 100% (34/34), respectively. Notably, among the 29 patients (85%, 29/34) who were followed up for a period of 2 years or longer, all cases maintained a consistently negative HR-HPV status, highlighting the effectiveness of second combined surgeries in achieving long-term HR-HPV clearance (100%, 29/29). (3) Pathological findings and postoperative follow-up of the AIS group following second combined surgeries: the residual rate of AIS in the ECT following second combined surgeries among AIS patients was 15% (5/33). Out of the 33 AIS patients, 11 cases (33%, 11/33) had positive endocervical margins post-operation, among whom AIS was detected in the ECT of 2 cases (2/11), while 1 case (1/11) was diagnosed with adenocarcinoma in the cervical canal tissue (subsequently underwent radical surgery and was excluded from this study). In contrast, 22 patients (67%, 22/33) had negative endocervical margins post-operation, with AIS found in the ECT of 2 cases (9%, 2/22) and no lesions detected in the remaining 20 cases (91%, 20/22). Follow-up evaluations conducted at 6 and 12 months postoperatively revealed HR-HPV clearance rates of 91% (29/32) and 97% (31/32), respectively. All 32 (100%, 32/32) AIS patients were followed up for a duration of ≥2 years post-second combined surgeries, during which HR-HPV remained consistently negative. (4) Complications and cervical length following second combined surgeries: neither the HSIL group nor the AIS group experienced significant complications such as hemorrhage, infection or cervical canal adhesion. At the 6-month follow-up, the cervical length of both HSIL and AIS patients exceeded 3 cm. By the 12-month follow-up, the cervical length had recovered to 96.5% and 97.5% when compared to the original length, respectively, for the HSIL and AIS groups. Conclusions: For patients with HSIL or AIS who exhibit positive endocervical margins following the initial LEEP procedure, undergoing second combined surgeries presents as an optimal choice. This surgical intervention guarantees thorough excision of the lesion, and subsequent colposcopic follow-up evaluations consistently demonstrate an absence of residual disease or recurrence. Moreover, it augments the rate of sustained HR-HPV negativity, thereby contributing to more favorable clinical outcomes.

The role of HIV as an independent risk factor to cervical HSIL recurrence.

To evaluate the role of being human immunodeficiency virus (HIV) positive for predicting the risk of recurrence in women with a cervical high grade squamous intraepithelial lesion (HSIL) diagnosis. Retrospective observational case-control study, comprising HIV positive (case) and HIV negative (control) women in a 1:4 ratio. Women assisted by the Erasto Gaertner Hospital, between 2009-2018, with cervical HSIL diagnosis, submitted to treatment by Loop electrosurgical excision procedure (LEEP), and with a minimum follow-up of 18 months, were included. The immunological status, number and time to recurrence were analyzed, with p<0.05 considered significant. In a second analysis, only patients with free margins were evaluated. The sample consisted of 320 women (64 cases and 256 controls). Presence of HIV, CD4 levels <200 and detectable viral load (CV) were associated with high risk of recurrence, with odds ratio (OR) of 5.4 (p<0.001/95CI:2.8-10); 3.6 (p<0.001 /IC95:0.6-21.1) and 1.8 (p=0.039 /IC95:0.3-9.3), respectively. In the sample with free margins (n=271), this risk was also higher among seropositive patients, with OR 4.18 (p=0.001/95CI:1.8-9.2). HIV is an independent risk factor for cervical HSIL recurrence and reduced disease-free survival time. Glandular involvement, compromised margins, undetectable CV and CD4<200 also increase the risk of relapse.

Trends in high-risk human papillomavirus infection and cervical cytology of women in Karamay City, 2012-2021.

Background To describe the changes in cervical lesions prevalence and high-risk human papillomavirus (HR-HPV) infections from 2012 to 2021, which have never been reported before, to provide direction for the effective implementation of cervical cancer prevention measures. Methods This retrospective study included women aged >25years who received either organised or opportunistic cervical HR-HPV screening from January 2012 to December 2021 in Karamay Central Hospital, Karamay, China. The patients were split into four groups according to age 25-35, 36-45, 46-55 and >55years, respectively. The Joinpoint Regression Program was used to analyse the trends of HR-HPV infection and the detection of cervical lesions. Results Data from 85,429 women revealed a decline in HR-HPV infection rates across all age groups from 2012 to 2021. Although HR-HPV infection rates decreased, cervical lesion detection rates increased, although the proportion of cervical cancer in these lesions declined, likely due to enhanced awareness and HPV vaccination in Karamay. From 2012 to 2021, the prevalence of low-grade squamous intraepithelial lesions was 9.70%, and high-grade squamous intraepithelial lesions was 5.85%. HR-HPV infections were highest in the ≥55years age group, with HPV52 (20.96%) being the most prevalent type. Conclusions In the past 10years, the prevalence of HR-HPV infection has shown a decreasing trend, whereas the detection prevalence of cervical lesions has shown an upward trend among women in Karamay City. Importantly, particular emphasis should be placed on cervical cancer screening in women aged >55years.

Artificial Intelligence and Colposcopy: Automatic Identification of Vaginal Squamous Cell Carcinoma Precursors

Background/Objectives: While human papillomavirus (HPV) is well known for its role in cervical cancer, it also affects vaginal cancers. Although colposcopy offers a comprehensive examination of the female genital tract, its diagnostic accuracy remains suboptimal. Integrating artificial intelligence (AI) could enhance the cost-effectiveness of colposcopy, but no AI models specifically differentiate low-grade (LSILs) and high-grade (HSILs) squamous intraepithelial lesions in the vagina. This study aims to develop and validate an AI model for the differentiation of HPV-associated dysplastic lesions in this region. Methods: A convolutional neural network (CNN) model was developed to differentiate HSILs from LSILs in vaginoscopy (during colposcopy) still images. The AI model was developed on a dataset of 57,250 frames (90% training/validation [including a 5-fold cross-validation] and 10% testing) obtained from 71 procedures. The model was evaluated based on its sensitivity, specificity, accuracy and area under the receiver operating curve (AUROC). Results: For HSIL/LSIL differentiation in the vagina, during the training/validation phase, the CNN demonstrated a mean sensitivity, specificity and accuracy of 98.7% (IC95% 96.7–100.0%), 99.1% (IC95% 98.1–100.0%), and 98.9% (IC95% 97.9–99.8%), respectively. The mean AUROC was 0.990 ± 0.004. During testing phase, the sensitivity was 99.6% and 99.7% for both specificity and accuracy. Conclusions: This is the first globally developed AI model capable of HSIL/LSIL differentiation in the vaginal region, demonstrating high and robust performance metrics. Its effective application paves the way for AI-powered colposcopic assessment across the entire female genital tract, offering a significant advancement in women’s healthcare worldwide.

Concomitant Cervical and Anal Screening for Human Papilloma Virus (HPV): Worth the Effort or a Waste of Time?

This study represents a follow-up analysis of the AnusGynecology (ANGY) study. This prospective, cross-sectional, single-center study recruited women for concomitant cervical and anal screening of HPV genotypes and cytology during a single appointment. All women with findings of either HPV or any type of dysplastic lesions on anal smears were offered follow-up in a specialized high-resolution anoscopy (HRA) outpatient clinic, representing the study cohort for this follow-up study. Overall, 275 patients (mean age 42 ± 12) were included. Among them, 102 (37%) had cervical high-risk (HR) HPV. In total, HPV was (incidentally) revealed in 91 patients (33%) on anal smears, while any degree of anal squamous intraepithelial lesion (SIL) was found in 30 patients (11%), 6 if which were high-grade SIL (H-SIL). Furthermore, 10 out of 19 biopsies were positive (3 H-SIL lesions). Only half (48/91, 53%) of the women agreed to undergo the recommended specialized follow-up evaluation. Of them, 18 (38%) were diagnosed with dysplastic lesions (9 low grade (L-SIL) and 9 H-SIL, respectively) on biopsies, while the remaining visits revealed no abnormalities. Multivariable analysis revealed cervical HR-HPV infection (OR 4, 95% CI 2.2-7.5) and anal intercourse (OR 3.1, 95% CI 1.7-5.9) as independent risk factors for anal HR-HPV infection. Close follow-up of these women is hence strongly recommended.

The Prevalence of Abnormal Cervical Cytology at Federal Teaching Hospital Gombe: A Cross-Sectional Study

Introduction: Cervical cancer continues to be a significant public health concern, ranking as the fourth most common cancer among women globally, with approximately 604,000 new cases and 342,000 deaths reported in 2020 (World Health Organization, 2020). The burden of cervical cancer disproportionately affects women in low- and middle-income countries (LMICs), where access to effective screening and treatment options is often limited. Early detection and treatment of cervical premalignant lesions are crucial in reducing the incidence and mortality associated with this preventable disease. The objectives of this study was to determine the prevalence of abnormal cervical cytology, the histological types and patient characteristics among patients attending the Gynaecology/postnatal clinic of Federal Teaching Hospital, Gombe State, Nigeria. Methods: A retrospective study of all cervical smears received and processed at the Pathology laboratory of Federal Teaching Hospital between January 2022 and December 2022. Results: The records of 596 smears of women between the ages of 20 and 65 years were retrieved and analyzed. Negative smears were predominant (62.6%) while 8.7% were inflammatory smears. Dyskaryotic smears were found in 155 smears (26.0%); this was made up atypical glandular cells of undetermined significance (AGCUS) in 1.8%, Atypical squamous cells of undetermined significance (ASCUS) in 10.23%, Low grade squamous intraepithelial lesion (LSIL) in 10.6% and High grade squamous intraepithelial lesion (HSIL) in 3.6%. Malignant cells were found in 0.5% of the smears while the remaining 2.1% were unsatisfactory. Conclusion: The relatively high frequency of dyskaryosis in this study lends credence to the need for us to widen our cervical screening coverage in order to achieve the highest possible coverage rate. This can be achieved through the use of public education by means of various media, women and religious organizations.

Gray zone Bethesda category III – Atypia of undetermined significance lesions of the thyroid: Potential diagnostic issues and image morphometry as a useful adjunct to cytomorphology

Gray zone Bethesda category III – Atypia of undetermined significance lesions of the thyroid: Potential diagnostic issues and image morphometry as a useful adjunct to cytomorphology

High-risk human papillomavirus diversity among indigenous women of western Botswana with normal cervical cytology and dysplasia

BackgroundCervical cancer remains a public health problem despite heavy global investment in health systems especially in low-and-middle-income countries (LMIC). Prophylactic vaccines against the most commonly detected human papillomavirus (HPV) types in cervical cancers are available and decisions on the selection of vaccine design depends on the prevalence of high-risk (hr) HPV genotypes for a particular region. In 2015, Botswana adopted the use of a quadrivalent HPV vaccine as a primary prevention strategy. Secondary prevention includes cervical smear screening whose uptake remains notably low among indigenous and marginalized communities despite efforts to improve access.AimTo determine the prevalence of hrHPV genotypes and cervical lesions’ burden in women from the indigenous and marginalized communities of Botswana.MethodsThis prospective survey enrolled 171 non-HPV vaccinated women aged 21 years and older. Face-to-face interviews, Pap smear screening, hr-HPV and Human Immuno-deficiency virus (HIV) testing were carried out. Conventional Papanicolau smears were analyzed and cervical brushes were preserved for hrHPV testing using the Ampfire Multiplex HR-HPV protocol which detects the following genotypes: HPV 16, 18, 31, 35, 39, 45, 51, 52, 53, 56, 58, 59 and 68.ResultsIn this study, 168/171 (98.6%) of the women consented to HIV testing; 53/171 (31%) were living with HIV and self-reported enrolment on antiretroviral therapy. Among the women examined, 23/171 (13.5%) had cervical dysplasia with most presenting with Atypical Squamous Cells of Undetermined Significance 8/23 (35%), Low-Grade Squamous Intraepithelial Lesions 8/23 (35%), Atypical Squamous Cells-High Grade 4/23 (17%), Atypical Endocervical Cells 2/23 (9%) and Atypical Endocervical Cell favoring neoplasia 1/23(4%). However, no High-Grade Squamous Intraepithelial Lesions (HSIL) or squamous cell carcinoma (SCC) were detected. Overall hrHPV prevalence in this study was at 56/171 (32.7%). The most commonly detected hrHPV genotypes in women with cervical dysplasia were HPV39 (6.25%), HPV51 (14.5%), HPV52 (12.5%) and HPV56 (4%). Notably, HPV 16 and 18 were not found in women with cervical dysplasia.ConclusionsOur study provides valuable insights into the prevalence and distribution of hrHPV genotypes in indigenous and marginalized communities in Botswana, and the need for further investigation of their potential role in cervical carcinogenesis in this population. These results may also serve as baseline data to facilitate future evaluation of the HPV vaccine needs.

An unusual liver tumor with challenging morphologic features and immunophenotype: A case report of metastatic HPV-driven basaloid anal squamous cell carcinoma

Abstract Introduction/Objective Basaloid squamous cell carcinoma (BSCC), a rare subtype of squamous cell carcinoma, occurs most commonly in esophagus, lungs, and head and neck. Anal BSCC is extremely rare and has a 10-20% rate of metastasis. High-risk HPV (HR-HPV) is the main causative agent. BSCC occurrence in an atypical site without a known primary tumor, and with atypical immunoprofile can be a diagnostic challenge. Methods/Case Report We report an 83-year-old female with history of breast carcinoma who presented for worsening chest pain. Imaging studies showed pulmonary nodules, 1.8 cm hepatic mass, and pelvic nodules. Liver biopsy showed infiltrating nests of carcinoma with solid and cribriform patterns and luminal necrosis. Some tumor nests had basaloid features with peripheral palisading. Tumor was positive for CK7 and pankeratin; and negative for ER, SOX10, GATA3, GCDFP-15 (Breast markers), CDX2 (GI marker), P63 and P40 (squamous markers), INSM1, Synaptophysin (Neuroendocrine) and TTF1 (lung adenocarcinoma). There was microfocal staining with CK20 and SATB2. Tumor morphology and immunophenotype were not entirely specific to the site of origin. Further search into patient’s medical history showed a recent anal mucosal biopsy revealing a high-grade squamous epithelial lesion with diffuse P16 reactivity. The slides for the anal lesion were reviewed and showed morphologic features similar to the liver biopsy. Additional studies showed both tumors were positive for HR-HPV ISH, P16 (diffuse), and CK5/6 (patchy); and negative for P63. The morphologic features and immunoprofile were supportive of metastasis from HPV-driven BSCC of anus. Subsequent PET Scan revealed a rectal/anal mass. Results (if a Case Study enter NA) NA Conclusion For tumors with unusual morphology and immunophenotype, complete medical history review, and communication with clinician are important tools in achieving correct diagnosis. HR-HPV ISH is a new tool that can be very useful in reaching correct diagnosis in metastatic anogenital or oropharyngeal squamous carcinomas with basaloid features.

Results of Pap Smear in Females Who are Actively Reproducing in Outlying Medical Centers at Parachinar

Objective: To ascertain the prevalence of different cervical abnormalities in connection t pap smear results with age distribution of patient.  Method The demographic makeup of the study population was deduced by calculating the percentages of patients in each age group. Numerous diseases were also identified using the results of the Pap smear test, and percentages associated with each diagnosis were computed. This methodology made it possible to thoroughly analyze the participants' diagnoses and age distribution, which revealed trends in cervical health. One hundred participants in all had Pap smears performed as part of the study. Four age groups were established based on the age distribution data gathered: 18–25, 25–35, 35–45, and 45–55 years old.  Result The majority of participants (37%) were found to be between the ages of 25 and 35, while there was a wide variation of participant ages overall. Pap smear tests are crucial for identifying potentially malignant or precancerous diseases, as evidenced by the majority of patients (71%) receiving a diagnosis of cancer or intraepithelial lesions. There was also representation from the following age groups: 18–25 (9%), 35–45 (28%), and 45–55 (4%). Four percent of the cases had atypical squamous cell lesions, two percent had low-grade squamous intraepithelial lesions, and one percent had high-grade lesions.  Conclusion These findings advance customized screening programs and therapies aimed at specific age groups and diagnostic categories as well as our knowledge of cervical health patterns. People who are fertile should definitely get screened for cervical cancer because the age group of 25 to 35 accounts for a substantial portion of diagnoses. The importance of Pap smear testing for early identification and preventive medicine is underscored by the prevalence of intraepithelial lesions or cancer.

Does the Diagnostic Performance of the Pathologist on the Indeterminate Categories of the Bethesda System for Reporting Thyroid Cytopathology Vary between Pediatric and Adult Patients?

The objectives of this study were to investigate the variation in the use of indeterminate categories of The Bethesda System for reporting thyroid cytopathology across age groups, particularly focusing on atypia of undetermined significance (AUS) category, and discern the potential role of a bias in pathologist's interpretation when dealing with pediatric patients. To highlight a more refined diagnostic pattern, thyroid fine-needle aspirations reported by a single pathologist over a span of 10 years enrolled to the study. A total of 8,827 cases from patients aged between 2 and 89 were categorized for each decades of ages. For the AUS category, AUS to malignant (AUS:M) ratio was calculated, and variations in distinct age groups and across the years were noted. The rate of indeterminate categories was 19% for the pediatric cases and 11% for the adults. When compared to adults, AUS diagnosis was more common in pediatric patients (14% vs. 9%), with rates of malignancy (ROMs) 54% and 45%, respectively. The AUS:M ratio during the study period ranged between 0.5 and 2.3 (mean 1.4). AUS:M ratio was highest in children below the age 11. Among AUS subtypes, AUS-nuclear predominated in both age groups, and papillary thyroid carcinoma emerged as the most common malignancy after resection. Follicular neoplasia category was higher in pediatric patients than in adults (4% vs. 1%), with similar ROMs (29% vs. 32%). Indeterminate cytology diagnosis and subsequent ROM is higher in pediatric patients, which might be attributable to a slightly higher use of AUS diagnosis in the youngest children.

CYTOLOGICAL DIAGNOSTICS OF THYROID DISEASES: BASIC PRINCIPLES AND FEATURES OF APPLICATION IN MODERN CONDITIONS

Introduction. Cytological diagnostics of thyroid diseases widely used in medical practice today. The standards and guidelines used in this examination ensure close cooperation between doctors of different specialties. Aim of research: To determine the methodological and organizational features of cytological examination of the thyroid gland, which can improve the use of this diagnostic method in Ukraine. The effectiveness of cytological examination depends on many factors. First of all, it is important to use this method in cases where the test result can be sufficiently informative and help identify thyroid diseases, choose further diagnostic and appropriate treatment tactics. Important stages in the actual cytological examination of thyroid diseases are: sampling, fixation and staining of cytological specimens, evaluation of microscopic changes, formulation of a cytological conclusion, and, if necessary, the use of immunocytochemical and molecular genetic methods. Compared to other countries, Ukraine has a higher incidence of uninformative reports in cytological diagnostics of thyroid diseases. The reasons for this are most likely more frequent violations of the technique of puncture, fixation and transportation of the material. It should be noted that cytologic examination in Ukraine is performed by a laboratory doctors, while in most countries of the world this examination is performed by a pathologist. Conclusions. In order to improve the effectiveness of the method of cytological diagnostics of thyroid diseases in Ukraine, it is necessary to ensure proper compliance with the relevant norms, standards and rules at all stages of its implementation. Taking into account the current regulatory norms and rules for cytological examinations in Ukraine, it is necessary to improve the qualifications of laboratory doctors in the field of cytological diagnostics of thyroid diseases, officially to include the method of cytological diagnostics into the work of a pathologist and to actively implement in medical practice The Bethesda System for Reporting Thyroid Cytopathology, 2023.

Development of a clinical prediction model for pathological upgrading in low-grade squamous intraepithelial lesions following cervical conization

Development of a clinical prediction model for pathological upgrading in low-grade squamous intraepithelial lesions following cervical conization